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Abstract Turner syndrome (TS) is a genetic condition characterized by partial or complete monosomy X. A reduced life expectancy has been shown in TS, depending on an increased risk of aortic dissection, and ischemic heart disease. Studies covering the occurrence of psychiatric conditions are sparse within TS. Several case reports describe concomitant TS and neuropsychiatric abnormalities that may represent a pathogenetic link to genetics, as well as feature correlates of TS. The aim of this study was to determine the presence, and the frequency of psychiatric diagnosis in women with TS in a Swedish cohort followed during 25 years’ time. Statistics from the entire female population in Sweden of corresponding age was used as reference. Data were retrieved from clinical examinations and validated from the National Board of Health and Welfare registries for women with TS (n = 487), aged 16 to 84 years, with respect to mental health disorders. The most common diagnoses in TS were mood and anxiety disorders. There was no increase in psychiatric diagnosis within the group with time, nor correlation to specific karyotype or somatic comorbidity as congenital heart disease and hypothyroidism, hormonal treatment, or childbirth. In addition, the frequency of psychiatric diagnosis in TS was lower than in the population-based data. Further investigations are needed in the view of the fact that women with Turner syndrome should not be burdened with more severe diagnoses.

Background Overweight and obesity are increasing globally with aging, as are life expectancy and aging‐associated disorders, including calcific aortic stenosis (AS). Studies investigating the correlation between high body mass index (BMI) and AS are contradictory and inconclusive. This study examines a potential association between BMI and AS in women. Methods and Results By linking the Swedish Medical Birth Register and the Swedish National Patient Register, we included women aged 18 to 55 years with a first childbirth from 1981 to 2020. Diagnosis of AS and comorbidities were defined according to the International Classification of Diseases (ICD) codes. The women were divided into groups on the basis of BMI. Cox proportional hazards regression models were used to investigate the difference in the risk of being diagnosed with AS, with reference BMI 20 to

Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, retrospective chart review describes treatment patterns and clinical outcomes among patients (≥18 years old) from Finland, Sweden, and France who developed grades II–IV aGVHD after their first HSCT (January 2016–June 2017). From 13 participating centers, 151 patients were included. The median (Q1, Q3) age at HSCT was 56 (45, 62) years old. One line of aGVHD treatment was received by 47.7%, and the most common first-line treatment was methylprednisolone (alone or in a combination regimen, 74.2%; monotherapy, 25.8%). Among patients treated with methylprednisolone, 79.5% achieved a complete or partial response. The median (Q1, Q3) number of treatment lines was 2.0 (1.0, 3.0). The median (Q1, Q3) time to obtain an aGVHD diagnosis from transplant was 29.5 (21.0, 44.0) days, and 14.5 (7.0, 34.0) days to achieve the best response for 110 evaluable patients. At 6 and 12 months, 53.6% and 49.0%, respectively, achieved a complete response. Chronic GVHD occurred in 37.7% of patients, and aGVHD reoccurred in 26.5%. Following aGVHD diagnosis, mortality rates were 30.0% at 6 months and 37.3% at 12 months. Findings from this study demonstrate a continuing unmet need for new therapies that control aGVHD and improve mortality.

Background It has been estimated that 80% of cases of out-of-hospital cardiac arrest (OHCA) are due to cardiac causes. It is well-documented that diabetes is a risk factor for conditions associated with sudden cardiac arrest. Type 1 diabetes (T1D) displays a threefold to fivefold increased risk of cardiovascular disease and death compared with the general population.Objective This study aims to assess the characteristics and survival outcomes of individuals with and without T1D who experienced an OHCA. Design: A registry-based nationwide observational study with two cohorts, patients with T1D and patients without T1D. Setting: All emergency medical services and hospitals in Sweden were included in the study.Participants Using the Swedish Cardiopulmonary Resuscitation Registry, we enrolled 54 568 cases of OHCA where cardiopulmonary resuscitation was attempted between 2010 and 2020. Among them, 448 patients with T1D were identified using International Classification of Diseases-code: E10.Methods Survival analysis was performed using Kaplan-Meier and logistic regression. Multiple regression was adjusted for age, sex, cause of arrest, prevalence of T1D and time to cardiopulmonary resuscitation.Main outcome measures The outcomes were discharge status (alive vs dead), 30 days survival and neurological outcome at discharge.Results There were no significant differences in patients discharged alive with T1D 37.3% versus, 46% among cases without T1D. There was also no difference in neurological outcome. Kaplan-Meier curves yielded no significant difference in long-term survival. Multiple regression showed no significant association with survival after accounting for covariates, OR 0.99 (95% CI 0.96 to 1.02), p value=0.7. Baseline characteristics indicate that patients with T1D were 5 years younger at OHCA occurrence and had proportionally fewer cases of heart disease as the cause of arrest (57.6% vs 62.7%).Conclusion We conclude, with the current sample size, that there is no statistically significant difference in long-term or short-term survival between patients with and without T1D following OHCA.

Background: Individuals with substance use disorder (SUD) and recovery support services often face significant social stigma, especially in rural areas. One method of addressing stigma is through education and personal recovery stories. It is unclear if such messages will work similarly across rural and non-rural areas. Methods: We conduct an exploratory analysis of data from a national randomized controlled trial (N = 2,721) to determine if there are differences in the effectiveness of messages at reducing stigma across rurality. Specifically, we test four interventions to reduce stigma: education about the effectiveness of recovery housing and three versions of a personal recovery story that varied social distance and delivery medium (identified written story, anonymous written story, and video). Results: We find that messages may not have the same effect across rurality, with non-rural participants in the identified and anonymous written recovery story groups having lower stigma scores and only rural participants exposed to the anonymous written story having lower stigma scores compared to their counterparts in the control group. Further, non-rural participants exposed to both written story treatments had higher positive feelings towards those in recovery compared to the control group, but only rural participants in the anonymous written story group had higher positive feelings compared to the control group. Conclusion: Our results suggest that messages may have different effects on stigma across rurality and that rural participants’ beliefs may be particularly hard to change. Future research should examine what types of stigma reduction interventions are most effective in rural areas.

Abstract Background Arsenic (ATO) and retinoic acid (ATRA) are successfully used as chemotherapy-free regimens to treat acute APL. Compared to traditional chemotherapy approaches, this therapy evokes fewer haematological side effects, such as severe neutropenia and thrombocytopenia, but little is known about the impact of the treatment on neutrophil function. Methods We included three patients undergoing consolidation treatment for APL. To evaluate the functionality of neutrophils, we assessed chemotaxis, ROS production, and neutrophil extracellular trap (NET) release during different time points of the treatment and compared them with neutrophils from healthy donors. Results We revealed that the chemotactic ability of neutrophils isolated from APL patients was decreased before starting each cycle of treatment. However, there was an increase in chemotactic ability in the first week of treatment compared to other time points. Additionally, we observed increased ROS production at the start of the treatment cycle. In vitro exposure of isolated neutrophils from healthy donors to ATO led to decreased chemotaxis at high ATO concentrations exceeding those achieved in vivo, while ROS production was not affected. Chemotaxis and ROS production were not altered by exposure to ATRA in vitro and neither ATO nor ATRA had an effect on neutrophils’ ability to release NETs. Conclusions Our study suggests that ATO and ATRA therapy alter neutrophil function by increasing chemotaxis and reducing ROS production. The effect on neutrophil function does not, however, seem to impact infection susceptibility in our patients, indicating that the enhanced functionality might compensate for the lowered neutrophil count.

Background and aims Pre-eclampsia complicates 3–5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia.Methods In a registry-based case–cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother’s birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases.Results Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls.Conclusion Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.

BackgroundThe use of chatbots in mental health support has increased exponentially in recent years, with studies showing that they may be effective in treating mental health problems. More recently, the use of visual avatars called digital humans has been introduced. Digital humans have the capability to use facial expressions as another dimension in human-computer interactions. It is important to study the difference in emotional response and usability preferences between text-based chatbots and digital humans for interacting with mental health services. ObjectiveThis study aims to explore to what extent a digital human interface and a text-only chatbot interface differed in usability when tested by healthy participants, using BETSY (Behavior, Emotion, Therapy System, and You) which uses 2 distinct interfaces: a digital human with anthropomorphic features and a text-only user interface. We also set out to explore how chatbot-generated conversations on mental health (specific to each interface) affected self-reported feelings and biometrics. MethodsWe explored to what extent a digital human with anthropomorphic features differed from a traditional text-only chatbot regarding perception of usability through the System Usability Scale, emotional reactions through electroencephalography, and feelings of closeness. Healthy participants (n=45) were randomized to 2 groups that used a digital human with anthropomorphic features (n=25) or a text-only chatbot with no such features (n=20). The groups were compared by linear regression analysis and t tests. ResultsNo differences were observed between the text-only and digital human groups regarding demographic features. The mean System Usability Scale score was 75.34 (SD 10.01; range 57-90) for the text-only chatbot versus 64.80 (SD 14.14; range 40-90) for the digital human interface. Both groups scored their respective chatbot interfaces as average or above average in usability. Women were more likely to report feeling annoyed by BETSY. ConclusionsThe text-only chatbot was perceived as significantly more user-friendly than the digital human, although there were no significant differences in electroencephalography measurements. Male participants exhibited lower levels of annoyance with both interfaces, contrary to previously reported findings.

Background: Aortic dilation, cardiac malformations and hypertension are known risk factors for aortic dissection in Turner syndrome (TS). In the current guidelines, rapid growth of the aorta has been added as a risk marker. This study aimed to estimate the growth of the ascending aorta over time, to identify risk factors of aortic growth, and to describe aortic complications in TS. Methods: A transthoracic echocardiogram was performed at least twice in 101 women with TS, mean age 28 years, with a mean follow-up of 8.3 ± 3.4 (range 1–17) years. The investigator was blinded to the clinical status. Logistic regression analysis was used to identify risk factors of aortic growth. Results: The prevalence of ascending aortic dilation (ASI >20 mm/m2) was 26 % and the mean ascending aortic diameter was 27.0 ± 4.8 mm at baseline. Significant aortic growth was found at sinus of Valsalva 1.08 (±2.11) mm, sinotubular junction 1.07 (±2.23) mm, and the ascending aorta 2.32 (±2.93) mm, p

The complex electronic structure of metallic ferromagnets is determined by a balance between exchange interaction, electron hopping leading to band formation, and local Coulomb repulsion. By combining high energy and temporal resolution in femtosecond time-resolved X-ray absorption spectroscopy with ab initio time-dependent density functional theory we analyze the electronic structure in fcc Ni on the time scale of these interactions in a pump-probe experiment. We distinguish transient broadening and energy shifts in the absorption spectra, which we demonstrate to be captured by electron repopulation respectively correlation-induced modifications of the electronic structure, requiring to take the local Coulomb interaction into account.

Objective Calm rooms have been developed and implemented in psychiatric inpatient care settings to offer patients a dedicated space for relaxation in a convenient and safe environment. Recent technology developments have enabled virtual reality (VR) equivalents of calm rooms that can be feasibly deployed in psychiatric care settings. While research has shown VR environments to be efficacious in inducing relaxation, little is known how these virtual calm rooms are perceived by patients. The aim of this study was to elucidate patient experiences of using a VR calm room in a psychiatric inpatient setting.Design Qualitative interview study. Semi-structured interviews were analysed using qualitive inductive content analysis, which focuses on the interpretation of texts for making replicable and valid inferences.Setting Swedish hospital psychiatric inpatient care setting with a wireless, three degrees-of-freedom VR head-mounted display running a calm room application simulating nature environment.Participants 20 adult patients (12 women) with bipolar disorder (n=18) or unipolar depression (n=2).Results Participants experienced the use of the VR calm room as having a positive impact on them, inducing awareness, calmness and well-being. They were thankful to be offered a non-pharmacological alternative for anxiety relief. Participants also expressed that they had some concerns about how they would react emotionally before using the VR device. However, after use, they highlighted that their overall experience was positive. They also expressed that they could see potential for further development of VR technology in psychiatric care.Conclusions VR technology has the potential to solve pressing logistic issues in offering calm rooms in psychiatric inpatient care. VR calm rooms appear to be appreciated by psychiatric inpatients, who value their accessibility, convenience and variety of modalities offered. Participants perceived an increase in their well-being after use.

Abstract Two distinct strategies for controlling an emerging epidemic are physical distancing and regular testing with self-isolation. These strategies are especially important before effective vaccines or treatments become widely available. The testing strategy has been promoted frequently but used less often than physical distancing to mitigate COVID-19. We compared the performance of these strategies in an integrated epidemiological and economic model that includes a simple representation of transmission by “superspreading,” wherein a relatively small fraction of infected individuals cause a large share of infections. We examined the economic benefits of distancing and testing over a wide range of conditions, including variations in the transmissibility and lethality of the disease meant to encompass the most prominent variants of COVID-19 encountered so far. In a head-to-head comparison using our primary parameter values, both with and without superspreading and a declining marginal value of mortality risk reductions, an optimized testing strategy outperformed an optimized distancing strategy. In a Monte Carlo uncertainty analysis, an optimized policy that combined the two strategies performed better than either one alone in more than 25% of random parameter draws. Insofar as diagnostic tests are sensitive to viral loads, and individuals with high viral loads are more likely to contribute to superspreading events, superspreading enhances the relative performance of testing over distancing in our model. Both strategies performed best at moderate levels of transmissibility, somewhat lower than the transmissibility of the ancestral strain of SARS-CoV-2.

Abstract This paper explores the potential for a system to be a co-author on an academic paper based on the criteria proposed by the International Committee of Medical Journal Editors (ICMJE). We used a third generation generative pretrained transformer (GPT-3) to write a review paper on the topic of its choice: The Effects of Sleep Deprivation on Cognitive Function. The system was asked to fulfill the four main criteria for co-authorship as recommended by ICMJE, which includes contributions to the conception or design of the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work. Our results showed that the system was able to fulfill the criteria, with significant difficulties with accurate and reliable referencing. We also explored the ethical implications of using AI systems for research and found that it is important to take a cautious approach when considering its use for scientific authorship. This case study provides a methodology for further investigations into the possibilities and limitations of automated writing.

Abstract Aims To determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up‐titration of guideline‐directed medical therapy (GDMT) in real‐world settings. Methods A retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6 months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6 months of up‐titration. Results Of 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8 years, mean EF of 29.4%). After up‐titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P

BackgroundInterest in sensory rooms or so-called “calm rooms” in psychiatric inpatient care has increased significantly. In a hospital setting, their purpose is to introduce a relaxing environment to increase well-being as well as to decrease anxiety and aggressive behaviors. Calm rooms can also be used as a tool to provide self-help through a convenient environment for the patients and, at the same time, strengthen the therapeutic relationship between the patient and the professional. Recent developments in virtual reality (VR) have made virtual calm rooms possible, but these have not yet been evaluated in psychiatric inpatient care. ObjectiveThis study aimed to compare the effects of VR and physical calm rooms on self-reported well-being and physiological markers of arousal. MethodsThe study was conducted in 2 inpatient psychiatric wards specializing in bipolar disorder from March 2019 to February 2021. Patients who were already admitted were asked if they were interested in using a calm room and willing to provide ratings. This study relied on the quasi-randomized allocation of patients to the wards, which either had a physical or VR calm room. Self-assessment scales (Montgomery-Åsberg Depression Rating Scale-Self Assessment [MADRS-S], Beck Anxiety Scale, and Clinical Global Impression) were used to determine the participants' baseline level of depressive and anxiety symptoms before their use of the physical or VR calm room. The study determined the state of well-being measured using an 11-point visual analog scale (VAS) as well as arousal measured by blood pressure (systolic and diastolic) and heart rate before and after the use of the calm rooms. The primary end point was self-reported well-being using the VAS. ResultsA total of 60 participants were included—40 used the VR calm room and 20 used the physical calm room. The mean age of participants was 39 years and the majority were women (35/60, 58%). Analysis of VAS measurement showed improved well-being at the group level from before to after the intervention (P20 or ≤20) despite an overall difference in reported well-being between subgroups. ConclusionsAlthough the power in this study was low, the findings of this first study indicate comparable effects with respect to well-being and arousal of a VR calm room and a physical calm room. This suggests that a VR calm room can be a viable alternative when the use of a physical calm room is not an option for logistic or other reasons. Trial RegistrationClinicalTrials.gov NCT03918954; https://clinicaltrials.gov/ct2/show/NCT03918954

Abstract We examine how salience of extreme actions to gain access to vaccines affect general vaccine preferences using a survey experiment conducted shortly after a limited supply of COVID-19 vaccines were made available to prioritized groups. We document that learning about people who jump the line (jostlers) or people who go through great lengths to secure left-over vaccine doses (hunters) is off-putting, and has a meaningful, negative effect on people’s vaccine preferences. Most people, however, predict the opposite—that news about extreme behavior would help the vaccination effort. If policy makers or public health authorities share these incorrect beliefs, they run the risk of implementing information policies that backfire in their effort to signal desirability of the vaccine.

Abstract Investigate trends in myocarditis incidence and prognosis in Sweden during 2000–2014. Little data exist concerning population-trends in incidence of hospitalizations for myocarditis and subsequent prognosis. Linking Swedish National Patient and Cause of Death Registers, we identified individuals ≥ 16 years with first-time diagnosis of myocarditis during 2000–2014. Reference population, matched for age and birth year (n = 16,622) was selected from Swedish Total Population Register. Among the 8 679 cases (75% men, 64%

Abstract Background Acquired aortic stenosis (AS) increases with age and has high mortality without intervention. Factors predicting its development are unclear, although atherosclerotic factors are assumed to be involved. Our aim in this study is to estimate the lifetime cumulative incidence and predictors of AS in middle-aged men. Methods We included a random sample of men (n = 9998) born 1915–1925 in Gothenburg, Sweden. From them, 7,494 were examined and followed until a diagnosis of AS or death (maximum follow-up time 42.8 years). We identified AS diagnosis from the Swedish National Patient Registry and deaths from the Swedish Cause of Death Registry by using International Classification of Disease (ICD) diagnostic criteria. To study time-dependent relationships between AS and risk factors with death as the competing risk, we divided the cohort into three overlapping follow-up groups: 25–43, 30–43 and 35–43 years. We used age-adjusted Cox proportional hazards model to identify predictors of AS. Results The lifelong cumulative incidence of AS was 3.2%. At baseline, participants in the third group had a healthier lifestyle, lower body mass index (BMI), blood pressure, and serum cholesterol levels. Higher BMI, obesity, cholesterol, hypertension, atrial fibrillation, smoking and heredity for stroke were associated with AS. With BMI of 20–22.5 as a reference, hazard ratios of being diagnosed with AS for men with a baseline BMI of 25–27.5 kg/m2, 27.5–30 kg/m2 and > 30 kg/m2 were 1.99 (95% CI 1.12–3.55), 2.98 (95% CI 1.65–5.40) and 3.55 (95% CI 1.84–6.87), respectively. Conclusions The lifetime cumulative incidence of AS in middle-aged male population was 3.2%. Multiple atherosclerotic risk factors, particularly high BMI might be associated with a higher risk of developing AS.

Abstract Background DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes. Six patients with variants in the DNA repair genes PRKDC (two siblings), DCLRE1C (two siblings), NBN, and MSH6 were included. Here, we used the cell division assay (CDA) and the γ-H2AX assay, which were both developed and clinically validated by us, to measure patient cell hypersensitivity in response to ionizing radiation, mitomycin C, cytarabine and doxorubicin. Results Radiation hypersensitivity was detected in the two patients with variants in the PRKDC gene (p