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New psychoactive substances (NPS) are life threatening through unpredictable toxicity and limited analytical options for clinicians. We present the retrospective identification of NPS in raw data from a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based multidrug panel analysis on 14 367 clinical oral fluid samples requested during 2019 mainly by psychiatric and addiction care clinics. Retrospectively analysed NPS included 48 notified originally in 2019 by the European Union Early Warning System (EU EWS) and 28 frequently reported in Sweden. Of 88 included NPS, 34 (mitragynine, flualprazolam, 3F/4F-α-P(i)HP, etizolam, 4F-MDMB-BINACA, cyproheptadine, 5F-MDMB-PICA, isotonitazene, isohexedrone, MDPEP, N-ethylpentedrone, tianeptine, flubromazolam, 4'-methylhexedrone, α-P(i)HP, eutylone, mephedrone, N-ethylhexedrone, 5F-MDMB-PINACA, ADB-BUTINACA, 3-methoxy PCP, 4F-furanylfentanyl, 4F-isobuturylfentanyl, acrylfentanyl, furanylfentanyl, clonazolam, norfludiazepam, 3F-phenmetrazine, 3-MMC, 4-methylpentedrone, BMDP, ethylphenidate, methylone and α-PVP) were identified as 219 findings in 84 patients. Eight NPS notified in 2019 were identified, five before EWS release. NPS occurred in 1.20% of all samples and 1.53% of samples containing traditional drugs, and in 1.87% of all patients and 2.88% of patients using traditional drugs. NPS use was more common in men and polydrug users. Legal (not scheduled) NPS were more used than comparable illegal ones. Retrospective identification could be useful when prioritizing NPS for clinical routine analysis and when studying NPS epidemiology.

Intermittent claudication requires treatment with secondary prevention to reduce disease progression and the risk of cardiovascular events and to improve quality of life. Health literacy and self-efficacy are important preconditions for the health behaviour changes necessary for adhering to secondary prevention.Evaluate health literacy in patients with intermittent claudication regarding clinical characteristics, demographics, self-efficacy and quality of life.A cross-sectional study evaluating health literacy, self-efficacy and quality of life using questionnaires. Patients with intermittent claudication from vascular units in the south of Sweden were included.In total, 158 patients were included, of which, 52.5% reported "inadequate" (0-8 points) or "problematic" (9-12 points) health literacy with no differences between men and women. A significant higher proportion of patients living alone reported "inadequate" or "problematic" health literacy than "sufficient" (13-16 points) health literacy. Patients with "sufficient" health literacy reported significantly higher self-efficacy and quality of life and were more physically active than patients with "inadequate" or "problematic" health literacy. Also, patients with a university degree reported a significantly higher ability to "access" (seek, find and obtain) and "understand" (comprehend the accessed) information relevant to health.The majority of patients with intermittent claudication have "inadequate" or "problematic" health literacy. Also, an "inadequate" or "problematic" health literacy level is more common among patients living alone, and education level appears to be more important when "accessing" and "understanding" information relevant to health. This illuminates the importance of not only the patients' health literacy but also demographics when planning for secondary prevention.

In men from the general population, BMI has been associated with a lower sperm DNA fragmentation index (DFI). We wondered whether this could be due to estradiol, which is associated with BMI and reported important for sperm function. Our objective was to investigate the association between estradiol and DFI. In 2008-2010, we recruited 284 young men from the general population to deliver samples of semen and blood and answer questionnaires. Serum concentrations of reproductive hormones and DFI were analyzed, the latter using the Sperm Chromatin Structure Assay. Associations were studied using general linear models. The first model utilized metric values of estradiol, whereas the second model compared men with high and low levels, dichotomized by the median value. A possible interaction between estradiol and testosterone was also examined. When investigating metric estradiol levels and DFI, an inverse association was seen without adjustments (p = .02), but the statistical significance was lost at adjustments for potential confounders (p = .08). Men with lower estradiol levels (88 pmol/L, mean 71 pmol/L) had a statistically significantly higher DFI than men with higher levels of estradiol (≥88 pmol/L, mean 110 pmol/L). Mean ratio difference was 1.21 (p = .002) without adjustments and 1.18 (p = .01) with adjustments. A statistically significant difference in DFI was observed in men with testosterone levels below median when comparing high and low estradiol (p .001). This study supports the idea that serum estradiol levels are protective for sperm DNA integrity, at least at lower testosterone levels.

Smoke-free tobacco via moist oral snuff (snus) is used daily in more than 20% of Swedish men. Negative effects of cigarette smoking on sperm parameters are well documented, unlike for snuff, despite relevance also for other smoke-free nicotine products.We wanted to investigate whether reproductive parameters differed between users and non-users of snuff, and whether the amount of snuff and nicotine exposure mattered.Men (n = 613) from the general population, recruited 2000-2010, were physically examined, answered questions on smoking and snuff use, and delivered urine, blood and semen samples. Sperm concentration, total sperm count, semen volume, percent morphologically normal and progressively motile sperm, and DNA fragmentation index (by the Sperm Chromatin Structure Assay) and reproductive hormones were analysed. Nicotine exposure was measured through urinary levels of cotinine. We used general linear models, with adjustments including cigarette smoking, and for semen parameters also abstinence time.After adjustments, total sperm count was 24% lower (P = 0.03) and testosterone 14% higher (P0.001) in 109 users of snuff than in non-users, whereas cotinine was positively associated with testosterone and oestradiol (P0.001). Numbers of boxes of snuff used per week were associated with testosterone and FSH (P0.001).Applied to the general population, the consumption of smoke-free tobacco by the use of snuff was associated with a lower sperm count and a higher testosterone, for which the extent seemed to play a role.Independent of smoking, consumption of snuff was associated with lower total sperm count and different hormone levels. Applying these results to a reported association between sperm count and the chance of pregnancy, men who used snuff would have about a 10% lower chance of fathering a child.

Tobacco smoking has been reported to cause DNA fragmentation and has been suggested to cause mutations in spermatozoa. These effects have been ascribed to the action of polycyclic aromatic hydrocarbons (PAH) present in the smoke. Simultaneously, DNA fragmentation has been associated with mutagenesis.The aim of this study was to investigate whether levels of urinary biomarkers of PAH and nicotine exposure were associated with sperm DNA fragmentation.In the urine of 381 men recruited from two cohorts of young men (17-21 years old) from the general Swedish population, the PAH metabolites 1-hydroxypyrene and 2-hydroxyphenanthrene, as well as the nicotine metabolite cotinine, were measured. The sperm DNA fragmentation index (DFI) was analysed using the sperm chromatin structure assay. Associations between the DFI, and PAH metabolite levels as continuous variables as well as in quartiles, were studied by general linear models adjusted for abstinence time. A similar analysis was carried out for cotinine levels, according to which the men were categorised as "non-smoking" (n = 216) and "smoking" (n = 165).No association was found between levels of any of the three biomarkers and DFI, either as a continuous variable (p = 0.87-0.99), or when comparing the lowest and the highest quartiles (p = 0.11-0.61). The same was true for comparison of men categorised as non-smoking or smoking (DFI 11.1% vs. 11.8%, p = 0.31).We found no evidence of PAH or nicotine exposure to be associated with DFI, which does not exclude that these exposures may have other effects on sperm DNA.In these young men, levels of biomarkers of nicotine and PAH exposure were not associated with DFI.

Background Infertility affects 15-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives Three overall questions will be studied: 1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? 2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And 3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up? Material and methods ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skane University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of bio-specimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem. This article is protected by copyright. All rights reserved.

With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in solid tissues and biofluids integrated with genetic variants offers a path to deeper functional insights. Here we present a large-scale proteogenomic study in 5,368 individuals, revealing 4,035 independent associations between genetic variants and 2,091 serum proteins, of which 36% are previously unreported. The majority of both cis- and trans-acting genetic signals are unique for a single protein, although our results also highlight numerous highly pleiotropic genetic effects on protein levels and demonstrate that a protein’s genetic association profile reflects certain characteristics of the protein, including its location in protein networks, tissue specificity and intolerance to loss of function mutations. Integrating protein measurements with deep phenotyping of the cohort, we observe substantial enrichment of phenotype associations for serum proteins regulated by established GWAS loci, and offer new insights into the interplay between genetics, serum protein levels and complex disease., Circulating proteins have been linked to many conditions, and understanding their genetic control can lead to understanding of disease. Here, the authors associate common genetic variants with protein levels, finding overlap of genetic associations with circulating proteins and complex disease.

Unhealthy sleep duration, either short or long, is associated with worse health and central subjective dimensions of sleep and health such as fatigue. It has been argued that the link between sleep duration and health may depend on the quality of the slept hours, and on its functional impact (ie, fatigue). The present study therefore assessed whether the relationship between last night's sleep duration and general self-rated health (SRH) differs as a function of sleep quality, and secondly, whether current fatigue and sleep quality are factors linking sleep duration and SRH. The present cross-sectional dataset involved 1304 individuals (57% female, Mage = 28.8, range 18–79). Participants completed surveys for general SRH, previous night's sleep duration and sleep quality, and current fatigue. Results showed the expected inverted U-shaped (ie, quadratic) relation between last night's sleep duration and SRH and a linear relation between last night's sleep quality and SRH. However, long sleep duration was only associated with poorer SRH in individuals who also reported poor sleep quality. Further, the quadratic relationship between sleep duration and SRH was partially mediated by fatigue and sleep quality. The results of this multi-study analysis suggest that SRH is particularly poor in those who slept both long and with poor quality the night before, while good sleep quality may protect those with a long sleep duration from poor SRH. Thus, last night's long sleep does not seem to be associated with poor subjective health unless it is coupled with poor sleep quality. Furthermore, fatigue and sleep quality are potential pathways linking short and long sleep duration with SRH. Different dimensions of sleep interact in their association with health, and future research will benefit from an integrative approach.

INTRODUCTION Infections due to COVID-19 can lead to life threatening pneumonia. Accompanying severe disease are more prominent pulmonary changes on Computed Tomography (CT) scan of the chest. The goal of this study was to describe pulmonary CT changes during acute COVID-19 and at follow up and whether the extent of changes correlate with severity of illness, demographics or other risk factors. MATERIALS AND METHODS Included in this study are all individuals that had confirmed COVID-19 and came for a follow up CT of the chest at Landspitali from May to September 2020. Information regarding medical history was obtained retrospectively from medical charts. All CT scans were reviewed using an international staging system to evaluate the extent of lung changes. RESULTS Eighty-five patients with a mean age of 59 years were included in the study. Sixty patients (71%) were hospitalized during the acute phase and 18 (21%) were admitted to the ICU. During the acute phase more pronounced lung involvement was seen in males and patients admitted to the ICU. At follow-up females had less lung involvement but there was a significant relationship between a higher CT score and age, ICU admissions and days in the ICU. Full recovery was seen at follow-up CT in 31% of patients (median 68,5 days between acute and follow-up imaging). CONCLUSION Patients with severe COVID-19 have more pronounced lung involvement on CT than patients with milder disease during the acute phase and follow-up. Older patients and males are at greater risk of acute and persistent COVID-19 related lung changes.

Objective: To determine the prevalence of sexual dysfunction and to identify the factors associated with sexual dysfunction in young adult childhood cancer survivors. Methods: All survivors of childhood cancer (aged 19-40 years) in Sweden were invited to this population-based study, and 2546 men and women (59%) participated. Sexual function was examined with the PROMIS Sexual Function and Satisfaction Measure. Logistic regression was used to assess the differences between survivors and a general population sample (n = 819) and to identify the factors associated with sexual dysfunction in survivors. Results: Sexual dysfunction in at least one domain was reported by 57% of female and 35% of male survivors. Among females, dysfunction was most common for Sexual interest (36%), Orgasm -ability (32%) and Vulvar discomfort -labial (19%). Among males, dysfunction was most common for the domains satisfaction with sex life (20%), Sexual interest (14%) and Erectile function ( 9%). Compared with the general population, male survivors more frequently reported sexual dysfunction in >2 domains (OR = 1.67, 95% CI: 1.03-2.71), with an increased likelihood of dysfunction regarding Orgasm -ability (OR = 1.82; 95% CI: 1.01-3.28) and Erectile function (OR = 2.30; 95% CI: 1.18-4.49). Female survivors reported more dysfunction regarding Orgasm pleasure (9% versus 5%, OR Z 1.86; 95% CI: 1.11-3.13). A more intensive cancer treatment, emotional distress and body image disturbance were associated with sexual dysfunction in survivors. Conclusions: The findings underscore the need for routine assessment of sexual health in follow-up care of childhood cancer survivors and highlight that those treated with more intensive cancer treatment and who experience concurrent psychological concerns may benefit from targeted screening and interventions. 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Fetal growth restriction is a strong risk factor for perinatal morbidity and mortality. Reliable standards are indispensable, both to assess fetal growth and to evaluate birthweight and early postnatal growth in infants born preterm. The aim of this study was to create updated Swedish reference ranges for estimated fetal weight (EFW) from gestational week 12–42. This prospective longitudinal multicentre study included 583 women without known conditions causing aberrant fetal growth. Each woman was assigned a randomly selected protocol of five ultrasound scans from gestational week 12 + 3 to 41 + 6. Hadlock’s 3rd formula was used to estimate fetal weight. A two-level hierarchical regression model was employed to calculate the expected median and variance, expressed in standard deviations and percentiles, for EFW. EFW was higher for males than females. The reference ranges were compared with the presently used Swedish, and international reference ranges. Our reference ranges had higher EFW than the presently used Swedish reference ranges from gestational week 33, and higher median, 2.5th and 97.5th percentiles from gestational week 24 compared with INTERGROWTH-21st. The new reference ranges can be used both for assessment of intrauterine fetal weight and growth, and early postnatal growth in children born preterm.

Background: Left ventricular noncompaction (LVNC) is characterized by excessive trabeculations of the LV and may be associated with reduced systolic function or severe adverse outcomes. Several aspects remain to be elucidated; there is controversy to whether LVNC cardiomyopathy is a distinct cardiomyopathy caused by failure of the spongy fetal myocardium to condense during fetal development or acquired later in life as a morphological trait associated with other types of cardiomyopathy; the prevalence in unselected populations is unknown and the distinction between normal variation and pathology remains to be defined. In this study, we aimed to determine the prevalence of LVNC and the association to LV systolic function in a large, population-based cohort of neonates. In addition, we assessed the normal ratio of noncompact to compact (NC:C) myocardium in 150 healthy neonates. Methods: Echocardiographic data were prospectively collected in the population study Copenhagen Baby Heart Study. The ratio of NC:C was measured in 12 ventricular segments. LVNC was defined as NC:C ≥2 in at least one segment. Neonates with LVNC were matched 1:10 to controls on sex, gestational age, and weight and age at the examination day. Results: In total, 25 590 neonates (52% males, median age 11 [interquartile range, 7–15] days) underwent echocardiography. Among 21 133 with satisfactory visualization of ventricular segments, we identified a prevalence of LVNC of 0.076% (95% CI, 0.047–0.123). LV ejection fraction was lower in neonates with LVNC compared with matched controls (median 49.5 versus 59.0%; P Conclusions: The prevalence of LVNC based on neonatal echocardiography was 0.076%. LVNC was associated with lower LV systolic function. The findings in normal newborns support the cutoff NC:C ≥2 as an appropriate diagnostic criterion. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02753348.

There is an urgent need for new treatment options in metastatic drug-resistant prostate cancer. Combining immunotherapy with other targeted therapies may be an effective strategy for advanced prostate cancer. In the present study, we sought to investigate to enhance the efficacy of anti-CTLA-4 therapy against prostate cancer by the combination with STAT3 inhibition. Male C57BL6 mice were subcutaneously inoculated with the murine prostate cancer cell line RM-1. Tumor progression was monitored following treatment with vehicle, the small molecule STAT3 inhibitor GPB730, anti-CTLA-4 or GPB730 + anti-CTLA-4. Treatment with anti-CTLA-4 or anti-CTLA-4 + GPB730 significantly inhibited tumor growth and enhanced survival compared to vehicle. Combining anti-CTLA-4 treatment with GPB730 resulted in a significantly prolonged survival compared to anti-CTLA-4 alone. GPB730 significantly increased infiltration of CD45 + cells in tumors of anti-CTLA-4-treated mice compared to anti-CTLA-4 alone. The levels of tumor-infiltrating Tregs were significantly decreased and the CD8:Treg ratio significantly increased by GPB730 treatment in combination with anti-CTLA-4 compared to anti-CTLA-4 alone. Immunohistochemical analysis showed a significant increase in CD45-positive cells in anti-CTLA-4 and anti-CTLA-4 + GPB730-treated tumors compared to vehicle or GPB730 monotherapy. Plasma levels of IL10 were significantly increased by anti-CTLA-4 compared to vehicle but no increase was observed when combining anti-CTLA-4 with GPB730. In conclusion, STAT3 inhibition by GPB730 enhances the antitumoral activity of anti-CTLA-4 and decreases the intratumoral Treg frequency in a prostate cancer mouse model. These results support the combination of STAT3 inhibition with anti-CTLA-4 therapy to increase clinical responses in patients with prostate cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02915-6.

Background Patient with dizziness are challenging in prehospital care. The aim was to describe final diagnosis among patients assessed by EMS as suffering from dizziness with focus on time-critical conditions. Methods Consecutive patients assessed by an EMS clinician during 12 months in a single large EMS system in Gothenburg, Sweden (660,000 inhabitants), were assessed. The study comprised patients given ESS code 11 dizziness. The main end-point was the final diagnosis (ICD code). Results There were 58,575 primary missions, of which 2,048 (3.5%) were assessed as ESS code 11 (dizziness). Of these, 161 (8%) were excluded. Among the remaining 1887 cases, there were 230 different ICD codes and 96 (5%) had a time-critical condition. The majority (88%) had a cerebrovascular disease. The most typical symptoms among time-critical conditions were an acute onset (63%) and nausea, vomiting (61%). When compared with non-time-critical conditions, those with time-critical conditions were older and had a higher median systolic blood pressure at EMS arrival. Conclusion Among primary missions by the EMS, 3.5% had dizziness. Of these, 5% had a time-critical condition and the majority had a cerebrovascular disease. Instruments to identify time-critical conditions among patients seen by EMS due to dizziness are required.

Background: Splanchnic vasodilation by inodilators is an argument for their use in critical cardiac dysfunction. To isolate peripheral vasoactivity from inotropy, such drugs were investigated, and contrasted to vasopressors, in a fixed low cardiac output (CO) model resembling acute cardiac dysfunction effects on the gastrointestinal tract. We hypothesized that inodilators would vasodilate and preserve the aerobic metabolism in the splanchnic circulation in low CO. Methods: In anesthetized pigs, CO was lowered to 60% of baseline by partial inferior caval vein balloon inflation. The animals were randomized to placebo (n = 8), levosimendan (24 μg kg−1 bolus, 0.2 μg kg−1 min−1, n = 7), milrinone (50 μg kg−1 bolus, 0.5 μg kg−1 min−1, n = 7), vasopressin (0.001, 0.002 and 0.006 U kg−1 min−1, 1 h each, n = 7) or norepinephrine (0.04, 0.12, and 0.36 μg kg−1 min−1, 1 h each, n = 7). Hemodynamic variables including mesenteric blood flow were collected. Systemic, mixed-venous, mesenteric-venous, and intraperitoneal metabolites were analyzed. Results: Cardiac output was stable at 60% in all groups, which resulted in systemic hypotension, low superior mesenteric artery blood flow, lactic acidosis, and increased intraperitoneal concentrations of lactate. Levosimendan and milrinone did not change any circulatory variables, but levosimendan increased blood lactate concentrations. Vasopressin and norepinephrine increased systemic and mesenteric vascular resistances at the highest dose. Vasopressin increased mesenteric resistance more than systemic, and the intraperitoneal lactate concentration and lactate/pyruvate ratio. Conclusion: Splanchnic vasodilation by levosimendan and milrinone may be negligible in low CO, thus rejecting the hypothesis. High-dose vasopressors may have side effects in the splanchnic circulation.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a fatal disease requiring palliative care. End-of-life care has been well studied in patients with incurable cancer, but less is known about the quality of such care for patients with ALS. AIM To study whether the quality of end-of-life care the last week in life for patients dying from ALS differed compared to patients with cancer in terms of registered symptoms, symptom management, and communication. DESIGN This retrospective comparative registry study used data from the Swedish Registry of Palliative Care for 2012-2016. Each patient with ALS (n = 825) was matched to 4 patients with cancer (n = 3,300). RESULTS Between-group differences in assessments for pain and other symptoms were significant (p

According to patterns of inheritance and incomplete penetrance, fewer than half of relatives to dilated cardiomyopathy probands will develop disease.The purpose of this study was to investigate the prevalence and incidence, and to identify predictors of developing familial dilated cardiomyopathy (FDC) in relatives participating in family screening.The study was a retrospective, longitudinal cohort study of families screened and followed from 2006 to 2020 at a regional assembly of clinics for inherited cardiomyopathies.In total, 211 families (563 relatives, 50% women) were included. At baseline, 124 relatives (22%) were diagnosed with FDC. Genetic sequencing identified the etiology in 37% of screened families and classified 101 (18%) relatives as unaffected carriers (n = 43) or noncarriers (ie, not at risk of FDC [n = 58]). The combined clinical and genetic baseline yield was 30%. During follow-up (2,313 person-years, median 5.0 years), 45 developed FDC (incidence rate of 2.0% per person-year; 95% CI: 1.4%-2.8%), increasing the overall yield to 34%. The incidence rate of FDC was high in relatives with baseline abnormalities on electrocardiogram or echocardiography compared with relatives with normal findings (4.7% vs 0.4% per person-year; HR: 12.9; P 0.001). In total, baseline screening identified 326 (58%) relatives to be at low risk of FDC.Family screening identified a genetic predisposition to or overt FDC in 1 of 3 relatives at baseline. Genetic and clinical screening was normal in more than half of relatives, and these relatives had a low risk of developing FDC during follow-up. Thus, baseline screening identified a large proportion, in whom follow-up may safely be reduced, allowing focused follow-up of relatives at risk.

Background High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control., Standardized definitions were used to estimate a 4-stage continuum of human immunodeficiency virus (HIV) care in 11 European Union (EU) countries in 2016. The EU is close to the 90-90-90 target, with the main challenge being the percentage of undiagnosed infections.

When viewing pupil sizes change, our own pupil sizes change, a phenomenon known as pupillary contagion. This involuntary response is reliable between humans but can be affected by familiarity and empathy. We investigated whether the pupillary contagion response occurs for humans viewing familiar species—cats and dogs—and whether it is modulated by preferences for particular species. Pupil sizes were measured while viewing cat, dog and human images with small, medium and large pupils. Trait empathy, cat and dog affiliation and experience were subsequently measured. There was an image pupil size effect, but this did not vary by species. There was greater pupil size change to cats and dogs than to humans, but this might have been due to the varying size and appearance of the cats and dogs. Greater dog affiliation was also associated with smaller overall pupil size change to dogs and larger change to humans, but this did not interact with image pupil size. Dog affiliation might be associated with less arousal to dog images. In sum, pupillary contagion responses indicate a spontaneous transfer of information about internal states and the findings suggest that humans are sensitive to this across species, regardless of individual preference.

Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000–2012; n = 6,541), the Framingham Heart Study (2005–2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002–2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.

Objectives The aim of this study was to investigate the sentinel lymph node biopsy (SLNB) method in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) guided by preoperative hybrid single-photon emission tomography/computed tomography (SPECT/CT) lymphoscintigraphy. Methods Thirty-nine patients with stage T1-T3, any N-stage, M0 cancer of the oesophagus or GOJ planned for curatively intended esophagectomy underwent preoperative SPECT/CT lymphoscintigraphy following endoscopically guided submucosal injection of radiocolloid and intraoperative radio-guided SLNB using a hand-held gamma scintillation device. Results The detection rate in preoperative SPECT/CT imaging was 88%. The median number of detected SLN stations in preoperative imaging was 1 (range 0-4). At least one suspected SLN was identified in all intraoperative SLNP procedures. In six cases, no lymph nodes were identified in the SLNB. In six cases, the SLNB was false negative. The sensitivity for successful SLNB procedures was 20%, the specificity was 100% and the accuracy was 75%. Conclusions Preoperative SLN mapping using SPECT/CT yields a high number of detected SLN stations compared to previous studies using planar imaging. The accuracy of the SLNB method in patients with predominantly ≥T3-stage tumours and with a history of previous neoadjuvant treatment is poor, and the method is not recommended in these patient groups.

Background Antenatally diagnosed urinary tract dilatation (UTD) still burdens healthcare providers and parents. This study was conducted to establish long-term outcome in an unselected group of children with antenatally detected UTD. Methods Seventy-one out of 103 children born in 2003–2005 and diagnosed with antenatal UTD agreed to participate in a 12–15-year follow-up including blood and urine samples, a kidney ultrasound exam, and kidney scintigraphy. The records were searched for previous urinary tract infections. Results Among children with an anteroposterior diameter (APD) ≤ 7 mm and no calyceal, kidney, ureteral, or bladder pathology in the early postnatal period, no one tested had reduced estimated glomerular filtration rate (eGFR), albuminuria, or UTD at the follow-up at a mean age of 13.6 years. One child had kidney damage not affecting kidney function. Among children with postnatal APD > 7 mm and/or kidney, calyceal, ureteral, or bladder pathology, 15% had persistent UTD and 32–39% (depending on the method used) had kidney damage. Major postnatal urinary tract ultrasound abnormalities and a congenital anomalies of the kidney and urinary tract (CAKUT) diagnosis were factors associated with an increased risk for permanent kidney damage (odds ratios 8.9, p = 0.016; and 14.0, p = 0.002, respectively). No one had reduced eGFR. One child (1/71, 1%) had a febrile urinary tract infection after the age of 2. Conclusions We conclude that in children with postnatal APD ≤ 7 mm, no calyceal dilatation, normal bladder, ureters, and kidney parenchyma, the outcome is excellent. There is no need for long-term follow-up in these patients.

Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology. Methods We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15–50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction. Results POTS patients were younger (26 vs. 31 years; p p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS. Conclusions Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

Background: Left atrial diameter (LAd) is included in the European Society for Cardiology's (ESC) risk model for assessment of sudden cardiac death (SCD) risk in hypertrophic cardiomyopathy (HCM), but the recommended measure of LA size is left atrial volume (LAv). Hypothesis: We hypothesized that LAv could be used instead of LAd in the HCM risk-SCD model. We aimed to determine the relation between LAd and LAv and to assess the impact of using LAv instead of LAd. Methods: Echocardiographic measurements of anteroposterior LAd in the parasternal long-axis window and LAv from Simpson's biplane method of disks were used. The 5-year risk of SCD by measured LAd and by LAd predicted from LAv were estimated using the ESC risk-SCD model. Results: In 205 HCM patients (age 56 ± 14 years, 62% male), the relation between LAd and LAv was linear. Median 5-year risk of SCD was 2.4% (interquartile range [IQR]: 1.6; 3.8) using measured LAd and 2.4% (IQR: 1.6; 3.7) using predicted LAd. The correlation between the SCD risk assessed by measured vs predicted LAd was excellent (r2 = 0.96). Use of predicted LAd resulted in four patients (2%) being recategorized between the moderate and high-risk categories. Conclusions: The relation between LAd and LAv was linear with good agreement. On a population level, the correlation between the risk of SCD using measured LAd or LAd predicted from LAv was excellent. On a patient level, using LAd predicted from LAv resulted in the vast majority remaining in the same risk category; however, for a minority of patients, it changed the recommendation.

Background: The number of elderly persons with cardiovascular disease is increasing. In Sweden, the incidence of acute myocardial infarction is the highest among individuals aged 85 years and over. However, there is still little evidence about whether this population benefits from established treatments. Furthermore, the values and preferences of octogenarians (age ⩾80 years), as well as how they could be involved in treatment decisions, have been largely overlooked in research. Overall, increased knowledge about the preferences and expectations of octogenarians is needed to incorporate their treatment expectations into the decision-making process. Aims: This study aimed to describe the treatment choice preferences and post-treatment life expectations of octogenarians with acute coronary syndrome. Methods: A total of 19 patients (eight women, 11 men) aged 80 years and older and diagnosed with non-ST-elevation myocardial infarction or unstable angina were enrolled in this qualitative study. Data were collected between May 2011 and June 2013 through semistructured interviews. The data were analysed using qualitative content analysis. Results: We identified two main categories: Wanting the best and Hope for increased wellbeing. Participant preferences were influenced by their own and others’ previous experiences and their confidence in healthcare professionals. With respect to treatment outcomes, the participants hoped to get well, stay active, experience fewer symptoms and regain vitality. Conclusion: The studied octogenarians desired the best treatment option and trusted that their healthcare providers will make appropriate recommendations. These patients expected their treatment to result in increased wellbeing and fewer symptoms.

Agricultural pesticides are extensively used for weed- and pest control, resulting in residues of these compounds in food. The general population is mainly exposed through dietary intake. Exposure to certain pesticides has been associated with adverse human health outcomes. Our aim was to assess urinary concentrations and temporal trends in the biomarkers of commonly used pesticides. Samples were collected from adolescents (n = 1060) in Scania, Sweden, from 2000 to 2017. Concentrations of 14 pesticide biomarkers were analyzed in urine using LC–MS/MS. Temporal trends in biomarker concentrations (ln-transformed) were evaluated using linear regression. Biomarkers of pyrethroids (3-PBA and DCCA), chlorpyrifos (TCPy), chlormequat (CCC), thiabendazole (OH-TBZ), and mancozeb (ETU) were detected in >90% of the population all sampling years. The biomarkers CCC and TCPy had the highest median concentrations (>0.8 µg/L), whereas the biomarkers of cyfluthrin (4F-3-PBA) and two pyrethroids (CFCA) had the lowest median concentrations (

Background: Severe asthma increases the risk of severe COVID-19 outcomes such as hospitalization and death. However, more studies are needed to understand the association between asthma and severe COVID-19. Methods: A cohort of 150,430 adult asthma patients were identified in the Swedish National Airway Register (SNAR) from 2013 to December 2020. Data on body mass index, smoking habits, lung function, and asthma control test (ACT) were obtained from SNAR, and uncontrolled asthma was defined as ACT ⩽19. Patients with severe COVID-19 were identified following hospitalization or in death certificates based on ICD-10 codes U07.1 and U07.2. The Swedish Prescribed Drug register was used to identify comorbidities and data from Statistics Sweden for educational level. Multivariate logistic regression analyses were used to estimate associations with severe COVID-19. Results: Severe COVID-19 was identified in 1067 patients (0.7%). Older age (OR = 1.04, 95% CI = 1.03–1.04), male sex (1.42, 1.25–1.61), overweight (1.56, 1.27–1.91), obesity (2.12, 1.73–2.60), high-dose inhaled corticosteroids in combination with long-acting β-agonists (1.40, 1.22–1.60), dispensed oral corticosteroids ⩾2 (1.48, 1.25–1.75), uncontrolled asthma (1.64, 1.35–2.00), cardiovascular disease (1.20, 1.03–1.40), depression (1.47, 1.28–1.68), and diabetes (1.52, 1.29–1.78) were associated with severe COVID-19, while current smoking was inversely associated (0.63, 0.47–0.85). When comparing patients who died from COVID-19 with those discharged alive from hospital until 31 December 2020, older age, male sex, and current smoking were associated with COVID-19 death. Conclusion: Patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, should be identified as risk patients for severe COVID-19. Furthermore, current smoking is strongly associated with COVID-19 death in asthma.

BACKGROUND Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. METHODS In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. FINDINGS Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14-1·68) for asundexian 20 mg (three events), 0·16 (0·01-0·99) for asundexian 50 mg (one event), and 0·33 (0·09-0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. INTERPRETATION The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. FUNDING Bayer.

In order to treat pain optimally, the Emergency Medical Service (EMS) clinician needs to be able to make a reasonable estimation of the severity of the pain. It is hypothesised that various physiological parameters will change as a response to pain.In a cohort of patients who were seen by EMS clinicians, to relate the patients' estimated intensity of pain to various physiological parameters.Patients who called for EMS due to pain in a part of western Sweden were included. The intensity of pain was assessed according to the visual analogue scale (VAS) or the Numerical Rating Scale (NRS). The following were assessed the same time as pain on EMS arrival: heart rate, systolic and diastolic blood pressure, respiratory rate, moist skin and paleness.In all, 19,908 patients (≥18 years), were studied (51% women). There were significant associations between intensity of pain and the respiratory rate (r = 0.198; p 0.0001), heart rate (r = 0.037; p 0.0001), systolic blood pressure (r = -0.029; p 0.0001), moist skin (r = 0.143; p 0.0001) and paleness (r = 0.171; p 0.0001). The strongest association was found with respiratory rate among patients aged 18-64 years (r = 0.258; p 0.0001).In the prehospital setting, there were significant but weak correlations between intensity of pain and physiological parameters. The most clinically relevant association was found with an increased respiratory rate and presence of pale and moist skin among patients aged 65 years. Among younger patients, respiratory rate may support in the clinical evaluation of pain.

Rationale Patients in secure forensic psychiatric care have reduced autonomy because of the constraints imposed on them by compulsion laws. Thus, it is vital that nurses enable patient participation whenever possible. Patient participation, and it's clinical use in forensic psychiatric care, is an understudied field. Aim To describe nurses' experiences of their work with patient participation in forensic psychiatric care. Methods Managers at different secure forensic psychiatric institutions in the south of Sweden approved the study, and oral consent was retrieved from informants. Interviews guided by a semi-structured interview guide were conducted with nine nurses from five different forensic psychiatric institutions and analysed with content analysis. Findings Nurses describe diverse understandings and abilities in an inflexible setting. This indicates that what participation is, and how to achieve it, is not the same for nurses as for patients. Moreover, patients have different abilities to participate, and the secure setting in itself is perceived as hindering participatory work. Still, participation is described as a crucial part of work that requires a caring relationship. Furthermore, nurses pronounce potentially excluding attitudes and strategies that may obstruct patient participation for all, and at the same time, they have a belief that improvement is possible. Conclusion Compulsory forensic psychiatric care is a complex care context that requires constant efforts from nurses to balance patients' rights and needs with mandatory care. The very nature of this caring context appears to be a major obstacle when promoting patient participation. Nevertheless, nurses express that they do aim for patient participation, 'they try'. From a patient's perspective, trying is not sufficient and a need for improvement is evident. The results can be of clinical interest in similar secure forensic psychiatric nursing settings, and a point of departure in future development of care striving for increased patient participation for all.

Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates.We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET withLongitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion.These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.

Background: Previous studies have suggested an increased prevalence of congenital heart disease among children born to women aged ≥35 years. In recent decades, the mother’s age at childbirth has increased dramatically in industrialized countries. It has not been investigated if increasing maternal age affects the neonatal cardiac electrical system. Methods: The Copenhagen Baby Heart Study is a prospective general population study that performed cardiac evaluation in newborns. Electrocardiograms were analyzed with a computerized algorithm. Results: We included 16,518 newborns with normal echocardiograms (median age 11 days; range 0–30 days; 52% boys). Median maternal age at delivery was 31 years; 790 newborns were born to mothers aged between 16 and 24 years, 11,403 between 25 and 34 years, 4,279 between 35 and 44 years, and 46 newborns had mothers aged between 45 and 54 years. The QRS axis and maximum R-wave amplitude in V1 (R-V1) differed across the four maternal age groups (both p < 0.01), with absolute differences of 3.5% (114 vs. 110°) and 12% (1,152 vs. 1,015 µV), respectively, between newborns with the youngest and oldest mothers. Associations between maternal age and the QRS axis and R-V1 remained significant after multifactorial adjustment. Heart rate, PR interval, QRS duration, uncorrected QT interval, QTcBazett, and maximum amplitudes of S-V1, R-V6, and S-V6 were not associated with maternal age (all p > 0.05). Conclusion: We observed a significant association between maternal age and the neonatal QRS axis and R-V1. However, the absolute differences were relatively small and maternal age is unlikely to have a clinically significant effect on the neonatal cardiac electrical system.

Background Pediatric healthcare today shows a rising demand for research focusing on children’s perspectives on and consumer satisfaction with the nursing care they receive. Therefore, the purpose of this study was to translate and adapt the Consumer Emergency Care Satisfaction Scale (CECSS), a paper-based, self-administered 19-item questionnaire originally developed in the United States and targeted towards adults, and then test the new version in Swedish pediatric emergency departments. Methods The study was designed with a two-phase approach. Firstly, a forward–backward translation of the CECSS, involving expert consensus, was performed, and then the questionnaire was adapted for children aged 10–18 and assessed for face and content validity. Secondly, the translated and adapted questionnaire was tested with a clinical sample for construct validity, internal consistency, and reliability. This last aspect was assessed using a structured telephone interview 7–10 days after the participant visited a pediatric emergency department. All children participating in this study gave their assent ( Results The paper-based, self-administered 19-item Swedish version of the CECSS was tested on a clinical sample consisting of 203 nonurgent children (boys: n = 109, 53.7 % and girls: n = 94, 46.3 %) between 10 and 18 years (mean age 13.8, SD 2.29). The factor analysis revealed three factors that explain 63.1 % of the total variation in the 15 items. The Cronbach’s alphas for the three dimensions (caring, teaching, and clinical competence) varied between 0.79 and 0.88. The intraclass correlation coefficient (ICC) for the entire Swedish version of the CECSS was 0.58, and the ICCs for the three dimensions varied between 0.56 and 0.71. Conclusions The results show that the developed Swedish Pediatric Consumer Emergency Care Satisfaction Scale (p-CECSS-S) is a valid, stable and easy-to-use-questionnaire that can be used to assess children’s satisfaction with nursing care.

To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels75 days post symptom onset.Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.

In this retrospective cohort study, men and women with eating disorders (n = 8867) had higher risk of injurious falls and hip fractures than age, sex, and county-matched controls (n = 88670).Eating disorders have been associated with decreased bone mineral density and increased fracture risk, but the association with fall injuries without fracture has not previously been investigated. Furthermore, fracture risk in men with eating disorders has been insufficiently studied.In the present study, 8867 patients (9.4% men) with a diagnosed eating disorders and 88670 age-, sex-, and county-matched controls were investigated.The mean (standard deviation) age of the patients and controls was 41.6 (13.7) years and the follow-up time 9.6 (5.2, 14.4) years (median, interquartile range) for patients and 10.1 (5.5, 14.2) years for controls. The proportions of injurious falls without fracture (17.3% vs. 9.0%) and of hip fracture (1.6% vs. 0.7%) were substantially greater in patients with an eating disorder than in their corresponding population controls. In an unadjusted Cox proportional hazards model, individuals with an eating disorder had a higher risk of injurious falls without fracture (Hazard ratio (HR) 95% confidence interval (CI): 2.07 (1.96-2.18), and hip fracture (HR 2.30 (1.92-2.75)) than the risk observed in the controls. The HR for any investigated outcome associated with an eating disorder did not differ by sex or age (interaction term p 0.10). The risk of injurious falls without fracture and hip fracture was increased in both women (HR 2.07 (1.95-2.19) and HR 2.41 (1.98-2.93), respectively) and men (HR 2.09 (1.76-2.49) and HR 1.84(1.12-3.02), respectively), with an eating disorder.The risk of injurious falls without fracture and of hip fracture is increased in both women and men with eating disorders, indicating measures to prevent both falls and fractures are important in these patients, regardless of age and sex.

Ultrasonic assessment of fetal growth is an important part of obstetric care to prevent adverse pregnancy outcome. However, lack of reliable reference ranges is a major barrier for accurate interpretation of the examinations. The aim of this study was to create updated Swedish national reference ranges for intrauterine size and growth of the fetal head, abdomen and femur from gestational week 12 to 42. This prospective longitudinal multicentre study included 583 healthy pregnant women with low risk of aberrant fetal growth. Each woman was examined up to five times with ultrasound from gestational week 12 + 3 to 41 + 6. The assessed intrauterine fetal biometric measurements were biparietal diameter (outer-inner), head circumference, mean abdominal diameter, abdominal circumference and femur length. A two-level hierarchical regression model was employed to account for the individual measurements of the fetus and the number of repeated visits for measurements while accounting for the random effect of the identified parameterization of gestational age. The expected median and variance, expressed in both standard deviations and percentiles, for each individual biometric measurement was calculated. The presented national reference ranges can be used for assessment of intrauterine size and growth of the fetal head, abdomen and femur in the second and third trimester of pregnancy.

Observers are better at discriminating upright bodies than inverted bodies, and this body inversion effect (BIE) is reliable with whole figures (bodies with heads), but not with bodies presented without heads or the heads occluded suggesting that heads may be key to BIEs. Some studies present whole figures and bodies without heads between groups, and BIEs are not found for bodies without heads [1]. Other studies present whole figures and bodies without heads in the same blocks and BIEs are found with bodies without heads [2]. Does seeing the heads of whole figures induce BIEs in bodies without heads? Here, participants discriminated bodies with either whole figures and bodies without heads presented within blocks, or in separate blocks with bodies without heads presented first. We tested body identity and posture discrimination and measured participants’ gaze. BIEs were found with whole figures and bodies without heads in both identity and posture discrimination, and in both study designs. However, efficiency scores were better for the whole figures than the bodies without heads, but only when whole figures appeared in separate blocks. The magnitude of the BIE was overall stronger for whole figures compared to bodies without heads, but only in identity discrimination. BIE magnitudes were similar in the identity and posture tasks. Participants were better at identity discrimination, yet, there was greater looking at heads and less at bodies. During posture discrimination, greater looking at bodies and less at heads was associated with better performance. Faces might influence BIEs but are not essential. Configural representations of bodies without heads are sufficient for BIEs in posture and identity discrimination.

Kappa free light chain (KFLC) index, a measure for intrathecal production of free kappa chains, has been increasingly recognized for its diagnostic potential in multiple sclerosis (MS) as a quantitative alternative to IgG oligoclonal bands (OCBs). Our objective was to investigate the sensitivity, specificity, and overall diagnostic accuracy of KFLC index in MS. KFLC index was prospectively determined as part of the diagnostic workup in patients with suspected MS (n = 327) between May 2013 and February 2020. Patients with clinically isolated syndrome (CIS), radiologically isolated syndrome (RIS), and MS had markedly higher KFLC index (44.6, IQR 16-128) compared with subjects with other neuro-inflammatory disorders (ONID) and symptomatic controls (SC) (2.19, IQR 1.68-2.98, p

Significance A consistent finding from functional MRI (fMRI) of externally focused cognitive control is negative signal change in the brain’s default mode network (DMN), but it is unknown whether this reflects an increase of synaptic activity during rest periods or active suppression during task. Using hybrid PET-MRI, we show that task-positive fMRI responses align with increasing glucose metabolism during cognitive control, but task-negative fMRI responses in DMN are not accompanied by corresponding decreases in metabolism. The results are incompatible with an interpretation of task-negative fMRI signal in DMN as a relative metabolic increase during a resting baseline condition. The present results open up avenues for understanding abnormal fMRI activity patterns in DMN in aging and psychiatric disease., The finding of reduced functional MRI (fMRI) activity in the default mode network (DMN) during externally focused cognitive control has been highly influential to our understanding of human brain function. However, these negative fMRI responses, measured as relative decreases in the blood-oxygenation-level–dependent (BOLD) response between rest and task, have also prompted major questions of interpretation. Using hybrid functional positron emission tomography (PET)-MRI, this study shows that task-positive and -negative BOLD responses do not reflect antagonistic patterns of synaptic metabolism. Task-positive BOLD responses in attention and control networks were accompanied by concomitant increases in glucose metabolism during cognitive control, but metabolism in widespread DMN remained high during rest and task despite negative BOLD responses. Dissociations between glucose metabolism and the BOLD response specific to the DMN reveal functional heterogeneity in this network and demonstrate that negative BOLD responses during cognitive control should not be interpreted to reflect relative increases in metabolic activity during rest. Rather, neurovascular coupling underlying BOLD response patterns during rest and task in DMN appears fundamentally different from BOLD responses in other association networks during cognitive control.

Background There are data suggesting that passive leg raising (PLR) improves hemodynamics during cardiopulmonary resuscitation (CPR). This trial aimed to determine the effectiveness and safety of PLR during CPR in out-of-hospital cardiac arrest (OHCA). Methods We conducted a randomized controlled trial with blinded assessment of the outcomes that assigned adults OHCA to be treated with PLR or in the flat position. The trial was conducted in the Camp de Tarragona region. The main end point was survival to hospital discharge with good neurological outcome defined as cerebral performance category (CPC 1–2). To study possible adverse effects, we assessed the presence of pulmonary complications on the first chest X-rays, brain edema on the computerized tomography (CT) in survivors and brain and lungs weights from autopsies in non-survivors. Results In total, 588 randomized cases were included, 301 were treated with PLR and 287 were controls. Overall, 67.8% were men and the median age was 72 (IQR 60–82) years. At hospital discharge, 3.3% in the PLR group and 3.5% in the control group were alive with CPC 1–2 (OR 0.9; 95% CI 0.4–2.3, p = 0.91). No significant differences in survival at hospital admission were found in all patients (OR 1.0; 95% CI 0.7–1.6, p = 0.95) and among patients with an initial shockable rhythm (OR 1.7; 95% CI 0.8–3.4, p = 0.15). There were no differences in pulmonary complication rates in chest X-rays [7 (25.9%) vs 5 (17.9%), p = 0.47] and brain edema on CT [5 (29.4%) vs 10 (32.6%), p = 0.84]. There were no differences in lung weight [1223 mg (IQR 909–1500) vs 1239 mg (IQR 900–1507), p = 0.82] or brain weight [1352 mg (IQR 1227–1457) vs 1380 mg (IQR 1255–1470), p = 0.43] among the 106 autopsies performed. Conclusion In this trial, PLR during CPR did not improve survival to hospital discharge with CPC 1–2. No evidence of adverse effects has been found. Clinical trial registration ClinicalTrials.gov: NCT01952197, registration date: September 27, 2013, https://clinicaltrials.gov/ct2/show/NCT01952197.

Background Hybrid SPECT/CT systems allow the shortening of lead time for investigation of cancer patients, since a complementary CT for radiological characterization of focally increased isotope uptake of unclear origin in bone scintigraphy can be performed simultaneously. The use of low-dose CT (sub-mSv CT) reduces radiation dose compared to standard-dose CT and facilitates the application of complementary CT. Purpose To test the feasibility of sub-mSv CT for the characterization of non-specific findings in the bone scintigraphy of oncological patients. Material and Methods Nineteen oncological patients with a total of 50 findings of unclear origin on bone scintigraphy which required further correlation with morphologic data were included in the study. Each patient underwent two CT scan series consecutively: one low-dose CT and one standard-dose CT. The CT studies were randomized and each finding was rated by four blinded experienced radiologists. A shift in ratings between standard-dose and low-dose images were assessed using the Stuart–Maxwell chi-squared test. Inter-observer agreement and intra-observer agreement was assessed using Light’s kappa and Cohen’s kappa, respectively. Results The mean effective dose of low-dose CT scans was 0.8 mSv compared to 4.2 mSv for the standard-dose CT scans. No statistically significant shift in ratings was observed ( P = 0.62). There was no statistically significant difference in the inter-observer agreements: the values for the standard-dose and low-dose groups were 0.68 (95% confidence interval [CI] 0.57–0.79) and 0.60 (95% CI 0.47–0.72), respectively. Conclusion These results indicate that sub-mSv CT for characterization of non-specific findings in bone scintigraphy of oncological patients is feasible.

Insufficient or excessive dopaminergic tone impairs cognitive performance. We examine whether the balance between transmitter availability and dopamine (DA) D2 receptors (D2DRs) is important for successful memory performance in a large sample of adults (n = 175, 64–68 years). The Catechol-O-Methyltransferase polymorphism served as genetic proxy for endogenous prefrontal DA availability, and D2DRs in dorsolateral prefrontal cortex (dlPFC) were measured with [11C]raclopride-PET. Individuals for whom D2DR status matched DA availability showed higher levels of episodic and working-memory performance than individuals with insufficient or excessive DA availability relative to the number of receptors. A similar pattern restricted to episodic memory was observed for D2DRs in caudate. Functional magnetic resonance imaging data acquired during working-memory performance confirmed the importance of a balanced DA system for load-dependent brain activity in dlPFC. Our data suggest that the inverted-U–shaped function relating DA signaling to cognition is modulated by a dynamic association between DA availability and receptor status.

Sepsis is a severe condition which affects 300-800/100,000 persons each year. There are indications that the prehospital identification of patients with sepsis is difficult. The aim of the study was, among patients with a final hospital diagnosis of sepsis, to compare emergency medical service (EMS) field assessments of patients in whom there was a prehospital suspicion of sepsis with those without this suspicion.The study had a retrospective, observational design. The data used in the study were retrieved from the prehospital and hospital medical records of patients with a final hospital diagnosis of sepsis, transported to hospital by the EMS within a region in the south west of Sweden during a period of one year.Among patients with a final diagnosis of sepsis (n=353), the EMS identified the condition in 36% of the cases. These patients were characterised by more abnormal vital signs (a higher respiratory rate and heart rate and more frequent temperature abnormalities) and were more ambitiously assessed (more lung auscultations and more assessments of the degree of consciousness).The EMS was already able to identify 36% of patients with a final diagnosis of sepsis in the prehospital phase. There were minor differences in the prehospital assessment between patients who were identified by the EMS nurse and those who were not.

Pain is subjective and largely shaped by context, yet, little is known about the boundaries for such influences, in particular in relation to conscious awareness. Here, we investigated processing of noxious stimuli during sleep. Four experiments were performed where participants (n = 114) were exposed to repetitions of noxious heat, either when awake or during sleep. A test-phase followed where participants were awake and exposed to painful stimuli and asked to rate pain. Two control experiments included only the test-phase, without any prior pain exposures. Participants in the awake condition rated all test-phase stimuli the same. Conversely, participants who had been sleeping, and thus unaware of getting noxious heat, displayed heightened pain during the first part of the test-phase. This heightened reaction to noxious stimuli—a pain alarm response—was further pronounced in the control conditions where participants were naïve to noxious heat. Results suggest that the pain alarm response is partly dependent on conscious awareness.