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Drug-facilitated sexual assault (DFSA) is an act of sexual violence towards a victim who is incapacitated due to the voluntary or involuntary consumption of intoxicating substances. Sexual assaults are generally considered underreported and the toxicological analysis of DFSA cases is particularly challenging when there is a time delay from assault to medical examination. The aim of this review was to investigate typical toxicological findings in global DFSA cases and describe a typical DFSA case.A database search was conducted in PubMed using relevant search terms in order to identify studies reporting toxicological results in DFSA cases.In total, 22 studies were included, covering toxicological findings in DFSA cases in North America, Europe, Asia, South Africa and Australasia from 1996 to 2018. Biological matrices used for analysis included blood, urine and hair. Toxicological findings were comparable among countries, with ethanol, cocaine, cannabis, benzodiazepines, amphetamines and analgesics being among the most frequently detected substances. Ethanol was frequently detected in combination with one or more drugs. A variety of benzodiazepines were observed, with the most common being diazepam, clonazepam, alprazolam, and oxazepam. The majority of cases involved women (87%-100%).The findings suggest that a diverse range of substances are associated with DFSA and that victims are rendered vulnerable through recreational substance consumption at social events. As such, typical DFSA cases appear to be opportunistic in nature and primarily involves women in their mid-twenties and an acquaintance as the perpetrator. more...

Early right heart failure (RHF) remains a major source of morbidity and mortality after left ventricular assist device (LVAD) implantation, yet efforts to predict early RHF have proven only modestly successful. Pharmacologic unloading of the left ventricle may be a risk stratification approach allowing for assessment of right ventricular and hemodynamic reserve.We performed a multicenter, retrospective analysis of patients who had undergone continuous-flow LVAD implantation from October 2011 to April 2020. Only those who underwent vasodilator testing with nitroprusside during their preimplant right heart catheterization were included (n = 70). Multivariable logistic regression was used to determine independent predictors of early RHF as defined by Mechanical Circulatory Support-Academic Research Consortium.Twenty-seven patients experienced post-LVAD early RHF (39%). Baseline clinical characteristics were similar between patients with and without RHF. Patients without RHF, however, achieved higher peak stroke volume index (SVI) (30.1 ± 8.8 vs 21.7 ± 7.4 mL/mPeak SVI with nitroprusside administration was independently associated with post-LVAD early RHF while resting hemodynamics were not. Vasodilator testing may prove to be a strong risk stratification tool when assessing LVAD candidacy though additional prospective validation is needed. more...

We introduce the public version of the BAyesian STellar Algorithm (BASTA), an open-source code written in PYTHON to determine stellar properties based on a set of astrophysical observables. BASTA has been specifically designed to robustly combine large data sets that include asteroseismology, spectroscopy, photometry, and astrometry. We describe the large number of asteroseismic observations that can be fit by the code and how these can be combined with atmospheric properties (as well as parallaxes and apparent magnitudes), making it the most complete analysis pipeline available for oscillating main-sequence, subgiant, and red giant stars. BASTA relies on a set of pre-built stellar isochrones or a custom-designed library of stellar tracks, which can be further refined using our interpolation method (both along and across stellar tracks or isochrones). We perform recovery tests with simulated data that reveal levels of accuracy at the few percent level for radii, masses, and ages when individual oscillation frequencies are considered, and show that asteroseismic ages with statistical uncertainties below 10 per cent are within reach if our stellar models are reliable representations of stars. BASTAis extensively documented and includes a suite of examples to support easy adoption and further development by new users., Funding for the Stellar Astrophysics Centre is provided by The Danish National Research Foundation (Grant agreement No. DNRF106). VAB-K acknowledges support from VILLUM FONDEN (research grant 10118), the Independent Research Fund Denmark (Research grant 7027-00096B), and the Carlsberg foundation (grant agreement CF19-0649). SC acknowledges support from Premiale INAF MITiC (PI: B. Garilli), from Istituto Nazionale di Fisica Nucleare (INFN) (Iniziativa specifica TAsP), from Progetto Mainstream INAF (PI: S. Cassisi) and grant AYA2013- 42781P from the Ministry of Economy and Competitiveness of Spain. AMS is partially supported by grant PID2019-108709GB-I00 of the MICINN of Spain. AS acknowledge support from the European Research Council Consolidator Grant funding scheme (project ASTEROCHRONOMETRY, G.A. n. 772293, http://www.asterochronometry.eu). more...

OBJECTIVES: Migraine and dementia, two major public health challenges, are associated, but more knowledge is needed to understand their relationship. Objectives of this study were to investigate 1) the association between non-self-reported measures of migraine and dementia, and whether dementia was associated with 2) migraine without aura (MO) and with aura (MA) in combination with migraine medication use, and 3) migraine severity operationalized as the number of migraine prescriptions.STUDY DESIGN: Matched cohort study.METHODS: National register data were obtained from individuals born between 1934 and 1958. Migraine cases (aged 25-58 years) were identified by migraine diagnoses and redeemed migraine medication. Migraine cases were matched with non-cases (N = 340,850) and date of diagnosis or medication redemption was defined as index year. Dementia was identified by dementia diagnoses and redeemed dementia medication.RESULTS: We observed a 1.46 (95% CI: 1.26-1.69) times higher dementia rate in individuals with a migraine diagnosis and a 0.86 (95% CI: 0.76-0.97) times lower rate when using migraine medication. We found the highest dementia rate among individuals with MA, who also used migraine medication (HR = 2.23; 95% CI: 1.19-4.17), and the lowest rate among individuals with MO, who also used medication (HR = 1.25; 95% CI: 0.75-2.10). The number of migraine medication prescriptions was not associated with dementia.CONCLUSIONS: Being registered with a migraine diagnosis was associated with a higher dementia rate, while use of prescribed migraine medication was not. The differences in the dementia rate among migraine cases identified via diagnoses versus medications warrants further investigation. more...

BackgroundVEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome was described in 2020 with overlapping features of rheumatology and hematology. VEXAS is an autoinflammatory condition caused by somatic mutations in the UBA1 gene at methionine-41.As patients present with highly variable clinical symptoms [1], their path in the clinical system is often complicated, and characterized by many strenuous examinations and biopsies. It is pivotal, that we familiarize with the VEXAS phenotype and advance identification of patients with VEXAS.ObjectivesWe aimed to characterize patients diagnosed with VEXAS in a tertiary rheumatology referral center since December 2020 when the syndrome was described [2].MethodsAll patients were identified and diagnosed at the department of Rheumatology, Aarhus University Hospital (AUH), Denmark. Patients underwent testing for the UBA1 somatic mutations using sanger sequencing at the department of Clinical Immunology, AUH. Sequencing analyzed for somatic variants in/at exon 3 (NM_003334.4: c.118-1G>C, c.121A>C/G, c.122T>C og c.167C>T). Clinical and biochemical data were retrieved from the hospital electronic patient chart.Continuous variables are presented as median with interquartile range (IQR) and categorical variables as percentages.ResultsA total of 11 male patients with clinical suspicion of VEXAS underwent sequencing. Five men were identified in the period December 2020 to December 2021 with UBA1 somatic mutations. Median age at diagnosis was 84 (75-87). Symptoms debuted on average 22 months (IQR 20-40) before diagnosis. All patients had significantly elevated markers of inflammation: median CRP 297 (196-386), IL-2-receptor, and ferritin and presented with macrocytic anemia. None of the patients were positive for autoimmune biomarkers like ANA, ACPA, MPO-, or PR3-ANCA.ConclusionThis is, to the best of our knowledge, the first report of Danish patients with the VEXAS syndrome. Patients are males with persistent inflammation, constitutional symptoms, and heterogeneous clinical presentations.Common features for all patients in this study were highly elevated inflammatory markers, macrocytic anemia, and negative autoimmune biomarkers.References[1]Georgin-Lavialle et al. Br J Dermaol. 2021 Oct 1. Online ahead of print[2]Beck et al. N Engl J Med. 2020 Dec 31;383(27):2628-2638.Table 1.Clinical, biochemical characteristics at diagnosis and treatment of Danish VEXAS patients.Patient 1Patient 2Patient 3Patient 4Patient 5Total n(%) or median (IQR)Clinical characteristicsAge at diagnosis738977848584 (75-87)Time from symptom onset till diagnosis (months)182147302222 (20-40)UBA1 variantc.122 T>C p.Met41Thrc.122 T>Cp.Met41Thrc.122 T>Cp.Met41Thrc.121 A>Cp.Met41Leuc.118-1 G>Cp.(splice)Macrocytic anemia+++++5 (100%)CRP(max, mg/ml)+(335)+(436)+(220)+(172)+ (297)5 (100%) (297 (196-386))Constitutional symptoms*+++++5 (100%)Vasculitis+++-+4 (80%)Chondritis--+-+2 (40%)Ocular inflammation--+--1 (20%)Arthritis+-++-3 (60%)Lung involvement-++++4 (80%)Proteinuria-++-+3 (60%)Thrombosis+--+-2 (40%)BM vacuoles-++NA-2/4 (50%)Biochemical characteristicsANA-----0 (0%)ACPANA---NA0 (0%)PR3 or MPO-ANCA-----0 (0%)IQR: inter quartile range, BM: bone marrow, ANA: anti-nuclear antibodies, ACPA: anti-citrullinated protein antibody, PR3-ANCA: proteinase-3 anti-cytoplasmatic antibody, MPO: myeloperoxidase, NR: within normal range, NA: not available.*Constitutional symptoms (fever, night sweats, weight loss).Disclosure of InterestsMads Nyhuus Bendix Rasch Speakers bureau: Speakers fee in context of alignment meeting in autoinflammatory diseases by Sobi, Fruzsina Szabados: None declared, Jens Magnus Bernth Jensen: None declared, Kirstine Overgaard Nielsen: None declared, Ellen-Margrethe Hauge Speakers bureau: Has received fees for speaking and/or consulting from AbbVie, Sanofi, Sobi, MSD, UCB, Consultant of: Has received fees for speaking and/or consulting from AbbVie, Sanofi, Sobi, MSD, UCB, Grant/research support from: Research funding to Aarhus University Hospital from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis;, Anne Troldborg: None declared more...

Aims The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals. Methods and results This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell’s concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1–19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17–1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58–2.29), and suPAR (HR: 1.35, 95% CI: 1.17–1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol ( p Conclusions Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals. more...

Background: The Faroe Islands currently have the highest recorded inflammatory bowel disease (IBD) incidence in the world.Objective: This study investigated environmental risk factors for IBD in the Faroese population.Methods: Environmental exposure data including lifestyle risk factors and neurotoxicants collected for over 30 years were retrieved from the Children's Health and the Environment in the Faroes (CHEF) cohorts including mainly mother-child pairs, with exposure data collected from pregnant mothers. For lifestyle risk factors, the incidence of IBD and ulcerative colitis (UC) was calculated as the rate ratio (RR) with 95% confidence intervals (CI) in exposed versus non-exposed persons. For neurotoxicants RR was calculated for persons with high versus low exposure.Results: Six cohorts included 5698 persons with complete follow-up data and at least one exposure, and 37 were diagnosed with IBD. For pilot whale/blubber, the RR was 1.02 (95% CI, 0.48-2.18); RR of 1.01 for fish (95% CI, 0.35-2.91); and of the pollutants studied, a statistical significantly increased risk was found for 1,1,1,-trichloro-2,2-bis-(p-chlorophenyl) ethane (p,p'-DDT); RR 3.04 (95% CI, 1.12-8.30). RRs were 1.96 (95% CI, 1.03-3.73) for smoking and 1.10 (95% CI, 0.55-2.19) for alcohol intake.Conclusion: The high IBD incidence is unlikely to be caused by special dietary habits or by environmental pollutants. more...

Box jellyfish have an elaborate visual system and perform advanced visually guided behaviors. However, the rhopalial nervous system (RNS), believed to be the main visual processing center, only has 1000 neurons in each of the four eye carrying rhopalia. We have examined the detailed structure of the RNS of the box jellyfish Tripedalia cystophora, using immunolabeling with antibodies raised against four putative neuropeptides (T. cystophora RFamide, VWamide, RAamide, and FRamide). In the RNS, T. cystophora RF-, VW-, and RAamide antibodies stain sensory neurons, the pit eyes, the neuropil, and peptide-specific subpopulations of stalk-associated neurons and giant neurons. Furthermore, RFamide ir+ neurites are seen in the epidermal stalk nerve, whereas VWamide antibodies stain the gastrodermal stalk nerve. RFamide has the most widespread expression including in the ring and radial nerves, the pedalium nerve plexus, and the tentacular nerve net. RAamide is the putative neurotransmitter in the motor neurons of the subumbrellar nerve net, and VWamide is a potential marker for neuronal differentiation as it is found in subpopulations of undifferentiated cells both in the rhopalia and in the bell. The results from the FRamide antibodies were not included as only few cells were stained, and in an unreproducible way. Our studies show hitherto-unseen details of the nervous system of T. cystophora and allowed us to identify specific functional groups of neurons. This identification is important for understanding visual processing in the RNS and enables experimental work, directly addressing the role of the different neuropeptides in vision. more...

It remains unclear which blood pressure (BP) characteristics best predict cardiovascular risk in different age groups and between sexes. We leveraged data from the MORGAM (MONICA [Monitoring of Trends and Determinants in Cardiovascular Disease], Risk, Genetics, Archiving and Monograph) Project to investigate determinants of BP characteristics and their prognostic importance, in younger and older (P interaction P P P P =0.03), enhanced continuous net reclassification improvement (0.150 [95% CI, 0.087–0.215]) and improved the prognostic value of the European Society of Cardiology/European Society of Hypertension hypertension definition (categorical net reclassification improvement=0.0255, P =0.005). In conclusion, diastolic BP may provide additional prognostic utility beyond systolic BP, in predicting composite cardiovascular events among younger individuals. more...

Aims There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts. Methods and results In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11–1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF. Conclusions In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention., Graphical Abstract Hazard ratio for incident atrial fibrillation for alcohol consumption in gram per day by non-linear Cox regression plotted on the log-scale (N = 92 452). The model uses age as time scale and is sex and cohort stratified. The reference value is 0 g/day. more...

Background: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the “Effects of Low-level Air Pollution: A Study in Europe” (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence. Methods: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants’ baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). Results: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m3 PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m3 PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m3 PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative. Conclusions: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies. © 2020 Elsevier Inc. more...

Background: Long-term exposure to air pollution has been linked to coronary cardiovascular disease andcerebrovascular disease mor, yet litearture on heart failure (HF) is rather new and limited. We... more...

BACKGROUND Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS). METHODS In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology. RESULTS We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA. CONCLUSIONS Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed. more...

OBJECTIVES: The aims of this cross-sectional study were to assess the pneumococcal antibody coverage in patients with autoimmune inflammatory rheumatic disease (AIRD) and to identify predictors associated with inadequate protective antibody levels.METHOD: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIRD patients with a diagnosis of rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis attending the Department of Rheumatology at the North Denmark Regional Hospital. Immunization against pneumococcal infection was defined as a geometric mean level ≥ 1 μg antibodies/mL. Clinical information about vaccination status and disease/treatment history was retrieved from the medical file system.RESULTS: Results of antibody measurement and vaccination status were available from 346 AIRD patients, of whom 200 (58%) were registered as receiving pneumococcal vaccination, whereas the remaining 146 patients (42%) were not. Of all 346 patients, only 61 (18%) were measured with an adequate level of protective antibodies (30% vs 1%, respectively). Methotrexate treatment at the time of vaccination and increasing age were identified as predictors of poor vaccination outcome in multiple logistic regression analysis.CONCLUSIONS: This post-vaccination study showed that less than one-fifth of the AIRD patients are adequately protected against pneumococcal infection, although the immunization programme had been implemented in more than half of the study population. Development of improved vaccination strategies is required to achieve a higher immunization coverage rate and more efficient lasting antibody response. more...

The number of patients supported with left ventricular assist devices (LVADs) is growing and support times are increasing. This has led to a greater focus on functional capacity of these patients. LVADs greatly improve heart failure symptoms, but surprisingly, improvement in peak oxygen uptake (pVO2) is small and remains decreased at approximately 50% of normal values. Inadequate increase in cardiac output during exercise is the main responsible factor for the low pVO2 in LVAD recipients. Some patients experience LV recovery during mechanical unloading and these patients have a higher pVO2. Here we review the various components determining exercise cardiac output in LVAD recipients and discuss the potential impact of cardiac recovery on these components. LV recovery may affect several components, leading to improved hemodynamics during exercise and, in turn, physical capacity in patients with advanced heart failure undergoing LVAD implantation. more...

Aim To map COVID‐19‐specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID‐19 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID‐19 pandemic. Methods A cross‐sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID‐19‐specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes‐specific social support, diabetes distress and changes in diabetes‐specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. Results People with diabetes have COVID‐19‐specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID‐19, about one‐third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID‐19 and diabetes. Conclusion People with diabetes have COVID‐19‐specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID‐19 and diabetes., What’s new? Little is known about how worldwide pandemics affect the psychosocial health of people with diabetes.This study showed a high prevalence of diabetes‐specific worries related to COVID‐19, especially fear of being overly affected by the virus, labelling of people with diabetes as a high‐risk group, and inability to manage diabetes if infected.Female gender, type 1 diabetes, diabetes complications, isolation, loneliness, high diabetes distress and behaviour changes were associated with being more worried about COVID‐19 and diabetes.When providing information and support to people with diabetes in time of crisis, attention should be payed to crisis‐specific worries in specific groups. more...

Objective: The aim of this study was to evaluate the impact of age on the associations between hemodynamic components derived from 24-h ambulatory blood pressure (24-h ABPM) and target organ damage, in apparently healthy, nonmedicated individuals. Methods: Twenty-four-hour ABPM and target organ damage (left ventricular mass index, pulse wave velocity, urine albumin : Creatinine ratio and carotid atherosclerotic plaques) were evaluated in 1408 individuals. Associations were examined in regression models, stratified for age [middle-aged (41 or 51 years) or elderly (61 or 71 years)], and adjusted for sex, smoking status, and total-cholesterol. Results: In middle-aged individuals, an increase of 10mmHg in 24-h SBP was independently associated with an increase of 3.8 (2.7-4.8) g/m2 in LVMI. The effect was nearly doubled in the elderly subgroup, where the same increase resulted in an increase in LVMI of 6.3 (5.0-7.6) g/ m2 (P for interaction 0.26). Conclusion: Age enhances the associations between hemodynamic components obtained from 24-h ABPM and measures of arterial stiffness, microvascular damage, and cardiac structure, but not atherosclerosis. more...

Background The Faroe Islands, a genetically and geographically isolated population in the North Atlantic, has the world’s highest prevalence of inflammatory bowel disease (IBD). Epidemiological studies have characterized this unique cohort, which consists predominately of an ulcerative colitis phenotype, and a decreased risk of developing IBD with emigration. Therefore, the well-characterized Faroese IBD cohort gives the opportunity to better understand the interplay between genetic predisposition and environmental triggers for this complex disease. This study represents the first investigation into the composition of the gut microbiome for the cohort. Methods This cross-sectional study consisted of 41 patients with established ulcerative colitis (UC) and 144 age-and sex matched healthy controls (HC) recruited through the Faroese Genome project (FarGen). Participants donated a one-time fecal sample and completed questionnaires on food-frequency, background health and lifestyle. DNA extractions were completed and 16S rRNA amplicon sequencing of the V3-V4 region was performed followed by bioinformatic analysis of taxonomy and diversity metrics. Results The overall composition of the sequenced fecal bacteria was dominated by Firmicutes (64,5% of total amplicon sequence variants) and Bacteroidetes (20,95% of total amplicon sequence variants). Akkermansia muciniphila was absent from 30% of the study samples. Discriminatory analysis for indicator taxa identified that Coprococcus and Prevotella_9 characterized healthy controls while genus Ruminiclostridium characterizes UC patients. However, no statistically significant differences were found between UC and HC based on metrics of alpha or beta diversity. Food frequency questionnaires revealed no differences in dietary patterns of the two groups. Conclusion The similarity between the microbiome of Faroese UC and HC samples within this study and the absence of the beneficial taxa Akkermansia muciniphila in both groups, raises further questions concerning the underlying susceptibility toward inflammatory and metabolic disorders within this population. This study represents the first 16s rRNA amplicon sequencing data and insights into the Faroese UC and background population. The results highlight the importance of having regionally tuned reference ranges for microbial data. more...

BACKGROUND In patients with advanced heart failure, a left ventricular assist device (LVAD) offers improved survival and quality of life. NTproBNP is commonly measured during routine follow-up in patients with a LVAD. While NTproBNP has been extensively studied in ambulatory heart failure patients, and proven a useful prognostic marker, there is scarce evidence on its prognostic utility in LVAD patients. This multi-centre study aims to evaluate the association between NTproBNP and mortality in patients with a LVAD as bridge to heart transplant or destination therapy. METHODS AND RESULTS This is a two-center retrospective cohort study including 165 consecutive adults discharged after implantation of a durable continuous flow LVAD either as bridge to heart transplant, or as destination therapy between 2006 and 2020 at the Toronto General Hospital (Toronto, ON) and the Rigshospitalet (Copenhangen, Denmark). Uni- and multi-variable extended Cox proportional hazard models were used to evaluate the association between multiple measures of NTproBNP and mortality in LVAD patients. Of the 165 patients included in the analysis, 84 patients died and 76 patients were successfully bridged to heart transplant. Multi-variable analysis were adjusted for age, gender, type of cardiomyopathy, hypertension and diabetes. There was an increasing mortality risk with increasing NTproBNP values (Figure), with a significantly increased risk in patients with NTproBNP >1600 pmol/L in comparison to CONCLUSION Our multi-centre study demonstrates that in patients with a LVAD for bridge to transplantation or destination therapy, NTproBNP values exceeding 1600 pmol/L are significantly associated with increased risk of mortality. Larger studies may be useful to examine the prognostic utility of lower levels of NTproBNP and its association with mortality or heart-failure related hospitalizations. more...

Markers of target-organ damage and 24-hour ambulatory blood pressure (BP) measurement improve cardiovascular risk stratification. The prevalence of target-organ damage and raised BP increases with aging. The study aim was to evaluate the impact of age and target-organ damage on the prognostic value of ambulatory BP. Markers of target-organ damage and ambulatory BP were measured in 1408 healthy people aged 41 or 51 (middle-aged group), and 61 or 71 (older group) years. The primary outcome was cardiovascular events after 16 years of follow-up, with data obtained from national registries. The prognostic value of BP was evaluated with Cox regression models, adjusted for traditional risk factors and target-organ damage, including left ventricular mass, pulse wave velocity, carotid plaques, and urine albumin/creatinine ratio. A total of 323 events were observed. In comparison with traditional risk factors, adding systolic BP and presence of target-organ damage improved risk stratification by increasing concordance index from 0.711 to 0.728 ( P =0.01). In middle-aged subjects with target-organ damage, increment in pulse pressure (hazard ratio, 1.70; 95% confidence interval, 1.31–2.21; P P =0.02) were associated with a greater risk of cardiovascular disease compared with subjects without target-organ damage: hazard ratio, 1.04 (95% confidence interval, 0.74–1.46; P =0.81); P for interaction, 0.02; and hazard ratio, 0.89 (95% confidence interval, 0.69–1.14; P =0.36); P for interaction, 0.01. Target-organ damage may be a marker of individual susceptibility to the harmful effects of pulse pressure and BP variability on the cardiovascular system in middle-aged individuals. more...

[Context] With the advent of space-based asteroseismology, determining accurate properties of red-giant stars using their observed oscillations has become the focus of many investigations due to their implications in a variety of fields in astrophysics. Stellar models are fundamental in predicting quantities such as stellar age, and their reliability critically depends on the numerical implementation of the physics at play in this evolutionary phase., [Aims] We introduce the Aarhus red giants challenge, a series of detailed comparisons between widely used stellar evolution and oscillation codes that aim to establish the minimum level of uncertainties in properties of red giants arising solely from numerical implementations. We present the first set of results focusing on stellar evolution tracks and structures in the red-giant-branch (RGB) phase., [Methods] Using nine state-of-the-art stellar evolution codes, we defined a set of input physics and physical constants for our calculations and calibrated the convective efficiency to a specific point on the main sequence. We produced evolutionary tracks and stellar structure models at a fixed radius along the red-giant branch for masses of 1.0 M⊙, 1.5 M⊙, 2.0 M⊙, and 2.5 M⊙, and compared the predicted stellar properties., [Results] Once models have been calibrated on the main sequence, we find a residual spread in the predicted effective temperatures across all codes of ∼20 K at solar radius and ∼30–40 K in the RGB regardless of the considered stellar mass. The predicted ages show variations of 2–5% (increasing with stellar mass), which we attribute to differences in the numerical implementation of energy generation. The luminosity of the RGB-bump shows a spread of about 10% for the considered codes, which translates into magnitude differences of ∼0.1 mag in the optical V-band. We also compare the predicted [C/N] abundance ratio and find a spread of 0.1 dex or more for all considered masses., [Conclusions] Our comparisons show that differences at the level of a few percent still remain in evolutionary calculations of red giants branch stars despite the use of the same input physics. These are mostly due to differences in the energy generation routines and interpolation across opacities, and they call for further investigation on these matters in the context of using properties of red giants as benchmarks for astrophysical studies., Funding for the Stellar Astrophysics Centre is provided by The Danish National Research Foundation (Grant agreement No. DNRF106). The research was supported by the ASTERISK project (ASTERoseismic Investigations with SONG and Kepler) funded by the European Research Council (Grant agreement No. 267864). VSA acknowledges support from VILLUM FONDEN (research grant 10118) and the Independent Research Fund Denmark (Research grant 7027-00096B). AS is partially supported by grant ESP2017-82674-R (MICINN) and 2017-SGR-1131 (Generalitat Catalunya). DS acknowledges support from the Australian Research Council. Part of this research was supported by the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no 338251 (StellarAges). RHDT acknowledges support from National Science Foundation grants ACI-1663696 and AST-1716436. This work was supported by FCT/MCTES through national funds and by FEDER – Fundo Europeu de Desenvolvimento Regional through COMPETE2020 – Programa Operacional Competitividade e Internacionalização by these grants: UID/FIS/04434/2019; PTDC/FIS-AST/30389/2017 and POCI-01-0145-FEDER-030389. DB is supported in the form of work contract funded by national funds through Fundação para a Ciência e Tecnologia (FCT). AM acknowledges the support of the Govt. Of India, Department of Atomic Energy, under Project No. 12-R&D-TFR-6.04-0600. We would like to thank Bill Paxton for assistance with the MESA solar calibration and for accommodating requested changes to the code along the way. more...

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians. more...

BACKGROUND: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up.METHODS: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery.FINDINGS: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (pINTERPRETATION: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease.FUNDING: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd. more...

Objective. To examine how liver function (LF) relates to invasive hemodynamics cross-sectionally and longitudinally, in advanced heart failure (AHF) patients treated with maximally tolerated medica... more...

Growing evidence from across the cognitive sciences indicates that iconicity plays an important role in a number of fundamental language processes, spanning learning, comprehension, and online use. One benefit of this recent upsurge in empirical work is the diversification of methods available for measuring iconicity. In this paper, we provide an overview of methods in the form of a ‘toolbox’. We lay out empirical methods for measuring iconicity at a behavioural level, in the perception, production, and comprehension of iconic forms. We also discuss large-scale studies that look at iconicity on a system-wide level, based on objective measures of similarity between signals and meanings. We give a detailed overview of how different measures of iconicity can better address specific hypotheses, providing greater clarity when choosing testing methods. more...

Background Sex differences in the performance of prognostic risk scores in heart failure (HF) patients have not previously been investigated. We examined the performance of 2 commonly used scores in predicting mortality and a composite end point consisting of ventricular assist device, heart transplantation, or mortality in women vs men with HF. Methods This was a retrospective study of 1,136 (25% women) consecutive ambulatory adult HF patients with reduced left ventricular ejection fraction (≤ 40%) followed at a single institution from 2000 to 2012. Discrimination, calibration, and absolute risk reclassification of the Seattle Heart Failure Model (SHFM) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score to predict 1- and 3-year outcomes were compared between women and men. Results At 1- and 3-year follow-ups, 116 (22% women) and 231 (21% women) patients died, respectively. Survival was equal between sexes (P = 0.41). The SHFM and the MAGGIC score showed similar discriminatory capacity in women (c-statistics 0.84, 95% CI 0.77-0.92, and 0.74, 95% CI 0.64-0.83) and men (c-statistics 0.74, 95% CI 0.69-0.79, and 0.70, 95% CI 0.64-0.75). There was no difference in the predicted and observed 1-year mortality by the scores in both sexes. Compared with the SHFM, the MAGGIC score better reclassified 10% (95% CI 7%-14%) of women and 18% (95% CI 15%-20%) of men. At 3-year follow-up, similar results were seen for discrimination, whereas both scores overestimated mortality with more marked overestimation in women. The results were reproducible for the composite end point, with improved calibration at 3-year follow-up in both scores. Conclusions Our findings support the use of the MAGGIC score in both women and men owing to better risk classification. more...

Background:Previous studies indicate that genetic susceptibility and phenotype of rheumatoid arthritis (RA) differ between the populations.Objectives:To compare the clinical, serologic expression and the presence of shared epitopes (SE) of incident RA in two different populations, one from Northern and the other from Southern Europe.Methods:Data on incident RA patients fulfilling EULAR/ACR 2010 classifications criteria for RA were collected at Rheumatology Departments in Denmark and Turkey in 2015-2016. Patients were assessed using the same standardized protocol in both populations. SE carrier status were assigned, according to the du Montcel classification based, into six allele groups:S1, S2,S3D,S3PandX, where S2 and S3P are RA risk-enhancing alleles and S1 and S3D are RA protective alleles of the shared epitope(1).Results:109 incident RA patients from Denmark and 114 incident RA patients from Turkey were enrolled. Genetic data were available from 87% of the patients.Table 1.Characteristics of incident rheumatoid arthritis patients in Denmark and TurkeyDanish patientsn=109Turkish patientsn=114P-valueAge at diagnosis, years60 (49-69)52 (43-64)0.003Female, %64740.12Symptom duration, months7 (4-21)6 (2-22)0.6Smoking status Never smoker, %43440.98 Former smoker, %28310.68 Current smoker, %29250.54VAS pain (0-100 mm)45 (28-66)60 (41-72)0.01VAS fatigue (0-100 mm)51 (29-69)50 (20-70)0.32VAS global, patient (0-100 mm)60 (31-80)60 (41-73)0.77Swollen joint count (0-28)7 (4-11)3 (1-6)Tender joint count (0-28)7 (3-11)5 (2-8)0.04HAQ score (0-3)0.75 (0.34-1.25)1.0 (0.25-1.75)0.02DAS284.7 (4.1-5.5)4.3 (3.3-5.2)0.01CRP, mg/l7 (3.0-18.5)8 (3.1-22.6)0.54IgM RF positive, %70660.58ACPA positive, %63750.1Medians (interquartile range) for continuous variablesVAS – Visual Analog Scale, HAQ - Health Assessment Questionnaire, DAS28 - Disease Activity Score 28 joints, CRP – C-reactive protein, RF – Rheumatoid Factor, ACPA - Anti-Citrullinated Protein Antibodies.Table 2.Shared epitope allele carrier frequencies.AlleleDanish patientsn=98Turkish patientsn=95P-valueS1, % (n)19 (37)22 (42)0,43S2, % (n)26 (51)8 (16)S3D, % (n)6 (12)21 (39)0,000029S3P, % (n)27 (52)29 (56)0,52X, % (n)22 (44)19 (37)0,47We found no associations between the risk-enhancing alleles and the presence of IgM rheumatoid factor or ACPA.Conclusion:The Turkish patients were younger and had lower disease activity than Danish at the time of diagnosis. Our study found an enhanced genetic susceptibility to RA in Danish compared to Turkish patients with a higher prevalence of risk-enhancing RA alleles and a lower prevalence of protective alleles.References:[1]Tezenas du Montcel S, Michou L, Petit-Teixeira E, Osorio J, Lemaire I, Lasbleiz S, et al. New classification of HLA–DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility.Arthritis Rheum2005; 52: 1063–8.Disclosure of Interests:None declared more...

Aphanomyces cochlioides and Rhizoctonia solani are important soilborne pathogens causing root diseases that are primary constraints to sugar beet production in Nebraska, Colorado, and Wyoming. These types of diseases are difficult to control because they are often not noticed until substantial damage has already occurred. Efforts to manage them would be more effective if techniques were available that were more predictive than reactive. Therefore, a preplant soil test was developed to estimate the relative pathogen populations in the soil and to predict potential root disease problems later in the growing season. Preplant soil samples collected from fields to be sown with sugar beet were planted with a susceptible cultivar and tests were conducted for 1 month in the greenhouse. A preplant disease index was developed based on the time period during the test that seedlings became infected and was calculated on a 0-to-100 scale. Disease index values were compared with yields obtained from the same fields after harvest. Analysis of data collected for 5 years (2003 to 2007) with analysis of covariance revealed a strong relationship between the preplant disease index values and recoverable sucrose and root yields but not sucrose concentration. Results indicated that, for each unit increase in the preplant disease index, root yield decreased by 0.27 metric tons (270 kg) per hectare (P < 0.05, R2 = 0.44) and recoverable sucrose decreased by 49 kg/ha (P < 0.05, R2 = 0.45). We concluded that this preplant soil test can accurately predict root disease potential due to R. solani and A. cochlioides, and has the potential to help producers make effective management decisions in production fields using the index procedure. This soil assay has additionally provided new information on the biology, incidence, and distribution of root pathogens in production fields throughout the Central High Plains. more...

Supplemental Material for Dietary risk factors for inflammatory bowel diseases in a high-risk population: Results from the Faroese IBD study by T Hammer, S Nymand Lophaven, K Rubek Nielsen, M Skaalum Petersen, P Munkholm, P Weihe, J Burisch and E Lynge in United European Gastroenterology Journal more...

Background The association between inflammatory bowel disease and malignancy is still controversial despite many observational studies. The Faroese population exhibits the highest occurrence of inflammatory bowel disease (IBD) in the world. The aim of this study was to investigate the risk of cancer in Faroese IBD patients within the nationwide Faroese IBD cohort. Methods This was a nationwide cohort study of all IBD patients diagnosed in the Faroe Islands from 1960 to 2014. Clinical demographics and cancer diagnosis were retrieved from patient files and from the Faroese cancer registry. Patients were followed until the event of cancer, death or emigration. Patients diagnosed with cancer prior to the IBD diagnosis were excluded. Observed numbers of cancer were compared with expected numbers based on ASR(N) (Nordic age- and sex-specific incidence rates) from Nordcan, by multiplying ASR(N) with person-years and follow-up in the study cohort and presented as standardised incidence ratios (SIRs) with 95 % intervals (CIs). Results The cohort consisted of 664 incidence IBD patients. After excluding 12 patients with cancer prior to IBD diagnosis, 652 patients with a total follow-up length of 11 476 person-years were included (414 UC with 7.494 patient-years, 128 IBDU with 2.038 patient-years and 110 CD with 1.944 patient-years). A total of 56 patients developed cancer during the follow-up period compared with 39.2 expected cases in the background population. We observed no gender difference. In UC, 33 observed compared with 25.7 expected patients developed cancer (SIR 1.28; 95% CI, 0.88–1.80). In IBDU, 13 observed compared with 6.9 expected patients developed cancer (SIR 1.88; 95% CI 1.00–0.22). In CD, 10 cases were observed compared with 6.6 expected (SIR 1.51; 95% CI 0.73–2.79). The most common types of cancers observed are shown in Table 1. Conclusion In this nationwide cohort study, we found no overall risk of cancer in IBD patients in the geographic isolated Faroe Island. However, skin cancer occurred more than expected in IBDU patients. This finding needs to be investigated further including the influence of treatment on cancer risk. more...

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing.MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores.RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053).CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke. more...

Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation. more...

Endometriosis is a common complex inflammatory condition characterised by the presence of endometrium-like tissue outside the uterus, mainly in the pelvic area. It is associated with chronic pelvic pain and infertility, and its pathogenesis remains poorly understood. The disease is typically classified according to the revised American Fertility Society (rAFS) 4-stage surgical assessment system, although stage does not correlate well with symptomatology or prognosis. Previously identified genetic variants mainly are associated with stage III/IV disease, highlighting the need for further phenotype-stratified analysis that requires larger datasets. We conducted a meta-analysis of 15 genome-wide association studies (GWAS) and a replication analysis, including 58,115 cases and 733,480 controls in total, and sub-phenotype analyses of stage I/II, stage III/IV and infertility-associated endometriosis cases. This revealed 27 genetic loci associated with endometriosis at the genome-wide p-value threshold (P−8), 13 of which are novel and an additional 8 novel genes identified from gene-based association analyses. Of the 27 loci, 21 (78%) had greater effect sizes in stage III/IV disease compared to stage I/II, 1 (4%) had greater effect size in stage I/II compared to stage III/IV and 17 (63%) had greater effect sizes when restricted to infertility-associated endometriosis cases compared to overall endometriosis. These results suggest that specific variants may confer risk for different sub-types of endometriosis through distinct pathways. Analyses of genetic variants underlying different pain symptoms reported in the UK Biobank showed that 7/9 had positive significant (p3) positive genetic correlations with endometriosis, suggesting a genetic basis for sensitivity to pain in general. Additional conditions with significant positive genetic correlations with endometriosis included uterine fibroids, excessive and irregular menstrual bleeding, osteoarthritis, diabetes as well as menstrual cycle length and age at menarche. These results provide a basis for fine-mapping of the causal variants at these 27 loci, and for functional follow-up to understand their contribution to endometriosis and its potential subtypes. more...

Background Severe pneumococcal infections contribute to increased mortality in patients with rheumatic diseases, and is preventable by vaccination against Streptococcus pneumoniae. EULAR recommends that pneumococcal vaccination should be strongly considered in patients with rheumatic diseases, however, need and timing of revaccination for this patient group remains unknown1. Since 2009, rheumatological patients from our department have been vaccinated against S. pneumoniae prior to initiation of bDMARD therapy, by use of the 23-valent pneumococcal polysaccharide vaccine (PPV23). To our knowledge, we are the only centre in Denmark to vaccinate these patients routinely. Objectives The aim of the study was to determine the prevalence of rheumatological patients receiving bDMARD therapy with a protective level of antibodies against S. pneumoniae, and to identify possible factors of relevance affecting antibody production. Methods Antibodies against 12 pneumoccocal serotypes were measured in the period of June to December 2017 in patients receiving bDMARD therapy initiated before March 1st 2017. A geometric mean level of all serotypes above 1 µg/ml was considered a protective antibody level. The patients had been diagnosed with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis or juvenile idiopathic arthritis. The study group consisted of both vaccinated and unvaccinated individuals, where unvaccinated individuals initiated bDMARD therapy before vaccination occurred routinely. Differences in protection between vaccinated and unvaccinated patients were evaluated using the χ2 test. We included the following variables in a logistic regression model, to analyse factors of possible significance to the protective level of antibodies: age, sex, diagnosis, methotrexate (MTX) and/or prednisolone treatment at time of vaccination, and years since vaccination. Results A total of 319 patients were included in the study: 186 (58%) vaccinated and 133 (42%) unvaccinated patients. Among the vaccinated patients, 30% had a protective antibody level versus 0% of the unvaccinated patients (p Logistic regression analysis showed that a significantly smaller proportion of patients treated with MTX at time of vaccination had a protective antibody level compared with patients not treated with MTX (p=0.03; odds ratio: 2.3; 95% CI [1.1;4.7]). The same applied for advanced age at time of vaccination (p=0.04), whereas years since vaccination did not decrease antibody protection significantly (p=0.12). Conclusions Only one third of PPV23 vaccinated rheumatological patients treated with bDMARD were observed with a GML of pneumococcal antibodies above 1 µg/ml. This suggests that a majority of these patients are not protected adequately against pneumococcal disease in spite of vaccination. MTX treatment at time of vaccination and advanced age were both independently associated with lack of protective antibody level. Reference [1] van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis2011;70(3):414–422. Disclosure of Interest None declared more...

Background and Aims: The ECCO-EpiCom study investigates the differences in the incidence and therapeutic management of inflammatory bowel diseases [IBD] between Eastern and Western Europe. The aim of this study was to analyse the differences in the disease phenotype, medical therapy, surgery, and hospitalization rates in the ECCO-EpiCom 2011 inception cohort during the first year after diagnosis. Methods: Nine Western, five Eastern European centres and one Australian centre with 258 Crohn’s disease [CD], 380 ulcerative colitis [UC] and 71 IBD unclassified [IBDU] patients [female/male: 326/383; mean age at diagnosis: 40.9 years, SD: 17.3 years] participated. Patients’ data were registered and entered in the web-based ECCO-EpiCom database [www.epicom-ecco.eu]. Results: In CD, 36 [19%] Western Europe/Australian and 6 [9%] Eastern European patients received biological therapy [ p = 0.04], but the immunosuppressive [IS] use was equal and high in these regions [Eastern Europe vs Western Europe/Australia: 53% vs 45%; p = 0.27]. Surgery was performed in 17 [24%] CD patients in Eastern Europe and 13 [7%] in Western Europe/Australia [ p < 0.001, p LogRank = 0.001]. Of CD patients from Eastern Europe, 24 [34%] were hospitalized, and 39 [21%] from Western Europe/Australia, [ p = 0.02, p LogRank = 0.01]. In UC, exposure to biologicals and colectomy rates were low and hospitalization rates did not differ between these regions during the 1-year follow-up period [16% vs 16%; p = 0.93]. Conclusions: During the first year after diagnosis, surgery and hospitalization rates were significantly higher in CD patients in Eastern Europe compared with Western Europe/Australia, whereas significantly more CD patients were treated with biologicals in the Western Europe/Australian centres. more...

Background & Aims Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis. Methods We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95, 605 incident cases of Crohn’s disease (CD) (42, 831 male and 52, 774 female) and 112, 004 incident cases of ulcerative colitis (UC) (61, 672 male and 50, 332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis. Results Female patients had a lower risk of CD during childhood, until the age range of 10–14 years (incidence rate ratio, 0.70 ; 95% CI, 0.53– 0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25–29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5–9 years) until age 45 years ; thereafter, men had a significantly higher incidence of ulcerative colitis than women. Conclusions In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence. more...