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Background: Migraine presents significant health and economic challenges. Despite the widespread use of triptans, some patients discontinue them because of insufficient relief or adverse effects. Using national registers, the present study investigates the excess costs and labour market disaffiliation of Danish patients discontinuing triptan treatment., Methods: The study included all individuals ≥18 years ("patients") who discontinued redemption of triptan prescriptions between 1998 and 2019. They were categorized by number of distinct triptans redeemed before discontinuation: one, two or three or more. A control group was established from the general population without triptan redemptions, three per patient, matched by year of birth, sex and region of residence. We estimated excess direct and indirect costs from 5 years prior ("year -5") to 10 years post ("year 10") the first triptan redemption., Results: We identified 211,026 patients who discontinued triptan redemption, 82% after one, 14% after two and 4% after three or more distinct triptans. Over the period from year -5 to year 10, average excess healthcare costs per patient in these cohorts were EUR 9,554, EUR 10,942 and EUR 12,812 respectively. Over the same period, these patients earned EUR 27,964, EUR 35,920 and EUR 50,076 less than their respective controls, and received higher public transfer payments of EUR 20,181, EUR 23,264 and EUR 26,459., Conclusions: Triptan discontinuers, who appear to have exhausted all current treatment avenues, face high direct and very high indirect excess costs attributable to migraine, and experience substantial increased labour market disaffiliation., Competing Interests: Declaration of conflicting interestsMA reports receiving personal fees from AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer and Teva Pharmaceuticals, and also reports serving as associate editor of Cephalalgia, associate editor of The Journal of Headache and Pain and associate editor of Brain. TJS is co-editor of the Journal of Headache and Pain, a director and trustee of Lifting The Burden, and reports receiving personal fees from Eli Lilly, Teva and Pfizer. JMH reports receiving personal fees from Pfizer. DSH and USL are current employees of Pfizer Denmark and may own shares in Pfizer Inc. MS, JO and SES are current employees of EY, a paid vendor to Pfizer. TFH declares no conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear., Objectives: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk., Methods: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated., Results: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81)., Conclusions: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases., Competing Interests: Funding Support and Author Disclosures This study was funded by Aarhus University Hospital. The funding source had no influence on study design, conduct or reporting. Dr Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, American Heart Association, and Aetna Foundation; has received grants and personal fees from Amgen; and has received personal fees from Sanofi, Regeneron, Novartis, Bayer, and Novo Nordisk outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC., Methods: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute -funded Multi-Ethnic Study of Atherosclerosis., Results: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level ( > 193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis., Conclusions: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Aims: The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) trial demonstrated that icosapent ethyl lowered the risk of atherosclerotic cardiovascular disease (ASCVD) among patients with elevated triglycerides. However, how to appropriately implement its use in clinical practice is not well-defined. We aimed to determine whether plaque burden as assessed by coronary artery calcium (CAC) could stratify ASCVD risk among patients eligible for icosapent ethyl., Methods and Results: Among 23 759 patients who underwent computed tomography angiography (CTA) in the Western Denmark Heart Registry, we identified eligibility for the REDUCE-IT trial. A total of 2146 participants (9%) met enrolment criteria for REDUCE-IT. During a median of 4.3 years of follow-up, 146 ASCVD events occurred. Overall, there was a stepwise increase in ASCVD event rates per 1000 person-years with increasing CAC (CAC = 0: 10.5, CAC 1-299: 18.7, CAC ≥300: 49.8). REDUCE-IT-eligible patients with CAC ≥300 had a multivariable-adjusted hazard ratio of 3.1 compared with CAC = 0 (95% confidence interval: 1.9-4.9). Coronary artery calcium differentiated risk similarly in patients with and without obstructive coronary artery disease (CAD). Overall, the 5-year estimated number needed to treat to prevent one event with icosapent ethyl was 45 and ranged from 87 in those with CAC = 0 to 17 in those with CAC ≥300. Some patients with non-obstructive CAD had lower estimated number needed to treat than patients with obstructive CAD when their plaque burden was higher., Conclusion: Atherosclerotic plaque burden as assessed by CAC can identify REDUCE-IT-eligible patients who are expected to derive most, and least, absolute benefit from treatment with icosapent ethyl regardless of obstructive versus non-obstructive CAD status., Competing Interests: Conflict of interest: Michael Blaha reports grants from the National Institutes of Health, US Food and Drug Administration, American Heart Association, and Aetna Foundation; grants and personal fees from Amgen; and personal fees from Sanofi, Regeneron, Novartis, Bayer, and Novo Nordisk outside the submitted work. The other authors have reported that they have no relationships relevant to the contents of this article to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The long-term cardiovascular risk for patients examined with coronary computed tomography angiography (CCTA) to rule out coronary heart disease compared with population controls remains unexplored. A nationwide register-based study including first-time CCTA-examined patients between 2007 and 2017 in Denmark alive 180 days post-CCTA was conducted. We evaluated 5-year outcomes of myocardial infarction (MI) or revascularization and all-cause mortality in 3 distinct CCTA-groups: (1) no post-CCTA preventive pharmacotherapy use (cholesterol-lowering drugs, antiplatelets, or anticoagulants); (2) post-CCTA preventive pharmacotherapy use; and (3) revascularization or MI within 180 days post-CCTA. For each patient group, population controls were matched on age, gender, and calendar year. Absolute risks standardized to the age, gender, selected co-morbidity, and anti-anginal pharmacotherapy distributions of the specific CCTA-examined patients and respective controls were obtained from multivariable Cox regression. Of 110,599 CCTA-examined patients, (1) 48,231 patients were not prescribed preventive pharmacotherapy 180 days post-CCTA; (2) 42,798 patients were prescribed preventive pharmacotherapy within 180 days post-CCTA; and (3) 19,570 patients were diagnosed with MI or revascularized within 180 days post-CCTA. For patient groups 1 to 3 versus respective controls, 5-year MI or revascularization risks were <0.1% versus 2.0%, <0.1% versus 3.8%, and 19.0% versus 2.5%, all p<0.001. Five-year all-cause mortality were 2.8% versus 4.2%, 5.5% versus 8.8%, and 6.7% versus 8.5%, all p <0.001. In conclusion, the 5-year MI or revascularization risk can be considered very low for CCTA-examined patients without ischemic events within 180 days post-CCTA. Conversely, CCTA-examined patients with MI or revascularization events within 180 days post-CCTA have significantly elevated 5-year MI or revascularization risk., Competing Interests: Disclosures K. Kragholm: Speaker's honoraria from Novartis. P. Sogaard: Speaker for GE Healthcare, advisory board member (Novartis Pharmaceuticals Corp., Astra Zeneca Pharmaceuticals, Biotronik), research grants Wics, Bayer, and GE Healthcare. T. Zaremba: speaker's fee from AstraZeneca. C. Byrne: Speaker's honoraria from Bayer. L. Kober: Speakers honorarium from Novo, Novartis AstraZeneca and Boehringer. These disclosures are unrelated to the topic of the current manuscript and have not influenced the design and conduct of the study, nor in the collection, analysis, and interpretation of the data, and finally, not in the preparation, review, or submission of the manuscript. All other authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A major barrier to adequate headache care is the relative lack of formal education and training of healthcare professionals. Concerted efforts should be made to pinpoint major gaps in knowledge in healthcare professionals to facilitate better educational policies in headache training. The aim of this study was to identify deficiencies and barriers in headache training among residents in neurology in Denmark., Methods: We conducted a national cross-sectional survey of residents in neurology in Denmark from April 2019 to September 2019. The survey included questions on participant demographics, knowledge of and barriers in headache disorders, guidelines and diagnostic tools usage, contact with primary and tertiary care, medication overuse, and non-pharmacological interventions. Furthermore, respondents were asked to provide a ranked list from most to least interesting for six sub-specializations/disorders, i.e., cerebrovascular disease, dementia, epilepsy, headache, multiple sclerosis, Parkinson's disease., Results: Sixty (40%) out of estimated a population of ~ 150 resident across Denmark accepted the invitation. Of these, 54/60 (90%) completed the survey. Although two-thirds, 35/54 (65%), of the respondents had prior formalized training in headache disorders, we identified gaps in all explored domains including diagnosis, management, and referral patterns. Particularly, there was an inconsistent use of guidelines and diagnostic criteria from the Danish Headache Society (2.74 (± 1.14)), the Danish Neurological Society (3.15 (± 0.86)), and the International Classification of Headache Disorders (2.33 (± 1.08)); 1: never/have not heard of, 4: always. Headache was ranked second to last out of six sub-specializations in interest., Conclusions: Overall knowledge on headache disorders amongst neurology residents in Denmark do not meet the expectations set out by national and international recommendations. Stakeholders should make strategic initiatives for structured education in headache for improved clinical outcomes in parallel with costs reduction through resource optimization., (© 2022. The Author(s).)

Importance: Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk., Objective: To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum., Design, Setting, and Participants: This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021., Exposures: Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden., Main Outcomes and Measures: Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death., Results: A total of 23 143 patients with a median age of 58 (IQR, 50-65) years (12 857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL to 4370 of 7964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of at least 190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque., Conclusions and Relevance: The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.

Importance: The diagnostic value is unclear of a 0 coronary artery calcium (CAC) score to rule out obstructive coronary artery disease (CAD) and near-term clinical events across different age groups., Objective: To assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD and to assess the implications of such a CAC score and obstructive CAD across different age groups., Design, Setting, and Participants: This cohort study obtained data from the Western Denmark Heart Registry and had a median follow-up time of 4.3 years. Included patients were aged 18 years or older who underwent computed tomography angiography (CTA) between January 1, 2008, and December 31, 2017, because of symptoms that were suggestive of CAD. Data analysis was performed from April 5 to July 7, 2021., Exposures: Obstructive CAD, which was defined as 50% or more luminal stenosis., Main Outcomes and Measures: Proportion of individuals with obstructive CAD who had a CAC score of 0. Risk-adjusted diagnostic likelihood ratios were used to assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD beyond clinical variables. Risk factors associated with myocardial infarction and death were estimated., Results: A total of 23 759 symptomatic patients, of whom 12 771 (54%) had a CAC score of 0, were included. This cohort had a median (IQR) age of 58 (49-65) years and was primarily composed of women (13 160 [55%]). Overall, the prevalence of obstructive CAD was relatively low across all age groups, ranging from 3% (39 of 1278 patients) in those who were younger than 40 years to 8% (52 of 619) among those who were 70 years or older. In patients with obstructive CAD, 14% (725 of 5043) had a CAC score of 0, and the prevalence varied across age groups from 58% (39 of 68) among those who were younger than 40 years, 34% (192 of 562) among those aged 40 to 49 years, 18% (268 of 1486) among those aged 50 to 59 years, 9% (174 of 1963) among those aged 60 to 69 years, to 5% (52 of 964) among those who were 70 years or older. The added diagnostic value of a CAC score of 0 decreased at a younger age, with a risk factor-adjusted diagnostic likelihood ratio of a CAC score of 0 ranging from 0.68 (approximately 32% lower likelihood of obstructive CAD than expected) in those who were younger than 40 years to 0.18 (approximately 82% lower likelihood than expected) in those who were 70 years or older. The presence of obstructive vs nonobstructive CAD among those with a CAC score of 0 was associated with a multivariable adjusted hazard ratio of 1.51 (95% CI, 0.98-2.33) for myocardial infarction and all-cause death; however, this hazard ratio varied from 1.80 (95% CI, 1.02-3.19) in those who were younger than 60 years to 1.24 (95% CI, 0.64-2.39) in those who were 60 years or older., Conclusions and Relevance: This cohort study found that the diagnostic value of a CAC score of 0 to rule out obstructive CAD beyond clinical variables was dependent on age, with the added diagnostic value being smaller for younger patients. In symptomatic patients who were younger than 60 years, a sizable proportion of obstructive CAD occurred among those without CAC and was associated with an increased risk of myocardial infarction and all-cause death.

Background: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value., Objectives: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC)., Methods: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease., Results: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD., Conclusions: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD., Competing Interests: Author Disclosures This study was funded by Aarhus University Hospital. Dr. Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, American Heart Association, and Aetna Foundation; has received grants and personal fees from Amgen; and has received personal fees from Sanofi, Regeneron, Novartis, Bayer, and NovoNordisk outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Covid-19 pandemic is causing changes in delivery of medical care worldwide. It is not known how the management of headache patients was affected by the lockdown during the pandemic. The aim of the present study was to investigate how the initial phase of the Covid-19 pandemic affected the hospital management of headache in Denmark and Norway., Methods: All neurological departments in Denmark (n = 14) and Norway (n = 18) were invited to a questionnaire survey. The study focused on the lockdown and all questions were answered in regard to the period between March 12th and April 15th, 2020., Results: The responder rate was 91% (29/32). Of the neurological departments 86% changed their headache practice during the lockdown. The most common change was a shift to more telephone consultations (86%). Video consultations were offered by 45%. The number of new headache referrals decreased. Only 36% administered botulinum toxin A treatment according to usual schemes. Sixty% reported that fewer patients were admitted for in-hospital emergency diagnostics and treatment. Among departments conducting headache research 57% had to halt ongoing projects. Overall, 54% reported that the standard of care was worse for headache patients during the pandemic., Conclusion: Hospital-based headache care and research was impacted in Denmark and Norway during the initial phase of the Covid-19-pandemic.

Objective: To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse., Methods: Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests., Results: Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P < .01), independent of clinical and radiographic measures, and was also associated with most of the hand-related HAQ items (P < .03). In multivariate models including MRI, SvH scores were not associated with PROs. MRI-assessed inflammation was not associated with PROs at remission or relapse., Conclusion: Magnetic resonance imaging-assessed wrist/hand damage, but not inflammation, in patients with established RA is associated with patient-reported physical impairment at remission and relapse. The amount of damage in the wrist/hand is associated with reduced hand function., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Cavo tricuspid isthmus ablation (CTIA) is considered an effective first-line treatment for typical atrial flutter (AFL). However, many patients develop atrial fibrillation (AF) after successful CTIA. Knowledge about recurrent arrhythmia after CTIA mainly comes from small cohort studies with limited follow-up., Objective: To describe incidences of re-ablation for AFL and ablation for AF after first-time CTIA in a nation-wide cohort., Methods: In the Danish National Ablation Registry we identified patients undergoing first-time CTIA during 2010-2016. Subsequent CTIA and AF-ablation procedures were identified until March 1st, 2018. We collected information on patient comorbidities in the Danish National Patient Registry., Results: We identified 2409 patients undergoing first-time CTIA. Median age was 66 (IQR 58-72) years, 1952 (81%) were men, and 78 (3%) patients had a history of previous ablation for AF. Acute procedural success was achieved in 2288 (95%) patients. During mean follow-up of 4.0 ± 1.7 years, 242 (10%) patients underwent CTI re-ablation and 326 (13.5%) underwent ablation for AF. Baseline characteristics associated with CTI re-ablation included prolonged procedural time, unsuccessful index CTIA, age <75 years and CHA2DS2-VASc score <2. Hypertension, history of AF-ablation, age <65 years use of a contact force sensing catheter and CHA2DS2-VASc score <2 were associated with later ablation for AF., Conclusion: In a nation-wide cohort undergoing first-time CTIA for AFL, 10% of patients underwent CTI re-ablation and 13.5% ablation for AF during mean follow-up of 4.0 ± 1.7 years. Probability of a second procedure was higher in younger patients with less comorbidities., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Multi-resistant bacteria (MRB) are an emerging problem. Early identification of patients colonized with MRB is mandatory to avoid in-hospital transmission and to target antibiotic treatment. Since most patients pass through specialized emergency departments (EDs), these departments are crucial in early identification. The Danish National Board of Health (DNBH) has developed exposure-based targeted screening tools to identify and isolate carriers of meticillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Enterobacteriaceae (CPE)., Aim: To assess the national screening tools for detection of MRSA and CPE carriage in a cohort of acute patients. The objectives were to investigate: (i) if the colonized patients were detected; and (ii) if the colonized patients were isolated., Methods: This was a multi-centre cross-sectional survey of adults visiting EDs. The patients answered the DNBH questions, and swabs were taken from the nose, throat and rectum. The collected samples were examined for MRSA and CPE. Screening performances were calculated., Findings: Of the 5117 included patients, 16 were colonized with MRSA and four were colonized with CPE. The MRSA screening tool had sensitivity of 50% [95% confidence interval (CI) 25-75%] for carrier detection and 25% (95% CI 7-52%) for carrier isolation. The CPE screening tool had sensitivity of 25% (95% CI 1-81%) and none of the CPE carriers were isolated., Conclusion: The national screening tools were of limited use as the majority of MRSA and CPE carriers passed unidentified through the EDs, and many patients were isolated unnecessarily., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to describe the carrier prevalence and demographic variation of four different multiresistant bacteria (MRB) among acute patients in Danish emergency departments (EDs): methicillin-resistant Staphylococcus aureus (MRSA), carbapenemase-producing enterobacteria (CPE), extended-spectrum beta-lactamase-producing enterobacteria (ESBL) and vancomycin-resistant enterococci (VRE), and to analyse the association of MRB carriage to a range of potential risk factors., Design: Multicentre descriptive and analytic cross-sectional survey., Setting: Eight EDs and four clinical microbiology departments in Denmark., Participants: Adults visiting the ED., Main Outcome Measures: Swabs from nose, throat and rectum were collected and analysed for MRSA, ESBL, VRE and CPE. The primary outcome was the prevalence of MRB carriage, and secondary outcomes relation to risk factors among ED patients., Results: We included 5117 patients in the study. Median age was 68 years (54-77) and gender was equally distributed. In total, 266 (5.2%, 95% CI 4.6 to 5.8) were colonised with at least one MRB. No significant difference was observed between male and female patients, between age groups and between university and regional hospitals. Only 5 of the 266 patients with MRB were colonised with two of the included bacteria and none with more than two. CPE prevalence was 0.1% (95% CI 0.0 to 0.2), MRSA prevalence was 0.3% (95% CI 0.2 to 0.5), VRE prevalence was 0.4% (95% CI 0.3 to 0.6) and ESBL prevalence was 4.5% (95% CI 3.9 to 5.1). Risk factors for MRB carriage were previous antibiotic treatment, previous hospital stay, having chronic respiratory infections, use of urinary catheter and travel to Asia, Oceania or Africa., Conclusion: Every 20th patient arriving to a Danish ED brings MRB to the hospital. ESBL is the most common MRB in the ED. The main risk factors for MRB carriage are recent antibiotic use and travel abroad., Trial Registration Number: NCT03352167;Post-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives. Left atrial flutter has been reported in up to 10% of patients following pulmonary vein isolation or cardiac surgery. Left atrial flutter is typically highly symptomatic, responds poorly to medical antiarrhythmic treatment, and is often treated by catheter ablation. We aimed to investigate midterm freedom from recurrent arrhythmia after catheter ablation for left atrial flutter. Design . In the National Danish Ablation Registry, we identified consecutive patients, who had undergone catheter ablation for left atrial flutter between 1 January 2014 and 1 April 2017 at our centre. Results. A total of 53 patients (median age 68 years (IQR 60-71) 37 (70%) male) were included. Forty-two patients had prior left atrial catheter ablation procedures (79%), one patient prior ablation for classic atrial flutter (2%), four patients had prior surgery for congenital heart disease (8%), and six patients (11%) had no previous cardiac intervention. Acute procedural success, defined as non-inducibility of any atrial arrhythmia, was achieved in 45 of 53 patients (85%). During midterm follow-up (mean 20 ± 12 months), 26 patients experienced an episode of recurrent atrial arrhythmia. Median EHRA-score was 3 (range 2-4) before catheter ablation and reduced to median 1 (range 1-3) evaluated at follow-up visits after three and twelve months (both p  < .001, Wilcoxon rank test). Conclusion. Left atrial flutter is preceded by catheter ablation or cardiac surgery in 89% of patients. Acute procedural success is achieved in majority of patients and ablation reduces symptoms effectively. During midterm follow-up, almost half the patients experience recurrent atrial arrhythmia.

Background: The aim of this study was to compare changes in health service utilization, preventive medical management, and cholesterol levels in patients without coronary artery disease (CAD) or with non-obstructive CAD as determined by coronary computed tomography angiography (CTA)., Methods: Single-center five-year observational registry-based cohort study of consecutive patients with chest pain undergoing coronary CTA with subsequent 12 months follow-up in general practice., Results: We included 3032 patients with a normal test result (n = 2179) or a diagnosis of non-obstructive CAD (n = 853) by coronary CTA. Median age was 55 (interquartile range: 47-63) years and 44% were males. After coronary CTA, the probability of a decrease in consultations with general practitioner was higher in patients with no CAD compared to patients with non-obstructive CAD (adjusted OR = 0.81 [95% CI: 0.68-0.96], P = 0.016). Accordingly, patients with non-obstructive CAD more frequently received prescriptions on lipid-lowering medical therapy (adjusted OR = 4.50 [95% CI: 3.31-6.12], P < 0.001) than patients with no CAD after coronary CTA. In patients with non-obstructive CAD, mean total-cholesterol reduction was 0.51 (P < 0.001) compared to 0.13 mmol/L (P < 0.001) in patients without non-obstructive CAD. The relative reduction in low-density lipoprotein was 14% higher (P < 0.001) in patients with compared to patients without non-obstructive CAD after coronary CTA., Conclusions: Coronary CTA with subsequent follow-up in general practice has the potential to align health service utilization that prioritizes high-risk patients and facilitate optimized preventive management., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Pain is a frequent symptom in patients attending emergency departments (EDs), but it remains unknown whether all patients with pain want pain-relieving treatment. The primary aim of this study was to investigate the frequency and intensity of pain. The secondary aim was to establish the proportion of patients wanting pain-relieving treatment., Methods: A cross-sectional study was performed at Aalborg University Hospital, Denmark. We interviewed all patients attending the ED using a structured questionnaire to evaluate patient and pain characteristics as well as pain management in the ED. Pain intensity was evaluated using the Verbal Numerical Rating Scale (VNRS)., Results: A total of 349 patients were included. Pain was present in 233 (67%) cases, and the median VNRS score (interquartile range) of patients with pain was 4 (2-6). In all, 100 (43%) patients had mild pain (VNRS 1-3) and 133 (57%) had moderate to severe pain (VNRS 4-10). Furthermore, 174 of patients with pain (n = 233) were asked if they wanted pain relieving treatment. Only, 59 (34%) of these patients were interested in this., Conclusions: Pain was frequent, as it was seen in two thirds of non-critical adult patients in the ED. The majority of patients with pain had moderate to severe pain, but only one third of the patients with pain wanted pain-relieving treatment., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Multiresistant bacteria (MRB) is an increasing problem. Early identification of patients with MRB is mandatory to avoid transmission and to target the antibiotic treatment. The emergency department (ED) is a key player in the early identification of patients who are colonized with MRB. There is currently sparse knowledge of both prevalence and risk factors for colonization with MRSA, ESBL, VRE, CPE and CD in acutely admitted patients in Western European countries including Denmark. To develop evidence-based screening tools for identifying carriers of resistant bacteria among acutely admitted patients, systematic collection of information on risk factors and exposures is required. Since a geographical variation is suspected, it is desirable to include emergency departments across the country. The aim of this project is to provide a comprehensive overview of prevalence and risk factors for MRSA, ESBL, VRE, CPE and CD colonization in patients admitted to Danish ED's. The objectives are to describe the prevalence and demography of resistance, co-infections, to identify risk factors for carrier state and to develop and validate a screening tool for identification of carriers., Methods: Multicenter descriptive and analytic cross-sectional survey from January-May 2018 of around 10.000 acutely admitted patients > 18 years in 8 EDs for carrier state and risk factors for antibiotic resistant bacteria. Information about the background and possible risk factors for carrier status together with swabs from the nose, throat and rectum is collected and analyzed for MRSA, ESBL, VRE, CPE and CD. The prevalence of the resistant bacteria are calculated at hospital level, regional level and national level and described with relation to residency, sex, age and risk factors. A screening model for identification of carrier stage of resistant bacteria is developed and validated., Discussion: The study will provide the prevalence of colonized patients with resistant bacteria on arrival to the ED and variation in demographic patterns, and will develop a clinical tool to identify certain risk groups. This will enable the clinician to target antibiotic treatments and to reduce the in-hospital spreading of resistant bacteria. This knowledge is important for implementing and evaluating antimicrobial stewardships, screening and infection control strategies., Trial Registration: Clinicaltrials.gov : NCT03352167 (registration date: 20. November 2017).

Objectives: Early diagnosis of childhood cancer is critical. Nevertheless, little is known about the potential role of inequality. This study aims to describe the use of primary care 2 years before a childhood cancer diagnosis and to investigate whether socioeconomic factors influence the use of consultations and diagnostic tests in primary care., Design: A national population-based matched cohort study., Setting and Participants: This study uses observational data from four Danish nationwide registers. All children aged 0-15 diagnosed with cancer during 2008-2015 were included (n=1386). Each case was matched based on gender and age with 10 references (n=13 860)., Primary and Secondary Outcome Measures: The primary outcome was additional rates for consultations and for invoiced diagnostic tests for children with cancer according to parental socioeconomic factors. Furthermore, we estimated the association between socioeconomic factors and frequent use of consultations, defined as at least four consultations, and the odds of receiving a diagnostic test within 3 months of diagnosis., Results: Children with cancer from families with high income had 1.46 (95% CI 1.23 to 1.69) additional consultations 3 months before diagnosis, whereas children from families with low income had 1.85 (95% CI 1.60 to 2.11) additional consultations. The highest odds of frequent use of consultations was observed among children from low-income families (OR: 1.94, 95% CI 1.24 to 3.03). A higher odds of receiving an invoiced diagnostic test was seen for children from families with mid-educational level (OR: 1.46, 95% CI 1.09 to 1.95)., Conclusion: We found a socioeconomic gradient in the use of general practice before a childhood cancer diagnosis. This suggests that social inequalities exist in the pattern of healthcare utilisation in general practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Emergency departments handle a large proportion of acute patients. In 2007, it was recommended centralizing the Danish healthcare system and establishing emergency departments as the main common entrance for emergency patients. Since this reorganization, few studies describing the emergency patient population in this new setting have been carried out and none describing diagnoses and mortality. Hence, we aimed to investigate diagnoses and 1- and 30-day mortality of patients in the emergency departments in the North Denmark Region during 2014-2016., Methods: Population-based historic cohort study in the North Denmark Region (580,000 inhabitants) of patients with contact to emergency departments during 2014-2016. The study included patients who were referred by general practitioners (daytime and out-of-hours), by emergency medical services or who were self-referred. Primary diagnoses (ICD-10) were retrieved from the regional Patient Administrative System. For non-specific diagnoses (ICD-10 chapter 'Symptoms and signs' and 'Other factors'), we searched the same hospital stay for a specific diagnosis and used this, if one was given. We performed descriptive analysis reporting distribution and frequency of diagnoses. Moreover, 1- and 30-day mortality rate estimates were performed using the Kaplan-Meier estimator., Results: We included 290,590 patient contacts corresponding to 166 ED visits per 1000 inhabitants per year. The three most frequent ICD-10 chapters used were 'Injuries and poisoning' (38.3% n = 111,274), 'Symptoms and signs' (16.1% n = 46,852) and 'Other factors' (14.52% n = 42,195). Mortality at day 30 (95% confidence intervals) for these chapters were 0.86% (0.81-0.92), 3.95% (3.78-4.13) and 2.84% (2.69-3.00), respectively. The highest 30-day mortality were within chapters 'Neoplasms' (14.22% (12.07-16.72)), 'Endocrine diseases' (8.95% (8.21-9.75)) and 'Respiratory diseases' (8.44% (8.02-8.88))., Conclusions: Patients in contact with the emergency department receive a wide range of diagnoses within all chapters of ICD-10, and one third of the diagnoses given are non-specific. Within the non-specific chapters, we found a 30-day mortality, surpassing several of the more organ specific ICD-10 chapters., Trial Registration: Observational study - no trial registration was performed.

Objective: To investigate whether adalimumab (ADA) reduces whole-body (WB-) magnetic resonance imaging (MRI) indices for inflammation in the entheses, peripheral joints, sacroiliac joints, spine, and the entire body in patients with axial spondyloarthritis (axSpA)., Methods: An investigator-initiated, randomized, placebo-controlled, double-blinded 48-week followup trial included 49 patients with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical indication for tumor necrosis factor inhibitor treatment. Patients were randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks; thereafter, all patients received ADA. Conventional MRI and WBMRI were performed at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of patients with an improvement in WBMRI total inflammation index above the smallest detectable change (SDC) at Week 6., Results: The primary WBMRI endpoint (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3 (13%) patients in the placebo group (p = 0.025, Fisher's exact test). The primary conventional MRI endpoint, the minimally important change in Spondyloarthritis Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at Week 24, was attained by 32 (65%) patients., Conclusion: ADA provided significant reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in patients with axSpA. WBMRI is promising for objective assessment and monitoring of peripheral and axial disease activity in future clinical trials.

Objective: To investigate changes in magnetic resonance imaging (MRI)-assessed inflammation and structural lesions in the sacroiliac (SI) joints during treatment with adalimumab versus placebo., Methods: In a 48-week double-blind, placebo-controlled trial, 52 patients with spondyloarthritis were randomized to receive subcutaneous injections of either adalimumab 40 mg (n = 25) or placebo (n = 27) every other week for 12 weeks. Patients in the adalimumab group continued to receive and patients in the placebo group were switched to adalimumab 40 mg every other week for an additional 12 weeks. MRI of the SI joints was performed at weeks 0, 12, 24, and 48, and the images were assessed independently in a blinded manner using the modified Berlin and the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores for inflammation and structural lesions of the SI joints., Results: At baseline, 56% of the adalimumab group and ∼72% of the placebo group had an MRI-assessed inflammation score of ≥1. Among the patients with inflammation at baseline, the mean percent reductions in MRI scores for inflammation from week 0 to 12 were greater in the adalimumab group compared with the placebo group (Berlin method, -62% versus -5%; SPARCC method, -58% versus -12% [both P < 0.04]). Furthermore, the mean SPARCC erosion score decreased (-0.6) and the SPARCC backfill score increased (+0.8) in the adalimumab group from week 0 to week 12. From week 12 to week 24, larger absolute reductions in the Berlin/SPARCC inflammation scores and the SPARCC erosion score and larger increases in the Berlin/SPARCC fatty lesion scores were seen in the placebo group compared with the adalimumab group. In univariate regression analyses (analysis of covariance) and multivariate stepwise regression analyses, treatment with adalimumab was independently associated with regression of the SPARCC erosion score from week 0 to 12 but not with changes in the other types of MRI lesions., Conclusion: Significant changes in the Berlin and SPARCC MRI-assessed inflammation scores and in the SPARCC MRI-assessed erosion scores occurred within 12 weeks after initiation of adalimumab. Tumor necrosis factor inhibitor treatment was associated with resolution of erosions and the development of backfill., (© 2016, American College of Rheumatology.)

Background: Guideline and reimbursement modifications have been introduced to optimize prescribing of antisecretory medication in Danish general practice. Impacts of the interventions have not been evaluated., Objectives: To analyse developments in prescribing of antisecretory medication in Denmark 2001-2011 and to assess the impacts of interventions on prescribing of antisecretory medication., Methods: Register-based cohort study covering the entire Danish population of currently 5.5 million inhabitants. Developments in the prescribing of antisecretory medication over time in Denmark between 2001 and 2011 and association with age and gender of users along with the impact of interventions on the prescribing of drug subgroups are analysed., Results: 96.8% of all antisecretory drugs sold are proton pump inhibitors (PPIs) and 94.4% of the PPIs are prescribed in primary care. Prescribing of PPIs has increased substantially during the past decade. Both number of users and the average individual use have increased. The prescribing of ulcerogenic drugs to the elderly has stagnated in the same time range. Reimbursement modifications and scientific guidelines do not seem to have had a substantial influence on the steadily increasing prescribing of PPIs., Conclusion: Use of PPIs has increased substantially during the past decade, without a change in indications for use of PPIs in the same time range. Interventions to enhance adherence to guidelines and promote rational use of PPIs do not seem to have had a substantial influence on the overall prescribing rate.

Background: Use of over-the-counter (OTC) high-dose acetylsalicylic acid (ASA) is a risk factor for experiencing gastric bleeding. However, more detailed knowledge on the characteristics of users of OTC ASA is needed., Objective: To characterise users of OTC high-dose ASA in a Danish pharmacy setting., Method: We conducted an interview based survey among users of OTC high-dose ASA. Questions were asked regarding: (1) demographic characteristics; (2) use patterns; (3) knowledge about adverse events; (4) risk factors for experiencing gastric bleeding; (5) reasons for choosing an ASA-containing medicine; and (6) whether their GP was informed on their use of high-dose ASA., Results: One-hundred-seventeen interviews were completed. Nineteen percent and 37 % used high-dose ASA on a daily or weekly basis respectively. Sixty-eighth percent found high-dose ASA to be more effective than other analgesics. Fourty-seven percent had one or more risk factors for experiencing ulcer bleeding, most commonly age >60 years (32 %) and previous peptic ulcer (9 %). The most well-known adverse events were abdominal pain (32 %) and peptic ulcer (26 %). The most common source of information was friends and family (32 %)., Conclusion: A large proportion of users of high-dose ASA have risk factors for experiencing gastric bleeding. Health-care professionals needs to provide more information on potential adverse events.

Aims: Understanding the determinants of social and coping inequalities in subclinical cardiovascular disease is an important prerequisite in developing and implementing preventive strategies. The aim of this study was to investigate the association between social factors and coping status, respectively, and subclinical coronary artery disease (CAD) in middle-aged Danes., Methods: This is a DanRisk screening substudy, thus including healthy Danish males and females aged 50 or 60 years. Social measures included grade of education, employment and co-habiting status. The coping status was estimated by the general self-efficacy (GES) scale. Coronary artery calcification (CAC) was assessed by computed tomography using the Agatston score (AS). Conventional clinical risk factors included sex, family history of CAD, BMI > 25, smoking, hypercholesterolaemia and hypertension., Results: In 568 individuals the prevalence of subjects with CAC was 267 (45%). Independent predictors of CAC in males were age (OR = 1.10, 95% CI = 1.04-1.16, p < 0.001), smoking (OR = 1.75, 95% CI = 1.03-2.99, p = 0.038), and low co-habiting status (OR = 3.66, 95% CI = 1.19-11.25, p = 0.023). Independent predictors in females were age (OR = 1.67, 95% CI = 1.02-1.12, p = 0.006), and smoking (OR = 1.71, 95% CI = 1.06-2.78, p = 0.029). Higher AS was associated to lower employment level in females (p = 0.001) but not in males (p = 0.833)., Conclusions: Social factors are associated to the prevalence and severity of CAC in asymptomatic middle-aged individuals with gender differences. The relative value of gender specific social versus conventional clinical risk factors in the risk assessment of subclinical CAC in middle-aged individuals needs further investigation in future prospective studies.

Objective: Childhood cancer is rare and symptoms tend to be unspecific and vague. Using the utilization of health care services as a proxy for symptoms, the present study seeks to determine when early symptoms of childhood cancer are seen in general practice., Methods: A population-based matched comparative study was conducted using nationwide registry data. As cases, all children in Denmark below 16 years of age (N = 1,278) diagnosed with cancer (Jan 2002-Dec 2008) were included. As controls, 10 children per case matched on gender and date of birth (N = 12,780) were randomly selected. The utilization of primary health care services (daytime contacts, out-of-hours contacts and diagnostic procedures) during the year preceding diagnosis/index date was measured for cases and controls., Results: During the six months before diagnosis, children with cancer used primary care more than the control cohort. This excess use grew consistently and steadily towards the time of diagnosis with an IRR = 3.19 (95%CI: 2.99-3.39) (p<0.0001) during the last three months before diagnosis. Children with Central Nervous System (CNS) tumours had more contacts than other children during the entire study period. The use of practice-based diagnostic tests and the number of out-of-hours contacts began to increase four to five months before cancer diagnosis., Conclusions: The study shows that excess health care use, a proxy for symptoms of childhood cancer, occurs months before the diagnosis is established. Children with lymphoma, bone tumour or other solid tumours had higher consultation rates than the controls in the last five months before diagnosis, whereas children with CNS tumour had higher consultation rates in all twelve months before diagnosis. More knowledge about early symptoms and the diagnostic pathway for childhood cancer would be clinically relevant.

Background: Knowledge of how children with cancer present in general practice is sparse. Timely referral from general practice is important to ensure early diagnosis., Aim: To investigate the presenting symptoms and GPs' interpretations of symptoms of children with cancer., Design and Setting: A Danish nationwide population-based study including children (<15 years) with an incident cancer diagnosis (January 2007 to December 2010)., Method: A questionnaire on symptoms and their interpretation was mailed to GPs (n=363). Symptoms were classified according to the International Classification of Primary Care (ICPC)-2 classification., Results: GPs' response rate was 87% (315/363) and GPs were involved in the diagnostic process of 253 (80.3%) children. Symptoms were few (2.4 per child) and most fell into the category 'general and unspecified' (71.9%), apart from patients with tumours of the central nervous system (CNS), whose symptoms fell mostly in the category 'neurological' (for example, headache). Symptoms like pain, swelling/lump, or fatigue were reported in 25% of the patients and they were the most commonly reported symptoms. GPs interpreted children's symptoms as alarm symptoms in 20.2%, as serious (that is, not alarm) symptoms in 52.9%, and as vague symptoms in 26.9%. GPs' interpretation varied significantly by diagnosis (P<0.001)., Conclusion: Children with cancer presented with few symptoms in general practice, of which most were 'general and unspecified' symptoms. Only 20% presented alarm symptoms, while 27% presented vague and non-specific symptoms. This low level of alarm symptoms may influence the time from symptom presentation in general practice to final diagnosis.

Objective: To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)., Materials: We investigated 1025 patients with hepatitis B virus infection in a nationwide study in Denmark., Results: Prevalence of genotypes were: 10.5% A, 17.3% B, 20.5% C, 45.7% D, 3.2% E, 0.6% F, 1.1% G and 1% had more than one genotype. Nearly 60% of patients with genotype A were from Africa, 82% and 93% with genotypes B or C were from East Asia, 62% with genotype D came from the Middle East and 91% with genotype E came from Africa. More women had genotypes B (p = 0.006) or C (p < 0.001) while more men had genotypes A (p = 0.015) or D (p < 0.001). Women with genotypes B and D were younger than men (p < 0.001, p = 0.026). Viral load differed in genotype A and D compared with B and C (p < 0.001), and between anti-HBe and hepatitis B e antigen (HBeAg) positive patients (median values 5.4 × 10(3) IU/ml and 7.4 × 10(7) IU/ml, respectively, p < 0.001). Viral load depended on the presence of HBeAg (p < 0.001; OR, 95% CI: 0.05, 0.03-0.07) in the adjusted analysis and was not affected by origin (p = 0.65), age (p = 0.12), gender (p = 0.06) or genotype (p = 0.10)., Conclusion: HBeAg status and not HBV genotype influenced viral load in this nationwide study. HBeAg positive patients had median HBV-DNA levels 10,000 times higher than those anti-HBe positive across genotypes.

Background & Aims: In vitro studies have shown that selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation. It is controversial whether use of SSRIs is a cause of clinically important bleeding; results from observational studies have been equivocal., Methods: A population-based case-control study was conducted in Denmark. The 3652 cases all had a first discharge diagnosis of serious upper gastrointestinal bleeding (UGB) from 1995 to 2006. Controls (n = 36,502), matched for age and sex, were selected by risk-set sampling. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by conditional logistic regression and the case-crossover design., Results: The adjusted odds ratio (OR) of UGB among current, recent, and past users of SSRIs was 1.67 (95% confidence interval [CI], 1.46-1.92), 1.88 (95% CI, 1.42-2.5), and 1.22 (95% CI, 1.07-1.39). The adjusted OR for concurrent use of SSRI and nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.0 (95% CI, 4.8-13). The adjusted OR for the concurrent use of NSAID, aspirin, and SSRI was 28 (95% CI, 7.6-103). Of the UGB cases, 377 were current users of SSRI; the adjusted OR for UGB in the case crossover analysis was 2.8 (95% CI, 2.2-3.6). The adjusted OR among users of proton pump inhibitors was 0.96 (95% CI, 0.50-1.82)., Conclusions: Use of SSRI was associated with UGB, consistent with its antiplatelet effects. SSRIs should be prescribed with caution for patients at high risk for UGB.

Objectives: The prevalence of gastroesophageal reflux symptoms (GERS) in the population is high; however, data on long-term follow-up and incidence of GERS in the population are sparse. This study describes the long-term natural history of GERS, the related health-care use, and quality of life in a population followed up for 5 years., Methods: A total of 10,000 randomly selected inhabitants, 40-65 years old, received, as a part of a controlled trial of Helicobacter pylori screening and treatment (control group), a mailed questionnaire regarding demographic data, gastrointestinal symptoms (the Gastrointestinal Symptom Rating Scale (GSRS)), and quality of life (the Short-Form 36-Item Health Survey (SF-36)) at inclusion and after 5 years. GERS was defined as a mean score > or =2 in the reflux dimension in the GSRS. Information on use of health-care resources was drawn from the questionnaires and registers., Results: In all, 6,781 individuals answered the first questionnaire and 5-year symptom data were complete for 5,578 (82.3%) of them. The mean age at inclusion was 52.4 years, 48% were men. At inclusion, 22% reported GERS. During follow-up, symptoms resolved in 43%, of whom 10% received acid inhibitory treatment at 5-year follow-up. The incidence of GERS was 2.2% per year. Health-care use during follow-up was significantly higher in individuals with GERS at baseline than in individuals without GERS. Quality of life at 5-year follow-up was lower in individuals with GERS at inclusion than in individuals without GERS at inclusion., Conclusions: GERS are prevalent, long lasting, and associated with an impaired quality of life and substantial health-care use.

Aims: Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial. We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other antithrombotic drugs., Methods: A population-based case-control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB from a hospital during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by a risk set sampling. Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register. Confounders were controlled by conditional logistic regression., Results: The adjusted odds ratios (ORs) associating use of statins with UGB were 0.94 (0.78-1.12) for current use, 1.40 (0.89-2.20) for recent use and 1.42 (0.96-2.10) for past use. The lack of effect was consistent across most patient subgroups, different cumulative or current statin doses and different statin substances. In explorative analyses, a borderline significant protective effect was observed for concurrent users of low-dose aspirin [OR 0.43 (0.18-1.05)]., Conclusion: Statins do not prevent UGB, except possibly in users of low-dose aspirin.

Introduction: The clinical behaviour of General Practitioners (GPs) can best be influenced by identifying their incitements and barriers in the first place. The purpose of this paper was to describe a model for the outreach visits, in which the purpose was to facilitate and evaluate the desired changes in the clinical behaviour of the GPs. We demonstrate the usefulness and workability of the model as a tool to be used in future implementations., Materials and Methods: A total of 41 GPs in the Counties of Aarhus and Vejle participated in the spring of 2000 in an advanced educational programme about how to diagnose and treat patients with functional disorders. All participating GPs received an invitation for a six-month follow-up visit. The purpose of the follow-up visit was to facilitate and evaluate their educational benefits and experience in using psychiatric rating scales. The strategy of the visit was to structure the dialogue with reference to identifying incitements and barriers and to emphasize their strengths, weaknesses, opportunities and threats in connection with the change of their clinical behaviour., Results: Thirty-eight (93%) of the GPs participated in the follow-up outreach visits. The chosen strategy proved to be useful in primary care settings. We identified several areas in which the motivation of the GPs and their possibilities to implement the desired behavioural changes could be strengthened., Conclusion: The results suggest that the incitements and barriers of the GPs to change their clinical behaviour can be identified using the strategy described. We suggest that the strategy should form part of the development and evaluation of outreach visits in Denmark.

Introduction: The study aimed to describe the postgraduate training of the general practitioners (GPs) in communication and psychiatric counselling., Material and Methods: GPs in Aarhus County, Denmark, received a mailed questionnaire about psychiatric hospital training, participation in courses and Balint groups (psychiatric supervision), and their need for further training., Results and Discussion: The questionnaire was returned by 320 (74.4%) GPs. Almost all GPs had received some kind of postgraduate training although to a very varying extent. Almost half had taken courses of more than three days' duration, and half were members of a psychiatric supervision group. Two-thirds of the GPs thought they needed further training. The need was independent of the GP's evaluation of his/her own psychiatric education.

Patients with homozygous homocystinuria are at greatly increased risk for development of atherosclerosis and thrombosis (1). Elevated plasma levels of homocysteine (HCY) are caused by reduced enzymatic catabolism or reduced enzymatic remethylation of HCY, due to either hereditary enzyme defects or to nutritional deficiencies of vitamins functioning as cofactors. However, several recent studies have suggested that persons with mildly elevated plasma levels of HCY also are at increased risk for coronary heart disease. (2-4). There are some indications that dietary n-3 polyunsaturated fatty acids (PUFAs) may offer protection against coronary heart disease (5-6). Several mechanisms may be involved, including beneficial effects of n-3 PUFAs on plasma lipids, platelet and leukocyte reactivity, blood pressure and vasoreactivity (7). Interestingly, Olszewski el al. recently found HCY-levels to be lowered 36% in 15 type IIa or IIb hyperlipemic men by n-3 PUFA supplementation. A possible beneficial effect of n-3 PUFA on the incidence of coronary heart disease was initially suggested from studies in Greenland Inuits by our group (8). We therefore investigated plasma levels of homocysteine in a group of traditionally living Greenland Inuits with a diet consisting mainly of marine food and with a very high content of n-3 PUFAs.