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AimTo examine the association between socioeconomic position and the risk of atrial fibrillation (AF) in different stages of life in a population of Danish citizens.MethodsRegister-based study. We followed all individuals turning 35, 50, 65 or 80 years from 1 January 1996 to 31 December 2005 until AF, death, emigration or the end of study period (31 December 2015). Exposure was education and income. We used Cox regression for the HRs (95% CI) and the pseudo-observation method for the adjusted risk difference (RD) (%).ResultsA total of 2 173 857 participants were enrolled and 151 340 incident cases of AF occurred over a median of 13.6 years of follow-up. Adjusted HR (95% CI) of incident AF for the youngest age group with the highest education (ref lowest) was 0.62 (0.50 to 0.77) (women) and 0.85 (0.76 to 0.96) (men). The associations attenuated with increasing age, that is, HRs for the oldest age group were 1.04 (0.97 to 1.10) and 0.98 (0.96 to 1.04), respectively. The corresponding adjusted RDs (%) were: −0.28 (−0.43 to −0.14), −0.18 (−0.36 to −0.01), 3.04 (−0.55 to 6.64) and −0.74 (−3.38 to 2.49), respectively. Similar but weaker associations were found for income.ConclusionHigher level of education and income was associated with a lower risk of being diagnosed with AF in young individuals but the association decreased with increasing age and was almost absent for the oldest age cohort. However, since AF is relatively rare in the youngest the RDs were low.

Summary Objective This study aims to investigate the risk of total knee replacement (TKR) following tibia plateau fractures. Secondary the study aims to investigate the risk of knee arthroscopy following tibial plateau fractures. Method The study was designed as a matched cohort study. All patients who sustained a tibial plateau fracture in Denmark between January 1, 1996, and December 31, 2000, were included and followed until December 31, 2015. For each patient with a tibial plateau fracture, 10 matched citizens without a tibial plateau fracture were included as a reference group. Results 7,950 patients sustained a tibial plateau fracture in Denmark during the study period. The median age of patients was 52.6 (IQR: 32.4–71.5) years. The mean observational period was 13.9 years. 5.7% were treated with a TKR (N = 452), and 2.0% of patients from the reference group were treated with a TKR (N = 1,623). Patients with a tibial plateau fracture had a 3.5 (95%CI: 3.1–3.9) times higher hazard ratio (HR) compared to patients from the reference group. 7.6% of patients with a tibial plateau fracture were treated with a secondary knee arthroscopy (N = 603) and 2.0% of patients from the reference group were treated with a knee arthroscopy (N = 1,565). Patients with a tibial plateau fracture presented with a 5.0 (95%CI: 4.5–5.6)) times higher HR compared to patients in the reference group. Conclusions Tibial plateau fractures are associated with a 3.5 times increased risk of TKR compared with an age- and gender-matched reference group with a mean follow-up of 13.9 years.

Automated chemical synthesis of oligonucleotides is of fundamental importance for the production of primers for the polymerase chain reaction (PCR), for oligonucleotide-based drugs, and for numerous other medical and biotechnological applications. The highly optimised automised chemical oligonucleotide synthesis relies upon phosphoramidites as the phosphate precursors and one of the drawbacks of this technology is the poor bench stability of phosphoramidites. Here, we report on the development of an on-demand flow synthesis of phosphoramidites from their corresponding alcohols, which is accomplished with short reaction times, near-quantitative yields and without the need of purification before being submitted directly to automated oligonucleotide synthesis. Sterically hindered as well as redox unstable phosphoramidites are synthesised using this methodology and the subsequent couplings are near-quantitative for all substrates. The vision for this technology is direct integration into DNA synthesisers thereby omitting manual synthesis and storage of phosphoramidites., The poor bench stability of phosphoramidites is a drawback for fast automised chemical oligonucleotide synthesis. Here, the authors report a method for on-demand flow synthesis of phosphoramidites within short reaction times, in near-quantitative yields and sufficient purity for integration with DNA synthesizers.

Rationale & Objective: Patients with kidney failure treated with maintenance dialysis experience a high rate of mortality, in part due to sudden cardiac death caused by arrhythmias. The prevalence of arrhythmias, including the subset that are clinically significant, is not well known. This study sought to estimate the prevalence of arrhythmias, characterize the pattern of arrhythmic events in relation to dialysis treatments, and identify associated clinical characteristics. Study Design: Cross-sectional study. Setting & Participants: 152 patients with kidney failure treated with maintenance dialysis in Denmark. Exposures: Dialysis treatment; clinical characteristics; cardiac output and preload defined using echocardiography. Outcomes: Prevalence and pattern of arrhythmias on 48-hour Holter monitoring; odds ratios for arrhythmias. Analytical Approach: Descriptive analysis of the prevalence of arrhythmias. Pattern of arrhythmias described using a repeated-measures negative binomial regression model. Associations between clinical characteristics and echocardiographic findings with arrhythmias were assessed using logistic regression. Results: Among the 152 patients studied, 83.6% were treated with in-center dialysis; 10.5%, with home hemodialysis; and 5.9%, with peritoneal dialysis. Premature atrial and ventricular complexes were seen in nearly all patients and 41% had paroxysmal supraventricular tachycardia. Clinically significant arrhythmias included persistent atrial fibrillation observed among 8.6% of patients, paroxysmal atrial fibrillation among 3.9%, nonsustained ventricular tachycardia among 19.7%, bradycardia among 4.6%, advanced second-degree atrioventricular block among 1.3%, and third-degree atrioventricular block among 2.6%. Premature ventricular complexes were more common on dialysis days, while tachyarrhythmias were more often observed during dialysis and in the immediate postdialytic period. Older age (OR per 10 years older, 1.53; 95% CI, 1.15-2.03; P = 0.003), elevated preload (OR, 4.02; 95% CI, 1.05-15.35; P = 0.04), and lower cardiac output (OR per 1 L/min greater, 0.66; 95% CI, 0.44-1.00; P = 0.05) were independently associated with clinically significant arrhythmias. Limitations: Arrhythmia monitoring limited to 48 hours; small sample size; heterogeneous nature of the population, risk for residual confounding. Conclusions: Arrhythmias, including clinically significant abnormal rhythms, were common. Tachyarrhythmias were more frequent during dialysis and the immediate postdialytic period. The relevance of these findings to clinical outcomes requires additional study.

Aims The aim of this study was to investigate the incidence of knee arthroplasty and arthroscopy following patellar fractures, and to compare this with an age- and gender-matched group without a prior patellar fracture. Patients and Methods A national matched cohort study based on the Danish National Patient Register including all citizens of Denmark (approximately 5.3 million) was undertaken. A total of 6096 patients who sustained a patellar fracture in Denmark between 1 January 1996 and 31 December 2000 were included. The median age of these patients was 50.6 years (interquartile range (IQR) 28.5 to 68.9); 49.1% were women. Patients were followed-up until 31 December 2015, with regard to treatment with knee arthroplasty and/or knee arthroscopy. Results Patients with a patellar fracture had an increased risk of knee arthroplasty (hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.57 to 2.13) compared with citizens without a patellar fracture, and the effect was strongest during the first five years (HR 3.02, 95% CI 2.26 to 4.03). Patients with a patellar fracture also had a higher risk of knee arthroscopy (HR 3.94, 95% CI 3.49 to 4.46), and the effect was highest during the first five years after the fracture (HR 7.40, 95% CI 6.32 to 8.66). Conclusion Patellar fractures are associated with an increased risk of knee arthroplasty and knee arthroscopy. The consequences of a patellar fracture may be more severe than previously considered, and patients must expect a lifelong increased risk of knee arthroplasty. Cite this article: Bone Joint J 2018;100-B:1477–81.

Background: Definition and elimination of outliers is a key element for medical laboratories establishing or verifying reference intervals (RIs). Especially as inclusion of just a few outlying observations may seriously affect the determination of the reference limits. Many methods have been developed for definition of outliers. Several of these methods are developed for the normal distribution and often data require transformation before outlier elimination. Methods: We have developed a non-parametric transformation independent outlier definition. The new method relies on drawing reproducible histograms. This is done by using defined bin sizes above and below the median. The method is compared to the method recommended by CLSI/IFCC, which uses Box-Cox transformation (BCT) and Tukey’s fences for outlier definition. The comparison is done on eight simulated distributions and an indirect clinical datasets. Results: The comparison on simulated distributions shows that without outliers added the recommended method in general defines fewer outliers. However, when outliers are added on one side the proposed method often produces better results. With outliers on both sides the methods are equally good. Furthermore, it is found that the presence of outliers affects the BCT, and subsequently affects the determined limits of current recommended methods. This is especially seen in skewed distributions. The proposed outlier definition reproduced current RI limits on clinical data containing outliers. Conclusions: We find our simple transformation independent outlier detection method as good as or better than the currently recommended methods.

Correct staging of pancreatic cancer is paramount, as treatment is stage specific. However, minimally invasive tools to facilitate staging are lacking. DNA promoter hypermethylation is a hallmark of cancer. The aim of this study is to evaluate promoter hypermethylation in cell-free DNA as a prognostic marker for stage classification of pancreatic adenocarcinoma. Consecutive patients with pancreatic adenocarcinoma were prospectively included. Plasma samples were obtained before diagnostic work-up and treatment. Patients were staged according to the TNM classification. Methylation-specific PCR of 28 genes was performed. Prognostic prediction models for staging of pancreatic adenocarcinoma were developed by multivariable logistic regression analysis using stepwise backwards elimination. Ninety-five patients with pancreatic adenocarcinoma were included. The mean number of hypermethylated genes was identical for stage I, II and III disease (7.09 (95% CI; 5.51-8.66), 7.00 (95% CI; 5.93-8.07) and 6.77 (95% CI; 5.08-8.46)), respectively, and highly significantly different from stage IV disease (10.24 (95% CI; 8.88-11.60)). The prediction model (SEPT9v2, SST, ALX4, CDKN2B, HIC1, MLH1, NEUROG1, and BNC1) enabled the differentiation of stage IV from stage I-III disease (AUC of 0.87 (cut point 0.55; sensitivity 74%, specificity 87%)). Model (MLH1, SEPT9v2, BNC1, ALX4, CDKN2B, NEUROG1, WNT5A, and TFPI2) enabled the differentiation of stage I-II from stage III-IV disease (AUC of 0.82 (cut point 0.66; sensitivity 73%, specificity 80%)). Cell-free DNA promoter hypermethylation has the potential to be blood-based prognostic markers for pancreatic adenocarcinoma, as panels of hypermethylated genes enables the differentiation according to cancer stage. However, further validation is required.

// Stine Dam Henriksen 1, 2, 3, 4 , Poul Henning Madsen 5 , Anders Christian Larsen 1 , Martin Berg Johansen 6 , Inge Sokilde Pedersen 5 , Henrik Krarup 4, 5 and Ole Thorlacius-Ussing 1, 3, 4 1 Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark 2 Department of General Surgery, Hospital of Vendsyssel, Hjorring, Denmark 3 Department of Clinical Medicine, Aalborg University, Aalborg, Denmark 4 Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark 5 Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark 6 Unit of Clinical Biostatistics and Bioinformatics, Aalborg University Hospital, Aalborg, Denmark Correspondence to: Stine Dam Henriksen, email: stdh@rn.dk Keywords: biomarker, epigenetics, methylation, pancreatic cancer, prognosis Received: December 12, 2016 Accepted: September 13, 2017 Published: September 30, 2017 ABSTRACT Introduction: Few prognostic biomarkers are available for pancreatic cancer. The aim of this study is to examine the correlation between the survival of pancreatic adenocarcinoma patients and hypermethylated genes in plasma-derived cell-free DNA. Methods: Consecutive patients with pancreatic adenocarcinoma were prospectively included and staged according to the TNM classification. Methylation-specific PCR of 28 genes was conducted. A survival prediction model independent of cancer stage and stage-specific survival prediction models were developed by multivariable Cox regression analysis using backward stepwise selection. Results: Ninety-five patients with pancreatic adenocarcinoma were included. Patients with more than 10 hypermethylated genes had a HR of 2.03 (95% CI; 1.15-3.57) compared to patients with fewer hypermethylated genes. Three survival prediction models were developed: Total group; (American Society of Anesthesiologists score (ASA)=3, GSTP1 , SFRP2 , BNC1 , SFRP1 , TFPI2, and WNT5A ) Risk groups 2, 3 and 4 had a HR of 2.65 (95% CI; 1.24-5.66), 4.34 (95% CI; 1.98-9.51) and 21.19 (95% CI; 8.61-52.15), respectively, compared to risk group 1. Stage I-II; (ASA=3, SFRP2, and MESTv2 ) Risk groups 2, 3 and 4 had a HR of 4.83 (95% CI; 2.01-11.57), 9.12 (95% CI; 2.18-38.25) and 70.90 (95% CI; 12.63-397.96), respectively, compared to risk group 1. Stage IV; ( BMP3 , NPTX2 , SFRP1 , and MGMT ) Risk group 2 had a HR of 5.23 (95% CI; 2.13-12.82) compared to risk group 1. Conclusion: Prediction models based on cell-free DNA hypermethylation stratified pancreatic adenocarcinoma patients into risk groups according to survival. The models have the potential to work as prognostic biomarkers. However, further validation of the results is required to substantiate the findings.

OBJECTIVE: To evaluate the association between chocolate intake and incident clinically apparent atrial fibrillation or flutter (AF).METHODS: The Danish Diet, Cancer, and Health Study is a large population-based prospective cohort study. The present study is based on 55 502 participants (26 400 men and 29 102 women) aged 50-64 years who had provided information on chocolate intake at baseline. Incident cases of AF were ascertained by linkage with nationwide registries.RESULTS: During a median of 13.5 years there were 3346 cases of AF. Compared with chocolate intake less than once per month, the rate of AF was lower for people consuming 1-3 servings/month (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.82 to 0.98), 1 serving/week (HR 0.83, 95% CI 0.74 to 0.92), 2-6 servings/week (HR 0.80, 95% CI 0.71 to 0.91) and ≥1 servings/day (HR 0.84, 95% CI 0.65 to 1.09; p-linear trend CONCLUSIONS: Accumulating evidence indicates that moderate chocolate intake may be inversely associated with AF risk, although residual confounding cannot be ruled out.

Background Parental mental illness has been associated with a number of consequences for the health and use of healthcare services of the child. However, most research has focused on maternal depression. Research examining the impact of paternal mental vulnerability (MV) as well as different degrees of MV are needed to plan interventions. Therefore, the aim of this study was to examine the association between different categories of individual and combined parental MV and the child’s use of healthcare services the first year of life. Methods A population-based birth cohort study was conducted including all Danish children born from 2000-2016 using the Danish national registers. Exposure was parental MV of three categories according to the degree of MV: Group 1 “minor MV” with mental related contacts to primary healthcare and/or prescribed psychopharmaceuticals, group 2 “moderate MV” and group 3 “severe MV” both with contacts to psychiatric hospital. Outcome was contacts to GP the first year of life expressed as incidence-rate ratios (IRR) using Poission’s regression analyses. Results The analyses included 952,709 children. 21% of the mothers and 11% of the fathers were in the MV groups. Parental MV (any parent, any MV-group) was associated with an increased risk of GP contacts daytime and out-of-hour contacts. If both parents were classified as group 1 MV, IRR were 1.21 (CI95 1.20-1.22). IRR were 1.18 (1.17-1.18) resp. IRR 1.05 (1.04-1.06) if only the mother resp. father were in MV group 1. The same pattern were seen for out-of-hour contacts; IRR 1.28 (1.26-1.31) for both parents in group 1 and IRR 1.19 (1.18-1.20) resp. IRR 1.09 (1.08-1.11) for the mother resp. father. Conclusions Maternal and paternal MV were associated with an increased risk of GP contacts daytime and out-of-hour contacts although maternal MV had the highest risk. Even minor MV had an impact on healthcare contacts and the risk increased further if both parents were classified as minor MV. Key messages Both maternal and paternal mental vulnerability has an impact on the child’s healthcare contacts. Our results indicate the need for a focus also on minor mental vulnerability in the planning of interventions.

Background The cut-off values for defining hypertension remains a matter of debate. Recently published guidelines from American College of Cardiology (ACC) /American Heart Association (AHA) defines hypertension at blood pressure (BP) of ≥130/80 in contrast to guidelines from European Society of Cardiology (ESC) defining hypertension as BP≥140/90. Adopting the ACC/AHA recommendation will lead to higher prevalence of hypertension in the general population and probably unnecessary medical treatment of persons at a low cardiovascular risk. Aim We aimed to explore whether the new definition of hypertension as defined from the ACC/AHA guidelines is associated with higher risk of mortality and cardiovascular death in the general population compared to their definition of normal BP. Methods A random sample of 20,000 Caucasian men and women aged 20–98 years were examined in a prospective cardiovascular population study. The population sample went through four examinations in 1976–78, 1981–83, 1991–94, and 2001–03. We defined the blood pressure levels according to the ACC/AHA guidelines: normal Results All outcomes were assessed according to the ACC/AHA BP thresholds. Primary outcome: Considering normal BP ( Mortality in BP thresholds by ACC/AHA Conclusion Hypertension as defined by the ACC/AHA guidelines is not associated with higher all-cause mortality or cardiovascular death in the general population. Applying ACC/AHA guidelines might lead to unnecessary medical treatment of a low-risk population. In contrast, the ESC-definition of hypertension refers to a high-risk population in terms of all-cause mortality and cardiovascular death. Acknowledgement/Funding Danish Heart Foundation

AIMS: To evaluate the association between education and living arrangements and the intake of fish, red meat and fruit and vegetables.METHODS: The study design was cross-sectional and conducted in Denmark in 2013. Participants filled in questionnaires about their educational level and living arrangements (living alone or with others) and dietary intake including fish, red meat, fruit and vegetables. Regression analyses were performed to assess the associations within 85,456 randomly sampled healthy men and women who were at least 25 years old.RESULTS: Length of education was statistically significant and positively associated with the intake of fruit and vegetables and negatively associated with the intake of red meat for both men and women. Men with a high level of education had a 187g/week (95% confidence interval: 199-175g/week) lower intake of red meat and a 109g/day (95% confidence interval: 102-117g/day) higher intake of fruit and vegetables than men with a low level of education. Women with a high level of education had a 175g/week (95% confidence interval: 186-164g/week) lower intake of red meat and a 106g/day (95% confidence interval: 97-114g/day) higher intake of fruit and vegetables than women with a low level of education. Living with others was statistically significant and positively associated with the intake of red meat, and fruit and vegetables. There were no clear associations between education, living arrangements and intake of fish.CONCLUSIONS: Men and women with a high educational level ate more fruit and vegetables but less red meat than men and women with a low educational level. Men and women living with others ate more red meat, fruit and vegetables than men and women living alone.

Background It is well-established that patients with rheumatoid arthritis (RA) have higher risk for development of atherosclerotic cardiovascular diseases (CVD) than the general population (1). The evidence shows that a CVD burden is already notable at the onset of RA (2). It is well-known, that atherosclerosis is an inflammatory condition (3). Therefore, we hypothesize that atherosclerotic CVD is positively associated with subsequent development of RA. Objectives To examine the risk of developing RA in persons who have had CVD, defined as acute myocardial infarction (AMI) or ischaemic stroke while controlling for established shared risk factors. Methods We conducted a population-based cohort study within the Danish Diet, Cancer and Health (DCH) cohort. The cohort was recruited 1993-97 and included individuals aged 50 to 64 years, born in Denmark and living in geographically defined parts of Denmark. Data on lifestyle factors and anthropometric measurements were collected at enrolment into the DCH. Information on incident AMI (ICD-10 code: I21), ischemic stroke (ICD-10 code: I63) and RA (ICD-10 codes: M05, M06 combined with ATC codes for DMARDs) was obtained from nationwide administrative registers. Participants were followed until development of RA, death, loss to follow-up or October 2016, whichever came first. Data were analyzed using Cox’s proportional hazards regression models with delayed entry and age as the underlying time scale and cardiovascular disease (CVD) as a time-varying exposure variable, stratifying by gender. Established shared risk factors - smoking, body mass index and waist circumference - were included in the multivariable analyses. Results Complete data were available on 53287 subjects (52% female) without a AMI, stroke or RA diagnosis prior to their enrolment into the DCH. Median age at entry into DCH was 56 years. During follow-up (median 21 years), 4,627 participants developed CVD (37% female) and 516 participants developed RA (69% female). The risk for developing RA was 30% higher in women with CVD than in women without CVD (adjusted hazard ratio (HR) 1.30 (95% CI 0.70-2.38)) (Table 1). In men, there was no clear association between CVD and development of RA (adjusted HR 0.73 (95% CI 0.34-1.58)). Conclusion The investigation showed tendency towards a higher risk of developing RA in women with previous CVD than women without CVD. Male gender was not associated with subsequent development of RA, possibly related to low sample size. References [1] Avina-Zubieta et al. Ann Rheum Dis. 2012;71(9):1524–9. [2] Hannawi et al. Arthritis Res Ther. 2007;9(6):R116. [3] Ross R. N Engl J Med. 1999 Jan 14;340(2):115–26 Disclosure of Interests None declared

Objective: To investigate the relationship between bioimpedance-derived total body fat percentage, waist circumference, and body mass index (BMI) and the subsequent development of rheumatoid arthritis (RA). Methods: A population-based prospective cohort study was conducted using 55,037 patients enrolled in the Danish Diet, Cancer, and Health cohort. Baseline data included anthropometric measures and lifestyle factors. Individuals who developed RA were identified through linkage with the Danish National Patient Registry. The relationships between bioimpedance-derived body fat percentage, waist circumference, and BMI and incident RA were assessed using Cox proportional hazards regression models, stratifying by sex. All analyses were performed for overall RA and the serologic subtypes seropositive and other RA. Results: A total of 210 men (37.6% with seropositive RA) and 456 women (41.0% with seropositive RA) developed RA during a median follow-up of 20.1 years. In women, the overall RA risk was 10% higher for each 5% increment of total body fat (hazard ratio [HR] 1.10 [95% confidence interval (95% CI) 1.02–1.18]), 5% higher for each 5-cm increment of waist circumference (HR 1.05 [95% CI 1.01–1.10]), and nearly 50% higher in those whose BMI was in the obese range compared to normal range BMI (HR 1.46 [95% CI 1.12–1.90]). These positive associations were also found for patients with other RA. In men, there were no clear associations between body fat percentage, waist circumference, or BMI and RA. No significant associations were found for seropositive RA in women or men, possibly related to low sample size. Conclusion: In women, higher body fat percentage, higher waist circumference, and obesity were associated with a higher risk of RA.

Objective: There is strong evidence that medication adherence and lifestyle changes are essential in patients undergoing secondary cardiovascular disease prevention. Cardiac rehabilitation (CR) increases medication adherence and improves lifestyle changes. Patients with cardiac diseases and a low educational level and patients with little social support are less responsive to improve medication adherence and to adapt lifestyle changes. The aim of the present study was to investigate the long-term effects of a socially differentiated CR intervention on medication adherence as well as changes in biological and lifestyle risk factors at two- five- and ten-year follow-up. Design: A prospective cohort study. Setting: The cardiac ward at Aarhus University Hospital, Denmark. Intervention: A socially differentiated CR intervention in addition to the standard CR program. Subjects: Patients admitted with first-episode myocardial infarction between 2000 and 2004, N = 379. Patients were defined as socially vulnerable or non-socially vulnerable according to their educational level and extent of social network. Main outcome measures: Primary outcome was medication adherence to antithrombotics, beta-blockers, statins and angiotensin-converting enzyme inhibitors. Secondary outcomes were biological and lifestyle risk factors defined as; total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glycated hemoglobin, blood pressure and smoking status. Results: No significant long-term effect of the intervention was found. Conclusions: The results indicate a non-significant effect of the intervention. However, it was found that equality in health was improved in the study population except concerning smoking. General practitioners manage to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status. Key points The socially differentiated intervention did not significantly improve medication adherence or biological and lifestyle risk factors. Despite the non-significant effect of the intervention, equality in health was improved except concerning smoking. General practitioners managed to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status.

Background Cardiovascular mortality is the leading contributor to the shortened life expectancy in patients with severe mental illness (SMI), but efforts to predict cardiovascular outcomes in these patients have been lacking. In this study, we aimed to determine the severity of coronary artery calcification (CAC), and its effect on mortality rates in patients with SMI, compared with the general population. Methods All individuals with a registered cardiac computed tomography for calcium scoring in the Western Denmark Heart Registry, from January 1, 2008 to December 31, 2016, were included. We identified patients diagnosed with SMI ( International Classification of Diseases, Tenth Revision: F20, F30, F31), whereas the remaining individuals were used as a comparison group. Results Among 48 757 individuals, including 564 patients with SMI (1.2%), we found no difference in CAC score between patients with SMI and the comparison group. SMI patients with CAC100 had an increased mortality rate (hazard ratio, 3.16; 95% CI, 1.41-7.06), as well as SMI patients with CAC100 (hazard ratio, 3.95; 95% CI, 2.36-6.62), compared with the comparison group with CAC100 as reference, adjusted for age, sex, and calendar period. Conclusions Patients with SMI have increased cardiovascular risks, but show no difference in CAC score, compared with the comparison group. Mortality rates were increased in patients with SMI, independent of CAC severity; however, the relatively large number of noncardiovascular causes of death in this sample might indicate other contributing factors to death than coronary artery disease in this sample of SMI patients.

Background Cardiovascular mortality is the leading contributor to the shortened life expectancy in patients with severe mental illness (SMI), but efforts to predict cardiovascular outcomes in these patients have been lacking. In this study, we aimed to determine the severity of coronary artery calcification (CAC), and its effect on mortality rates in patients with SMI, compared with the general population. Methods All individuals with a registered cardiac computed tomography for calcium scoring in the Western Denmark Heart Registry, from January 1, 2008 to December 31, 2016, were included. We identified patients diagnosed with SMI ( International Classification of Diseases, Tenth Revision : F20, F30, F31), whereas the remaining individuals were used as a comparison group. Results Among 48 757 individuals, including 564 patients with SMI (1.2%), we found no difference in CAC score between patients with SMI and the comparison group. SMI patients with CAC >100 had an increased mortality rate (hazard ratio, 3.16; 95% CI, 1.41–7.06), as well as SMI patients with CAC Conclusions Patients with SMI have increased cardiovascular risks, but show no difference in CAC score, compared with the comparison group. Mortality rates were increased in patients with SMI, independent of CAC severity; however, the relatively large number of noncardiovascular causes of death in this sample might indicate other contributing factors to death than coronary artery disease in this sample of SMI patients.

Purpose: Implantable cardioverter defibrillators (ICDs) can treat life-threatening tachyarrhythmia with high-voltage shocks. The aims were to compare the efficacy of single and dual coil shock vectors in modern ICDs and to identify predictors of shock failure. Methods: This is a single-center paired randomized study including 216 patients with mixed indications and ICDs from four manufacturers. All patients underwent two implant defibrillation tests using single and dual coil vectors with the test order randomized. Tested shock energy differed slightly between manufacturers because of differences in device programmability: first shock approximately 15 J below maximal output—if failed, second shock approximately 10 J below maximal output—if failed, third shock at maximal output. Results: First shock success rate was 399/432 (92.4%). Comparing single and dual coil vectors, no differences were seen in first shock efficacy (91.7% vs. 93.1%, P = 0.629) or lowest tested succesfully stored energy (27.2 J vs. 27.1 J, P = 0.620). All successive internal shocks failed in 4/432 (0.9%) of inductions requiring external rescue shocks to restore circulation. Multivariate predictors of first shock failure were QRS duration (relative risk 0.81 per 10 ms, P = 0.001), amiodarone treatment (relative risk 3.30, P = 0.003), and body height (relative risk 1.70 per 10 cm, P = 0.019). Conclusions: Implant defibrillation testing of modern intravenous ICD systems demonstrates high shock efficacy with no difference between single and dual coil vectors.

ObjectiveTo examine the long-term effect of a socially differentiated cardiac rehabilitation (CR) intervention tailored to reduce social inequalities in health regarding use of healthcare services in general practice and hospital among socially vulnerable patients admitted with first-episode myocardial infarction (MI).DesignA prospective cohort study with 10 years’ follow-up.SettingDepartment of cardiology at a university hospital in Denmark between 2000 and 2004.ParticipantsPatients InterventionA socially differentiated CR intervention. The intervention consisted of standard CR and expanded CR with focus on cross-sectional collaboration.Main outcome measuresParticipation in annual chronic care consultations in general practice, contacts to general practice, all-cause hospitalisations and cardiovascular readmissions.ResultsAt 2-year and 5-year follow-up, socially vulnerable patients receiving expanded CR participated significantly more in annual chronic care consultations (p=0.02 and p0.05).ConclusionsThe present study found no persistent association between the socially differentiated CR intervention and use of healthcare services in general practice and hospital in patients admitted with first-episode MI during a 10-year follow-up.

BACKGROUND: There have been discrepant findings on whether coffee consumption is associated with the rate of developing atrial fibrillation (AF).METHODS AND RESULTS: We used data on 57,053 participants (27,178 men and 29,875 women) aged 50-64 years in the Danish Diet, Cancer and Health study. All participants provided information on coffee intake via food-frequency questionnaires at baseline. Incident AF was identified using nationwide registries. During a median follow-up of 13.5 years, 3415 AF events occurred. Compared with no intake, coffee consumption was inversely associated with AF incidence, with multivariable-adjusted hazard ratios of 0.93 (95% confidence interval [CI] 0.74-1.15) for more than none to 7 cups/day (p-linear trend = 0.02).CONCLUSIONS: In this large population-based cohort study, higher levels of coffee consumption were associated with a lower rate of incident AF.

ObjectiveTo evaluate the association between socioeconomic status (SES) and referral to cardiac rehabilitation (CR) after incident acute coronary syndrome (ACS) by dividing the referral process into three phases: (1) informed about CR, (2) willingness to participate in CR, (3) and assigned CR setting.DesignCross-sectional study.SettingDepartment of Cardiology at a Danish University Hospital from 1 January 2011 to 31 December 2014.ParticipantsA total of 1229 patients assessed for CR during hospitalisation with ACS were prospectively registered in the Rehab-North Register from 2011 to 2014. SES was assessed using data from national registers, concerning: personal income, occupational status, educational level and civil status. Patients were excluded if one of the following criteria was fulfilled: (1) missing data on SES, or (2) acceptable reason for not informing patients about CR (treatment with coronary artery bypass grafting, transfer to another hospital, still under treatment or death).Main outcome measuresOutcomes were defined by dividing the referral process into three phases: (1) informed about CR, (2) willingness to participate, and (3) assigned CR setting (in-hospital/community centre) after ACS.ResultsA total of 854 (69.5 %) patients were referred to CR. After adjustment for age, gender, ACS diagnosis (ST-elevated myocardial infarction, non-ST-elevated myocardial infarction, unstable angina pectoris) and comorbidity, high income had the strongest association of referral to CR in all three phases (informed about CR: OR 2.17, 95% CI 1.01 to 4.64; willingness to participate in CR: OR 1.55, 95% CI 1.02 to 2.35; assigned in-hospital CR: OR 1.47, 95% CI 0.91 to 2.36). Educational level showed similar tendencies, however not statistically significant. The results did not vary according to gender.ConclusionThis is the first study to investigate the referral process to CR using a three-phase structure. It suggests income and education to influence all phases in the referral process to CR after ACS.

Diet may influence the risk of ischemic stroke by several mechanisms. A potential and hitherto unknown mechanism may relate to an effect on the lipophilic index, which is a new and convenient indicator of membrane fluidity. This study investigated the association between the adipose tissue lipophilic index and ischemic stroke and its subtypes. A case-cohort study was conducted based on the Danish cohort study Diet, Cancer, and Health, which includes 57,053 subjects aged 50&ndash, 64 years at enrolment. A subcohort (n = 3500) was randomly drawn from the whole cohort. All ischemic stroke cases were validated and categorized into subtypes. The lipophilic index was calculated based on fatty acid profiles in adipose tissue. Subjects were divided into quintiles and a weighted Cox proportional hazards regression model was used to calculate hazard ratios. After appropriate exclusions, a subcohort of 3194 subjects and 1752 cases of ischemic stroke were included. When comparing the fifth quintile of the lipophilic index with the first quintile, the hazard ratio for ischemic stroke was 0.92 (95% confidence interval 0.75, 1.13) and the trend across quintiles was not statistically significant (p = 0.1727). In conclusion, no association was found between the lipophilic index and ischemic stroke or its subtypes.

Marine n-3 polyunsaturated fatty acids (PUFA) may improve autonomic dysfunction, as indicated by an increase in heart rate variability (HRV) and reduce the risk of sudden cardiac death. Hence, the aim of this study was to investigate the effects of marine n-3 PUFA on 24-h HRV in patients on chronic dialysis, who have a high risk of sudden cardiac death. Between June 2014 and March 2016, 112 patients on chronic dialysis from Denmark were allocated to a daily supplement of 2 g marine n-3 PUFA or control for three months in a randomized, double-blinded, controlled trial. A 48-h Holter monitoring was performed and mean 24-h HRV indices for the two days were available in 85 patients. The mean age was 62.3 years (SD: 14.3) and median dialysis vintage was 1.7 years (IQR: 0.5, 6.4). Within-group and between-group changes in outcome were evaluated by a paired and two sample t-test, respectively. Marine n-3 PUFA did not change the primary endpoint SDNN (SD of all RR-intervals) reflecting overall HRV, but other HRV indices increased and the mean RR-interval increased significantly, corresponding to a decrease in heart rate by 2.5 beats per minute (p = 0.04). In conclusion, marine n-3 PUFA did not change SDNN, but the mean heart rate was significantly reduced and changes in other HRV-indices were also observed, indicating an increase in vagal modulation that might be protective against malignant ventricular arrhythmias.

AimTo quantify the contribution of changes in different risk factors population levels and treatment uptake on the decline in CHD mortality in Denmark from 1991 to 2007 in different socioeconomic groups.DesignWe used IMPACTSEC, a previously validated policy model using data from different population registries.ParticipantsAll adults aged 25–84 years living in Denmark in 1991 and 2007.Main outcome measureDeaths prevented or postponed (DPP).ResultsThere were approximately 11,000 fewer CHD deaths in Denmark in 2007 than would be expected if the 1991 mortality rates had persisted. Higher mortality rates were observed in the lowest socioeconomic quintile. The highest absolute reduction in CHD mortality was seen in this group but the highest relative reduction was in the most affluent socioeconomic quintile. Overall, the IMPACTSEC model explained nearly two thirds of the decline in. Improved treatments accounted for approximately 25% with the least relative mortality reduction in the most deprived quintile. Risk factor improvements accounted for approximately 40% of the mortality decrease with similar gains across all socio-economic groups. The 36% gap in explaining all DPPs may reflect inaccurate data or risk factors not quantified in the current model.ConclusionsAccording to the IMPACTSEC model, the largest contribution to the CHD mortality decline in Denmark from 1991 to 2007 was from improvements in risk factors, with similar gains across all socio-economic groups. However, we found a clear socioeconomic trend for the treatment contribution favouring the most affluent groups.

Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled in clinical trials are not known. A systematic review was conducted using electronic databases up to October 2016. The main outcome of interest was the reporting of indeterminate bone scans, analyses of how such scans were managed, and exploratory analyses of the association of study characteristics and the reporting of indeterminate bone scan results. Seventy-four eligible clinical trials were identified. The trials were mostly retrospective (85%), observational (95%), large trials (median 195 patients) from five continents published over four decades. The majority of studies had university affiliation (72%), and an author with imaging background (685). Forty-five studies (61%) reported an indeterminate option for the bone scan and 23 studies reported the proportion of indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to handle indeterminate scans. Most trials (n = 39) used add-on supplementary imaging, follow-up bone scans, or both. Exploratory analyses showed a significant association of reporting of indeterminate results and number of patients in the study (p = 0.024) but failed to reach statistical significance with other variables tested. Indeterminate bone scan for staging of prostate cancer was insufficiently reported in clinical trials. In the case of indeterminate scans, most studies provided adequate measures to obtain the final status of the patients.

Asta Linauskas,1,2 Kim Overvad,3 Martin Berg Johansen,4 Kristian Stengaard-Pedersen,1,5 Annette de Thurah1,5 1Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Rheumatology, North Denmark Regional Hospital, Hjoerring, Denmark; 3Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark; 4Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark; 5Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Purposes: To assess whether the positive predictive value (PPV) of first-time rheumatoid arthritis (RA) diagnosis registration in the Danish National Patient Registry increases when data are linked to the RA treatment codes and to assess the PPV of first-time RA diagnoses according to RA serological subtypes.Methods: Participants from the Danish Diet, Cancer, and Health cohort with at least one RA diagnosis, registered at one of the Central Denmark Region hospitals in the Danish National Patient Registry during the period 1977–2016, were identified. Register-based RA diagnoses were verified by scrutinizing medical records against RA classification criteria or clinical case RA. PPVs for overall RA, seropositive RA, and other RA were calculated for two models: first-time RA diagnosis registration ever in the Danish National Patient Registry and first-time RA diagnosis registration ever where subsequently a prescription had been redeemed for a synthetic disease-modifying antirheumatic drug.Results: Overall, 205 of 311 first-time register-based RA diagnoses were verified (PPV: 61.9%; 95% CI: 56.9–67.0). Regarding RA serological subtypes, 93 of 150 register-based seropositive RA (PPV: 62.0; 95% CI: 53.9–69.5) and 36 of 144 other RA (PPV: 25.0; 95% CI: 18.5–32.8) were confirmed. When register-based RA diagnosis codes were linked to RA treatment codes, the PPVs increased substantially: the PPV for overall RA was 87.7% (95% CI: 82.5–91.5), the PPV for seropositive RA was 80.2% (95% CI: 71.6–86.7), and the PPV for other RA was 41.1% (95% CI: 30.2–52.9).Conclusion: The first-time RA diagnoses in the Danish National Patient Registry should be used with caution in epidemiology research. However, linking registry-based RA diagnoses to the subsequent RA treatment codes increases the probability of identifying true RA diagnoses, especially overall RA and seropositive RA. Keywords: administrative database research, Danish National Prescription Registry, Anatomical Therapeutic Chemical codes, seropositive rheumatoid arthritis, Denmark

Background Pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) may develop malfunction during external beam radiotherapy (RT). We aimed to describe clinical practice in PM/ICD patients undergoing RT and to assess the rate and predictors of device malfunctions. Methods We reviewed medical records of all PM/ICD patients undergoing RT at four centers in Western Denmark during 2003–2012. Logistic regression was applied to identify predictors of PM/ICD malfunctions. Results Five hundred sixty patients were included. The annual rate of RT courses in PM/ICD patients increased by 199% from 1.45 treatments per 100,000 person-years in 2003 to 4.33 in 2012. Safety measures included supplementary evaluations of PM/ICD (38.3%), reprogramming (1.5%), relocation of the device (3.5%), and application of a magnet to the ICD during RT (10.8%). At device evaluations after the RT (n = 453), malfunctions were detected in 10 (2.5%) PMs and four (6.8%) ICDs. Electrical resets constituted 11 (78.6%) of the malfunctions, and no failures were life-threatening or warranted PM/ICD removal. Factors associated with device malfunctions in logistic regression analysis were beam energy ≥15 MV (odds ratio [OR] 5.73; 95% confidence interval [CI], 1.58–20.76) and location of tumor below the diaphragm (OR 4.31; 95% CI, 1.42–13.12). However, the effect of tumor location declined (OR 2.27; 95% CI, 0.65–7.95) after adjustment for beam energy. Conclusions Although the rate of RT in PM/ICD patients is increasing, the damaging effects of RT on the devices seem to be usually transient. Our data suggest that high beam energy plays the pivotal role in inducing impairments in these devices.

AIM: Barriers to participation in cardiac rehabilitation (CR) may occur at three levels of the referral process (lack of information, declining to participate, and referral to appropriate CR programme). The aim is to analyse the impact of socioeconomic status on barriers to CR and investigate whether such barriers influenced the choice of referral.METHODS: The Rehab-North Register, a cross-sectional study, enrolled 5455 patients hospitalised at Aalborg University Hospital with myocardial infarction (MI) during 2011-2014. Patients hospitalised with ST-elevated MI and complicated non-ST-elevated MI were to be sent to specialized CR, whereas patients with uncomplicated non-ST-elevated MI and unstable angina pectoris were to be sent to community-based CR. Detailed selected socioeconomic information was gathered from statistical registries in Statistics Denmark. Data was assessed using logistic regression.RESULTS: Patients being retired, low educated, and/or with an annual gross income CONCLUSION: Patients with low socioeconomic status received less information about and were less willing to participate in cardiac rehabilitation. The same patient population was to a higher extent referred to community-based CR. Knowledge about barriers at different levels and the impact of social inequality may help in tailoring a better approach in the referral process to CR.

// Simon Ladefoged Rasmussen 1, 2, 3 , Henrik Bygum Krarup 2, 4 , Kare Gotschalck Sunesen 1 , Martin Berg Johansen 5 , Mogens Tornby Stender 1 , Inge Sokilde Pedersen 2, 4 , Poul Henning Madsen 2, 4 and Ole Thorlacius-Ussing 1, 2, 3 1 Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark 2 Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark 3 Department of Clinical Medicine, Aalborg University, Aalborg, Denmark 4 Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark 5 Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark Correspondence to: Simon Ladefoged Rasmussen, email: simon.rasmussen@rn.dk Keywords: colorectal cancer; DNA hypermethylation; prognosis; staging Received: September 08, 2017 Accepted: January 03, 2018 Published: January 09, 2018 ABSTRACT Epigenetic alterations in colorectal cancer (CRC) cause important differences in the underlying tumor biology and aggressiveness. DNA hypermethylation is central for the development of CRC but the prognostic impact remains elusive. We aimed to assess the association between cell-free hypermethylated DNA and stage and survival in colorectal cancer (CRC). We analyzed pre-treatment plasma samples from 193 patients with CRC. Thirty gene-promoter regions were analyzed using methylation specific PCR. We compared the median number (range) of hypermethylated promoter regions with CRC stage, and constructed a multivariable Cox-regression model adjusted for stage, to evaluate the added prognostic information. The median number of hypermethylated promoter regions was nine (0-28) in patients with distant metastasis compared to five (0-19) in patients without metastatic disease (p < 0.0001). The majority of the hypermethylated promoter regions inferred a poor prognosis. Cox-regression analysis adjusted for patient age, sex, pre-treatment CEA-levels, and disease stage, showed that RARB (HR = 1.99, 95% CI [1.07, 3.72]) and RASSF1A (HR = 3.35, 95% CI [1.76, 6.38]) hypermethylation inferred a significant effect on survival. The risk of metastasis increase with the number of cell-free hypermethylated promoter regions. The presence of RARB and RASSF1A hypermethylation indicated aggressive disease, regardless of stage at the time of diagnosis.

Background Coronary heart disease (CHD) mortality has declined substantially during recent decades but is still one of the leading causes of death, morbidity and healthcare costs in Denmark. Furthermore, socioeconomic inequalities persist. Quantifying the contributions of prevention and treatment to these recent declines might help to identify the most successful health policies, particularly for reducing inequalities. Methods We used IMPACT SEC , a previously validated policy model, to apportion the recent decline in Danish CHD mortality to changes in major cardiovascular risk factors, and to increases in treatments in nine non-overlapping patient groups. Participants: All Danish adults aged 25–84 years, stratified by gender, age group and quintiles of financial income. Main outcome measure: Deaths prevented or postponed (DPP), stratified by socio-economic circumstance (SEC). Results There were 11 110 fewer CHD deaths in 2007 than would be expected if the 1991 mortality rates had persisted. This reflected a dramatic 74% fall in CHD mortality rates (from 433 to 113 deaths per 100,000). Improved treatments accounted for approximately 24% (95% confidence interval=21%–28%). This contribution was higher in more affluent quintiles (approximately 26%) and least in the most deprived group (19%). The biggest contributions came from the treatment of congestive heart failure in the community (630 DPPs=5.7% of all DPPs) and in hospital (410 DPPs=3.7%). Risk factor improvements accounted for approximately 40% (37%–44%) of the mortality fall. This contribution was higher in the central quintiles -approximately 51% (47%–58%) and least in the most deprived quintile – approximately 36% (29%–39%). The largest contribution came from population falls in cholesterol levels approximately 24% (22.7%–25.4%) of all DPPs; and decreases in smoking, some 10% (8.4%–12.2%). Overall, the IMPACTSEC model could explain two thirds of the mortality fall. The 36% gap most likely reflects deficiencies in data, notably in population blood pressure and income. Conclusion Denmark has benefited from one of biggest falls in CHD mortality in high income countries. The treatment uptake rate in Denmark was comparable with that in other countries and treatments accounted for approximately one third of the total mortality fall, much as in other, comparable populations. The largest contributions came from population-wide, non-phamacological reductions in major risk factors, notably cholesterol and smoking. Future strategies should therefore prioritise population-wide prevention policies.

Background Several studies have investigated the association between overweight and the development of rheumatoid arthritis (RA) and have come out with conflicting results. Body Mass Index (BMI) has been the preferred surrogate measure for overweight in these studies. However, BMI correlates only modestly with total amount of body fat and does not reflect fat distribution. Objectives To investigate the association between BMI, waist circumference, bio-impedance-derived total body fat percentage and the incidence of RA. Methods A population-based cohort study conducted within the Danish Diet, Cancer and Health cohort, which included individuals aged 50 to 64 years at the recruitment in the period between 1993 and 1997. Body fat composition measurements and data on lifestyle factors were collected at the enrolment into the cohort. The participants who subsequently developed RA were identified via linkage to The Danish National Patient Registry. The participants were followed until development of RA, death, loss to follow-up or October 2016, whichever came first. Data were analyzed by Cox proportional hazards regression model with delayed entry and age as the underlying time variable. Analyses were stratified by gender. Cox regression analyses with restricted cubic spline were carried out to elucidate the dose-response association between anthropometric measures and risk of RA. Smoking, socio-economic status, alcohol consumption, physical activity and intake of n-3 fatty acids were included in multivariate analyses as potential confounders. Results Data were available on 54 284 subjects (52% female). During follow-up (median 21 years), 283 women and 110 men developed RA. The median (IQR) time to onset of RA was 7 (4–11) years. The adjusted hazard ratio9s (HR) for developing RA are presented in Table 1. Restricted cubic spline analysis of body fat percentage displayed a positive slope in women (Image). There was no linear association between amount of fat and incidence of RA among men. Conclusions Overweight and obesity, defined by BMI, abdominal obesity and higher body fat percentage, especially above 30%, were in women associated with a higher risk for the development of RA. In men the associations were not consistent. Acknowledgements The Danish Rheumatism Association, The Danish Heart Foundation, Central Denmark Region, North Denmark Regional Hospital, Scandinavian Rheumatology Research Foundation Disclosure of Interest None declared

BACKGROUND: A correlation between excess mortality from myocardial infarctions (MI) and schizophrenia has already been established. What remains unclear is whether the initial communication between the treating doctor and the corresponding patient contributes to this excess mortality.AIM: The aim of this study is to investigate whether a patient with schizophrenia receives the same offers for examination and treatment following a MI compared to a psychiatric healthy control (PHC).METHODS: This cohort study includes patients diagnosed with schizophrenia at the time of their first MI (n = 47) in the years between 1995-2015 matched 1:2 to psychiatric healthy MI patients on gender, age and year of first MI. All existing hospital files for the 141 patients were thoroughly reviewed and the number of offered and accepted examinations and treatments were extracted for comparisons between the two groups.RESULTS: In general patients with schizophrenia were less likely to be offered and accept examination and at the same time be offered and accept treatment as compared to PHCs (pCONCLUSIONS: Being diagnosed with schizophrenia limits the treatment received following a first MI compared to PHCs. However, we are unable to pinpoint, whether Physician bias, patient's unwillingness to receive health care or both contribute to the excess mortality seen in these comorbid patients.

Health resource utilization (HRU) and outcomes associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are not well described. Therefore, a population-based cohort study was conducted to characterize patients hospitalized with AECOPD with regard to HRU, mortality, recurrence, and predictors of readmission with AECOPD.Using Danish healthcare databases, this study identified COPD patients with at least one AECOPD hospitalization between 2005-2009 in Northern Denmark. Hospitalized AECOPD patients' HRU, in-hospital mortality, 30-day, 60-day, 90-day, and 180-day post-discharge mortality and recurrence risk, and predictors of readmission with AECOPD in the year following study inclusion were characterized.This study observed 6612 AECOPD hospitalizations among 3176 prevalent COPD patients. Among all AECOPD hospitalizations, median length of stay was 6 days (interquartile range [IQR] 3-9 days); 5 days (IQR 3-9) among those without ICU stay and 11 days (IQR 7-20) among the 8.6% admitted to the ICU. Mechanical ventilation was provided to 193 (2.9%) and non-invasive ventilation to 479 (7.2%) admitted patients. In-hospital mortality was 5.6%. Post-discharge mortality was 4.2%, 7.8%, 10.5%, and 17.4% at 30, 60, 90, and 180 days, respectively. Mortality and readmission risk increased with each AECOPD hospitalization experienced in the first year of follow-up. Readmission at least twice in the first year of follow-up was observed among 286 (9.0%) COPD patients and was related to increasing age, male gender, obesity, asthma, osteoporosis, depression, myocardial infarction, diabetes I and II, any malignancy, and hospitalization with AECOPD or COPD in the prior year.The study included only hospitalized AECOPD patients among prevalent COPD patients. Furthermore, information was lacking on clinical variables.These findings indicate that AECOPD hospitalizations are associated with substantial mortality and risk of recurrence.

Background Data on the prognostic impact of diabetes and diabetic complications in intensive care unit (ICU) patients are limited and inconsistent. We, therefore, examined mortality in ICU patients with type 2 diabetes with and without pre-existing heart and kidney diseases compared with nondiabetic patients. Design We conducted this population-based cohort study in Northern Denmark during 2005–2011. We included all ICU patients aged 40 years or older from the 17 ICUs in the area and identified type 2 diabetes by either a filled prescription for an antidiabetic drug, a previous diagnosis of diabetes, or an elevated glycosylated haemoglobin level. Diabetic patients were disaggregated according to pre-existing diagnoses of heart disease (myocardial infarction or heart failure) and kidney disease. We estimated 1-year mortality by the Kaplan–Meier method and hazard ratios of death (HRs) during follow-up using Cox regression, controlling for confounding factors and stratified by relevant subgroups. Results Among 45 018 ICU patients, 7219 (16·0%) had type 2 diabetes. Overall, 1-year mortality was 36·0% in ICU patients with type 2 diabetes, rising to 54·6% in patients with pre-existing heart and kidney diseases, compared with 29·1% in nondiabetic patients. Comparing diabetic with nondiabetic patients, the adjusted 0- to 30-day HR was 1·20 (95% confidence interval (CI): 1·13–1·26) and 1·19 (95% CI: 1·10–1·28) during the 31- to 365-day follow-up period. Pre-existing kidney disease further increased the impact of diabetes, while heart disease alone had no such effect. Conclusions ICU patients with type 2 diabetes had higher 1-year mortality compared with nondiabetic ICU patients, particularly those with pre-existing kidney disease.

Correct staging of pancreatic cancer is paramount, as treatment is stage specific. However, minimally invasive tools to facilitate staging are lacking. DNA promoter hypermethylation is a hallmark of cancer. The aim of this study is to evaluate promoter hypermethylation in cell-free DNA as a prognostic marker for stage classification of pancreatic adenocarcinoma. Consecutive patients with pancreatic adenocarcinoma were prospectively included. Plasma samples were obtained before diagnostic work-up and treatment. Patients were staged according to the TNM classification. Methylation-specific PCR of 28 genes was performed. Prognostic prediction models for staging of pancreatic adenocarcinoma were developed by multivariable logistic regression analysis using stepwise backwards elimination. Ninety-five patients with pancreatic adenocarcinoma were included. The mean number of hypermethylated genes was identical for stage I, II and III disease (7.09 (95% CI; 5.51-8.66), 7.00 (95% CI; 5.93-8.07) and 6.77 (95% CI; 5.08-8.46)), respectively, and highly significantly different from stage IV disease (10.24 (95% CI; 8.88-11.60)). The prediction model (SEPT9v2, SST, ALX4, CDKN2B, HIC1, MLH1, NEUROG1, and BNC1) enabled the differentiation of stage IV from stage I-III disease (AUC of 0.87 (cut point 0.55; sensitivity 74%, specificity 87%)). Model (MLH1, SEPT9v2, BNC1, ALX4, CDKN2B, NEUROG1, WNT5A, and TFPI2) enabled the differentiation of stage I-II from stage III-IV disease (AUC of 0.82 (cut point 0.66; sensitivity 73%, specificity 80%)). Cell-free DNA promoter hypermethylation has the potential to be blood-based prognostic markers for pancreatic adenocarcinoma, as panels of hypermethylated genes enables the differentiation according to cancer stage. However, further validation is required.

Background Enthesitis is a major feature of psoriatic arthritis. However, clinical assessment of enthesitis is known to lack accuracy and have poor interobserver reliability. Objective To determine effect of training on clinical assessment of enthesitis and to compare ultrasonography with clinical examination for the detection of entheseal abnormalities. Methods 20 rheumatologists performed repeated assessment of enthesitis in patients with established psoriatic arthritis before and after a 2-hour training session in standardised enthesitis count according to Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Moreover, 20 patients underwent clinical and ultrasonographic examination of entheses to evaluate consensus-based elementary lesions of enthesitis. Results Training significantly increased Intra-class Correlation Coefficient for LEI from 0.18 to 0.82 and for SPARCC from 0.38 to 0.67. Ultrasound examination showed high associations between hypoechogenicity and increased thickness of the entheses and clinical examination. There was no correlation between erosions and enthesophytes found by ultrasound and clinical assessments. Conclusion Training in standardised enthesitis scoring systems significantly improved clinical assessments of enthesitis and should be performed before use in daily clinical practice. Ultrasound revealed more advanced stages of enthesitis, such as enthesophytes and erosions, which were not detected with clinical examination.

Background The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis. Methods The study was conducted as a randomized, double-blind, placebo-controlled trial, where 145 patients with psoriatic arthritis were supplemented with 3 g of n-3 PUFA or olive oil (control) daily for 24 weeks. Blood pressure, heart rate, heart rate variability (HRV), central blood pressure, pulse wave velocity (PWV) and fatty acid composition of granulocytes, were determined at baseline and after supplementation. Results At baseline we found a significant difference in the mean of all normal RR intervals (inverse of heart rate, vary from beat to beat) when comparing subjects with the highest vs the lowest fish intake (p = 0.03). After supplementation for 24 weeks there was a trend towards an increase in RR (p = 0.13) and decrease in heart rate (p = 0.12) comparing the n-3 PUFA group with the control group. However, per-protocol analysis showed significantly increased RR (p = 0.01) and lowered heart rate (p = 0.01) in the n-3 PUFA supplemented patients compared with controls. Blood pressure, PWV and Central blood pressure did not change after supplementation with n-3 PUFA. Adjustment for disease activity and conventional cardiovascular risk factors did not change the results. Conclusions Marine n-3 PUFA increased RR intervals in patients with psoriatic arthritis which may suggest a protective effect of n-3 PUFA against cardiovascular disease in this population. Trial registration Clinicaltrials.gov Identifier: NCT01818804

Objective: This study aimed to investigate the effects of marine n-3 polyunsaturated fatty acids (PUFAs) on disease activity, use of analgesics, and inflammatory biomarkers in patients with psoriatic arthritis (PsA). Method: Patients with established PsA (n = 145) were investigated in a randomized, double-blind, placebo-controlled study. The participants received a supplement of 3 g n-3 PUFA/day or 3 g olive oil/day (control) for 24 weeks. Outcome measures for disease activity, use of analgesics, and leukotriene formation from activated granulocytes were assessed at baseline and at study end. Results: In total, 145 patients were included and 133 completed the study. After 24 weeks, the n-3 PUFA group showed a decrease in Disease Activity Score (DAS28-CRP), 68 tender joint count, enthesitis score, and psoriasis area and severity index, although not significantly different from the controls. There was a significant reduction in non-steroidal anti-inflammatory drug (NSAID) and paracetamol use compared with controls (p = 0.04). In addition, the participants in the n-3 PUFA group had significantly lower formation of leukotriene B 4 (p = 0.004) from stimulated granulocytes and significantly higher formation of leukotriene B 5 (p 4 formation in the n-3 PUFA group compared with controls.

BACKGROUND: The best choice of defibrillator lead in patients with routine implantable cardioverter-defibrillator (ICD) is not settled. Traditionally, most physicians prefer dual-coil leads but the use of single-coil leads is increasing.OBJECTIVE: The purpose of this study was to compare clinical outcomes in patients with single- and dual-coil leads.METHODS: All 4769 Danish patients 18 years or older with first-time ICD implants from 2007 to 2011 were included from the Danish Pacemaker and ICD Register. Defibrillator leads were 38.9% single-coil leads and 61.1% dual-coil leads. The primary end point was all-cause mortality. Secondary end points were lowest successful energy at implant defibrillation testing, first shock failure in spontaneous arrhythmias, structural lead failure, and lead extraction outcomes.RESULTS: Single-coil leads were associated with lower all-cause mortality with an adjusted hazard ratio of 0.85 (95% confidence interval 0.73-0.99; P = .04). This finding was robust in a supplementary propensity score-matched analysis. However, dual-coil leads were used in patients with slightly higher preimplant morbidity, making residual confounding by indication the most likely explanation for the observed association between lead type and mortality. The lowest successful defibrillation energy was higher using single-coil leads (23.2 ± 4.3 J vs 22.1 ± 3.9 J; P < .001). No significant differences were observed for other secondary end points showing high shock efficacies and low rates of lead failures and extraction complications.CONCLUSION: Shock efficacy is high for modern ICD systems. The choice between single-coil and dual-coil defibrillator leads is unlikely to have a clinically significant impact on patient outcomes in routine ICD implants.

Background Pancreatic cancer has a 5-year survival rate of only 5–7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagnostic biomarker for pancreatic cancer will have a major impact on patient survival by facilitating early detection and the possibility for curative treatment. DNA promoter hypermethylation is a mechanism of early carcinogenesis, which can cause inactivation of tumour suppressor genes. The aim of this study was to examine promoter hypermethylation in a panel of selected genes from cell-free DNA, as a diagnostic marker for pancreatic adenocarcinoma. Methods Patients with suspected or biopsy-verified pancreatic cancer were included prospectively and consecutively. Patients with chronic/acute pancreatitis were included as additional benign control groups. Based on an optimized accelerated bisulfite treatment protocol, methylation-specific PCR of a 28 gene panel was performed on plasma samples. A diagnostic prediction model was developed by multivariable logistic regression analysis using backward stepwise elimination. Results Patients with pancreatic adenocarcinoma (n = 95), chronic pancreatitis (n = 97) and acute pancreatitis (n = 59) and patients screened, but negative for pancreatic adenocarcinoma (n = 27), were included. The difference in mean number of methylated genes in the cancer group (8.41 (95% CI 7.62–9.20)) vs the total control group (4.74 (95% CI 4.40–5.08)) was highly significant (p 65, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) had an area under the curve of 0.86 (sensitivity 76%, specificity 83%). The model performance was independent of cancer stage. Conclusions Cell-free DNA promoter hypermethylation has the potential to be a diagnostic marker for pancreatic adenocarcinoma and differentiate between malignant and benign pancreatic disease. This study brings us closer to a clinical useful diagnostic marker for pancreatic cancer, which is urgently needed. External validation is, however, required before the test can be applied in the clinic. Trial registration ClinicalTrials.gov, NCT02079363 Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0286-2) contains supplementary material, which is available to authorized users.

Valid and up-to-date data on cancer diagnoses are needed for clinical quality monitoring and epidemiological research. The Danish National Registry of Patients (DNRP) is continuously updated, recording all Danish hospital contacts including cancer diagnoses. The Danish Cancer Registry (DCR) is updated once a year and includes quality control of diagnoses. We compared the quality of urological cancer diagnoses in the DNRP with the DCR to assess whether data in an administrative hospital registry are valid compared with data from a well-established cancer registry. We identified 60 434 incident urological cancer cases in the DNRP and/or the DCR from 2001 to 2009. Completeness and the positive predictive value (PPV) of urological cancer registration in the DNRP were estimated using the DCR as the reference standard. To examine the impact of potential misclassification, we computed mortality estimates for urological cancer patients in each registry. Because DCR registration procedures changed in 2004, the periods 2001-2003 and 2004-2009 were analyzed separately. In 2004-2009, the overall completeness and PPV of urological cancer registration in the DNRP were 94.9% (95% confidence interval: 94.7-95.2%) and 86.6% (95% confidence interval: 86.3-86.9%), respectively, compared with diagnoses recorded in the DCR. Completeness and PPV of cancer registration in the DNRP varied between cancer subgroups. In 2001-2003, both completeness and PPV in the DNRP were slightly lower compared with 2004-2009. Mortality estimates in patients registered in the DNRP and the DCR varied slightly. The DNRP could be a valuable source of data for clinical quality monitoring and epidemiological research for some urological cancers, especially when current data are essential.