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Simple Summary: This study reports updates on colon and rectum cancer survival differences in the German–Danish border region and investigates the effects of tumor stage at diagnosis and first-line treatment on cancer survival. Based on cancer registry data from 2004 to 2016, we estimated the risk of dying from all causes after a colon or rectum cancer diagnosis while also controlling for stage and treatment. We observed that colon and rectum cancer survival improved in the entire German–Danish border region, but much more in the Danish regions. At first, colon and rectal cancer survival was higher on the German side of the border, but the Danish regions caught up. In the end, colon cancer survival was similar across the border and rectal cancer survival was better in Denmark. Stage and treatment could not explain the observed survival differences. Health care reforms and early detection strategies may also contribute to the regional differences. The aim of this study was (i) to update the reporting of colorectal cancer survival differences over time in the German–Danish border region (Schleswig-Holstein, Southern Denmark, and Zealand) and (ii) to assess the extent to which it can be explained by stage and primary treatment. Incident invasive colorectal cancer cases diagnosed from 2004 to 2016 with a follow-up of vital status through 31 December 2017 were extracted from cancer registries. Analyses were conducted by anatomical subsite and for four consecutive periods. Kaplan–Meier curves and log-rank tests were computed. Cox regression models using data from Schleswig-Holstein from 2004 to 2007 as the reference category were run while controlling for age, sex, stage, and treatment. The cox regression models showed decreasing hazard ratios of death for all three regions over time for both anatomical subsites. The improvement was stronger in the Danish regions, and adjustment for age, sex, stage, and treatment attenuated the results only slightly. In 2014–2016, colon cancer survival was similar across regions, while rectal cancer survival was significantly superior in the Danish regions. Regional survival differences can only partially be explained by differing stage distribution and treatment and may be linked additionally to healthcare system reforms and screening efforts. [ABSTRACT FROM AUTHOR]

Background: Disseminated intravascular coagulation (DIC) is a devastating disease of the coagulation system. We examined the association between ABO blood type and short-term mortality in patients with infection-associated DIC., Methods: The study cohort was drawn from the Danish Disseminated Intravascular Coagulation (DANDIC) cohort. Our subcohort was restricted to patients with infection-associated DIC. All-cause 30-day and 90-day mortality were computed by Kaplan-Meier estimates and odds ratios between ABO blood types were examined using logistic regression analysis adjusted for age, sex, comorbidity, and location of infection. Blood type O was used as a reference., Results: The DANDIC cohort included 3023 patients with DIC. Among these, 1853 (61%) had infection-associated DIC. Data on ABO blood type were unavailable in 34 patients (1.8%), who were excluded. The median age was 68 years and 58.2% were males. The 30-day mortality ranged between 38.6% and 42.5% and the 30-day mortality odds ratios were 1.15 (95% confidence interval (CI), 0.92-1.42) for blood type A; 0.84 (95% CI, 0.49-1.43) for AB; and 0.95 (95% CI, 0.67-1.33) for B compared to blood type O., Conclusions: We found no clinically meaningful difference in short-term mortality between the various ABO blood types in patients with infection-associated DIC., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Introduction: Most postmenopausal women with early-stage oestrogen receptor-positive breast cancer are allocated to five years of endocrine therapy. This treatment is not without adverse effects, which may lead to treatment discontinuation. This study aimed to assess compliance with endocrine therapy among postmenopausal women with early-stage oestrogen receptor-positive breast cancer and examine its association with disease-free survival., Methods: This study retrospectively identified a cohort of 360 postmenopausal women diagnosed in the period from 1 January 2015 to 31 December 2017 at Rigshospitalet, Copenhagen, Denmark, with early-stage oestrogen receptor-positive breast cancer in the clinical database of the Danish Breast Cancer Group. Kaplan-Meier was used to estimate compliance and disease-free survival., Results: A total of 346 patients receiving endocrine therapy were included, 240 were compliant, and 106 were non-compliant. The median follow-up was 6.5 years (95% confidence interval (CI): 6.4-6.7 years). The compliance at 4.5 years was 68.8% (95% CI: 64.1-74.0%). Disease-free survival was significantly higher for the compliant group (adjusted HR = 2.29; 95% CI: 1.34-3.91)., Conclusions: We found a low compliance at 4.5 years and most discontinuations were due to adverse effects. The study provides evidence that low compliance with endocrine therapy had a negative impact on disease-free survival., Funding: The study was funded by the Danish Cancer Society., Trial Registration: The study was approved by the research overview of the Capital of Denmark and the Center for Health., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: Halm's clinical stability criteria have long guided antibiotic treatment and hospital discharge decisions for patients hospitalised with community-acquired pneumonia (CAP). Originally introduced in 1998, these criteria were established based on a relatively small and select patient population. Consequently, our study aims to reassess their applicability in the management of CAP in a contemporary real-world setting., Methods: This cohort study included 2918 immunocompetent patients hospitalised with CAP from three hospitals in Denmark between 2017 and 2020. The primary outcome was time to achieve clinical stability as defined by Halm's criteria. Additionally, we examined recurrence of clinical instability and severe complications. Cumulative incidence function or Kaplan-Meier survival curves were used to analyse these outcomes, considering competing risks., Results: The study population primarily comprised elderly individuals (median age 75 years) with significant comorbidities. The median time to clinical stability according to Halm's criteria was 4 days, with one-fifth experiencing recurrence of instability after early clinical response (stability within 3 days). Severe complications within 30 days mainly comprised mortality, with rates of 5.1% (64/1257) overall in those with early clinical response, 1.7% (18/1045) in the subgroup without do-not-resuscitate orders and 17.3% (276/1595) among the rest., Conclusion: Halm's clinical stability criteria effectively classify CAP patients with different disease courses, yet achieving stability required more time in this ageing population with substantial comorbidities and more severe disease. Early clinical response indicates reduced risk of complications, especially in those without do-not-resuscitate orders., Competing Interests: Conflict of interest: T. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Foundation, Erik and Susanna Olesen's Charitable Fund, GSK, Pfizer, Boehringer Ingelheim, Gilead Sciences, MSD, Roche, Novartis and Kancera AB, consultancy fees from GSK and Pfizer, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, AbbVie and AstraZeneca, participation on a data safety monitoring board or advisory board with GSK, Pfizer, Gilead Sciences, MSD, Pentabase, Janssen and AstraZeneca, and receipt of equipment, materials, drugs, medical writing, gifts or other services from Eli Lilly (donation of trial medication (baricitinib)). M. Fally reports leadership roles with the European Respiratory Society (member of the Clinical Practice Guidelines Methodology Network and Secretary of Assembly 10, Group 1 (Bronchiectasis and Respiratory Infections)) and Danish Medical Journal (Associate Editor). The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Purpose: The primary aim of our study was to identify the absolute incidence and implant survival of multiply revised knee arthroplasties based on nationwide register data. The secondary aim was to determine the change in the absolute incidence and implant survival of multiply revised knee arthroplasties Methods: We performed a retrospective observational study of primary knee arthroplasties using several nationwide Danish registers. All primary knee arthroplasties performed in Denmark from 1998 to 2021 were identified. From these primary arthroplasties, revision procedures were identified. Kaplan-Meier plots were used in survival analysis to estimate the likelihood of implant survival., Results: 161,384 primary knee arthroplasties and their revisions performed between 1998 and 2021 were identified; of 13,786 (8.5%) revisions there were 10,638 1st revisions, 2,148 2nd revisions, 624 3rd revisions, 223 4th revisions, and 153 procedures that had been revised more than 4 times. The 10-year revision-free survival of primary arthroplasties was 92.3% (95% confidence interval [CI] 92.2-92.5). First-time revisions had a 10-year revision-free survival of 75.9% (CI 74.9-76.9). The 10-year survival of second- and third-time revisions was 65.1% (CI 62.6-67.6) and 57.8% (CI 53.4-62.5), respectively. The 10-year implant survival probabilities of primary knee arthroplasties were 91.4% in 1998-2009 and 93.3% in 2010-2021 (difference 2.2%). The 10-year implant survival probabilities of 1st revisions were 77% in 1998-2009 and 75% in 2010-2021 (difference -2.4%)., Conclusion: We found that 0.3% of all primary knee arthroplasties resulted in 3 or more revisions. The implant survival decreased for each consecutive revision, with almost half of the 3rd revisions being re-revised within 10 years. The 10-survival of the primary implant was higher in 2010-2021, and the 10-year survival of the 1st revision was higher in 1998-2009.

Background: Textbook outcome is a composite quality measurement in esophageal cancer surgery. This study aimed to estimate the rate of textbook outcome esophagectomies at a high-volume center and investigate associations between textbook outcome and overall and recurrence-free survival., Methods: A retrospective single-center study was conducted at Copenhagen University Hospital, Rigshospitalet, Denmark, analyzing esophagectomies performed from November 1, 2016, to December 31, 2021. Patients with primary carcinoma of the gastroesophageal junction who underwent elective and curative esophagectomy were included. The rate of textbook outcome esophagectomies was calculated, and the impact of textbook outcome on overall and recurrence-free survival was analyzed using Kaplan-Meier and Cox regression., Results: A total of 433 patients were included in the study. Textbook outcome was achieved in 195 patients (45%). Achieving textbook outcome was independently associated with improved overall survival (HR 0.67; P = .011) and with a median overall survival of 57 months and 32 months for patients with or without textbook outcome, respectively. A trend for improved recurrence-free survival was observed for patients with textbook outcome (HR 0.74; P = .064)., Conclusion: The present study found a consensus-based textbook outcome rate of 45%. Textbook outcome was found to be directly associated with improved overall survival. These results emphasize the association between improved short-term outcomes and long-term survival., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Cirrhosis affects hemostasis, but its effects across the spectrum of thromboses remain poorly understood. We examined risks and outcomes of venous and arterial thrombosis., Approach and Results: We used nation-wide Danish health care registries to identify outpatients with cirrhosis and a sex- and age-matched comparison cohort without cirrhosis from the general population. Patients with cirrhosis and comparators were followed until they had a venous thromboembolism (VTE), acute myocardial infarction (AMI), or ischemic stroke (IS) or died. We computed absolute risks and HRs of thrombosis and compared outcomes after thrombosis. We included 5,854 patients with cirrhosis (median Model for End-Stage Liver Disease score, 9; interquartile range, 7-13), and their risk of any of the thrombotic events was 0.8% after 1 year and 6.3% after 10 years. They were more likely than the 23,870 matched comparators to have a VTE (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.5-2.6) or IS (aHR, 1.7; 95% CI, 1.3-2.3), but not AMI (aHR, 0.7; 95% CI, 0.5-0.9). Among patients with cirrhosis, decompensation increased the risk of AMI, but not the other thromboses. Following thrombosis, patients with cirrhosis had higher 90-day mortality than comparators (after VTE: 17% vs. 7%; after AMI: 27% vs. 5%; after IS: 10% vs. 7%) and were less likely to receive antithrombotic treatment., Conclusions: Patients with cirrhosis had an increased risk of VTE and IS, but not AMI. Among patients with cirrhosis, decompensation increased the risk of AMI, exclusively. Mortality after thrombosis was higher in patients with cirrhosis than in other patients. These findings are relevant for decisions about antithrombotic prophylaxis in patients with cirrhosis., (© 2021 by the American Association for the Study of Liver Diseases.)

Background and Aim: Denmark reports slightly lower breast cancer survival before 2010 than its neighbouring country Germany. Previous research is limited by lacking stage and treatment information. This study aims to investigate differences in breast cancer survival between the bordering regions Schleswig-Holstein (Germany), Southern Denmark and Zealand (Denmark) using registry data including stage and treatment information., Method: Invasive female breast cancer cases diagnosed during 2004-2013 with follow up through 31st December 2014 were extracted from cancer registries. Cases notified by death certificates only and those aged 90+ years were excluded. Kaplan-Meier curves and log-rank tests were computed. Cox regression analysis was conducted with adjustment for year of diagnosis, age, stage, and treatment., Results: The analytical sample included 42,966 cases. Kaplan-Meier curves and log-rank tests show significant survival differences between the regions. The Cox regression model adjusted for year of diagnosis and age shows significantly worse overall survival of breast cancer patients in both Danish regions compared to Schleswig-Holstein with hazard ratios (HR) of 1.09 (95 % CI: 1.04; 1.15) for patients from Southern Denmark (SD) and 1.25 (95 % CI: 1.18; 1.32) for residents of Zealand (ZL). This effect diminished after adjustment for stage and treatment (HR: 1.05 (SD), 1.09 (ZL) 95 % CI: 0.99; 1.10 (SD), 1.03; 1.15 (ZL))., Conclusion: Survival differences can be explained by differing stage distribution and treatment administration, which formerly were more favourable in Schleswig-Holstein. The survival gap will probably close due to Denmark's national screening program and increased use of adjuvant cancer therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Programmed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001-2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ([Formula: see text] 1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan-Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors-51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8-17.9) and 13.4 (95% CI = 9.5-16.3) in PD-L1+ and PD-L1- tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74-1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63-1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39-0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients., (© 2021. The Author(s).)

Objective: The risk of ipsilateral neurological recurrence (NR) was assessed in patients awaiting carotid endarterectomy (CEA) due to symptomatic carotid artery stenosis and whether current national guidelines of performing CEA within 14 days are adequate in present day practice., Methods: This was a retrospective multicentre observational cohort study. Patients scheduled for CEA due to symptomatic carotid artery stenosis in a five year period, 1 January 2014 to 31 December 2018, from four centres were included. Data from the Danish Vascular Registry (www.karbase.dk), operative managing systems, and electronic medical records were reviewed., Results: In total, 1 125 patients scheduled for CEA were included and 1 095 (97%) underwent the planned surgery. During a median delay from index event to CEA of 11 days (interquartile range 8-16 days), 40 patients (3.6%; 95% confidence interval [CI] 2.5%-5%) experienced a NR. One third were minor strokes (n = 12, 30%); half were transient ischaemic attacks (TIA) (n = 22, 55%); and amaurosis fugax accounted for 15% (n = 6). Twenty-six (2%) CEA procedures was cancelled, of which one was due to a disabling recurrent ischaemic event (aphasia). There were no deaths or major strokes in the waiting time for CEA. Best medical treatment (BMT) with platelet inhibitory or anticoagulation drugs and a statin was initiated in nearly all patients (98%) at first assessment. The overall 30 day risk of a post-operative major event (death or stroke) was (Kaplan-Meier [KM] estimate) 2.7% (95% CI 1.8-3.8), and not significantly correlated with the timing of surgery. Most (69%) occurred within the first three days. One, two, and three year mortality rate for CEA patients was (KM estimate) 4.8%, 7.8%, and 11.5% respectively., Conclusion: In symptomatic carotid artery stenosis patients awaiting CEA, very few NRs occurred within 14 days. Institution of immediate BMT in specialised TIA/stroke units followed by early, but not necessarily urgent, CEA is a reasonable course of action in patients with high grade symptomatic carotid artery stenosis., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Nationwide studies of ocular adnexal lymphoma (OAL) are very rare in the literature, and knowledge on incidence, subtype distribution and long-term survival data is limited. This is the largest national study of OAL to date. This study sought to find information on incidence, changes in incidence, clinical findings, distribution of subtypes, survival and prognostic factors., Methods: Patients diagnosed with OAL from January 1, 1980 to December 31, 2017 were identified in Danish registers, and clinical as well as survival data were collected. The data were analysed with Kaplan-Meier plots and log-rank test., Results: 387 patients were included in the study. The major lymphoma subtypes were extranodal marginal-zone B cell lymphoma (EMZL) (55%), diffuse large B cell lymphoma (DLBCL) (13%), mantle cell lymphoma (MCL) (11%) and follicular lymphoma (FL) (10%). OAL is a disease of the elderly (median age 69 years). The incidence of lymphoma of the ocular adnexal region has increased significantly throughout the time period of the study (Pearson correlation coefficient, r=0.65; P<0.001). In the period 1980-1984, the incidence was 0.086 per 100 000, which increased to 0.307 per 100 000 in the period 2013-2017. Low-grade, low-stage primary lymphomas were treated with radiotherapy, whereas patients with high-stage, high-grade and/or relapsed disease were treated with chemotherapy. Low-grade subtypes EMZL (89%) and FL (56%) had better 10-year disease-specific survival than the high-grade lymphomas DLBCL (38%) and MCL (31%)(p<0.001)., Conclusion: OAL is increasing in incidence in the Danish population for unknown reasons. However, the prognosis for most OAL is favourable, as highlighted in this national long-term study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate health-care utilisation and costs, myeloma complications and survival in Danish patients with multiple myeloma (MM) before and after implementation of new early-line treatments in 2009., Methods: Based on data from the Danish National Health Registers, 3518 patients diagnosed with MM during 2002-2005 or 2010-2013 and randomly matched control individuals were identified, and health-care utilisation and costs were estimated., Results: Health-care utilisation showed a marked shift from inpatient admissions towards outpatient visits. From early to late period, the mean annual number of outpatient visits increased by 22% and 28% in patients <65 years and ≥65 years, respectively. Additionally, the mean annual outpatient service costs increased correspondingly from 17 001€ to 23 643€ in younger patients and from 11 317€ to 16 144€ in the elderly. Increasing outpatient costs were outbalanced by lower inpatient admission costs and the adjusted total mean annual costs decreased in younger patients, probably partly due to fewer myeloma complications. The five-year survival rates increased markedly in both younger (HR = 0.51) and elderly (HR = 0.69) patients., Conclusion: Despite the introduction of new expensive early-line MM treatments in 2009, health-care costs remained stable due to a shift in health-care utilisation towards outpatient clinic care and fewer complications., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The incidence of cancer-associated venous thromboembolism has increased, but whether short-term mortality after cancer-associated venous thromboembolism has changed remains uncertain. We investigated whether the increasing incidence of venous thromboembolism in cancer patients is associated with a change in mortality., Methods: We used administrative medical registries to identify a cohort of all Danish patients diagnosed with a first primary cancer from 2006 to 2017. We examined temporal changes in 1-year risks of venous thromboembolism and in mortality risks at 30 days and 1 year after venous thromboembolism. Cox regression was used to assess changes in mortality rate ratios over time., Results: We included 350,272 cancer patients (median age 68 years, 49.1% female), of whom 8167 developed venous thromboembolism within 1 year after cancer diagnosis. The cumulative 1-year risk of venous thromboembolism was 1.8% in 2006-2008, increasing to 2.8% for patients diagnosed in 2015-2017. The 30-day mortality after venous thromboembolism decreased from 15.1% in 2006-2008 to 12.7% in 2015-2017, and the 1-year mortality decreased from 52.4% to 45.8%, equivalent to a hazard ratio (HR) of 0.83 (95% confidence interval [CI], 0.75-0.90). This pattern of declining 1-year mortality was consistent for patients with pulmonary embolism, HR 0.79 (95% CI, 0.69-0.90), and deep venous thrombosis, HR 0.76 (95% CI, 0.67-0.87). Lower mortality over time was evident across all strata of cancer stage, cancer type, and cancer treatment., Conclusions: The 1-year risk of venous thromboembolism after a first primary cancer diagnosis in Denmark increased during 2006-2017. This increase was accompanied by declining mortality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome., Methods: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality., Results: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76)., Conclusions: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials., Objective: This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort., Methods: The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS') was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS' was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis., Results and Conclusions: Both ΔFS' and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS', is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

The effects of smoking on the molecular response (MR) and overall survival (OS) in patients with chronic myeloproliferative neoplasms (MPNs) have not been investigated before. We analysed a historical cohort of 498 consecutive patients diagnosed with MPNs. Moreover, we analysed a subgroup of 270 consecutive patients with MPNs with > 1 measurement of the JAK2V617F variant allele frequency. The data were analysed using Kaplan-Meier plots and Cox regression analysis, along with linear regression models. In all patients, the rate of MR was significantly higher in never-smokers compared with current smokers in the univariate model (HR, 1·9; 95% CI, 1·1-3·3; P = 0·033) and the multivariate model (HR, 1·9; 95% CI, 1·1-3·5; P = 0·029). Similar findings were observed with different cut-off values for a partial MR. A subgroup analysis including only interferon-α2-treated patients showed similar results. In multivariate analyses, the OS was significantly better for never-smokers (HR, 0·46; 95% CI, 0·29-0·75; P = 0·002) than current smokers. The differences were more pronounced in the pegylated interferon-α2-treated patients. However, no significant interaction of interferon-α2 treatment was observed. In conclusion, we found that tobacco smoking reduced the rate of MR and OS in patients with MPNs. Cessation of smoking should be encouraged., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Human papillomavirus infection and p16-overexpression is a principal cause and favorable prognostic factor for oropharyngeal squamous cell carcinomas but the value as prognostic marker in oral cavity squamous cell carcinomas (OSCC) is undetermined., Materials and Methods: All patients diagnosed with OSCC in Eastern Denmark in the period 2008-2014 were enrolled. Survival estimates were evaluated as overall survival (OS) and progression free survival (PFS) by Kaplan-Meier survival curves and multivariate Cox-regression analyses., Results: We included 575 patients from which 13% (n = 69) had p16-positive tumors. The 5-year OS were 55% and 62% for the p16-negative and p16-positive patients, respectively, and the 5-year PFS were 48% and 50%. In a multivariate survival analysis, p16-positivity showed no significant influence on OS (HR: 1.06 [0.67-1.70], p = 0.79) and PFS (HR: 1.11 [0.76-1.63], p = 0.58)., Conclusion: In this population-based cohort of non-selected OSCC patients, we found no difference in survival outcomes when stratified on p16-overexpression status., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The association between QRS voltage and QTc interval prolongation with mortality for up to 1 year after recording an ECG on patients attending emergency departments (EDs) was examined in a retrospective register-based observational study on 37,473 patients attending 2 Danish EDs. Of 37,473 patients who had an ECG performed on their first ED presentation 2,164 (5.8%) died within 30 days of presentation and 6,395 (17.1%) died within a year. Compared with survivors, patients who died had significantly longer QRS intervals and lower QRS voltages. A combined lead I and II QRS voltage <=1.4 mV was consistently associated with approximately twice the risk of mortality for up to at least 1 year after the ECG recording and this risk was not influenced by the length of the QTc interval. The increased mortality risk of a low QRS voltage remained even after adjustment for age, gender, Charlson co-morbidity index, and abnormal sodium and urea levels. In conclusion, low QRS voltage is a simple measurement that could potentially be used as an objective prognostic marker., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: In heritable retinoblastoma, there is a significantly increased risk of second primary cancers (SPCs). Improved knowledge about the incidence and influence of heritability and treatment is important during therapy for patients with retinoblastoma., Objective: To assess the incidence of SPC in patients diagnosed with retinoblastoma in Denmark from 1943 to 2013 with a focus on heritability and the association of external radiotherapy with mortality., Design, Setting, and Participants: In this retrospective cohort study, data were extracted from the Danish Ocular Oncology Group Database containing complete data on all patients diagnosed with retinoblastoma , and obtained from the Danish Cancer Registry, which includes information on all patients with cancer from 1943 to December 31, 2013. Data analysis was conducted from December 1, 2017, to October 1, 2019. Data on 323 patients were included., Exposures: Heritability and retinoblastoma treatment., Main Outcomes and Measures: Standardized incidence rate, excess absolute risk, cumulative incidence of SPC, and mortality from SPC. Association of heritability and treatment with outcomes was estimated., Results: Of the 323 patients included in the analysis, 181 were men (56%), 133 had heritable retinoblastoma (41%), and 190 had nonheritable retinoblastoma (59%). The median age at diagnosis of SPC was 32.4 (interquartile range, 15.4-43.9) years in patients with heritable retinoblastoma and 38.6 (interquartile range, 20.5-49.4) years in those with nonheritable retinoblastoma. Twenty-five SPCs were identified in patients with heritable retinoblastoma vs 14 in patients with nonheritable retinoblastoma. Standardized incidence rate (SIR) of SPC in patients with heritable retinoblastoma was 11.39 (95% CI, 7.37-16.81) with an excess absolute risk of 70 cases per 10 000 person-years; the highest SIRs were for sarcoma (181.13; 95% CI, 98.94-303.92) and malignant melanoma (26.78; 95% CI, 9.78-58.30). The SIR for SPC in patients with nonheritable retinoblastoma was 1.52 (95% CI, 0.81-2.60). The cumulative incidence of SPCs at age 60 years was significantly higher in patients with heritable retinoblastoma (51%) compared with those with nonheritable retinoblastoma (13%) (P < .001) (hazard ratio, 5.0; 95% CI, 2.5-10.3). No significant differences were identified in overall risk of SPC in patients with heritable retinoblastoma treated with 3 different modalities: external radiotherapy, plaque (but no external) radiotherapy, and enucleation only, but an increased proportion of sarcomas was noted in the irradiated field. Mortality due to SPC was also higher in survivors of heritable retinoblastoma compared with those with nonheritable retinoblastoma (cumulative mortality, 34% vs 12% at age 60 years; P = .03)., Conclusions and Relevance: The findings of this study suggest that the incidence and mortality associated with SPC were significantly higher in patients with heritable retinoblastoma vs patients with nonheritable retinoblastoma. The largest increases in risk were noted for sarcoma and malignant melanoma. External radiotherapy did not appear to increase the risk. These findings are relevant when treating patients with retinoblastoma to manage the risk for SPC.

Background: Porphyria cutanea tarda (PCT) is a rare hepatocutaneous disease for which the prognosis is largely unknown., Objective: To compare all-cause and cause-specific mortality between a nationwide cohort of patients with PCT and a matched population sample., Methods: We included all Danish patients who received a diagnosis of PCT from 1989 through 2012. Each patient was matched by age and sex to 10 random population control individuals. We compared survival and cause-specific mortality between patients and control individuals and adjusted for confounding from alcohol-related diseases, hepatitis, hemochromatosis, HIV, diabetes, acute myocardial infarction, stroke, cancer, chronic obstructive pulmonary disease, and cirrhosis., Results: The 20-year survival was 42.9% (95% confidence interval [CI], 36.9-48.7) for patients with PCT compared with 60.5% (95% CI, 58.6-62.4) for matched control individuals. All-cause mortality hazard ratio (HR) was 1.80 (95% CI, 1.56-2.07) before adjustment and 1.22 (95% CI, 1.04-1.44) after adjustment. The cause-specific mortality was markedly increased for nonmalignant gastrointestinal diseases (HR, 5.32; 95% CI, 2.71-10.43) and cancers of the gut (HR, 2.05; 95% CI, 1.24-3.39), liver/gallbladder (HR, 11.24; 95% CI, 4.46-28.29), and lungs (HR, 2.17; 95% CI, 1.41-3.33)., Limitations: We had no data on lifestyle factors., Conclusions: Patients with PCT have increased mortality, primarily explained by an increased mortality from gastrointestinal diseases and from cancers of the gut, liver/gallbladder, and lungs., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Brain metastases (BMs) are an uncommon presentation of metastatic colorectal cancer (mCRC) with reported incidence of about 2-4%. Today, there is an increased awareness towards a metastasis directed treatment approach with either surgical resection, stereotactic radiotherapy (SRT) or both. We examined patient characteristics and survival for patients treated with a localized modality for BM from CRC in a nationwide population-based study. Methods: A registry-based cohort study of all patients with a resected primary colorectal cancer and localized treatment of BM during 2000-2013. We computed descriptive statistics and analysed overall survival by the Kaplan-Meier method and Cox regression. Results: A total of 38131 patients had surgery for a primary CRC and 235 patients were recorded with a metastasis directed treatment for BM, comprising resection alone ( n  = 158), SRT alone ( n  = 51) and combined resection and SRT ( n  = 26). Rectal primary tumor (48.9% vs. 36.2%, p  < .001) and lung metastasectomy (11.9 vs 2.8%, p  < .001) were more frequent in the BM group. The median survival of patients receiving localized treatment for BM was 9.6 months (95% confidence interval (CI) 7.2-10.8). The 1- and 5-year overall survival were 41.7% (95% CI 35-48%) and 11.2% (95% CI 6.9-16.3%). In multivariate analysis, nodal stage was associated with increased mortality with a hazard ratio of 1.63 (95% CI 1.07-2.60, p  = .03) for N2 stage with reference to N0. Conclusion: We report a median overall survival of 9.6 months for patients receiving localized treatment for BM from CRC. Lung metastases and rectal primary tumor are more common in the population treated for BM.

Introduction: The Danish Cancer Registry (DCR) and the Danish Lung Cancer Registry (DLCR) are nation-wide registries recording Danish patients with lung cancer (LC). The aim of this study was to assess data agreement and possible consequences hereof on estimation of survival between patients in the two registries., Methods: Descriptive statistics were used for comparison of registered patients in 2013-2014 in the DCR and the DLCR. Furthermore, the one-year relative survival (1y-RS) and Cox proportional mortality hazard rates (MRR) were calculated., Results: In 2013-2014, a total of 9,111 Danish residents were identified with LC in the DCR and 9,316 were found in the DLCR. Merging the two registries showed an agreement of 87%, whereas 6% were included only in the DCR and 8% only in the DLCR. Including patients only registered in one registry, but who seemed to meet the inclusion criteria of both registries, would increase the agreement to 95%. No differences were seen for 1y-RS. However, MRR for patients in the DLCR was significantly lower than for patients in the DCR: 0.94 (95% confidence interval: 0.91-0.98)., Conclusions: Surprisingly, the DCR registered fewer patients in 2013-2014 than the DLCR, even though they employ the same primary data source. The agreement between the DCR and the DLCR was 87%; this may be increased to 95% if patients who seemed to meet the inclusion criteria of the other register were also included. The discrepancies found were mainly due to different definitions of dates of diagnosis, registrations probably missed by the algorithms and possible registration errors. Discrepancies resulted in a significant difference in MRR, but not in 1y-RS., 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: An association between sexually transmitted diseases (STDs) and occurrence of head and neck cancer (HNC) is proposed. Aims/objectives: We aimed to determine the association between selected STDs (syphilis, gonorrhoea, HIV) and HNC. Materials and methods: Patients diagnosed with HNC in Denmark between 1978 and 2014 identified through the Danish Cancer Registry were included. Patients were age- and sex-matched in a 1:10 ratio with general population controls. Uni- and multivariate analyses were performed using the Cox regression model to assess the correlation between STD and HNC. Results: A total of 39,405 HNC patients (63% men; 63.0 years at HNC diagnosis) and 393,238 controls were included. STD in HNC patients was 0.27%, vs. 0.11% in controls. Patients with cancer of the upper airways had a significantly higher prevalence of an STD prior to the HNC compared to controls. Most HNC patients with a prior STD (64.1%) developed the HNC within five years after the STD diagnosis. Conclusions: Although the studied STDs are rare, patients with cancer of the upper aerodigestive tract more commonly had a previous diagnosis of STD compared to controls. The study promotes the hypothesis that a causal link exists between STD and HNC.

Background: To describe relevant pathological parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980 to 2009, and to relate these data to treatment, overall survival (OS) and standardized mortality rate (SMR)., Materials and Methods: The MBCP cohort was defined from national Danish registers. A total of 643 MBCP were identified with tissue available in 457. Among these, 384 were primary operable. Where tissue blocks were available, tumor type, grade, estrogen receptor (ER), progesteron receptor (PgR) and androgen-receptor (AR) status as well as HER 2 and Ki67 were performed. OS was quantified by Kaplan-Meier estimates and SMR was calculated based on mortality rate among patients relative to the mortality rate in the general population., Results: Male breast cancer was more often of ductal type, grade II and a very high proportion were ER and AR positive and HER2 negative. Intrinsic subtypes based on immunohistochemical evaluation showed luminal subtype. Ki67 ratio increased over period of study. OS declined by increased age, bigger tumor size, positive lymph node status, higher grade and Luminal B subtype. Hazard ratio and relative risk of SMR were highest for patients aged < 60 years., Conclusion: Male breast cancer is of luminal subtype, but more often Luminal B. Ki67 is crucial in evaluation of subtypes by immunohistochemistry, but have limitations. Subtyping seems to be of major importance. AR also can have a role in future treatment.

Background and purpose - Few studies have evaluated the long- and mid-term outcomes after minimally invasive periacetabular osteotomy (PAO). We investigated: (1) the long-term hip survival rate after PAO; (2) the risk of complications and additional surgery after PAO; and (3) the hip function at different follow-up points.Patients and methods - We reviewed 1,385 hips (1,126 patients) who underwent PAO between January 2004 and December 2017. Through inquiry to the Danish National Patient Registry we identified conversions to total hip arthroplasty (THA) and complications after PAO. We evaluated the Hip disability and Osteoarthritis Outcome Score (HOOS) obtained preoperatively, and at 6 months, 2-, 5-, and 10-years' follow-up.Results - 73 of the 1,385 hips were converted to THA. The overall Kaplan-Meier hip survival rate was 80% (95% CI 68-88) at 14 years with a mean follow-up of 5 years (0.03-14). 1.1% of the hips had a complication requiring surgical intervention. The most common additional surgery was removal of screws (13%) and 11% received a hip arthroscopy. At the 2-year follow-up, HOOS pain improved by a mean of 26 points (CI 24-28) and a HOOS pain score > 50 was observed in 86%.Interpretation - PAO preserved 4 of 5 hips at 14 years, with higher age leading to lower survivorship. The PAO technique was shown to be safe; 1.1% of patients had a complication that demanded surgical intervention. The majority of the patients with preserved hips have no or low pain. The operation is effective with a good clinical outcome.

Objectives : To evaluate the influence of low socioeconomic status (SES) on mortality among patients with granulomatosis with polyangiitis (GPA). Methods : Using nationwide registers, we established a cohort of 827 patients diagnosed with GPA in the public hospital system of Denmark. For each patient, information regarding educational level, civil status, employment status, and comorbidities at time of GPA diagnosis was collected. We used Cox regression analyses to calculate hazard ratios (HRs) adjusted for age, gender, calendar period of GPA diagnosis, and Charlson Comorbidity Index score for preceding illnesses as a measure of relative risk of death. We assessed the risk of death associated with three measures of low SES: basic schooling only, civil status as single, and being unemployed or recipient of disability pension. Results : The median age of patients at GPA diagnosis was 61 (interquartile range 51-69) years, and 508 were 18-64 years old. During a total of 4337 person-years, 237 patients died. Among patients aged 18-64 years at GPA diagnosis, all three measures of low SES were identified as risk factors for death [basic schooling only: HR = 2.04, 95% confidence interval (CI) 1.30-3.19; civil status as single: HR = 1.95, 95% CI 1.24-3.05; being unemployed or recipient of disability pension: HR = 2.96, 95% CI 1.72-5.08]. The association between low SES and mortality was less pronounced among patients aged ≥ 65 years. Conclusions : Our observations indicate that low SES is associated with increased mortality in GPA, especially among patients of working age.

Background and purpose - Both medial unicompartmental knee arthroplasties (UKA) and high tibial osteotomies (HTO) are reliable treatments for isolated medial knee osteoarthritis. However, both may with time need conversion to a total knee arthroplasty (TKA). We conducted the largest nationwide registry comparison of the survival of TKA following UKA with TKA following HTO.Patients and methods - From the Danish Knee Arthroplasty Registry, aseptic conversions to TKA from UKA and TKA converted from HTO within the period of 1997-2018 were retrieved. The Kaplan-Meier method and the Cox proportional hazards regression were used to estimate the survival and hazard ratio (HR) for revision, considering confounding by indication utilizing propensity-score based inverse probability of treatment weighting (PS-IPTW).Results - PS-IPTW yielded a well-balanced pseudo-cohort (standard mean difference (SMD) < 0.1 for all covariates, except implant supplementation) of 963.8 TKAs following UKA and 1139.1 TKAs following HTO. The survival of TKA following UKA was significantly less than that of TKA following HTO with a 5-year estimated survival of 0.88 (95% confidence interval (CI) 0.85-0.90) and 0.94 (CI 0.93-0.96), respectively. The differences in survival corresponded to an implant-supplementation adjusted HR of 2.7 (CI 2.4-3.1) for TKA following UKA compared with TKA following HTO.Interpretation - Previous UKA more than doubled the revision risk of a subsequent TKA compared with previous HTO. This potential risk should be considered in the shared treatment decision of patients who are candidates for both UKA and HTO.

Background: IL6 and YKL-40 (also known as chitinase 3-like 1 protein, CHI3L1) are produced by pancreatic cancer cells and macrophages and activate inflammation. C-reactive protein (CRP) is synthesized mainly in hepatic cells and primarily stimulated by IL6. The aim of this study was to determine the prognostic value of combined detection of serum IL6, YKL-40, and CRP in patients with pancreatic cancer receiving palliative chemotherapy., Methods: In all, 592 patients with unresectable pancreatic cancer from five hospitals in Denmark were included in the BIOPAC biomarker study between 2008 and 2017. Pretreatment and longitudinal serum values of IL6 and YKL-40 were determined. Baseline CRP and CA19-9 values were available for the whole cohort. Patients were dichotomized as low versus high using cutoffs for IL6 of >4.92 pg/mL, YKL-40 of >95% age-corrected percentile, and CRP of >10 mg/L. The main outcome was overall survival., Results: Combined elevations of serum IL6, YKL-40, and CRP were associated with worse survival in contrast to an isolated high concentration of a single marker. Serum IL6, YKL-40, and CRP were higher in patients with advanced stage disease and in patients with poor performance status. Higher IL6 and YKL-40 levels at the time of tumor progression and serum IL6 measured over time were associated with shorter overall survival., Conclusions: Combined high baseline serum levels of IL6, YKL-40, and CRP are associated with poor survival., Impact: Assessment of systemic inflammation via measurements of IL6, YKL-40, and CRP may be important for pancreatic cancer prognostication., (©2019 American Association for Cancer Research.)

Objective: The effect of antibiotics on survival in patients with pulmonary Pseudomonas aeruginosa is controversial. The aim of this study is to i) determine the prevalence of adequate antibiotic treatment of P. aeruginosa in an unselected group of adult non-cystic fibrosis patients and ii) to assess the overall mortality in study patients treated with adequate vs. non-adequate antibiotics., Methods: Prospective, observational study of all adult patients with culture verified P. aeruginosa from 1 January 2010-31 December 2012 in Region Zealand, Denmark. Patients with cystic fibrosis were excluded. Adequate therapy was defined as any antibiotic treatment including at least one antipseudomonal beta-lactam for a duration of at least 10 days. Furthermore, P. aeruginosa had to be tested susceptible to the given antipseudomonal drug and treatment had to be approved by senior clinician to fulfil the adequate-criteria., Results: A total of 250 patients were identified with pulmonary P. aeruginosa. The vast majority (80%) were treated with non-adequate antibiotic therapy. All-cause mortality rate after 12 months was 49% in adequate treatment group vs. 52% in non-adequate treatment group. Cox regression analysis adjusted for age, gender, bacteraemia, comorbidities and bronchiectasis showed no significant difference in mortality between treatment groups (adequate vs. non-adequate: hazard ratio 0.95, 95% CI 0.59-1.52, P = 0.82)., Conclusion: Adequate antipseudomonal therapy was only provided in a minority of patients with pulmonary P. aeruginosa. Adequate therapy did not independently predict a favourable outcome. New research initiatives are needed to improve the prognosis of this vulnerable group of patients., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: TSI reports personal fees from AstraZeneca outside the submitted work. The other authors report no conflicts of interest relevant to this article.

Diagnosis of mycosis fungoides and Sézary syndrome can be very challenging. Clinical and histopathological data for patients with mycosis fungoides and Sézary syndrome in Denmark are limited. A retrospective study was performed in Region Zealand, Denmark from 1990 to 2016. A total of 43 patients with mycosis fungoides or Sézary syndrome were identified during the period. At the time of diagnosis the patients' mean age was 64.3 years and 74.5% had early-stage (≤IIA) disease. The mean time from onset of skin disease to diagnosis was 4.4 years. Surprisingly, 43% progressed to a higher disease stage, and risk of disease progression was higher for stage IB than IA (p = 0.01). All cases displayed some degree of epidermotropism and the infiltrates consisted of pleomorphic lymphocytes with a T-helper (CD4+/CD8-) phenotype. This study describes, for the first time, all aspects of clinical and histopathological findings in patients with mycosis fungoides and Sézary syndrome in a well-characterized Danish cohort.

Background: the increasing number of multimorbid older people places high demands on future health care systems. To inform the discussion on how to structure future care strategies, we aimed to describe the temporal relationship between admission, and morbidity and mortality in nursing home residents., Methods: data on 5,179 older individuals admitted to 94 Danish nursing homes in 12 municipalities during 2015-2017 were linked to the nationwide Danish health registries to retrieve information on the temporal relation between nursing home admission and morbidity and mortality., Results: at the time of nursing home admission, the majority were women (63%). Male residents were younger than women (median 82 vs 85 years) and had a higher prevalence of comorbidities (median Charlson score 2 vs 1 among women). The median survival after nursing home admission was 25.8 months, with the 3-year survival being 37%. Three-year survival was lower among men (29 vs 43% among women) and among the oldest residents (23% among those aged ≥90 years vs 64% among individuals ≤65 years). In addition to age and sex, predictors of mortality included hospitalisations prior to nursing home admission and a high burden of comorbidity. The rate of hospitalisations, primarily for reasons related to frailty, increased substantially during the 9 months prior to nursing home admission., Conclusion: we provide detailed information on differences in morbidity and mortality across age span and sex at the time of nursing home admission, thereby contributing to the ongoing discussion of how to structure the future health care system., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Lymphopenia has been associated with poor outcomes in patients with cancer. We sought to describe the lymphocyte kinetics in patients who received radiation therapy; to identify factors associated with the end-of-radiation-therapy (EoRT) lymphocyte count; and to determine the association of radiation therapy-induced lymphopenia with subsequent infection., Methods and Materials: Patients with solid malignant tumors treated at the Department of Oncology at Rigshospitalet, University of Copenhagen, Denmark, were included if they had received their first external beam radiation therapy with curative intent from January 2005 to December 2016 and had pretreatment and EoRT lymphocyte counts measured. Factors associated with the EoRT lymphocyte count were identified using regression analyses. The risk of subsequent infection was estimated using Cox proportional hazards regression., Results: We included 3920 patients. More patients had lymphopenia (<1000 cells/μL) at EoRT than at pretreatment (67.1% vs 14.9%; P < .001). Patients who received schemes with higher intensities (equivalent dose in 2-Gy fractions [EQD2] >65 Gy) in shorter time (<25 days) had a higher predicted EoRT lymphocyte count than patients who received schemes delivering EQD2 of 50 to 65 Gy in 25 to 45 days (1439 cells/μL, 95% confidence interval [1293-1585] vs 784 [754-814]). Radiation to multiple sites and concomitant chemotherapy use, particularly platinum compounds versus none, were associated with a lower EoRT lymphocyte count (698 [655-742] vs 852 [833-870]; and 612 [565-659] vs 937 [909-964], respectively). Patients with EoRT lymphopenia grade ≥3 (<500 cells/μL) had a higher risk of infection in the 3 months after radiation therapy (hazard ratio, 2.15 [95% confidence interval, 1.53-3.02]; P < .001), compared with patients with an EoRT lymphocyte count >1000 cells/μL., Conclusions: The lymphocyte count declined during radiation therapy. Short duration schemes (<25 days), despite high total radiation dose (EQD2 >65 Gy), were associated with a higher EoRT lymphocyte count, whereas radiation to multiple sites and concomitant chemotherapy were associated with a lower count. EoRT lymphopenia was associated with an increased risk of infection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort., Design: Retrospective cohort study., Setting: Danish nationwide registries., Participants: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year., Primary and Secondary Outcome Measures: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA 2 DS 2 VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes., Results: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA 2 DS 2 VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60)., Conclusion: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA 2 DS 2 VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding., Competing Interests: Competing interests: KF has received research grants Bayer/Janssen and AstraZeneca and Consulting/Fees Bayer, Sanofi/Regeneron and Verseon. FV has received honoraria for consulting and presentations from Bayer HealthCare, Boehringer Ibgelheimy, BMSPfizer and Daiichi-Sankyo. GHG has ownership of stocks in Novo Nordisk Pharmaceuticals and reports research grants from Pfizer, Bristol Myers Squibb, Boehringer Ingelheim and Bayer. CTP declares grants for studies from Bayer. Other authors have no conflicts of interest to declare., (© 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.)

Importance: New-onset postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. However, data on the long-term risk of thromboembolism in patients who develop POAF after heart valve surgery are conflicting. In addition, data on stroke prophylaxis in this setting are lacking., Objective: To assess the long-term risk of thromboembolism in patients developing new-onset POAF after isolated left-sided heart valve surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF)., Design, Setting, and Participants: This observational cohort study was conducted from January 1, 2000, through December 31, 2015, using Danish nationwide registries and the Eastern Danish Heart Surgery Database. Patients who developed POAF after isolated left-sided heart valve surgery (bioprosthetic aortic or mitral valve replacement and/or aortic or mitral valve repair) from 2000 through 2015 were included. These patients were matched with patients with nonsurgical NVAF in a 1:3 ratio by age, sex, heart failure, hypertension, diabetes, a history of thromboembolism, ischemic heart disease, and year of diagnosis. Data analyses took place from January to March 2019., Main Outcomes and Measures: Rates of thromboembolism., Results: Of the 1587 patients who underwent isolated left-sided heart valve surgery, 741 patients (46.7%) developed POAF during admission. Of the 712 patients with POAF who were eligible for matching, 675 patients were matched with 2025 patients with NVAF and made up the study population. In the matched study population, the median age was 71 (interquartile range, 65-77) years, and 1600 (59.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 420 patients with POAF (62.9%) and in 1030 patients with NVAF (51.4%). The crude incidence rates of thromboembolism were 21.9 (95% CI, 17.4-27.6) and 17.7 (95% CI, 15.2-20.6) events per 1000 person-years for patients with POAF and patients with NVAF, respectively. In the adjusted analysis, the long-term risk of thromboembolism was similar in patients with POAF and NVAF (hazard ratio, 1.22 [95% CI, 0.88-1.68]). Oral anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in patients with POAF (hazard ratio, 0.45 [95% CI, 0.22-0.90]) as well as patients with NVAF (hazard ratio, 0.63 [95% CI, 0.45-0.87]) compared with no anticoagulation therapy., Conclusions and Relevance: New-onset POAF after isolated left-sided heart valve surgery was associated with a similar long-term risk of thromboembolism as NVAF. These data warrant studies addressing the role of anticoagulation therapy in POAF after left-sided heart valve surgery.

Objectives: The aim was to describe population-based incidence and emergency department-based prevalence and 1-year all-cause mortality of patients with new organ failure present at arrival., Design: This was a population-based cohort study of all citizens in four municipalities (population of 230 000 adults)., Setting: Emergency department at Odense University Hospital, Denmark., Participants: We included all adult patients who arrived from 1 April 2012 to 31 March 2015., Primary and Secondary Outcome Measures: Organ failure was defined as a modified Sequential Organ Failure Assessment score≥2 within six possible organ systems: cerebral, circulatory, renal, respiratory, hepatic and coagulation.The primary outcome was prevalence of organ failure, and secondary outcomes were 0-7 days, 8-30 days and 31-365 days all-cause mortality., Results: We identified in total 175 278 contacts, of which 70 399 contacts were further evaluated for organ failure. Fifty-two per cent of these were women, median age 62 (IQR 42-77) years. The incidence of new organ failure was 1342/100 000 person-years, corresponding to 5.2% of all emergency department contacts.The 0-7-day, 8-30-day and 31-365-day mortality was 11.0% (95% CI: 10.2% to 11.8%), 5.6% (95% CI: 5.1% to 6.2%) and 13.2% (95% CI: 12.3% to 14.1%), respectively, if the patient had one or more new organ failures at first contact in the observation period, compared with 1.4% (95% CI: 1.3% to 1.6%), 1.2% (95% CI: 1.1% to 1.3%) and 5.2% (95% CI: 5.0% to 5.4%) for patients without. Seven-day mortality ranged from hepatic failure, 6.5% (95% CI: 4.9% to 8.6%), to cerebral failure, 33.8% (95% CI: 31.0% to 36.8%), the 8-30-day mortality ranged from cerebral failure, 3.9% (95% CI: 2.8% to 5.3%), to hepatic failure, 8.6% (95% CI: 6.6% to 10.8%) and 31-365-day mortality ranged from cerebral failure, 9.3% (95% CI: 7.6% to 11.2%), to renal failure, 18.2% (95% CI: 15.5% to 21.1%)., Conclusions: The study revealed an incidence of new organ failure at 1342/100 000 person-years and a prevalence of 5.2% of all emergency department contacts. One-year all-cause mortality was 29.8% among organ failure patients., 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.)

Objective: To evaluate whether visual acuity impairment was an independent predictor of mortality in patients with type 2 diabetes., Research Design and Methods: This is a 19-year follow-up of a cohort of 1241 patients newly diagnosed with type 2 diabetes and aged 40 years or over. Visual acuity was assessed by practicing ophthalmologists both at diabetes diagnosis and after 6 years. The logarithmic value of the visual acuity (logMAR) was the exposure. Multivariable Cox regression models were adjusted for multiple potential confounders including cardiovascular disease, and censored for potential mediators, that is, fractures/trauma. Primary outcomes were from national registers: all-cause mortality and diabetes-related mortality., Results: Visual impairment at diabetes diagnosis was robustly associated with subsequent 6-year all-cause mortality. Per 1 unit reduced logMAR acuity the incidence rate of all-cause mortality increased with 51% (adjusted HR: 1.51; 95% CI 1.12 to 2.03) and of fractures/trauma with 59% (HR: 1.59; 95% CI 1.18 to 2.15), but visual acuity was not associated with diabetes-related mortality. After censoring for fractures/trauma, visual acuity was still an independent risk factor for all-cause mortality (HR: 1.68; 95% CI 1.23 to 2.30). In contrast, visual acuity 6 years after diabetes diagnosis was not associated with the subsequent 13 years' incidence of any of the outcomes, as an apparent association with all-cause mortality and diabetes-related mortality was explained by confounding from comorbidity., Conclusions: Visual acuity measured by ophthalmologists in patients newly diagnosed with type 2 diabetes was an independent predictor of mortality in the short term., Competing Interests: Competing interests: NdFO reports grants from The Danish Medical Research Council, grants from The Danish Research Foundation for General Practice, grants from The Danish Ministry of Health, grants from The Health Insurance Foundation, grants from The Pharmacy Foundation and grants from the Novo Nordisk Farmaka Denmark, during the conduct of the study., (© 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.)

Background: The study aimed to evaluate Hyperfractionated, Accelerated Radiotherapy (HART) with nimorazole for patients with head and neck squamous cell carcinoma (HNSCC) using loco-regional failure (LRF), overall survival (OS), early and late morbidity as endpoints. Material and methods: From February 2007 to January 2018, 295 patients with unresected HNSCC, T1-T4, N0-N3, M0, were treated with HART prescribed as 76 Gy in 56 fractions (fx), 10 fx weekly. IMRT was used in >90% of patients. No chemotherapy was given. Patients were prospectively registered in the DAHANCA database. Results: The median age was 64 years, 75% of patients were males. Primary sites were larynx (25%), pharynx (64%) and oral cavity (11%). In total, 59% were stage III-IV (UICC 2002). Of the 150 oropharyngeal cancer (OPC) patients, 42% were p16+. The proportion of patients receiving HART as planned was 97%. The median follow-up time was 66 months. Three-year actuarial LRF was 19% and OS was 66%. LRF was significantly higher for stage III-IV patients compared to stage I-II (25% vs. 11%, HR 2.12 [1.21-3.74]). The site-specific LRF rates were: for larynx 22% [12-32], hypopharynx 30% [16-45], non-p16+ oropharynx 15% [8-23], p16+ oropharynx 7% [1-13] and oral cavity 35% [18-53]. During therapy, 51% reported severe dysphagia and 60% required feeding tubes. The peak incidence of late, severe dysphagia and xerostomia was 21% and 9%, respectively. A comparison to historical data from previous DAHANCA trials showed that tumor control and morbidity are comparable to treatment with acceleration and/or chemo-radiation. Conclusions: HART represents an attractive approach for patients with HNSCC where treatment intensification is indicated.

In this study, we analyzed the evolution of the prognosis of primary central nervous system lymphoma (PCNSL) patients as they reach selected progression-free survival (PFS) milestones after high-dose methotrexate (HD-MTX)-based therapy. In total, 258 and 146 patients were included from Denmark and British Columbia, respectively. All patients were diagnosed during 2000-2017. The 5-year PFS was 27% (95% CI 23; 32); however, for patients reaching 5 years of PFS, this increased to 71% (95% CI 57; 86). Within the first 5 years after diagnosis, patients lost 2.0 years (95% CI 1.8; 2.2) when compared to a similar background population. This reduced to 0.5 years (95% CI 0.2; 0.9) for patients reaching 5 years of PFS. Treatment with rituximab was associated with improved outcomes. The prognosis of patients with PCNSL treated with HD-MTX-based regimens in this cohort is poor, although it improves as patients survive without progression/relapse. However, survival does not conclusively normalize to that of a similar background population.

Hip fractures are associated with increased mortality and it is important to identify risk factors. This study demonstrates that preexisting cardiovascular disease as well as cardiovascular biomarkers that are associated with increased 30-day mortality. These findings can be used to identify high-risk patients who might benefit from specialized care., Introduction: This study investigates the association between cardiovascular disease (CVD), cardiovascular biomarkers, and 30-day mortality following a hip fracture., Methods: The Danish National Patient Registry was used to investigate the association between CVD and mortality following hip fracture in a nationwide population-based cohort study. In a subset of the included patients (n = 355), blood samples were available from a local biobank. These samples were used for analyzing the association between specific biochemical markers and mortality. The primary outcome was 30-day mortality., Results: A total of 113,211 patients were included in the population-based cohort study. Among these, heart failure was present in 9.4%, ischemic heart disease in 15.9%, and ischemic stroke in 12.0%. Within 30 days after the hip fracture, 11,488 patients died, resulting in an overall 30-day mortality of 10.1%. The 30-day mortality was significantly increased in individuals with preexisting CVD with multivariably adjusted odds ratios of 1.69 (95% confidence interval, 1.60-1.78) for heart failure, 1.23 (1.17-1.29) for ischemic heart disease, and 1.06 (1.00-1.12) for ischemic stroke. In the local database including 355 patients, 41 (11.5%) died within 30 days. The multivariably adjusted odds ratio for 30-day mortality increased with increasing NT-proBNP (2.36 [1.53-3.64] per quartile) and decreased with increasing HDL cholesterol (0.58 [0.41-0.82] per quartile). On this basis, we established a model for predicting the probability of death based on the biochemical markers., Conclusion: Preexisting CVD was associated with increased 30-day mortality after a hip fracture. Furthermore, high levels of NT-proBNP and low levels of HDL cholesterol were associated with increased 30-day mortality.

Objective: To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer., Methods: This national cohort study (2005-2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates., Results: LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI., Conclusion: LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

We aimed to investigate the pathogenicity of cardiac ion channel variants previously associated with SIDS. We reviewed SIDS-associated variants previously reported in databases and the literature in three large population-based cohorts; The ExAC database, the Inter99 study, and the UK Biobank (UKBB). Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Of the 92 SIDS-associated variants, 59 (64%) were present in ExAC, 18 (20%) in Inter99, and 24 (26%) in UKBB. Using the Inter99 cohort, we found no difference in J-point amplitude and QTc-interval between carriers and non-carriers for 14/18 variants. There was no difference in the risk of syncope (P = 0.32), malignant ventricular arrhythmia (P = 0.96), and all-cause mortality (P = 0.59) between carriers and non-carriers. The ACMG guidelines reclassified 75% of all variants as variant-of-uncertain significance, likely benign, and benign. We identified ~2/3 of variants previously associated with SIDS and found no significant associations with electrocardiographic traits, syncope, malignant ventricular arrhythmia, or all-cause mortality. These data indicate that many of these variants are not highly penetrant, monogenic causes of SIDS and underline the importance of frequent reappraisal of genetic variants to avoid future misdiagnosis.

Background and purpose - Several studies suggest a global increase of centenarians during the 21st century. We describe temporal trends of hip fracture incidence and mortality in this group and compare these patients with a group of younger hip fracture patients with regards to comorbidities and mortality. Patients and methods - The full study population included all hip fractures that occurred in Denmark (n = 154,047) between 1996 and 2012. Patients aged 100 or above were identified (n = 507) and hip fracture patients between the ages of 70 to 99 years (n = 124,007) were used for comparison. Data were accessed from national registries. Trends in incidence over time were analyzed using a log-linear regression model, mortality was analyzed using the Kaplan-Meier estimator and trends in mortality over time were analyzed using a log-binomial regression model to obtain relative risk estimates. Results and interpretation - The centenarian patients had fewer comorbidities than the younger comparison group, but mortality was higher at all timepoints. There was no statistically significant change in mortality over time but the incidence of hip fracture among centenarians decreased during the same time period. Our findings describe the characteristics of an emerging group of hip fracture patients and could be of use in the planning of healthcare in the years to come.

Aim: The aim of this study was to describe patient characteristics, event characteristics, and outcomes for patients with in-hospital cardiac arrest in Denmark., Methods: Data was obtained from DANARREST. DANARREST is a nationwide registry that covers all in-hospital cardiac arrests in Denmark with a clinical indication for cardiopulmonary resuscitation (i.e. without a prior "do-not-resuscitate" order)., Results: A total of 4069 adult in-hospital cardiac arrests were registered between January 1st, 2017 and December 31st, 2018. The median age was 74 years (quartiles: 65, 81) and 37% were female. 71% had a non-shockable rhythm and the presumed etiology was primarily non-cardiac (57%). A total of 2180 patients (53.8%) achieved ROSC, with an additional 36 patients (0.9%) receiving extracorporeal cardiopulmonary resuscitation. At 30-days 1124 patients (27.8%) were alive. Of cardiac arrests from 2017, 404 patients (20.0%) survived to 1 year after the cardiac arrest. The incidence of adult in-hospital cardiac arrest in Denmark was estimated at 1.8 per 1000 admissions or 0.6 per 1000 in-patient days., Conclusion: In-hospital cardiac arrest occurs in at least 2000 patients each year in Denmark with a 30-day survival of approximately 28%. The establishment of a national registry for in-hospital cardiac arrest in Denmark will allow for quality improvement and research projects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Biologics targeting interleukin 17 are increasingly being used for treatment of moderate-to-severe psoriasis, but data on drug survival for these therapies remain scarce., Objectives: To investigate the drug survival of secukinumab and ixekizumab in a nationwide cohort of patients with psoriasis in Denmark., Methods: Using DERMBIO, we examined Danish patients receiving treatment with secukinumab or ixekizumab according to the standard in-label dosing. Kaplan-Meier plots were used to present survival curves., Results: In all, 368 and 62 patients received treatment with secukinumab and ixekizumab, respectively. In total, 40.7% and 12.9% of secukinumab- and ixekizumab-treated patients were bionaive. Ixekizumab-treated patients had received significantly more previous treatments. Over 12 months, 23.5% and 0.0% of bionaive secukinumab- and ixekizumab-treated patients discontinued therapy, respectively. Drug survival for bionaive and non-naive patients was lower for secukinumab than for ixekizumab. During the maximum 3 years of follow-up, secukinumab drug survival was lowest for patients who had previously been treated with 2 or more biologics, followed by patients treated with secukinumab as their second-ever biologic., Limitations: The total number of patients and follow-up time were modest., Conclusions: Drug survival was higher for ixekizumab even though secukinumab-treated patients had been treated with significantly fewer biologics before starting this drug., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To investigate effect and toxicity of immune checkpoint inhibition (ICI) in a Danish real-life non-small cell lung cancer (NSCLC) population. By including patients underrepresented in clinical trials, such as those with brain metastasis (BM), higher age, more comorbidity and poorer performance status (ECOG), comparison of unselected patients to clinical trial populations is possible. Material and methods: Real life data were gathered from 118 consecutive NSCLC patients with incurable NSCLC treated with ICI at the Department of Oncology at the University Hospital of Odense, Denmark from September 2015 to April 2018. Immune-related adverse events (irAEs) grades 3-5 were registered prospectively during the same period. Additional patient related data were obtained retrospectively from patients' files. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier estimates, the log-rank test and cox regression analysis performed for factors affecting survival. Results: Median age for patients was 66 years (IQR 59-71) and 62 years (range: 55-64) for those with BM. Females 63%; adenocarcinoma (AC)/squamous/others 69%/23%/8%; ECOG ≥ 2 10%; bone/brain/liver metastases 36%/18%/15%; PD-L1 (TPS) <1%/ ≥ 1%/ ≤ 49%/ ≥ 50%/NR: 3%/14%/68%/15%; baseline autoimmunity 10%, Charlson's Comorbidity Index Score (CCIS) ≥ 2 39%, treatment line: 1st/2nd/ ≥ 3rd 39%/30%/31%. Median OS for patients receiving ICI in ≥2 line was 11.5 months versus not reached in first line (HR 2.6, [95% CI: 1.3-5.0], p  = .005). For patients with BM, the median OS was 8.2 months (HR 1.38, [95% CI: 0.7-2.5], p  = .37). Twenty-four percent of patients terminated ICI due to irAE grades 3-5 alone (grade 5, n   =  1), which were not associated with higher age or BM. Conclusions: OS and PFS were comparable to clinical trial reports. Long-lasting remission is also possible in patients with BM. Real-life populations have higher rates of irAE grades 3 and 4 than reported in clinical trials, but it does not seem to impact median OS.

Introduction: Recent studies have reported an asso-ciation between the day of week of surgery and post-operative mortality, meaning that patients undergoing surgery at the end of the week or during weekends may be at higher risk. The aim of this study was to investigate the influence of the day of week of surgery on mortality and morbidity rates in a national Danish cohort of patients undergoing major elective surgery for colorectal cancer., Methods: In a register-based study design, all patients undergoing elective major surgery for colorectal cancer in Denmark during a ten-year period (2005-2014) were studied. Patients were identified in the National Colorectal Cancer Database. Any associations between short-time mortality and morbidity rates within 30 days after operation and the day of week of surgery, as well as patient characteristics, treatment data and socioeconomic data were analysed., Results: We were unable to show that the day of week had a significant impact on short-term mortality or on surgical or medical complications. There was no evidence that patients undergoing surgery on Fridays had more risk factors or were more socioeconomically deprived than patients undergoing surgery from Monday to Thursday., Conclusions: The day of week of operation could not be shown to have any significant impact on the risk of post-operative surgical or medical complications or on short-term mortality in patients undergoing elective surgery for colorectal cancer in Denmark., 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.)

Objective: The benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA., Design: Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA., Results: A total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF., Conclusion: In two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial., Competing Interests: Competing interests: RCU has served as an advisory board member or consultant for Janssen, Pfizer and Takeda; research grant from AbbVie. JFC has served as an advisory board member or consultant for AbbVie, Amgen, Boehringer-Ingelheim, Arena Pharmaceuticals, Celgene, Celltrion, Enterome, Eli Lilly, Ferring Pharmaceuticals, Genentech, Janssen and Janssen, Medimmune, Merck & Co, Nextbiotix, Novartis Pharmaceuticals, Otsuka Pharmaceutical Development & Commercialization, Pfizer, Protagonist, Second Genome, Gilead, Seres Therapeutics, Shire, Takeda, Theradiag; speaker for AbbVie, Ferring, Takeda, Celgene; stock options: Intestinal Biotech Development, Genefit; research grants: AbbVie, Takeda, Janssen and Janssen., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)