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Background: Biodegradable polymer drug-eluting stents were developed to improve safety and efficacy outcomes for patients undergoing percutaneous coronary intervention. However, few long-term follow-up efficacy studies are available. The study sought to investigate 5-year results from the SORT OUT VII trial (Scandinavian Organization for Randomized Trials With Clinical Outcome) comparing the biodegradable polymer ultrathin-strut sirolimus-eluting Orsiro stent (O-SES) versus the biodegradable polymer biolimus-eluting Nobori stent (N-BES). Methods: This registry-based, randomized, multicenter, single-blinded, noninferiority trial compared O-SES and N-BES in an all-comer population. The composite primary end point, target lesion failure, consisted of cardiac death, myocardial infarction related to the target lesion, or target lesion revascularization within 1 year. Follow-up was extended to 5 years. Results: Five-year follow-up was completed for 2521 patients (99.8%). Five-year target lesion failure did not differ between O-SES (12.4%) and N-BES (13.1%; rate ratio [RR], 0.94 [95% CI, 0.75–1.18]). Cardiac death (RR, 0.95 [95% CI, 0.67–1.34]), target myocardial infarction (RR, 1.14 [95% CI, 0.76–1.71]), target lesion revascularization (RR, 0.90 [95% CI, 0.67–1.21]), and definite stent thrombosis rates (RR, 0.73 [95% CI, 0.41–1.33]) did not differ significantly between the 2 stents. Within the first year, definite ST was significantly lower for O-SES (0.4%) compared to N-BES (1.2%; RR, 0.33 [95% CI, 0.12–0.92]), but no difference was from 1 through 5 years: O-SES 1.2% and N-BES 0.9% (RR, 1.28 [95% CI, 0.58–2.82]). Conclusions: Five years after treatment with biodegradable polymer stents, target lesion failure did not differ among O-SES and N-BES. Definite stent thrombosis was less often seen within the first year in the O-SES but the difference was not maintained after 5 years. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT01879358.

OBJECTIVES: To compare the efficacy and safety of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (O-SES) in patients with and without acute coronary syndrome (ACS) included in the SORT OUT X study.BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with ACS when compared to patients without ACS. Whether the results from the SORT OUT X study apply to patients with and without ACS remains unknown.METHODS: In total, 3146 patients were randomized to stent implantation with DTS (n = 1578; ACS: n = 856) or O-SES (n = 1568; ACS: n = 854). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year.RESULTS: At 1 year, the rate of TLF was higher in the DTS group compared to the O-SES group, both among patients with ACS (6.7% vs. 4.1%; incidence rate ratio: 1.65 [95% confidence interval, CI: 1.08-2.52]) and without ACS (6.0% vs. 3.2%; incidence rate ratio: 1.88 [95% CI: 1.13-3.14]). The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without ACS CONCLUSION: Compared to the O-SES, the DTS was associated with a higher risk of TLF at 12 months in patients with and without ACS. The differences were mainly explained by higher rates of TLR.

Introduction: The sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin has shown reductions in major adverse cardiac events similar to glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, evidence is limited about how these therapies compare regarding overall healthcare resource utilization and costs in routine clinical care. Methods: We conducted a comparative cohort study based on linked prospective healthcare databases for the entire population of Denmark during 2015–2018. We included 13,747 new users of empagliflozin and 13,249 new users of GLP-1RAs. Propensity scores were applied to balance potential confounders across the two treatment groups through inverse probability treatment weighting (IPTW). We assessed directly referable costs per person-year associated with healthcare resource utilization (inpatient, emergency room, and outpatient clinic hospital care, primary care health services, and prescription medication costs at pharmacies) among drug initiators while on-treatment. Results: The two IPTW cohorts were well balanced at baseline (median age 61 years, 60% men, diabetes duration 6.7 years, 19% with pre-existing ischemic heart disease, 8% with pre-existing cerebrovascular disease), with similar healthcare costs in the previous year. During follow-up, average on-treatment costs per person-year were very similar among empagliflozin and GLP-1 RA initiators for the following services: inpatient hospitalizations (13,565 DKK versus 13,275 DKK), hospital outpatient clinic visits (12,007 DKK versus 12,152 DKK), emergency room visits (370 DKK versus 399 DKK), and primary care services (4108 DKK versus 4302 DKK). Total costs for any prescription drugs were clearly lower for empagliflozin initiators than for GLP-1 RA initiators (8946 DKK versus 14,029 DKK). In sum, overall healthcare costs on-treatment were lower for empagliflozin initiators (38,995 DKK per person-year) than for GLP-1RA initiators (44,157 DKK per person-year). Conclusions: In this nationwide population-based cohort study, average healthcare costs after drug initiation and while on treatment were lower for empagliflozin initiators than for GLP-1RAs initiators, driven by lower drug costs. Registration: The study protocol and analysis plan have been registered on the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) (http://www.encepp.eu/encepp/viewResource.htm?id=37726, first protocol registration 4 June 2019), and on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03993132, first posted 20 June 2019).

Kathrine Dyhr Lycke,1,2 Johnny Kahlert,3 Rikke Damgaard,1,2 Ole Mogensen,2,4 Anne Hammer1,2,4 1Department of Obstetrics and Gynecology, NIDO | Denmark, Gødstrup Hospital, Herning, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Kathrine Dyhr LyckeDepartment of Obstetrics and Gynecology, NIDO | Denmark, Gødstrup Hospital, Gl. Landevej 61, Herning, DK-7400, DenmarkEmail katlyc@clin.au.dkBackground: Hysterectomy (removal of the uterus) is a common surgical procedure in gynecology. Although minimally invasive surgical procedures have been introduced, hysterectomy is still associated with risk of short- and long-term complications. Given that hysterectomized women are no longer at risk of either hysterectomy or being diagnosed with endometrial or cervical cancer, it is important to describe trends in hysterectomy rates.Objective: To describe trends in hysterectomy incidence rates overall and stratified by age, indication, and procedure.Methods: Nationwide population-based cohort study using Danish national registries, 2000– 2015, was conducted. We calculated the overall hysterectomy-corrected and age-standardized incidence rates of hysterectomy among women ≥ 20 years old. Incidence rates were stratified by age group, indication, and surgical procedure. We performed trend analyses using Joinpoint regression, thereby estimating the average annual percentage change (AAPC).Results: A total of 98,484 women had a hysterectomy during the study period, corresponding to an overall age-standardized, hysterectomy-corrected hysterectomy incidence rate (SIR) of 351.1 per 100,000 person-years (95% CI 348.9;353.3). SIR of hysterectomy declined over time (AAPC − 1.4; 95% CI − 1.9;-1.0), which was driven by a decline in rates of benign hysterectomy (AAPC − 2.1; 95% CI − 2.7;-1.6). Irrespective of indication, rates of abdominal hysterectomy declined substantially during the study period and were surpassed by rates of minimally invasive procedures (ie, laparoscopy and robot-assisted laparoscopy) in 2013.Conclusion: Hysterectomy-corrected incidence rates of benign hysterectomy declined over time. Irrespective of indication, we observed a shift in surgical procedure over time, from abdominal hysterectomy to minimally invasive surgical procedures.Keywords: hysterectomy, incidence, surgical procedure, indication, epidemiology

OBJECTIVE We examined temporal trends in risk of first-time ischemic stroke in patients with incident type 2 diabetes mellitus (T2DM) and no prior atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS Using nationwide health registries, we identified all patients with incident T2DM without a prior hospital diagnosis of ASCVD from 1996 to 2015 in Denmark. Patients were assigned to 5-year periods based on the date of T2DM diagnosis and were followed for 5 years. Each patient was matched by sex and age with up to three individuals from the general population. Temporal trends in ischemic stroke were examined using Cox regression to compute hazard ratios (HRs). Temporal use of prophylactic cardiovascular medications was also assessed. RESULTS The study comprised 288,825 patients with incident T2DM and 782,232 general population individuals. From 1996–2000 to 2011–2015, the 5-year risk of first-time ischemic stroke was approximately halved in the T2DM cohort (5.2% vs. 2.7%; sex- and age-adjusted HR 0.52 [95% CI 0.49–0.55]). Patients diagnosed in 2011–2015 had increased risk of ischemic stroke compared with individuals in the general population; however, the risk difference narrowed over time (5.2% vs. 2.9% in 1996–1999 [difference 2.3%]; 2.7% vs. 2.0% in 2011–2015 [difference 0.7%]). Use of prophylactic cardiovascular medications increased markedly during the overall study period, especially use of statins (from 5% to 50%) and multiple antihypertensive drugs (from 18% to 33%). CONCLUSIONS From 1996 to 2015, the 5-year risk of first-time ischemic stroke was approximately halved in patients with incident T2DM and no prior ASCVD, coinciding with markedly increased use of prophylactic cardiovascular medications.

Cervical intraepithelial neoplasia grade 2 (CIN2) represents a spectrum of lesions with variable progression and regression. Pathological diagnosis of CIN2 is subjective and poorly reproducible. Accurate diagnosis and identification of different patterns of CIN2 related to outcome are essential to reduce the risks of overtreatment or undertreatment. It is important to explore novel methods for risk stratification of CIN2 to enable targeted treatment of women at high risk of progression or persistent disease and follow-up of women at low risk. The combination of the novel biomarker human papillomavirus (HPV) E4 with p16We will conduct a historical cohort study including 500 women aged 23-40 years with a first CIN2 diagnosis in Aarhus, Denmark during 2000-2010. Women will be eligible if they have undergone active surveillance and have no previous record of hysterectomy, cone biopsy, and CIN2 or worse. Women will be randomly selected through the Danish Pathology Databank. Tissue samples from women included will be sectioned for p16The study has been approved by the Ethical Committee in Central Denmark Region (1-10-72-60-20) and registered at the Faculty of Health, Aarhus University. Results will be published in a peer-reviewed journal and presented at scientific meetings.NCT05049252.

BACKGROUND: For patients with high bleeding risk, the BioFreedom stent is safer and more effective than a bare metal stent. However, at the one-year follow-up of the SORT OUT IX trial, the BioFreedom stent did not meet the criteria for non-inferiority for target lesion failure (TLF) when compared with the Orsiro stent and had a higher incidence of target lesion revascularisation (TLR).AIMS: The aim of the study was to compare the two-year outcomes following coronary implantation of the BioFreedom or the Orsiro stents in all-comer patients.METHODS: The Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) IX trial is a prospective, multicentre, randomised clinical trial comparing the BioFreedom and the Orsiro stents. The primary endpoint, TLF, was a composite of cardiac death, myocardial infarction (MI; not related to other lesions) and TLR.RESULTS: A total of 1,572 patients were randomised to treatment with the BioFreedom stent and 1,579 patients with the Orsiro stent. At two-year follow-up, TLF was 7.8% in the BioFreedom and 6.3% in the Orsiro stent groups (rate ratio [RR] 1.23, 95% confidence interval [CI]: 0.94-1.61). Risks of cardiac death, MI and definite stent thrombosis did not differ significantly between the groups, whereas more patients in the BioFreedom group had TLR (5.1% vs 2.6%; RR 1.98, 95% CI: 1.26-2.89) attributable to a higher risk of TLR within the first year (3.5% vs 1.3%; RR 2.77, 95% CI: 1.66-4.62).CONCLUSIONS: At two years, there were no significant differences between the BioFreedom and Orsiro stents for TLF. TLR was significantly higher with the BioFreedom stent due to higher risk of TLR within the first year.

Introduction The public–private ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data. Methods Event rates were calculated for the following outcomes: acute disseminated encephalomyelitis, Bell’s palsy, Guillain–Barré syndrome, immune thrombocytopenia purpura, Kawasaki disease, optic neuritis, narcolepsy, systemic lupus erythematosus, and transverse myelitis. Cases were identified by diagnosis codes. Participating organizations/databases originated from Denmark, Italy, Spain, and the UK. The source population comprised all persons registered, with at least 1 year of data prior to the study start, or follow-up from birth. Stratified incidence rates were computed per database over the period 2003 to 2014. Results Between 2003 and 2014, 148,947 incident cases of nine autoimmune diseases were identified. Crude incidence rates were highest for Bell’s palsy [23.8/100,000 person-years (PYs), 95% confidence interval (CI) 23.6–24.1] and lowest for Kawasaki disease (0.7/100,000 PYs, 95% CI 0.6–0.7). Specific patterns were observed by sex, age, calendar time, and data sources. Rates were comparable with published estimates. Conclusion A range of autoimmune events could be identified in the ADVANCE system. Estimation of rates indicated consistency across selected European healthcare databases, as well as consistency with US published data. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-020-01031-1.

OBJECTIVES: To compare the efficacy and safety of the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (SES) in patients with and without diabetes mellitus (DM) included in the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X study.BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with DM when compared to patients without DM. Thus, whether the results from the SORT OUT X study apply to patients with and without DM remains unknown.METHODS: In total 3146 patients were randomized to stent implantation with DTS (n = 1578; DM: n = 279) or SES (n = 1568; DM: n = 271). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year.RESULTS: At 1 year, the rate of TLF was increased in the DTS group compared to the SES group, both among patients with DM (9.3% vs. 4.8%; risk difference: 4.5%; incidence rate ratio: 1.99, 95% confidence interval [CI]: 1.02-3.90) and without DM (5.7% vs. 3.5%; incidence rate ratio: 1.67, 95% CI: 1.15-2.42). The differences were mainly explained by higher rates of TLR.CONCLUSION: Compared to the SES, the DTS was associated with an increased risk of TLF at 12 months in patients with and without DM. The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without DM.

This sub-study of the SORT OUT IX trial sought to compare clinical outcomes between patients with diabetes randomized to implantation of either the polymer-free biolimus A9-coated BioFreedom stent (BF-BES) or the ultra-thin strut, biodegradable polymer sirolimus-eluting Orsiro stent (O-SES). Patients with diabetes have an increased risk of target lesion failure (TLF) after percutaneous coronary intervention (PCI). The impact of different stent types in patients with diabetes is still discussed. A total of 607 of the 3151 patients (19.3%) enrolled in the SORT OUT IX study had diabetes. Randomization was stratified by patients with/without diabetes; 304 received BF-BES and 303 O-SES. The primary endpoint was TLF, which was a composite of cardiac death, myocardial infarction (not related to other than the index lesion) and target lesion revascularization (TLR) within 1 year. After 1 year, patients with diabetes had higher TLF (7.2% vs. 3.7%, incidence rate ratio [IRR]: 1.65; 95% confidence interval [CI]: 1.08–2.50), than patients without diabetes. TLF did not differ significantly between BF-BES and O-SES in patients with diabetes (8.2% vs. 6.3%, IRR: 1.17; 95% CI: 0.63–2.20). In patients with diabetes, cardiac death occurred in 2.3% of BF-BES and in 3.6% of O-SES (IRR: 0.58; 95% CI: 0.23–1.45) and TLR occurred in 5.3% and 2.3% of BF-BES and O-SES, respectively (IRR: 2.12; 95% CI: 0.81–5.56). Definite stent thrombosis rates of 1.3% were found in both stent types. Patients with diabetes had higher 1-year TLF rate after PCI compared to patients without diabetes, whereas TLF did not differ significantly between the two stent types BF-BES and O-SES in patients with diabetes.

Objectives The aim of this study was to compare the thin-strut biodegradable-polymer everolimus-eluting platinum-chromium stent (EES) with the biodegradable-polymer biolimus-eluting stainless-steel stent (BES). Background Currently available drug-eluting coronary stents have been refined to reduce the risk for coronary events following implantation. Methods This randomized, multicenter, all-comers, noninferiority trial was undertaken at 3 sites in western Denmark. Patients with clinical indications for percutaneous coronary intervention were eligible for inclusion. Patients were randomly assigned (1:1) to either EES or BES. The primary endpoint, target lesion failure, was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a nontarget lesion) and efficacy (target lesion revascularization) at 12 months, analyzed using intention-to-treat principles. The trial was powered to assess target lesion failure noninferiority of the EES compared with the BES with a predetermined noninferiority margin of 3%. Results A total of 1,385 patients were assigned to treatment with EES and 1,369 patients to treatment with BES. The analysis showed that 55 patients (4.0%) assigned to the EES and 60 (4.4%) assigned to the BES met the primary endpoint (absolute risk difference 0.4%; upper limit of 1-sided 95% confidence interval: 1.7%; p Conclusions At 1-year follow-up, the EES was found to be noninferior to the BES with respect to target lesion failure. (Everolimus-eluting SYNERGY Stent Versus Biolimus-Eluting Biomatrix NeoFlex Stent—SORT-OUT VIII; NCT02093845)

Background: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody–coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. Methods: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. Results: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26–2.41]; P =0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37–3.61]; P =0.0012). Conclusions: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03216733.

Background In cardiovascular outcome trials, the sodium glucose cotransporter 2 inhibitor empagliflozin and glucagon‐like peptide‐1 (GLP‐1) receptor agonist liraglutide caused similar reductions in major adverse cardiac events (MACE). We compared clinical outcomes in routine clinical care. Methods and Results EMPLACE (Cardiovascular and Renal Outcomes, and Mortality in Danish Patients with Type 2 Diabetes Who Initiate Empagliflozin Versus GLP‐1RA: A Danish Nationwide Comparative Effectiveness Study) is an ongoing nationwide population‐based comparative effectiveness cohort study in Denmark. For the present study, we included 14 498 new users of empagliflozin and 12 706 new users of liraglutide, 2015 to 2018. Co‐primary outcomes were expanded major adverse cardiac events (stroke, myocardial infarction, unstable angina, coronary revascularization, hospitalization for heart failure [HHF], or all‐cause death); HHF or all‐cause death; and first HHF or first initiation of loop‐diuretic therapy. Secondary outcomes included all‐cause hospitalization or death. We applied propensity score balancing and Cox regression to compute adjusted hazard ratios (aHRs) in on‐treatment (OT) and intention‐to‐treat (ITT) analyses. Cohorts were well balanced at baseline (median age 61 years, 59% men, diabetes mellitus duration 6.6 years, 30% with preexisting cardiovascular disease). During mean follow‐up of 1.1 years in OT and 1.5 years in ITT analyses, empagliflozin versus liraglutide was associated with a similar rate of expanded major adverse cardiac events (OT aHR, 1.02; 95% CI, 0.91–1.14; ITT aHR, 1.06; 95% CI, 0.96–1.17), and HHF or all‐cause death (OT aHR, 0.97; 95% CI, 0.85–1.11; ITT aHR, 1.02; 95% CI, 0.91–1.14); and a decreased rate of a first incident HHF or loop‐diuretic initiation (OT aHR, 0.80; 95% CI, 0.68–0.94; ITT aHR, 0.87; 95% CI, 0.76–1.00), and of all‐cause hospitalization or death (OT aHR, 0.93; 95% CI, 0.89–0.98; ITT aHR, 0.93; 95% CI, 0.90–0.97). Conclusions Empagliflozin and liraglutide initiators had comparable rates of expanded major adverse cardiac events, and HHF or all‐cause death, whereas empagliflozin initiators had a lower rate of a first HHF or loop‐diuretic initiation.

Purpose: We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice. Methods: This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011–2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOI – hepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation-related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta-analysis; results from the US were reported separately. Results: There were 456 patients in the crizotinib cohort and 2957 patients in the erlotinib cohort. Rates of the SOI per 1000 person-years in the crizotinib cohort ranged from 0 to 65 in the EU and from 0 to 374 in the US. Rates of the SOI per 1000 person-years in the erlotinib cohort ranged from 0 to 91 in the EU and from 3 to 394 in the US. In the crizotinib cohort, 2-year OS was ~50% in both EU and US. In the erlotinib cohort, 2-year OS was 21% in the EU and 35% in the US. Conclusions: This study describes clinical outcomes among lung cancer patients initiating crizotinib or erlotinib in routine clinical practice. Differences between SOI rates in EU and US may be partially attributable to differences in the underlying databases.

Objectives: Severe depression is associated with an increased risk of developing dementia, however, whether treatment with electroconvulsive therapy (ECT) modify this risk remains unknown. Methods: In this matched cohort study, 1089 consecutive in-patients with affective disorders, receiving ECT during the period 1982 to 2000, were matched with 3011 in-patients with affective disorders not treated with ECT (non-ECT), and 108,867 individuals randomly selected from the background population. The comparison cohorts were matched on sex, age, and the non-ECT cohort was further matched according to diagnoses and admission period and hospital. Dementia diagnoses were retrieved from the national patient health registry. Analyses were adjusted for disease severity, somatic, and psychiatric comorbidities. Results: The cumulative incidence of dementia was 13.45% (10.75-16.46%) in the ECT cohort after 34 years of follow-up, 10.53% (8.5-12.81%) in the non-ECT cohort, and 8.43% (8.17-8.7%) in the background cohort. Using the ECT cohort as reference and age as the underlying time scale, the adjusted hazard ratio of developing dementia was 0.73 (0.52-1.04) in the non-ECT cohort and 0.61 (0.49-0.76) in the background cohort. The stratified analysis based on age at index (80 years) found no age-related difference in the risk of developing dementia between the ECT cohort and non-ECT cohort. Conclusions: The ECT treatment of affective disorders was not associated with an increased long-term risk of developing dementia compared with in-patients with affective disorders not treated with ECT.

Corpus uteri cancer is the most common gynecological malignancy in most developed countries. The disease is typically diagnosed at an early stage, is of endometrioid histologic subtype, and has a fairly good prognosis. Here, we describe hysterectomy-corrected mortality rates of corpus uteri cancer, overall and stratified by age, stage, and histologic subtype. Using data from nationwide Danish registries, we calculated uncorrected and hysterectomy-corrected age-standardized mortality rates of corpus uteri cancer among women ≥ 35 years during 2002-2015. Individual-level hysterectomy status was obtained from national registries; hysterectomy-corrected mortality rates were calculated by subtracting post-hysterectomy person-years from the denominator, unless hysterectomy was performed due to corpus uteri cancer. Correction for hysterectomy resulted in a 25.5% higher mortality rate (12.3/100,000 person-years vs. 9.8/100,000 person-years). Mortality rates were highest in women aged 70+, irrespective of year of death, histologic subtype, and stage. A significant decline was observed in overall hysterectomy-corrected mortality rates during 2002-2015, particularly among women aged 70+. Mortality rates of endometrioid cancer declined significantly over time (annual percent change (APC): -2.32, 95% CI -3.9, -0.7, p=0.01), whereas rates of non-endometrioid cancer increased (APC: 5.90, 95% CI: 3.0, 8.9, p

In the past the European otter Lutra lutra was distributed throughout most of Europe but since the 1980s its distributional range has been reduced. Currently, the otter population is increasing. Conservation efforts have been implemented, however due to the natural elusiveness of the species it is difficult to monitor. Non-invasive sampling has proven to be the most effective method to derive population parameters such as presence/absence, genetic variability and population structure in European otters. The method to collect non-invasive samples is robust and provides reliable data. This study investigates the validity of the present state-of-The-Art method of identifying otter feces, and suggests modifications and improvements of the method. Results from the comparison of field collected data and data derived from a blind test show that the method is applicable in areas abundant with otters, however the method loses its power in the periphery of the distributional range. In these areas, it would be relevant to supplement traditional sampling with DNA analysis to verify the identification of the sample.

OBJECTIVE Statins may reduce the risk of diabetic polyneuropathy (DPN) as a result of lipid-lowering and anti-inflammatory effects, but statins have also been associated with neurotoxicity. We examined whether statin therapy affects the risk of DPN. RESEARCH DESIGN AND METHODS We identified all Danish patients with incident type 2 diabetes during 2002–2016. New users initiated statins between 180 days before and 180 days after their first diabetes record, while prevalent users had initiated statins before that period. Patients were followed for incident DPN using validated hospital diagnosis codes, starting 180 days after their first diabetes record. Cox proportional hazard analysis was used to compute adjusted hazard ratios (aHRs) for DPN. RESULTS The study cohort comprised 59,255 (23%) new users, 75,528 (29%) prevalent users, and 124,842 (48%) nonusers; median follow-up time was 6.2 years (interquartile range 3.4–9.6). The incidence rate of DPN events per 1,000 person-years was similar in new users (4.0 [95% CI 3.8–4.2]), prevalent users (3.8 [3.6–3.9]), and nonusers (3.8 [3.7–4.0]). The aHR for DPN was 1.05 (0.98–1.11) in new users and 0.97 (0.91–1.04) in prevalent users compared with statin nonusers. New users had a slightly increased DPN risk during the first year (1.31 [1.12–1.53]), which vanished after >2 years of follow-up. Findings were similar in on-treatment and propensity score–matched analyses and with additional adjustment for pretreatment blood lipid levels. CONCLUSIONS Statin therapy is unlikely to increase or mitigate DPN risk in patients with type 2 diabetes, although a small acute risk of harm cannot be excluded.

Introduction The public-private ADVANCE consortium (Accelerated development of vaccine benefit-risk collaboration in Europe) aimed to assess if electronic healthcare databases can provide fit-for purpose data for collaborative, distributed studies and monitoring of vaccine coverage, benefits and risks of vaccines. Objective To evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. Methods Characterisation was conducted using open-source Java-based (Jerboa) software and R scripts. We obtained: (i) The general characteristics of the database and data source (meta-data) and (ii) a detailed description of the database population (size, representatively of age/sex of national population, rounding of birth dates, delay between birth and database entry), vaccinations (number of vaccine doses, recording of doses, pattern of doses by age and coverage) and events of interest (diagnosis codes, incidence rates). A total of nine databases (primary care, regional/national record linkage) provided data on events (pertussis, pneumonia, death, fever, convulsions, injection site reactions, hypotonic hypo-responsive episode, persistent crying) and vaccines (acellular pertussis and whole cell pertussis) related to the pertussis proof of concept studies. Results The databases contained data for a total population of 44 million individuals. Seven databases had recorded doses of vaccines. The pertussis coverage estimates were similar to those reported by the World Health Organisation (WHO). Incidence rates of events were comparable in magnitude and age-distribution between databases with the same characteristics. Several conditions (persistent crying and somnolence) were not captured by the databases for which outcomes were restricted to hospital discharge diagnoses. Conclusion The database characterisation programs and workflows allowed for an efficient, transparent and standardised description and verification of electronic healthcare databases which may participate in pertussis vaccine coverage, benefit and risk studies. This approach is ready to be used for other vaccines/events to create readiness for participation in other vaccine related studies.

Background: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. Methods: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021. Results: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; P noni nferiority =0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66–4.62]; P Conclusions: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02623140.

AIMS: The aim of the study was to evaluate the incidence and causes of rehospitalisation within one year after percutaneous coronary intervention (PCI) in a country where the National Health Service provides universal tax-supported healthcare, guaranteeing residents free hospital access.METHODS AND RESULTS: Between January 2010 and September 2014, 17,111 patients were treated with PCI in two University Hospitals in Western Denmark. Patients who were readmitted within one year after PCI were identified. The overall one-year readmission rate was 50.4%. The cause was angina/myocardial infarction (MI) in 4,282 patients (49.7%), and other reasons in 4,334 (50.3%). Predictors of angina/MI-related readmissions were female gender (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.07-1.25), diabetes (OR 1.14, 95% CI: 1.04-1.26), age (per 10-year increase) (OR 0.86, 95% CI: 0.83-0.88), and indication for index PCI (stable angina pectoris as reference): ST-segment elevation myocardial infarction (OR 1.34, 95% CI: 1.23-1.47) and non-ST-segment elevation myocardial infarction (OR 1.18, 95% CI: 1.08-1.29). Predictors for other readmissions were female gender (OR 1.09, 95% CI: 1.01-1.18), diabetes (OR 1.29, 95% CI: 1.18-1.42), age (OR 1.30, 95% CI: 1.26-1.34) and Charlson comorbidity index ≥3 (OR 3.03, 95% CI: 2.71-3.27).CONCLUSIONS: In an unselected patient cohort treated with PCI, half of the patients were rehospitalised within one year, highlighting the impact of comorbidity in patients with ischaemic heart disease.

Introduction The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing healthcare databases in Europe. The objective of this paper was to assess the feasibility of using electronic healthcare databases to estimate dose-specific acellular pertussis (aP) and whole cell pertussis (wP) vaccine coverage. Methods Seven electronic healthcare databases in four European countries (Denmark (n = 2), UK (n = 2), Spain (n = 2) and Italy (n = 1)) participated in this study. Children were included from birth and followed up to age six years. Vaccination exposure was obtained from the databases and classified by type (aP or wP), and dose 1, 2 or 3. Coverage was estimated using period prevalence. For the 2006 birth cohort, two estimation methods for pertussis vaccine coverage, period prevalence and cumulative incidence were compared for each database. Results The majority of the 2,575,576 children included had been vaccinated at the country-specific recommended ages. Overall, the estimated dose 3 coverage was 88–97% in Denmark (birth cohorts from 2003 to 2014), 96–100% in the UK (2003–2014), 95–98% in Spain (2004–2014) and 94% in Italy (2006–2007). The estimated dose 3 coverage per birth cohort in Denmark and the UK differed by 1–6% compared with national estimates, with our estimates mostly higher. The estimated dose 3 coverage in Spain differed by 0–2% with no consistent over- or underestimation. In Italy, the estimates were 3% lower compared with the national estimates. Except for Italy, for which the two coverage estimation methods generated the same results, the estimated cumulative incidence coverages were consistently 1–10% lower than period prevalence estimates. Conclusion This study showed that it was possible to provide consistent estimates of pertussis immunisation coverage from the electronic healthcare databases included, and that the estimates were comparable with the national estimates.

Introduction/Background Corpus uteri cancer is the most common gynaecological malignancy in Denmark. Whereas the incidence of less aggressive histologic subtypes (i.e. endometrioid cancer) has been stable since 2000, the incidence of more aggressive subtypes (i.e. non-endometrioid cancer) has been reported to increase in Denmark. It is important to assess whether this trend may be reflected in an increased mortality rate. Here, we aimed to describe hysterectomy-corrected mortality rates of corpus uteri cancer, overall and stratified by age and histologic subtype. Methodology Using data from nationwide registries, we calculated uncorrected and hysterectomy-corrected age-standardized mortality rates of corpus uteri cancer among women aged 35 years and older during 2002–2015. Individual-level hysterectomy status was obtained from the Danish National Patient Registry; hysterectomy-corrected mortality rates were calculated by subtracting post-hysterectomy person-years from the denominator, unless hysterectomy was performed due to corpus uteri cancer. Results During 2002–2015, the age-standardized hysterectomy-corrected mortality rate of corpus uteri cancer was 25.5% higher than the corresponding uncorrected rate (12.3/100,000 vs. 9.8/100,000 person-years). Hysterectomy-corrected rates increased with age, reaching 43.2/100,000 person-years in women aged 70 years and older. Among all women, rates decreased from 2002 (14.0/100,000 person-years) until 2009 after which they stabilized at about 11.5/100,000 person-years, This decrease was mainly due to a decline in women aged 70 years and older. Of note, the hysterectomy-corrected mortality rate of endometrioid cancer declined slightly during the study period, from 5.8/100,000 to 4.2/100,000 person-years, whereas the mortality rate of non-endometrioid cancer increased, from 1.4/100,000 to 3.7/100,000 person-years. Conclusion Among all women, the mortality rate declined over calendar time and increased with age. While the mortality of less aggressive histologic subtypes declined, although incidence rates were stable in this time period, the mortality of more aggressive histologic subtypes paralleled the incline in the incidence of these subtypes. Disclosure The Danish Cancer Society funded this study. All authors have nothing to disclose.

Diabetes mellitus is associated with a higher risk of target lesion revascularization after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus, treated with everolimus-eluting stents (EES; Synergy; Boston Scientific, Marlborough, Massachusetts) or biolimus-eluting stents (BES; BioMatrix NeoFlex; Biosensors Interventional Technologies Pte Ltd., Singapore). In total, 2,764 patients were randomized to stent implantation with EES (n = 1,385, diabetes: n = 250) or the BES (n = 1,379, diabetes: n = 262), stratified by gender and diabetes. The primary end point, target lesion failure (TLF), was a composite of cardiac death, target-lesion myocardial infarction, or target lesion revascularization at 12 months. Secondary end points included individual components of TLF, all-cause death, and stent thrombosis. TLF was 2.1% lower in the EES versus the BES groups in patients with diabetes (3.6% vs 5.7%; rate ratios 0.61, 95% confidence interval [CI] 0.27 to 1.41) and similar in patients without diabetes (4.1% vs 4.0%; rate ratios 0.99, 95% CI 0.66 to 1.51). In patients with diabetes, the point estimates of the individual components of TLF also favored the EES but CIs were wide. No interaction between stent type and presence of diabetes was found. The current subgroup analysis found that a thin-strut EES as compared with a thicker strut BES had a numerically lower TLF rate in patients with diabetes, but the subgroup analysis was underpowered for definite conclusions.

BACKGROUND: In patients with increased bleeding risk during dual antiplatelet therapy, the biolimus A9-coated BioFreedom, a stainless steel drug-coated stent devoid of polymer, has shown superiority compared to a bare-metal stent. The aim of this study was to investigate whether the polymer-free biolimus A9-coated BioFreedom is noninferior to a modern thin-strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention.METHODS: The multicenter SORT OUT IX trial (NCT02623140) randomly assigned all-comers patients to treatment with the BioFreedom drug-coated stent or the biodegradable polymer Orsiro stent in 4 Danish University Hospitals. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection based on Danish registries will be used and continue through 5 years. Assuming an event rate of 4.2% in each stent group, 1,563 patients in each treatment arm will provide 90% power to detect noninferiority of the drug-coated BioFreedom stent with a noninferiority margin of 2.1%.RESULTS: A total of 3,150 patients have been randomized and enrolled in the study.CONCLUSIONS: The SORT OUT IX trial will determine whether the drug-coated BioFreedom stent is noninferior to a modern biodegradable polymer Orsiro stent.

OBJECTIVES: In this substudy of the SORT OUT VII trial, the clinical outcomes among patient with diabetes mellitus treated with Orsiro sirolimus-eluting stent (O-SES; Biotronik, Bülach, Switzerland) or Nobori biolimus-eluting stent (N-BES; Terumo, Tokyo, Japan) were compared.BACKGROUND: Diabetes is associated with increased risk of target lesion failure (TLF) after percutaneous coronary intervention.METHODS: In total, 2525 patients were randomized to stent implantation with O-SES (n = 1261, diabetes: n = 236) or N-BES (n = 1264, diabetes: n = 235). The primary endpoint, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 2 years.RESULTS: At 2 year, TLF did not differ between O-SES vs N-BES in diabetic (9.3% vs 9.4%; RR 0.98, 95% CI 0.54-1.78) patients. The individual components of the primary endpoint did not differ among stent type. In diabetics, cardiac death occurred in 3% of O-SES-treated and in 3.8% of N-BES-treated patients (RR 0.77, 95% CI 0.29-2.08), MI occurred in 3.0% of O-SES-treated and in 3.8% of N-BES-treated patients (RR 0.76, 95% CI 0.28-2.06) and TLR occurred in 5,5% of O-SES-treated and in 6.0% of N-BES-treated patients (RR 0.91, 95% CI 0.43-1.95).CONCLUSION: TLF did not differ between O-SES- and N-BES-treated diabetic patients.

Introduction Hysterectomy is a common gynecological procedure; however, the incidence of total and subtotal hysterectomy varies across countries, by age, and over time. As only women with an intact cervix are at risk of cervical cancer, failing to remove hysterectomized women from the denominator may underestimate the cervical cancer incidence. We aimed to describe the temporal and age-dependent patterns of cervical cancer incidence in Denmark before and after correction for hysterectomy. Material and methods Using data from national registries we calculated uncorrected and hysterectomy-corrected cervical cancer incidence rates among women ≥20 years during 2000-11. Hysterectomy-corrected rates were calculated by subtracting post-hysterectomy person-years from the denominator. Results The overall uncorrected cervical cancer incidence rate was 17.8/100 000 person-years (95% CI 17.3-18.3). After correction for hysterectomy, the rate increased by 8.4% to 19.3/100 000 person-years (95% CI 18.8-19.9). The highest uncorrected incidence was seen in women aged 35-39 years, peaking at 24.4/100 000 person-years, whereas the highest hysterectomy-corrected cervical cancer incidence rate was observed in women aged 75-79 years (29.4/100 000 person-years). Over time, women ≥60 years had the highest hysterectomy-corrected cervical cancer incidence. Conclusions Correcting for hysterectomy incidence resulted in a higher cervical cancer incidence and a shift in the peak incidence from age 35-39 years to age 75-79 years. Over time, women ≥60 years were at the highest risk of cervical cancer. Given the high incidence in women >60-65 years, when women are eligible to exit screening, a revision of the screening guidelines may be warranted.

Aims We examined risk of developing acute renal failure and the associated mortality among patients aged > 65 years undergoing surgery for a fracture of the hip. Patients and Methods We used medical databases to identify patients who underwent surgical treatment for a fracture of the hip in Northern Denmark between 2005 and 2011. Acute renal failure was classified as stage 1, 2 and 3 according to the Kidney Disease Improving Global Outcome criteria. We computed the risk of developing acute renal failure within five days after surgery with death as a competing risk, and the short-term (six to 30 days post-operatively) and long-term mortality (31 days to 365 days post-operatively). We calculated adjusted hazard ratios (HRs) for death with 95% confidence intervals (CIs). Results Among 13 529 patients who sustained a fracture of the hip, 1717 (12.7%) developed acute renal failure post-operatively, including 1218 (9.0%) with stage 1, 364 (2.7%) with stage 2, and 135 (1.0%) with stage 3 renal failure. The short-term mortality was 15.9% and 5.6% for patients with and without acute renal failure, respectively (HR 2.8, 95% CI 2.4 to 3.2). The long-term mortality was 25.0% and 18.3% for those with and without acute renal failure, respectively (HR 1.3, 95% CI 1.2 to 1.5). The mortality was higher in patients with an increased severity of renal failure. Conclusion Acute renal failure is a common complication of surgery in elderly patients who sustain a fracture of the hip, and is associated with increased mortality up to one year after surgery despite adjustment for coexisting comorbidity and medication before surgery. Cite this article: Bone Joint J 2016;98-B:1112–18.

The aim of this study was to compare the thin-strut biodegradable-polymer everolimus-eluting platinum-chromium stent (EES) with the biodegradable-polymer biolimus-eluting stainless-steel stent (BES).Currently available drug-eluting coronary stents have been refined to reduce the risk for coronary events following implantation.This randomized, multicenter, all-comers, noninferiority trial was undertaken at 3 sites in western Denmark. Patients with clinical indications for percutaneous coronary intervention were eligible for inclusion. Patients were randomly assigned (1:1) to either EES or BES. The primary endpoint, target lesion failure, was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a nontarget lesion) and efficacy (target lesion revascularization) at 12 months, analyzed using intention-to-treat principles. The trial was powered to assess target lesion failure noninferiority of the EES compared with the BES with a predetermined noninferiority margin of 3%.A total of 1,385 patients were assigned to treatment with EES and 1,369 patients to treatment with BES. The analysis showed that 55 patients (4.0%) assigned to the EES and 60 (4.4%) assigned to the BES met the primary endpoint (absolute risk difference 0.4%; upper limit of 1-sided 95% confidence interval: 1.7%; p 0.001).At 1-year follow-up, the EES was found to be noninferior to the BES with respect to target lesion failure. (Everolimus-eluting SYNERGY Stent Versus Biolimus-Eluting Biomatrix NeoFlex Stent-SORT-OUT VIII; NCT02093845).

Introduction We aimed to describe the cervical cancer mortality rates after correcting for hysterectomy and to evaluate trends over calendar time and by age. Material and methods Using data from nationwide registries, we calculated uncorrected and hysterectomy-corrected cervical cancer mortality rates among women age ≥20 years in Denmark during 2002-2015. We calculated hysterectomy-corrected rates by subtracting post-hysterectomy person-years from the denominator, unless hysterectomy was performed due to cervical cancer. Results The age-standardized hysterectomy-corrected cervical cancer mortality rate of 5.8/100 000 was 18.4% higher than the corresponding uncorrected rate. The hysterectomy-corrected cervical cancer mortality rate increased significantly with age, particularly in women aged 65+ (annual percent change +4.57), peaking at 26.1/100 000 person-years in women aged ≥85. The hysterectomy-corrected cervical cancer mortality declined significantly over calendar time, from 6.3/100 000 person-years in 2002 to 4.5/100 000 person-years in 2015 (annual percent change -0.22). This was mainly due to a significant decline in women aged 60 years and older, from 20.4/100 000 person-years in 2003 to 9.3/100 000 person-years in 2015 (annual percent change -0.75). Conclusions The mortality of cervical cancer increased significantly by age, particularly among women aged 65 years and older for whom routine cervical cancer screening is not recommended. Understanding reasons for the high mortality rate in older women is critical, as this may help identify interventions needed to ensure a continued decline in cervical cancer mortality in older Danish women.

Harvest records are often assumed to offer an indirect measure of population abundance in huntable species. However, this requires population density changes are reflected in comparable linear changes in harvest rates. We tested this assumption for common snipe Gallinago gallinago, common wood pigeon Columba palumbus, coot Fulica atra, grey partridge Perdix perdix, roe deer Capreolus capreolus and brown hare Lepus europaeus in Denmark. If we consider hunting a form of predator-prey interaction, the annual kill can be viewed as a predator functional response to prey population size. Convergence of the annual kill to a type I functional response with similar auto-correlative structures in the harvest and count data would support the hypothesis that fluctuations in harvest and population abundance occurred with similar periodicity. The annual kill of common snipe showed the best fit to a type I functional response to the point count indices, with similar auto-correlative structures in the two variables. Other species showed different functional responses, the result of hunter behaviour, such as voluntary hunting restraint on species of concern and saturation effects from rapidly expanding abundant species. Relationships between the annual kill and population abundance were complex and incorporation of hunting legislation changes improved optimal model fits between harvest statistics and count data. Consideration of the validity of the underlying assumptions is necessary before harvest records are used as an index for population size. It is essential that detectability/accessibility of a species does not change systematically over time. Such bias may derive from habitat shifts, difference in timing of counts and hunting harvest, changes in migration patterns and annual reproduction and mortality. We recommend the continued collation of hunting harvest statistics, supported by sociological studies, to provide insight into the mechanisms that affect the hunting effort, to understand relationships between harvest statistics and population abundance.

BACKGROUND/OBJECTIVE: Prenatal exposure to antibacterials may permanently dysregulate fetal metabolic patterns via epigenetic pathways or by altering maternal microbiota. We examined the association of prenatal exposure to systemic antibacterials with overweight and obesity in schoolchildren.SUBJECTS/METHODS: We conducted a prevalence study among Danish schoolchildren aged 7 to 16 years using data from routine school anthropometric evaluations conducted during 2002-2013. Prenatal exposure to antibacterials was ascertained by using maternal prescription dispensations and infection-related hospital admissions during pregnancy. We defined overweight and obesity among the children using standard age- and sex-specific cut-offs. We computed sex-specific adjusted prevalence ratios (aPR) of overweight and obesity associated with exposure to prenatal antibacterials, adjusting for maternal age at delivery, marital status, smoking in pregnancy, and multiple gestation; we also stratified the analyses by birth weight.RESULTS: Among 9 886 schoolchildren, 3 280 (33%) had prenatal exposure to antibacterials. Adjusted PRs associated with the exposure were 1.26 (95% confidence interval [CI]: 1.10-1.45) for overweight and 1.29 (95% CI: 1.03-1.62) for obesity. Among girls, aPRs were 1.16 (95% CI: 0.95-1.42) for overweight, and 1.27 (95% CI: 0.89 to 1.82) for obesity. Among boys, aPRs were 1.37 (95% CI: 1.13-1.66) for overweight, and 1.29 (95% CI: 0.96-1.73) for obesity. The aPR for overweight was higher among schoolchildren with birth weight CONCLUSIONS: Prenatal exposure to systemic antibacterials is associated with an increased risk of overweight and obesity at school age, and this association varies by birth weight.International Journal of Obesity accepted article preview online, 16 July 2015. doi:10.1038/ijo.2015.129.

AIMS: The SORT OUT VII trial compared the thin-strut cobalt-chromium sirolimus-eluting Orsiro stent with a slow polymer degradation and the thicker-strut stainless steel biolimus-eluting Nobori stent with a moderate-term polymer degradation in an all-comer patient population.METHODS AND RESULTS: The 2-year pre-specified endpoint target lesion failure did not differ significantly between the sirolimus-eluting stent: 6.7% and the biolimus-eluting stent: 7.0% (rate ratio (RR) 0.94, 95% confidence interval (CI) 0.70-1.28). Definite stent thrombosis were numerically lower in the sirolimus-eluting stent group (0.8%) compared to the biolimus-eluting stent group (1.4%) (RR 0.56, 95% CI 0.26-1.21), which largely was attributable to a lower risk of definite stent thrombosis within 1 year: 0.4% versus 1.2% (RR 0.33, 95% CI 0.12-0.92), whereas risk of very late definite stent thrombosis was similar in the two groups (0.4% versus 0.2%, RR 1.68, 95% CI 0.40-7.03).CONCLUSIONS: In an all-comer patient population, 2-year target lesions failure was similar for the sirolimus-eluting Orsiro stent and the biolimus-eluting Nobori stent.

Uffe Heide-Jørgensen, Kasper Adelborg, Johnny Kahlert, Henrik Toft Sørensen, Lars Pedersen Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background: For a patient cohort, access to linkable population-based registries permits sampling of a comparison cohort from the general population, thereby contributing to the understanding of the disease in a population context. However, sampling without replacement in random order can lead to immortal time bias by conditioning on the future.Aim: We compared the following strategies for sampling comparison cohorts in matched cohort studies with respect to time to ischemic stroke and mortality: sampling without replacement in random order; sampling with replacement; and sampling without replacement in chronological order.Methods: We constructed index cohorts of individuals from the Danish general population with no particular trait, except being alive and without ischemic stroke on the index date. We also constructed index cohorts of persons aged >50 years from the general population. We then applied the sampling strategies to sample comparison cohorts (5:1 or 1:1) from the Danish general population and compared outcome risks between the index and comparison cohorts. Finally, we sampled comparison cohorts for a heart failure cohort using each strategy.Results: We observed increased outcome risks in comparison cohorts sampled 5:1 without replacement in random order compared to the index cohorts. However, these increases were minuscule unless index persons were aged >50 years. In this setting, sampling without replacement in chronological order failed to sample a sufficient number of comparators, and the mortality risks in these comparison cohorts were lower than in the index cohorts. Sampling 1:1 showed no systematic difference between comparison and index cohorts. When we sampled comparison cohorts for the heart failure patients, we observed a pattern similar to when index persons were aged >50 years.Conclusion: When index persons were aged >50 years, ie, had high outcome risks, sampling 5:1 without replacement introduced bias. Sampling with replacement or 1:1 did not introduce bias. Keywords: matched cohort study, survival analysis, population-based registry, observational study

OBJECTIVE To investigate whether the use of incretin-based drugs (GLP-1 receptor agonists and dipeptidyl peptidase 4 [DPP4] inhibitors) is associated with acute pancreatitis. RESEARCH DESIGN AND METHODS The study was a nationwide population-based case-control study using medical databases in Denmark. Participants were 12,868 patients with a first-time hospitalization for acute pancreatitis between 2005 and 2012 and a population of 128,680 matched control subjects. The main outcome measure was the odds ratio (OR) for acute pancreatitis associated with different antihyperglycemic drugs. We adjusted for history of gallstones, alcoholism, obesity, and other pancreatitis-associated comorbidities and medications. RESULTS A total of 89 pancreatitis patients (0.69%) and 684 control subjects (0.53%) were ever users of incretins. The crude OR for acute pancreatitis among incretin users was 1.36 (95% CI 1.08–1.69), while it was 1.44 (95% CI 1.34–1.54) among users of other antihyperglycemic drugs. After confounder adjustment, the risk of acute pancreatitis was not increased among incretin users (OR 0.95 [95% CI 0.75–1.21]), including DPP4 inhibitor users (OR 1.04 [95% CI 0.80–1.37]) or GLP-1 receptor agonist users (OR 0.82 [95% CI 0.54–1.23]), or among nonincretin antihyperglycemic drug users (OR 1.05 [95% CI 0.98–1.13]), compared with nonusers of any antihyperglycemic drugs. Findings were similar in current versus ever drug users and in patients with pancreatitis risk factors. The adjusted OR comparing incretin-based therapy with other antihyperglycemic therapy internally while also adjusting for diabetes duration and complications was 0.97 (95% CI 0.76–1.23). CONCLUSIONS Our findings suggest that the use of incretin-based drugs appears not to be associated with an increased risk of acute pancreatitis.

BACKGROUND: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new clinically diagnosed type 2 diabetes.METHODS: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes.RESULTS: Among 5813 patients diagnosed with incident type 2 diabetes in the community clinical setting, 0.4% had rare subtypes of diabetes, 2.8% had LADA, 0.7% had secondary diabetes, 2.4% had glucocorticoid-associated diabetes, and 93.7% had WHO-defined type 2 diabetes. In the latter group, 9.7% had insulinopenic, 63.1% had classical, and 27.2% had hyperinsulinemic type 2 diabetes. Classical patients were obese (median waist 105 cm), and 20.5% had cardiovascular disease (CVD) at diagnosis, while insulinopenic patients were fairly lean (waist 92 cm) and 17.5% had CVD (P = 0.14 vs classical diabetes). Hyperinsulinemic patients were severely obese (waist 112 cm), and 25.5% had CVD (P < 0.0001 vs classical diabetes).CONCLUSIONS: Patients clinically diagnosed with type 2 diabetes are a heterogeneous group. In the future, targeted treatment based on pathophysiological characteristics rather than the current "one size fits all" approach may improve patient prognosis.

Johnny Kahlert,1 Sigrid Bjerge Gribsholt,1,2 Henrik Gammelager,1,3 Olaf M Dekkers,1,4,5 George Luta1,6 1Department of Clinical Epidemiology, Institute of Clinical Medicine, 2Department of Endocrinology and Internal Medicine, 3Department of Anaesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Epidemiology, 5Department of Medicine, Section Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; 6Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA Abstract: In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residual confounding and suffer from the difficulty of identifying true confounders. Even in large health care databases, insufficient or poor data may contribute to these challenges. The trend in data collection is to compile more fine-grained data on lifestyle and severity of diseases, based on self-reporting and modern technologies. This will surely improve our ability to incorporate relevant confounders or their proxies. However, despite a remarkable development of methods that account for confounding and new data opportunities, confounding will remain a serious issue. Considering the advantages and disadvantages of different methods, we emphasize the importance of the clinical input and of the interplay between clinicians and analysts to ensure a proper analysis. Keywords: observational studies, confounding, adjustment, stratification, multivariable analysis, propensity score

Kasper Adelborg,1 Lotte Brix Christensen,1 Troels Munch,1 Johnny Kahlert,1 Ylva Trolle Lagerros,2,3 Grethe S Tell,4 Ellen M Apalset,4,5 Fei Xue,6 Vera Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark; 2Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, 3Department of Medicine, Clinic of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden; 4Department of Global Public Health and Primary Care, University of Bergen, 5Department of Rheumatology, Haukeland University Hospital, Bergen, Norway; 6Center for Observational Research, Amgen Inc. Thousand Oaks, CA, USA Background: Clinical epidemiology research studies, including pharmacoepidemiology and pharmacovigilance studies, use routinely collected health data, such as diagnoses recorded in national health and administrative registries, to assess clinical effectiveness and safety of treatments. We estimated positive predictive values (PPVs) of International Classification of Diseases, 10th revision (ICD-10) codes for primary diagnoses of dermatologic events and hypersensitivity recorded at hospitalization or emergency room visit in the national patient registries of Denmark and Sweden among women with postmenopausal osteoporosis (PMO). Methods: This validation study included women with PMO identified from the Danish and Swedish national patient registries (2005–2014). Medical charts of the potential cases served as the gold standard for the diagnosis confirmation and were reviewed and adjudicated by physicians. Results: We obtained and reviewed 189 of 221 sampled medical records (86%). The overall PPV was 92.4% (95% confidence interval [CI], 85.1%–96.3%) for dermatologic events, while the PPVs for bullous events and erythematous dermatologic events were 52.5% (95% CI, 37.5%–67.1%) and 12.5% (95% CI, 2.2%–47.1%), respectively. The PPV was 59.0% (95% CI, 48.3%–69.0%) for hypersensitivity; however, the PPV of hypersensitivity increased to 100.0% (95% CI, 67.6%–100.0%) when restricting to diagnostic codes for anaphylaxis. The overall results did not vary by country. Conclusion: Among women with PMO, the PPV for any dermatologic event recorded as the primary diagnosis at hospitalization or at an emergency room visit was high and acceptable for epidemiologic research in the Danish and Swedish national patient registries. The PPV was substantially lower for hypersensitivity leading to hospitalization or emergency room visit. Keywords: dermatology, positive predictive value, validation, pharmacoepidemiology

In the SORT OUT IX trial, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent devoid of polymer (BF-BES), did not show noninferiority to the biodegradable polymer ultrathin strut sirolimus-eluting Orsiro stent (O-SES). The aim of this substudy was to compare the clinical

Troels Munch,1 Lotte B Christensen,1 Kasper Adelborg,1 Grethe S Tell,2 Ellen M Apalset,2,3 Anna Westerlund,3,4 Ylva T Lagerros,5,6 Johnny Kahlert,1 Fei Xue,7 Vera Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 3Department of Rheumatology, Bergen Group of Epidemiology and Biomarkers in Rheumatic Disease, Haukeland University Hospital, Bergen, Norway; 4Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden; 5Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; 6Department of Medicine, Clinic of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Sweden; 7Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Background: Validation of definitions used to identify conditions of interest is imperative to epidemiologic studies based on routinely collected data. The objective of the study was thus to estimate positive predictive values (PPVs) of International Classification of Diseases, 10th Revision (ICD-10) codes to identify cases of incident acute pancreatitis leading to hospitalization and incident primary malignancy in the Scandinavian (Denmark, Norway, and Sweden) national patient registries in women with postmenopausal osteoporosis (PMO). Methods: This validation study included postmenopausal (defined as 55 years or older) women with osteoporosis, identified between 2005–2014. Potential cases were sampled based on ICD-10 codes from the three national patient registries. Cases were adjudicated by physicians, using medical record review as gold standard. PPVs with corresponding 95% CIs were computed. Results: Medical records of 286 of 325 (retrieval rate 88%) women with PMO were available for adjudication. Acute pancreatitis leading to hospitalization had a PPV of 87.6% (95% CI: 80.8%–90.2%). Incident primary malignancy had a PPV of 88.1% (95% CI: 81.3%–92.7%). The PPVs did not vary substantially across the three countries. Conclusion: ICD-10 codes to identify acute pancreatitis leading to hospitalization, and incident primary malignancy in the Scandinavian national patient registries had high PPVs among women with PMO. This allows identification of cases of acute pancreatitis and incident primary malignancy with reasonable validity and to use these as outcomes in comparative analyses. Keywords: validation, primary malignancy, acute pancreatitis, positive predictive value, postmenopausal women

Definite stent thrombosis definition maximizes specificity, but it may be insufficiently sensitive to capture completely this relatively rare event. Sensitivity can be increased by including probable stent thrombosis in the analysis. There is limited head-to-head data on late stent thromboses for

Diabetes is associated with increased risk of target lesion failure after percutaneous coronary intervention. In this substudy of the SORT OUT VII ([NCT01879358][1]) trial we compared the clinical outcome among patient with and without diabetes mellitus treated with sirolimus-eluting stent (O-SES