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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. [ABSTRACT FROM AUTHOR]

• Feasibility of estimating pertussis vaccination covering using 7 European healthcare databases. • The majority of children were vaccinated at the recommended age of vaccination. • Two estimation methods provided comparable coverage estimates. • Benchmarking using national coverage estimates showed comparable results. • The approached used provided reliable estimates for pertussis vaccination coverage. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Contemporary data on cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) is needed to guide appropriate preventive management. The authors sought to investigate sex- and age-specific 10-year CVD risk in patients with newly diagnosed T2DM compared with the general population. A cohort study was conducted of all Danish patients with T2DM diagnosed between 2006 and 2013 (n = 142,587) and sex- and age-matched individuals from the general population (n = 388,410), all without prior atherosclerotic CVD. Ten-year CVD risk (myocardial infarction, stroke, and fatal CVD) was estimated. A total of 52,471 CVD events were recorded. Compared with the general population, the 10-year CVD risks were higher in patients with T2DM in both sexes and across all age groups, especially among younger individuals. For example, patients aged 40 to 49 years had the largest 10-year CVD risk difference (T2DM 6.1% vs general population 3.3%; risk difference: 2.8%, subdistribution HR: 1.91; 95% CI: 1.76-2.07). The age when a given CVD risk was reached differed substantially between the cohorts. Thus, a 10-year CVD risk of 5% was reached at age 43 in men with T2DM compared with 12 years later, at age 55, in men without T2DM. A 10-year CVD risk of 5% was reached at age 51 in women with T2DM and 10 years later, at age 61, in women without T2DM. Newly diagnosed T2DM increased 10-year CVD risk across both sexes and all age groups, especially among younger patients, with CVD occurring ≤12 years earlier than in general population individuals. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ) may result in severe complications requiring hospital treatment, particularly in patients with comorbidity. Nevertheless, data on HZ from nationwide population-based hospital registries are sparse.Methods: We conducted a cohort study describing first-time hospital-based (inpatient, outpatient, and emergency room) HZ diagnoses in the Danish National Patient Registry, 1994-2012. We computed the diagnosis rate; prevalence of demographic characteristics, comorbidities, and complications; length of hospital stay; and standardized mortality ratios (SMRs) using the Danish population as reference. We classified comorbidity using the Charlson Comorbidity Index (CCI) scoring system and categorized patients in groups of no (score 0), moderate (score 1), severe (score 2), and very severe comorbidity (score ≥3). In addition, we computed the prevalence of certain conditions associated with immune dysregulation (stem cell or bone marrow transplantation, solid organ transplantation, HIV infection, primary immunodeficiency, any cancer, and autoimmune diseases).Results: The diagnosis rate increased almost exponentially from 6 to 91.9 per 100,000 person-years between age 50 and ≥90 years. The age-standardized rate was stable throughout the study period. The median length of hospital stay was 4 days (interquartile range: 1-8 days) for inpatients with HZ as the main reason for admission. According to the CCI, 44.3 % of patients had no comorbidity, 17.3 % moderate comorbidity, 17.4 % severe comorbidity, and 21.0 % very severe comorbidity. Comorbidities involving immune dysregulation, such as malignant (21 %) and autoimmune diseases (17 %), were particularly prevalent. Thirty percent had neurological, ophthalmic, or other complications. HZ was associated with increased all-cause mortality overall (SMR 1.8, 95 % CI: 1.7-1.8), but not in analyses restricted to patients without comorbidity (SMR 1.0, 95 % CI: 0.9-1.0).Conclusions: This study provides estimates of the epidemiology of hospital-based (severe) HZ. The diagnosis rate increased substantially with age. Complications and comorbidities were prevalent, likely resulting in increased mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article examines the effects of weather, temporal factors and distance to coast on the flight altitude of migrating waterbirds in Western Estonia. A laser range finder and marine surveillance radar were used to measure flight altitudes. Visible effects on avian flight altitude due to weather conditions such as wind conditions, visibility and cloud cover were identified. Tailwinds were found to be associated with elevated flight altitude, while reductions in altitude were reportedly due to high wind speed. It was noted that behavioural and physical adaptations to the environment also helped in specific flight altitude selection.

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). [ABSTRACT FROM AUTHOR]

Non-local population stocking can have adverse genetic effects on wild populations through loss of genetic diversity and introgressive hybridization. The grey partridge ( Perdix perdix) has been an important European game species for centuries, widely subject to translocation and stocking. After c. 80 years of releasing reared grey partridges in Denmark, this study investigated whether an indigenous Danish grey partridge still existed. If so, they would (1) belong to the western European clade (W1) and (2) be more closely related to the historical, indigenous grey partridges than to farm-bred partridges. These predictions were tested by analysing the variation in both the mitochondrial control region (CR1) and microsatellite markers in museum samples representing the ancestral indigenous Danish grey partridge, contemporary wild grey partridges and farmed grey partridges from the five largest farms in Denmark. Phylogeography and population structure analyses showed traces of the indigenous Danish grey partridges amongst recent wild partridges in certain areas and significant genetic differences between farmed partridges and historical and recent partridges. The results also showed that the indigenous Danish grey partridges belonged to the western European clade (W1 haplotype). A foreign stocking effect was detected on the remote island of Bornholm, where the current population originated from introduced Danish and Bohemian grey partridges. The loss of haplotype diversity over time in certain geographical areas probably results from serious declines in wild Danish grey partridge numbers in recent decades. This, combined with the observation that hybridization between released stocked and wild partridges can occur, may complicate recovery of partridge populations. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105, 694-710. [ABSTRACT FROM AUTHOR]

The “cost-benefit” hypothesis states that specific body organs show mass changes consistent with a trade-off between the importance of their function and cost of their maintenance. We tested four predictions from this hypothesis using data on non-breeding greylag geese Anser anser during the course of remigial moult: namely that (i) pectoral muscles and heart would atrophy followed by hypertrophy, (ii) leg muscles would hypertrophy followed by atrophy, (iii) that digestive organs and liver would atrophy followed by hypertrophy and (iv) fat depots be depleted. Dissection of geese captured on three different dates during wing moult on the Danish island of Saltholm provided data on locomotory muscles and digestive organ size that confirmed these predictions. Locomotory organs associated with flight showed initial atrophy (a maximum loss of 23% of the initial pectoral muscle mass and 37% heart tissue) followed by hypertrophy as birds regained the powers of flight. Locomotory organs associated with running (leg muscles, since geese habitually run to the safety of water from predator-type stimuli) showed initial hypertrophy (a maximum gain of 37% over initial mass) followed by atrophy. The intestines and liver showed initial atrophy (41% and 37% respectively), consistent with observed reductions in daily time spent feeding during moult, followed by hypertrophy. The majority of the 22% loss in overall body mass (mean 760 g) during the flightless period involved fat utilisation, apparently consumed to meet shortfalls between daily energetic needs and observed rates of exogenous intake. The results support the hypothesis that such phenotypic plasticity in size of fat stores, locomotor and digestive organs can be interpreted as an evolutionary adaptation to meet the conflicting needs of the wing moult. [ABSTRACT FROM AUTHOR]

The effects of simulated goose grazing on common saltmarsh-grass Puccinellia maritima plants were tested on a Danish salt marsh during the flightless moulting period of greylag geese Anser anser (3–21 June 1998). Plants in an area exclosed from the influence of grazing and the nutrient effects of goose faeces were subject to removal of youngest lamina at 3-, 6-, 9- and 18-day intervals during this period. Average biomass and protein accumulation between harvests was highest at defoliation intervals of 9 days or more. Field observations from two separate study areas demonstrated geese returned to regraze the Puccinellia sward after 6–8 days and oesophageal contents from feeding geese showed selection for lamina lengths consistent with the results of clipping every 6 days. Geese therefore regrazed Puccinellia patches at shorter intervals than expected were they to maximise their intake of biomass or protein at each visit. However, total cumulative lamina elongation, equivalent to the long term gain during the entire moult period, showed no significant difference between the three most intensive defoliation treatments, which were significantly greater than those of plants defoliated at 18 day intervals. Highest overall lamina protein levels were maintained at 6- and 9-day defoliation intervals. This suggests geese regrazed Puccinellia patches at a rate that maximised their number of harvests during the flightless period, but maintained highest protein levels and overall biomass in the sward. This suggests, in line with earlier studies, that moulting greylag geese combine dietary selection, reduced nitrogen excretion and regrazing patterns to meet protein demands during regrowth of flight feathers. [ABSTRACT FROM AUTHOR]

Authors' response: Higher cervical cancer mortality among older women in Denmark could be due to insufficient screening coverage Trends in invitation to screening represent one additional aid to trying to understand the temporal and age-specific cervical cancer mortality trends. 1 Joergensen S, Njor S. Higher cervical cancer mortality among older women in Denmark could be due to insufficient screening coverage. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Background: Elevated triglyceride levels are a clinically useful marker of remnant cholesterol. It is unknown whether triglycerides are associated with residual cardiovascular risk in CVD-naïve patients with newly diagnosed type 2 diabetes mellitus (T2DM), who are already on statin therapy. We aimed to assess the association between triglyceride levels and risk of major cardiovascular events (MACE) in statin-treated patients with newly diagnosed T2DM managed in routine clinical care. Methods: This cohort study included newly diagnosed T2DM patients without a previous diagnosis of cardiovascular disease in Northern Denmark during 2005–2017. Individual triglyceride levels while on statin treatment were assessed within 1 year after T2DM diagnosis. The primary outcome was a composite of myocardial infarction, ischemic stroke, or cardiac death (MACE). Patients were followed from one year after T2DM diagnosis until 30 April 2021, MACE, emigration, or death. We used Cox regression to compute hazard ratios (HRs) controlling for confounding factors. Results: Among 27,080 statin-treated patients with T2DM (median age 63 years; 53% males), triglyceride levels were < 1.0 mmol/L in 17%, 1.0–1.9 mmol/L in 52%, 2.0–2.9 mmol/L in 20%, and ≥ 3.0 mmol/L in 11%. During follow-up, 1,957 incident MACE events occurred (11.0 per 1000 person-years). Compared with triglyceride levels < 1.0 mmol/L, confounder-adjusted HRs for incident MACE were 1.14 (95% CI 1.00–1.29) for levels between 1.0 and 1.9 mmol/L, 1.30 (95% CI 1.12–1.51) for levels between 2.0 and 2.9 mmol/L, and 1.44 (95% CI 1.20–1.73) for levels ≥ 3.0 mmol/L. This association was primarily driven by higher rates of myocardial infarction and cardiac death and attenuated only slightly after additional adjustment for LDL cholesterol. Spline analyses confirmed a linearly increasing risk of MACE with higher triglyceride levels. Stratified analyses showed that the associations between triglyceride levels and MACE were stronger among women. Conclusions: In statin-treated patients with newly diagnosed T2DM, triglyceride levels are associated with MACE already from 1.0 mmol/L. This suggests that high triglyceride levels are a predictor of residual cardiovascular risk in early T2DM and could be used to guide allocation of additional lipid-lowering therapies for CVD prevention. [ABSTRACT FROM AUTHOR]

Agent-based simulation models provide a viable approach for developing applied models of species and systems for predictive management. However, there has been some reluctance to use these models for policy applications due to complexity and the need for improved testing and communication of the models. We present the development and testing of a comprehensive model for Skylark (Alauda arvensis) in Danish agricultural landscapes. The model is part of the ALMaSS system, which considers not only individual skylarks, but also the detailed dynamic environment from which they obtain the information necessary to simulate their behaviour. Population responses emerge from individuals interacting with each other and the environment. Model development and testing was carried out using pattern-oriented modelling. The testing procedure was based on the model's ability to represent detailed real world patterns of distribution and density, reproductive performance and seasonal changes in territory numbers. Data to support this was collected over a 13-year period and comprised detailed field observations of breeding birds and intensive surveys. The model was able to recreate the real world data patterns accurately; it was also able to simultaneously fit a number of other secondary system properties which were not formally a part of the testing procedure. The correspondence of model output to real world data and sensitivity analysis are presented and discussed, and the model's description is provided in ODdox format (a formal description inter-linked to the program code). Detailed and stringent tests for model performance were carried out, and standardised model description and open access to the source code were provided to open development of the skylark model to others. Over and above documenting the utility of the model, this open process is essential to engender the user trust and ensure continued development of these comprehensive systems for applied purposes. [ABSTRACT FROM AUTHOR]

Feather stable isotope composition may not reflect local isoscapes in which they were grown if supplemented with protein of endogenous origin. Thus, feather isotope analysis, combined with knowledge of local isoscapes can be used to infer endogenous nutrient composition to feathers in cases where birds travel to moult. We investigated this possibility in a study of flightless moulting greylag geese Anser anser on the Danish island of Saltholm, which are known to mobilise endogenous protein stores (acquired at previous terrestrial staging locations in Sweden) to reconstitute muscle blocks and organs whilst feeding on a saltmarsh (i.e. marine-influenced) diet with contrasting stable isotope ratios. We used stable isotope (δ13C, δ15N) measurements to test the prediction that new-grown flight feathers would have stable isotope values intermediate between those derived from a purely terrestrial C3 diet and one composed purely of saltmarsh plants. Feather δ13C and δ15N values were intermediate between those expected for feather material derived from local saltmarsh (i.e. exogenous) food items and Swedish terrestrial (endogenous muscle) sources, suggesting a mixing of endogenous and exogenous sources. These results confirm that moult migrant Anatidae exploit body stores to meet specific protein needs during the flightless period of remige regrowth and caution against the use of feather stable isotope ratios as direct indicators of the isotopic environment in which they were regrown, where endogenous contributions may occur. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• This paper describes 9 electronic healthcare datasources covering more than 40 million persons. • Background rates for 11 events of interest and pertussis vaccine coverage were benchmarked. • All datasources were fit-for-purpose to generate reliable evidence on vaccine coverage, benefits and risks. 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. To evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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%]; Pnoninferiority=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<0.0001).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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses research being done on the pancreatic safety of incretin-based therapies. It references te study "Incretin-Based Therapy and Risk of Acute Pancreatitis: Nationwide Population-Based Case-Control Study," by R. W. Thomsen et al. in the 2015 issue. Topics discussed include the risk from using glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4I), the link between DPP-4I and increased AP risk, and the cardiovascular safety trials.