Publications by authors named "Johnny Kahlert"

31 Publications

Incidence Rates of Autoimmune Diseases in European Healthcare Databases: A Contribution of the ADVANCE Project.

Drug Saf 2021 Mar 19;44(3):383-395. Epub 2021 Jan 19.

Julius Global Health, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40264-020-01031-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892524PMC
March 2021

Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post-authorization safety cohort study conducted in Europe and in the United States.

Pharmacoepidemiol Drug Saf 2021 Jan 11. Epub 2021 Jan 11.

Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus N, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pds.5193DOI Listing
January 2021

Statin Therapy and Risk of Polyneuropathy in Type 2 Diabetes: A Danish Cohort Study.

Diabetes Care 2020 Dec 30;43(12):2945-2952. Epub 2020 Sep 30.

Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-1004DOI Listing
December 2020

Trends in hysterectomy-corrected uterine cancer mortality rates during 2002 to 2015: mortality of nonendometrioid cancer on the rise?

Int J Cancer 2021 Feb 17;148(3):584-592. Epub 2020 Aug 17.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

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 to 2015. Individual-level hysterectomy status was obtained from national registries; hysterectomy-corrected mortality rates were calculated by subtracting posthysterectomy 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 (12.3/100000 person-years vs 9.8/100000 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 from 2002 to 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 = .01), whereas rates of nonendometrioid cancer increased (APC: 5.90, 95% CI: 3.0, 8.9, P < .001). With respect to stage, mortality rates increased significantly over time for FIGOI-IIa (APC: 6.18 [95% CI: 1.9, 10.7] P = .01) but remained unchanged for FIGO IIb-IV. In conclusion, increasing mortality rates of nonendometrioid cancer paralleled the previously observed rise in incidence rates of this histologic subtype. Given the poor prognosis of nonendometrioid cancer, more studies are needed to clarify the underlying reason for these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33219DOI Listing
February 2021

Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

Circulation 2020 06 21;141(25):2052-2063. Epub 2020 May 21.

Department of Cardiology, Aarhus University Hospital, Skejby Hospital, Denmark (M.M., L.J., S.D.K., S.C., C.J.T., H.E.B., T.T., A.E., E.H.C.).

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%]; =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]; <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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040241DOI Listing
June 2020

Clinical outcomes three-year after revascularization with biodegradable polymer stents: ultrathin-strut sirolimus-eluting stent versus biolimus-eluting stent: from the Scandinavian organization for randomized trials with clinical outcome VII trial.

Coron Artery Dis 2020 09;31(6):485-492

Department of Cardiology, Odense University Hospital, Odense.

Background: Drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy. However, drug-eluting stents with biodegradable polymers may not be a class effect, as stent strut thickness, polymer coating, and drug resorption differ between these groups of stents. Twelve months results of Scandinavian Organization for Randomized Trials With Clinical Outcome VII showed that ultrathin-strut sirolimus-eluting Orsiro stent was noninferior to the biolimus-eluting Nobori stent. The sirolimus-eluting Orsiro stent was associated with a reduced risk of definite stent thrombosis.

Methods: The Scandinavian Organization for Randomized Trials With Clinical Outcome VII trial is a prospective multicenter randomized clinical trial comparing sirolimus-eluting Orsiro stent and biolimus-eluting Nobori stent in all-comers patients. The endpoint target lesion failure was a composite of cardiac death, myocardial infarction (not related to other than index lesion) and target lesion revascularization.

Results: A total of 1261 patients were randomized to treatment with sirolimus-eluting Orsiro stent and 1264 patients to biolimus-eluting Nobori stent and followed for 3 years. At 3-year the target lesion failure was comparable for sirolimus-eluting Orsiro stent (9.0%) and the biolimus-eluting Nobori stent (9.1%), (rate ratio, 0.99; 95% confidence interval, 0.77-1.29). Cardiac death (sirolimus-eluting Orsiro stent 3.0% vs. biolimus-eluting Nobori stent 2.6% [rate ratio, 1.16; 95% confidence interval, 0.73-1.86]), target lesion revascularization (sirolimus-eluting Orsiro stent 5.2% vs. biolimus-eluting Nobori stent 5.9% [rate ratio, 0.90; 95% confidence interval, 0.64-1.25]), myocardial infarction (sirolimus-eluting Orsiro stent 4.7% vs. biolimus-eluting Nobori stent 4.5% [rate ratio, 1.04; 95% confidence interval, 0.72-1.50]), and definite stent thrombosis (sirolimus-eluting Orsiro stent 1.0% vs. biolimus-eluting Nobori stent 1.7% [rate ratio, 0.59; 95% confidence interval, 0.30-1.18]) did not differ significantly between the two groups.

Conclusion: At 3-year follow-up, target lesion failure did not differ among ultrathin-strut sirolimus-eluting Orsiro stent and biolimus-eluting Nobori stent with biodegradable polymers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000000875DOI Listing
September 2020

ADVANCE database characterisation and fit for purpose assessment for multi-country studies on the coverage, benefits and risks of pertussis vaccinations.

Vaccine 2020 12 12;38 Suppl 2:B8-B21. Epub 2020 Feb 12.

219 East 42nd St, NY, NY 10017, USA. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2020.01.100DOI Listing
December 2020

ADVANCE system testing: Can coverage of pertussis vaccination be estimated in European countries using electronic healthcare databases: An example.

Vaccine 2020 12 31;38 Suppl 2:B22-B30. Epub 2019 Oct 31.

P-95 Epidemiology and Pharmacovigilance, Leuven, Belgium; VACCINE.GRID Foundation, Spitalstrasse 33, Basel, Switzerland; Julius Global Health, Julius Center, University Medical Center Utrecht, Heidelberglaan 100, the Netherlands. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2019.07.039DOI Listing
December 2020

Authors' response: Higher cervical cancer mortality among older women in Denmark could be due to insufficient screening coverage.

Acta Obstet Gynecol Scand 2019 11 13;98(11):1491. Epub 2019 Sep 13.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aogs.13710DOI Listing
November 2019

Everolimus-Eluting Versus Biolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus.

Am J Cardiol 2019 09 6;124(5):671-677. Epub 2019 Jun 6.

Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2019.05.060DOI Listing
September 2019

Comparison of the polymer-free biolimus-coated BioFreedom stent with the thin-strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population treated with percutaneous coronary intervention: Rationale and design of the randomized SORT OUT IX trial.

Am Heart J 2019 07 14;213:1-7. Epub 2019 Mar 14.

Department of Cardiology, Aarhus University Hospital, Skejby Hospital, Aarhus, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2019.02.017DOI Listing
July 2019

Everolimus-Eluting Versus Biolimus-Eluting Stents With Biodegradable Polymers in Unselected Patients Undergoing Percutaneous Coronary Intervention: A Randomized Noninferiority Trial With 1-Year Follow-Up (SORT OUT VIII Trial).

JACC Cardiovasc Interv 2019 04;12(7):624-633

Department of Cardiology, Odense University Hospital, Odense, Denmark.

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 < 0.001).

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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcin.2018.12.036DOI Listing
April 2019

Hysterectomy-corrected cervical cancer mortality rates in Denmark during 2002-2015: A registry-based cohort study.

Acta Obstet Gynecol Scand 2019 08 10;98(8):1063-1069. Epub 2019 Apr 10.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aogs.13608DOI Listing
August 2019

Sampling strategies for selecting general population comparison cohorts.

Clin Epidemiol 2018 25;10:1325-1337. Epub 2018 Sep 25.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CLEP.S164456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165733PMC
September 2018

Impact of diabetes on clinical outcomes after revascularization with sirolimus-eluting and biolimus-eluting stents with biodegradable polymer from the SORT OUT VII trial.

Catheter Cardiovasc Interv 2019 03 23;93(4):567-573. Epub 2018 Sep 23.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.27891DOI Listing
March 2019

Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool.

Diabetes Metab Res Rev 2018 07 26;34(5):e3005. Epub 2018 Apr 26.

Diabetes Research Centre, Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital, Odense, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dmrr.3005DOI Listing
July 2018

One-year rehospitalisation after percutaneous coronary intervention: a retrospective analysis.

EuroIntervention 2018 Oct;14(8):926-934

Department of Cardiology, Odense University Hospital, Odense, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4244/EIJ-D-17-00800DOI Listing
October 2018

Positive predictive values of ICD-10 codes to identify incident acute pancreatitis and incident primary malignancy in the Scandinavian national patient registries among women with postmenopausal osteoporosis.

Clin Epidemiol 2017 17;9:411-419. Epub 2017 Aug 17.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CLEP.S139895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566398PMC
August 2017

Control of confounding in the analysis phase - an overview for clinicians.

Clin Epidemiol 2017 31;9:195-204. Epub 2017 Mar 31.

Department of Clinical Epidemiology, Institute of Clinical Medicine.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CLEP.S129886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384727PMC
March 2017

Positive predictive values of International Classification of Diseases, 10th revision codes for dermatologic events and hypersensitivity leading to hospitalization or emergency room visit among women with postmenopausal osteoporosis in the Danish and Swedish national patient registries.

Clin Epidemiol 2017 24;9:179-184. Epub 2017 Mar 24.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CLEP.S126370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373846PMC
March 2017

Patterns of migrating soaring migrants indicate attraction to marine wind farms.

Biol Lett 2016 Dec;12(12)

DHI, Agern Alle 5, 2960 Hørsholm, Denmark.

Monitoring of bird migration at marine wind farms has a short history, and unsurprisingly most studies have focused on the potential for collisions. Risk for population impacts may exist to soaring migrants such as raptors with K-strategic life-history characteristics. Soaring migrants display strong dependence on thermals and updrafts and an affinity to land areas and islands during their migration, a behaviour that creates corridors where raptors move across narrow straits and sounds and are attracted to islands. Several migration corridors for soaring birds overlap with the development regions for marine wind farms in NW Europe. However, no empirical data have yet been available on avoidance or attraction rates and behavioural reactions of soaring migrants to marine wind farms. Based on a post-construction monitoring study, we show that all raptor species displayed a significant attraction behaviour towards a wind farm. The modified migratory behaviour was also significantly different from the behaviour at nearby reference sites. The attraction was inversely related to distance to the wind farm and was primarily recorded during periods of adverse wind conditions. The attraction behaviour suggests that migrating raptor species are far more at risk of colliding with wind turbines at sea than hitherto assessed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsbl.2016.0804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206590PMC
December 2016

The temporal and age-dependent patterns of hysterectomy-corrected cervical cancer incidence rates in Denmark: a population-based cohort study.

Acta Obstet Gynecol Scand 2017 Feb 28;96(2):150-157. Epub 2016 Dec 28.

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aogs.13057DOI Listing
February 2017

Hospital-based herpes zoster diagnoses in Denmark: rate, patient characteristics, and all-cause mortality.

BMC Infect Dis 2016 Mar 1;16:99. Epub 2016 Mar 1.

Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200, Aarhus N, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-016-1369-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773995PMC
March 2016

Validation of algorithms to detect distant metastases in men with prostate cancer using routine registry data in Denmark.

Clin Epidemiol 2015 10;7:259-65. Epub 2015 Apr 10.

Center for Observational Research, Amgen, Thousand Oaks, CA, USA.

Objective: Among patients with prostate cancer, diagnostic codes for bone metastases in the Danish National Registry of Patients have a sensitivity of 44%. In an attempt to improve the sensitivity of registry-based identification of metastases from prostate cancer, we tested a series of algorithms, combining elevated prostate-specific antigen (PSA) levels, use of antiresorptive therapy, and performed bone scintigraphy.

Patients And Methods: We randomly selected 212 men diagnosed with prostate cancer in 2005-2010 in the Central Denmark Region with prespecified PSA values, antiresorptive therapy, and bone scintigraphy who did not have a registry-based diagnostic code indicating presence of distant metastases. We defined three candidate algorithms for bone metastases: 1) PSA >50 μg/L and bone scintigraphy, 2) PSA >50 μg/L and antiresorptive therapy, and 3) PSA ≤50 μg/L with antiresorptive therapy or bone scintigraphy. An algorithm for distant metastasis site other than bone was defined as PSA >50 μg/L alone. Medical chart review was used as the reference standard to establish the presence or absence of metastases. Validity was expressed as a positive predictive value (PPV) or a negative predictive value, based on whether the algorithms correctly classified metastases compared with the reference standard.

Results: We identified 113 men with evidence of metastases according to the candidate algorithms, and 99 men without evidence of metastases according to the candidate algorithm. The PPVs of PSA >50 μg/L were 0.10 (95% confidence interval [CI] 0.04-0.19) for bone metastases and 0.14 (95% CI 0.07-0.24) for nonbone metastases, regardless of receipt of antiresorptive therapy or presence of bone scintigraphy. The PPVs for any metastases were 0.16 (95% CI 0.06-0.32) for PSA >50 μg/L and 0.28 (95% CI 0.14-0.47) for PSA >50 μg/L with bone scintigraphy. Adding antiresorptive treatment to the algorithm did not improve PPV. All negative predictive values approached 1.00.

Conclusion: Algorithms based on elevated PSA, antiresorptive therapy, or bone scintigraphy are not suitable for supplementing diagnostic codes to identify additional cases of distant metastases among men with prostate cancer. However, it is possible that in this setting, medical chart review is not a gold standard to identify metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CLEP.S74991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401359PMC
April 2015

Global epidemiology of hysterectomy: possible impact on gynecological cancer rates.

Am J Obstet Gynecol 2015 Jul 25;213(1):23-29. Epub 2015 Feb 25.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Despite the fact that hysterectomy is the most common surgical procedure worldwide in gynecology, national reporting of the incidence rate of gynecological cancers rarely removes the proportion no longer at risk of the disease from the population-at-risk-denominator (ie, women who have had a hysterectomy). The incidence rate of gynecological cancers is thus likely underestimated. Because hysterectomy, as well as oophorectomy, incidence varies across countries, age, and over time, meaningful comparison of gynecological cancer incidence rates may be compromised. Without accurate estimates of gynecological cancer incidence rates, performed via removing the proportion of hysterectomized or oophorectomized women from the population-at-risk-denominator, the impact of prevention strategies may be masked or misinterpreted. Furthermore, because national cervical cancer screening guidelines are at least in part based on the national reporting of cervical cancer incidence, it is important that the incidence rate reflects the true population at risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2015.02.019DOI Listing
July 2015

Incretin-based therapy and risk of acute pancreatitis: a nationwide population-based case-control study.

Diabetes Care 2015 Jun 29;38(6):1089-98. Epub 2015 Jan 29.

Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc13-2983DOI Listing
June 2015

Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target.

Elife 2014 Oct 15;3. Epub 2014 Oct 15.

Department of Environmental Health, Harvard School of Public Health, Boston, United States.

To identify new approaches to enhance innate immunity to bacterial pneumonia, we investigated the natural experiment of gender differences in resistance to infections. Female and estrogen-treated male mice show greater resistance to pneumococcal pneumonia, seen as greater bacterial clearance, diminished lung inflammation, and better survival. In vitro, lung macrophages from female mice and humans show better killing of ingested bacteria. Inhibitors and genetically altered mice identify a critical role for estrogen-mediated activation of lung macrophage nitric oxide synthase-3 (NOS3). Epidemiologic data show decreased hospitalization for pneumonia in women receiving estrogen or statins (known to activate NOS3). Pharmacologic targeting of NOS3 with statins or another small-molecule compound (AVE3085) enhanced macrophage bacterial killing, improved bacterial clearance, and increased host survival in both primary and secondary (post-influenza) pneumonia. The data identify a novel mechanism for host defense via NOS3 and suggest a potential therapeutic strategy to reduce secondary bacterial pneumonia after influenza.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.03711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215537PMC
October 2014

Modelling Skylarks (Alauda arvensis) to predict impacts of changes in land management and policy: development and testing of an agent-based model.

PLoS One 2013 6;8(6):e65803. Epub 2013 Jun 6.

Department of Bioscience, University of Aarhus, Rønde, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065803PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675089PMC
January 2014