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BACKGROUND: More than half of patients with pulmonary embolism (PE) experience persistent functional limitations. Despite guideline recommendations for a structured integrated care model for patients with pulmonary embolism (PE), consensus on an optimal follow-up strategy is lacking, and evidence is insufficient. OBJECTIVES: To describe the development of a structured model for pulmonary embolism (PE) follow-up using co-production methods. METHODS: Co-production of the Attend-PE-model was conducted from October 2021 to June 2022, featuring participatory design techniques. This was combined with a stepwise approach based on Intervention Mapping, to ensure that the developed model was evidence-based and theoretically grounded. RESULTS: Development of the Attend-PE included 1) A needs assessment mapping follow-up at 18 sites treating PE in Denmark; 2) Definition of the overall goal and performance objectives of the Attend-PE model, based on the needs assessment in combination with a literature review; 3) Co-production of the Attend-PE model in workshops with patient representatives, healthcare professionals, and experts in the field 4) Refinement of the structure and organization of the Attend-PE model and production of patient education material. The Attend-PE model outlines a structured approach for in-hospital follow-up, involving group-based patient education, individual consultations, and patient-reported outcomes to assess physical and psychological well-being. The model supports a personalized post-hospitalization care plan. CONCLUSIONS: The co-production process was successful in developing a structured follow-up model aligned with patients' needs, health provider perspectives and existing guidelines. The Attend-PE model is currently undergoing clinical evaluation to determine its effectiveness and usability.
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INTRODUCTION: Hospital discharge diagnoses from administrative registries are frequently used in studies of cancer-associated venous thromboembolism, but the validity of International Classification of Diseases (ICD) codes for identifying such events is unknown. MATERIALS AND METHODS: Using patient samples from the Danish National Patient Register, we calculated positive predictive values (PPV), i.e., the proportion of registered ICD codes, which could be confirmed after manual search of the electronic health record. Sensitivity was estimated in a sample of patients with imaging-verified venous thromboembolism but without prior knowledge about their ICD coding status. Sensitivity was calculated as the proportion of these patients, who were discharged with an ICD code for venous thromboembolism. RESULTS: The overall PPV of an ICD-10 diagnosis of cancer-associated venous thromboembolism was 75.9 % (95 % confidence interval 71.3-80.0). In subgroups, the PPV was particularly low for recurrent venous thromboembolism (44.2 %), diagnoses in a secondary position (55.7 %), outpatient diagnoses (65.3 %), and diagnoses given at surgical (66.7 %), emergency wards (48.4 %), or via hospices/palliative teams (0 %). The overall sensitivity was 68 %, meaning 32 % of patients with cancer diagnosed in hospital with venous thromboembolism were discharged without any registered ICD code for venous thromboembolism. CONCLUSIONS: The positive predictive value of an ICD diagnosis of cancer-associated venous thromboembolism in the Danish Patient Register was overall adequate for research purposes, but with notable variation across subgroups. Sensitivity was limited, as 1/3 of patients with venous thromboembolism were discharged without any relevant ICD code. Cautious interpretation of incidence of cancer-associated venous thromboembolism based on administrative register-based data is warranted.
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Neoplasias , Sistema de Registros , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/diagnóstico , Neoplasias/complicaciones , Neoplasias/epidemiología , Dinamarca/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Clasificación Internacional de Enfermedades , Anciano , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , AdultoRESUMEN
With the main aim of identifying biomarkers that contribute to defining the concept of ideal protein in growing rabbits under the most diverse conditions possible this work describes two different experiments. Experiment 1: 24 growing rabbits are included at 56 days of age. The rabbits are fed ad libitum one of the two experimental diets only differing in lysine levels. Experiment 2: 53 growing rabbits are included at 46 days of age, under a fasting and eating one of the five experimental diets, with identical chemical composition except for the three typically limiting amino acids (being fed commercial diets ad libitum in both experiments). Blood samples are taken for targeted and untargeted metabolomics analysis. Here we show that the metabolic phenotype undergoes alterations when animals experience a rapid dietary shift in the amino acid levels. While some of the differential metabolites can be attributed directly to changes in specific amino acids, creatinine, urea, hydroxypropionic acid and hydroxyoctadecadienoic acid are suggested as a biomarker of amino acid imbalances in growing rabbits' diets, since its changes are not attributable to a single amino acid. The fluctuations in their levels suggest intricate amino acid interactions. Consequently, we propose these metabolites as promising biomarkers for further research into the concept of the ideal protein using rabbit as a model.
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Aminoácidos , Alimentación Animal , Biomarcadores , Metabolómica , Animales , Conejos , Biomarcadores/sangre , Biomarcadores/metabolismo , Metabolómica/métodos , Aminoácidos/metabolismo , Aminoácidos/sangre , Alimentación Animal/análisis , Proteínas en la Dieta/metabolismo , Dieta , MasculinoRESUMEN
BACKGROUND: Venous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non-small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. MATERIALS AND METHODS: A nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen-Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. RESULTS: Among the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. CONCLUSION: VTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Sistema de Registros , Tromboembolia Venosa , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Neoplasias Pulmonares/patología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/epidemiología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Estudios de Cohortes , Dinamarca/epidemiología , Incidencia , Factores de Riesgo , Anciano de 80 o más Años , Adulto , Estudios de SeguimientoRESUMEN
Ecological nutrition aims to unravel the extensive web of nutritional links that drives animals in their interactions with their ecological environments. Nutrition plays a key role in the success of European wild rabbit (Oryctolagus cuniculus) and could be affected by the breeding status of the animals and reflected in the metabolome of this species. As nutritional needs are considerably increased during pregnancy and lactation, the main objective of this work was to determine how the breeding status (pregnant and lactating) of European wild rabbit does affects nutritional requirements and their metabolome (using targeted and untargeted metabolomics), aiming to find a useful biomarker of breeding status and for monitoring nutritional requirements. To address this gap, 60 wild European rabbits were studied. Animals were divided according to their breeding status and only pregnant (n = 18) and lactating (n = 11) rabbit does were used (n = 29 in total). The body weight and length of each animal were analyzed. The relative and absolute chemical composition of the gastric content and whole blood sample were taken, and targeted and untargeted metabolomics were analyzed. As a main result, there were no differences in biometric measurements, gastric content, and targeted metabolomics, except for live weight and nonesterified fatty acids (NEFA), as pregnant animals showed higher live weight (+12%; p = 0.0234) and lower NEFA acid levels (-46%; p = 0.0262) than lactating females. Regarding untargeted metabolomics, a good differentiation of the metabolome of the two breeding groups was confirmed, and it was proven that pregnant animals showed higher plasmatic levels of succinic anhydride (3.48 more times; p = 0.0236), succinic acid (succinate) (3.1 more times; p = 0.0068) and propionic acid (3.98 more times; p = 0.0121) than lactating animals. However, lactating animals showed higher levels of N-[(3a,5b,7b)-7-hydroxy-24-oxo-3-(sulfoxide) cholan-24-yl]-Glycine (cholestadien) (2.4 more times; p < 0.0420), 4-maleyl-acetoacetate (MAA) (3.2 more times; p < 0.0364) and irilone (2.2 more times; p = 0.0451) than pregnant animals, any of these metabolites could be used as a potential biomarker. From these results, it can be concluded that the most notable changes were observed in the metabolome of individuals, with most of the changes observed being due to energy and protein mobilisation.
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Lactancia , Animales , Femenino , Conejos , Lactancia/fisiología , Embarazo , Metaboloma , Metabolómica , Fenómenos Fisiológicos Nutricionales de los Animales , Animales SalvajesRESUMEN
Ecometabolomics could be implemented as a powerful tool in molecular ecology studies, but it is necessary to know the baseline of certain metabolites and understand how different traits could affect the metabolome of the animals. Therefore, the main objective of this study was to provide values for the nutritional metabolome profile of different diet groups and animal species, as well as to study the differences in the metabolomic profile due to the effect of diet type and species. To achieve this goal, blood samples were taken from healthy animals (n = 43) of different species: lion (Panthera leo), jaguar (Panthera onca), chimpanzee (Pan troglodytes), bison (Bison bison), gazelle (Gazella cuvieri) and fallow deer (Dama dama), and with different types of diet (carnivore, herbivore and omnivore). Each blood sample was analysed to determine nutritional metabolites. The main results this study provides are the nutritional metabolic profile of these animals based on the type of diet and the animal species. A significant effect of the dietary type was found on nutritional metabolite levels, with those metabolites related to protein metabolism (total protein and creatine) being higher in carnivores. There is also an effect of the species on nutritional metabolites, observing a metabolome differentiation between lion and jaguar. In the case of herbivores, bison showed higher levels of uric acid and cholesterol, and lower urea levels than gazelle and fallow deer. More molecular ecology studies are needed to further the knowledge of the metabolism of these animals.
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Antílopes , Bison , Ciervos , Leones , Panthera , Animales , Herbivoria , Dieta/veterinaria , MetabolomaRESUMEN
BACKGROUND: This Nordic observational cohort study aims to assess the effectiveness and safety of reduced-dose direct-acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared to standard warfarin for stroke prevention in nonvalvular atrial fibrillation. METHODS: The study, utilizing nationwide administrative databases from Denmark, Sweden, Norway, and Finland, spanned from January 1, 2011 to December 31, 2018 (2017 for Sweden). The cohort included 26,883 patients initiating reduced-dose DOACs and 108,014 comparable warfarin patients. Effectiveness was measured by the composite endpoint of ischemic stroke and systemic embolism, while safety was assessed through intracranial hemorrhage. RESULTS: The meta-analysis across countries revealed similar or lower incidences of ischemic stroke and systemic embolism in patients on reduced-dose DOACs compared to standard warfarin (rivaroxaban: HR 0.93, dabigatran: HR 0.88, apixaban: HR 0.79). Incidences within warfarin groups ranged from 2.16 to 3.71 per 100 person-years, comparable to DOAC recipients. Intracranial hemorrhage rates were generally low, ranging from 0.16 to 1.85 per 100 person-years. In comparison with warfarin patients, meta-analyses yielded HRs for rivaroxaban (1.41), dabigatran (0.35), and apixaban (0.72). CONCLUSIONS: In this study, atrial fibrillation patients initiating reduced-dose rivaroxaban and dabigatran exhibited incidences of ischemic stroke and systemic embolism similar to warfarin, and for apixaban, even lower. Rates of intracranial hemorrhage were comparable to or lower for patients on DOACs compared to warfarin.
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Fibrilación Atrial , Dabigatrán , Pirazoles , Piridonas , Rivaroxabán , Accidente Cerebrovascular , Warfarina , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Piridonas/efectos adversos , Dabigatrán/uso terapéutico , Dabigatrán/efectos adversos , Dabigatrán/administración & dosificación , Warfarina/uso terapéutico , Warfarina/efectos adversos , Warfarina/administración & dosificación , Anciano , Masculino , Femenino , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anciano de 80 o más Años , Administración Oral , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/epidemiología , Persona de Mediana EdadRESUMEN
In postweaning calves, it is a challenge to maintain the plasma vitamin E level at or above the recommended level (3 µg/mL), which is linked to a good immune response. It has been unclear until now why the provision of solid feed with concentrations below 200 mg/kg feed of vitamin E is ineffective in maintaining the plasma vitamin E level of calves above the recommended plasma level postweaning. The present study was conducted to investigate if a high fat to vitamin E ratio in the concentrate could protect and improve the delivery of the natural form of vitamin E (RRR-α-tocopherol) to calves postweaning. Thirty calves were included in the experiment from 2 weeks preweaning until 2 weeks postweaning (Weeks -2, -1, 0 [weaning], 1, and 2 relative to weaning) and fed one of three concentrates in which lecithin mixture provided the fat supplement: control (77 mg/kg of vitamin E and 4.9% DM of crude fat; CONT), medium level of vitamin E supplemented (147 mg/kg of vitamin E and 7.7% DM of crude fat; MedVE) or high level of vitamin E supplemented (238 mg/kg of vitamin E and 12.4% DM of fat; HiVE). Thus, there was a comparable ratio of fat to vitamin E (520-630) in the three concentrates. During the 2 weeks postweaning, final body weight (92 ± 2 kg), average daily gain (917 ± 51 g/day) and concentrate intake (2.2 ± 0.09 kg/day; mean of treatment ± standard error) were unaffected by treatment and the interaction between treatment and week. There was an interaction between treatment and week for vitamin E intake pre- (p < 0.001) and postweaning (p < 0.001). There was an interaction between treatment and week (p < 0.001) for plasma vitamin E level postweaning, and it was 2.5, 3.1, and 3.8 µg/mL in CONT, MedVE, and HiVE, respectively, at Week 1 postweaning. In addition, plasma vitamin E levels at Week 2 postweaning were 2.6, 3.6 and 4.8 µg/mL in CONT, MidVE and HiVE respectively. The results show that 147 mg/kg of lecithin-protected vitamin E in the concentrate is needed to secure a plasma vitamin E level well above the recommended level. In addition, lecithin-protected vitamin E elevated the plasma level of triglycerides and nonesterified fatty acids.
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Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Dieta , Vitamina E , Destete , Animales , Bovinos , Masculino , Alimentación Animal/análisis , Dieta/veterinaria , Grasas de la Dieta/farmacología , Grasas de la Dieta/administración & dosificación , Suplementos Dietéticos , Vitamina E/administración & dosificación , Vitamina E/farmacología , Vitamina E/sangreRESUMEN
BACKGROUND: Frail people with atrial fibrillation are often undertreated with oral anticoagulants (OACs), and evidence for the net clinical benefit (NCB) of OAC is sparse. We, therefore, examined the risk of thromboembolic events, major bleeding, and NCB of anticoagulation treatment. METHODS: This was a nationwide cohort study including frail patients aged with incident atrial fibrillation between 2013 and 2018. Patients were categorized according to OAC treatment exposure. One-year risks of thromboembolic events and major bleeding were ascertained where death was treated as a competing risk. The NCB of anticoagulation was assessed by a bivariate trade-off between thromboembolism and bleeding. RESULTS: We identified 36â 223 frail patients with atrial fibrillation (median age, 79 years; 50.5% female), of whom 61.8% started OAC therapy, while 38.2% were untreated despite indication for stroke prevention. At 1 year, the risk of thromboembolic events was 2.1% (95% CI, 1.8%-2.3%) among patients not receiving OAC versus 1.5% (95% CI, 1.4%-1.7%) in patients with OAC. The bleeding risk was 3.2% (95% CI, 2.9%-3.5%) among patients without OAC versus 3.5% (95% CI, 3.2%-3.8%) among anticoagulated patients. The NCB was 0.70% (95% CI, 0.32%-1.08%), suggesting a benefit of OAC treatment; however, the NCB declined with age and increasing frailty and was lowest among patients >75 years of age or with high frailty level. CONCLUSIONS: Frail patients with atrial fibrillation are often untreated with OAC in routine clinical care despite an indication for stroke prevention. The NCB balancing thromboembolic events and major bleeding was in favor of anticoagulation but decreased with advancing age and increasing frailty.
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Fibrilación Atrial , Fragilidad , Accidente Cerebrovascular , Tromboembolia , Humanos , Femenino , Anciano , Masculino , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Estudios de Cohortes , Anciano Frágil , Fragilidad/epidemiología , Anticoagulantes/efectos adversos , Tromboembolia/epidemiología , Tromboembolia/etiología , Tromboembolia/prevención & control , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in patients with lung cancer undergoing thoracic operation. We examined the risk and timing of VTE after surgery for primary non-small cell lung cancer (NSCLC). METHODS: All patients undergoing operation for NSCLC in Denmark between 2003 and 2021 were identified in the Danish Lung Cancer Registry. VTE events in the year after operation were assessed by stage, patient characteristics, and surgical procedure. RESULTS: We identified 13,197 patients who underwent operation for NSCLC in 2003 to 2021 (mean age, 67.6 years; 50% female); 10,524 (79.7%) had stage I-II NSCLC, and 2673 (20.3%) had stage III-IV. During 1-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI, 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I vs 3.9% for stage IV) but varied little by pathologic type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%; 95% CI, 3.2-6.9), followed by pneumonectomy (3.5%; 95% CI, 2.3-5.0). The hazard of VTE was highest during the first 3 months after operation, after which it declined. For stage IV cancer, hazards increased again after 6 months. At 1 year, all-cause death was 12.6% (95% CI, 12.0%-13.1%). CONCLUSIONS: VTE developed in 3.3% of patients undergoing operation for NSCLC, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Tromboembolia Venosa , Humanos , Femenino , Anciano , Masculino , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Anticoagulantes , Factores de Riesgo , IncidenciaRESUMEN
AIMS: Although frail patients with atrial fibrillation (AF) carry a high risk of stroke and treatment-related bleeding complications, evidence for the safety and effectiveness of anticoagulation remains sparse. This study investigated the effectiveness and safety of direct oral anticoagulant (DOAC) vs. warfarin in frail AF patients. METHODS AND RESULTS: Nationwide registry-based cohort study including 32 048 anticoagulation naïve frail patients (median age 80 years, 53% female) with incident AF during 2012-20. Frailty was assessed using the hospital frailty risk score. To address baseline confounding, we applied inverse probability of treatment weighting (IPTW) and marginal structural models with weighted pooled regression to compute weighted hazard ratios (wHRs) and risk differences for thromboembolism and major bleeding comparing specific DOAC doses with warfarin. After AF diagnosis, 6747 (21.1%) initiated warfarin, 17 076 (50.3%) initiated standard-dose DOAC, and 9179 (28.6%) initiated reduced-dose DOAC. Comparative effectiveness analyses in the IPTW pseudo-populations revealed similar thromboembolism risk between standard-dose DOAC and warfarin [wHR 0.95, 95% confidence interval (CI) 0.80-1.13] and between reduced-dose DOAC and warfarin (wHR 0.97, 95% CI 0.77-1.23). The 1-year thromboembolic event-free survival difference was -0.2% for DOAC, regardless of dosing, vs. warfarin. Major bleeding risk was significantly lower with standard-dose DOAC (wHR 0.69, 95% CI 0.59-0.87) and reduced-dose DOAC (wHR 0.67, 95% CI 0.55-0.81) vs. warfarin. The 1-year bleeding risk difference with DOAC ranged from -1.3% to -3.0%. CONCLUSION: Our findings indicate comparable thromboembolism risk and significantly lower bleeding risk with both standard and reduced DOAC regimens compared with warfarin in frail AF patients in routine care.
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Fibrilación Atrial , Fragilidad , Tromboembolia , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Masculino , Warfarina , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Anticoagulantes , Estudios de Cohortes , Anciano Frágil , Fragilidad/diagnóstico , Fragilidad/epidemiología , Fragilidad/complicaciones , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Tromboembolia/diagnóstico , Tromboembolia/epidemiología , Tromboembolia/etiologíaRESUMEN
Importance: Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated. Objective: To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease. Design, Setting, and Participants: A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021. Exposure: Prescription filled for aspirin or clopidogrel. Main Outcomes and Measures: Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival. Results: A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131â¯047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127â¯684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar. Conclusions and Relevance: In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.
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Aneurisma de la Aorta Abdominal , Aterosclerosis , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Anciano , Femenino , Humanos , Masculino , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/epidemiología , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Investigación sobre la Eficacia ComparativaRESUMEN
BACKGROUND: Predictive factors for recurrent cancer-associated venous thromboembolism have been inconsistent across previous studies. To provide data for improved risk stratification, we described the risk of recurrent venous thromboembolism overall and across age, sex, calendar period, cancer type, Ottawa risk score, cancer stage, and cancer treatment in a nationwide cohort of patients with active cancer. METHODS: Using Danish administrative registries, we identified a cohort of all adult patients with active cancer and a first-time diagnosis of venous thromboembolism during 2003-2018. We accounted for the competing risk of death and calculated absolute risks of recurrent venous thromboembolism at six months. RESULTS: The population included 34,072 patients with active cancer and venous thromboembolism. Recurrence risks at six months were higher for patients with genitourinary cancer (6.5%), lung cancer (6.1%), gastrointestinal cancer (5.6%), brain cancer (5.2%), and hematological cancer (5.1%) than for patients with gynecological cancer (4.7%), breast cancer (4.1%), and other cancer types (4.8%). Recurrence risks were similar for men (5.2%) and women (4.9%), with and without chemotherapy (5.1%), across Ottawa risk score group (low: 5.0%; high: 5.1%) and across calendar periods but increased with increasing cancer stage. The overall six-month all-cause mortality risk was 26%, and highest for patients with lung cancer (49%) and lowest among breast cancer patients (4.1%). CONCLUSIONS: Six-month recurrence risk after first-time cancer-associated venous thromboembolism was high and varied by cancer type and patient characteristics. Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism.
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Neoplasias de la Mama , Neoplasias Pulmonares , Tromboembolia Venosa , Adulto , Masculino , Humanos , Femenino , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Estudios de Cohortes , Recurrencia Local de Neoplasia , Dinamarca/epidemiologíaRESUMEN
PURPOSE: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in patients undergoing surgery, but conflicting data exist on VTE risk in patients undergoing head and neck surgery for malignant and non-malignant conditions. Our aim was to examine the risk of VTE among patients with and without cancer undergoing head and neck surgery. METHODS: We conducted a nationwide cohort study to examine the risk of VTE among patients with an otolaryngological diagnosis using data from the Danish National Patient Register between 2010 and 2018. Analyses were stratified by cancer and anatomical areas of the surgical procedure. RESULTS: In total, 116,953 patients were included of whom 10% (n = 12,083) had active cancer. After 3 months, 1.2% of the patients with cancer and 0.3% of the patients without cancer experienced VTE, respectively. For patients undergoing mouth/throat surgery, 0.8% with cancer and 0.2% without cancer had VTE, respectively. After nose/sinuses surgery 0.7% and 0.2%, respectively. No patients experienced VTE after ear surgery; and after endoscopies the numbers were 1.3% and 0.6% respectively. CONCLUSIONS: While the minority of patients undergoing head and neck surgery develop VTE postoperatively, the risk increases among those with cancer. To support clinical decision making on anticoagulation, risk stratification tools could be further developed to recognize this hazard in patients with cancer undergoing head and neck surgery.
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Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/complicaciones , Estudios de Cohortes , Incidencia , Procedimientos Quirúrgicos Otorrinolaringológicos/efectos adversos , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
PURPOSE: The hospital registration of retinal artery occlusions in the Danish National Patient Registry has not previously been validated. In this study, the diagnosis codes were validated to ensure the diagnoses had an acceptable validity for research. The validation was performed both for the overall diagnosis population and at the subtype diagnosis level. METHODS: The medical records for all patients with retinal artery occlusion with an incident hospital record in the years 2017-2019 in Northern Jutland (Denmark) were assessed in this population-based validation study. Furthermore, fundus images and two-person verification were assessed for the included patients when available. The positive prediction values for the overall diagnosis of retinal artery occlusion, as well as for the central or branch subtypes, were calculated. RESULTS: A total of 102 medical records were available for review. The overall positive prediction value for a retinal artery occlusion diagnosis was 79.4% (95% CI: 70.6-86.1%), while the overall positive prediction value at the subtype diagnosis level was 69.6% (95% CI: 60.1-77.7%), with 73.3% (95% CI: 58.1-85.4%) for branch retinal artery occlusion and 71.2% (95% CI: 56.9-82.9%) for central retinal artery occlusion. For the stratified analyses at the subtype diagnosis, age, sex, diagnosis year, and primary or secondary diagnosis, the positive prediction values ranged from 73.5 to 91.7%. In the stratified analyses at the subtype level, the positive prediction values ranged from 63.3 to 83.3%. The differences among the positive prediction values of the individual strata of both analyses were not statistically significant. CONCLUSIONS: the validities of the retinal artery occlusion and subtype level diagnoses are comparable to other validated diagnoses and considered acceptable for use in research.
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Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin ~100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants.
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Mariposas Diurnas , Filogenia , Animales , Evolución Biológica , Mariposas Diurnas/genéticaRESUMEN
The ecological interest in the European rabbit (Oryctolagus cuniculus) has grown since it was declared an endangered species. Nutrition is fundamental in its dispersion and the key to its success. This is the main reason why knowledge of their nutritional preferences/requirements could play a fundamental role in rabbit biology and, therefore, in their conservation. The objectives of the work will be to elucidate how age and sex affect both nutritional preferences/requirements, and the nutrient optimisation of European rabbits. To address this gap, 70 wild European rabbits were studied. The rabbits were divided according to their age: adult (n = 43) and young (n = 27). Two groups were differentiated according to the adult rabbits' sex: females (n = 28) and males (n = 15). We analysed the relative (%) and absolute (g) chemical composition of the rabbits' gastric contents: dry matter (DM), ashes (ASH), crude protein (CP), ether extract (EE), neutral detergent fibre (NDF), acid detergent fibre (ADF), and lignin, hemicelluloses and celluloses, highly digestible nonnitrogenous nutrients (HDNN: fat, starch, and soluble fibre), well from the blood was analysed with plasmatic urea nitrogen (PUN), nonesterified fatty acid (NEFA) and glucose (GLU). As a nutrient optimisation measure, the following indices between blood metabolites and stomach content were calculated: PUN/CP total content, NEFA/DM total content and GLU/DM total content ratios. Our works showed that age and sex affected the nutritional strategy of rabbits. Regarding age: adults showed lower CP (-14%; p = 0.0217) and higher HDNN (+21%; p = 0.0399) relative content than young rabbits, and absolute amount of most nutrients: DM (+59%; p = 0.001), OM (+43%; p = 0.0049), ASH (+54%; p = 0.0085), Hemicelluloses (+73%; p = 0.0084), Cellulose (+27%; p = 0.0452), and HDNN (+63%; p = 0.0012). In addition, adults showed better nutrient optimisation. Sex did not affect the relative chemical composition of the gastric content, but it showed a clear higher gastric content by females (+85%; p < 0.0001) and higher intake of most of the absolute chemical components: DM (+64%; p < 0.001), CP (+56%; p = 0.0005), OM (+58%; p = 0.0001), ASH (+44%; p = 0.0123), HDNN (+39%; p = 0.001), NDF (+59%; p = 0.001), ADF (+64%; p = 0.0003), lignin (+82%; p = 0.0036) and cellulose (+58%; p = 0.0002). Finally, we observed that females had better nutrient optimisation than males. This works supports the idea that feeding ecology and nutrition are particularly relevant to reproductive success and fitness in wild animals.
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Digestión , Lignina , Masculino , Animales , Conejos , Femenino , Ácidos Grasos no Esterificados , Detergentes , Nutrientes , Fibras de la Dieta/análisis , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los AnimalesRESUMEN
Purpose: The majority of bleeding diagnoses in the Danish National Patient Registry have not been validated despite extensive use in epidemiological research. Therefore, we examined the positive predictive value (PPV) of non-traumatic bleeding diagnoses in the Danish National Patient Registry. Study Design: Population-based validation study. Patients and Methods: Based on a manual review of electronic medical records, we estimated the PPV of diagnostic coding (International Classification of Diseases, Tenth Revision (ICD-10)) for non-traumatic bleeding for all patients ≥65 years of age with any hospital contact in the North Denmark Region during March-December 2019 as registered in the Danish National Patient Registry. We calculated PPVs and associated 95% confidence intervals (CI) for non-traumatic bleeding diagnoses overall and stratified according to primary or secondary diagnosis, and according to major anatomical sites. Results: A total of 907 electronic medical records were available for review. The population mean age was 79.33 years (standard deviation (SD)=7.73) and 57.6% were males. Primary bleeding diagnoses accounted for 766 of the records and 141 were secondary bleeding diagnoses. The overall PPV for bleeding diagnoses was 94.0% (95% CI: 92.3-95.4). The PPV was 98.7% (95% CI: 97.6-99.3) for the primary diagnoses and 68.8% (95% CI: 60.7-75.9) for the secondary diagnoses. When stratified according to subgroups of major anatomical sites, the PPVs ranged between 94.1% and 100% for the primary diagnoses, and between 53.8% and 100% for secondary diagnoses. Conclusion: The overall validity of non-traumatic bleeding diagnoses in the Danish National Patient Registry is high and considered acceptable for epidemiological research. However, PPVs were substantially higher for primary than for secondary diagnosis.
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OBJECTIVES: To investigate geographical variation in initiation and extended treatment with anticoagulants and clinical outcomes among patients hospitalized with first-time venous thromboembolism (VTE) in Denmark between 2007 and 2018. METHODS: Using nationwide health care registries, we identified all patients with a first-time VTE hospital diagnosis supported by imaging data from 2007 to 2018. Patients were grouped according to residential region (5) and municipality (98) at the time of VTE diagnosis. Cumulative incidence of initiation of and extended (beyond 365 days) anticoagulation treatment as well as clinical outcomes, including recurrent VTE, major bleeding, and all-cause death, were assessed. Sex- and age-adjusted relative risks (RRs) of the outcomes were computed when comparing across individual regions and municipalities. Overall geographic variation was quantified by computing the median RR. RESULTS: We identified 66,840 patients with a first-time VTE hospitalization. A difference in initiation of anticoagulation treatment of more than 20 percentage points between regions was observed (range: 51.9-72.4%, median RR: 1.09, 95% confidence interval [CI]: 1.04-1.13). Variation was also observed for extended treatment (range: 34.2-46.9%, median RR: 1.08, 95% CI: 1.02-1.14). The cumulative incidence of recurrent VTE ranged from 3.6 to 5.3% at 1 year (median RR: 1.08, 95% CI: 1.01-1.15). The difference remained after 5 years, and variation was also observed for major bleeding (median RR: 1.09, 95% CI: 1.03-1.15), whereas it appeared smaller for all-cause mortality (median RR: 1.03, 95% CI: 1.01-1.05). CONCLUSION: Substantial geographical variation in anticoagulation treatment and clinical outcomes occurs in Denmark. These findings indicate a need for initiatives to ensure uniform high-quality care for all VTE patients.
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Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/epidemiología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Estudios de Cohortes , Análisis de Área Pequeña , Neoplasias/complicaciones , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/complicaciones , Dinamarca/epidemiologíaRESUMEN
There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.