The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Degeneración macular asociada a la edad: aspectos clínicos en el manejo de los Anti-vegf

La DMAE es la principal causa de ceguera en pacientes por encima de los 65 años. La investigación de esta enfermedad está adquiriendo gran importancia desde hace años por su alta prevalencia a nivel mundial. Desde la introducción de los fármacos anti-VEGF ha mejorado de manera sustancial el pronóstico de los pacientes afectos por la forma húmeda de esta enfermedad. El propósito de esta tesis es evaluar nuestra experiencia en un centro terciario de referencia con el uso de los anti- VEFG en la práctica clínica diaria para el tratamiento de esta enfermedad. En concreto nuestros objetivos son estudiar los resultados anatómico funcionales con nuestra pauta de tratamiento basada en 2+ PRN, comparar los principales fármacos utilizados ( Bevacizumab y Ranibizumab) y evaluar algunos factores de riesgo generales, locales y maculares para predecir si los mismos pueden influir en el resultado funcional final. Inicialmente se realiza una revisión de la literatura. Se profundiza en la etiopatogenia, epidemiología, factores de riesgo y clasificación de la enfermedad, para terminar revisando de manera amplia la evolución de los diferentes tratamientos utilizados para el tratamiento de la DMAE neovascular. El estudio diseñado es prospectivo, intervencional, comparativo y no randomizado y comprende una muestra de 94 ojos, homogénea a nivel de características demográficas y oculares basales, con valores medios en cuanto a las características poblacionales coincidentes con los de la típica población utilizada en la mayoría de los grandes estudios randomizados, todos los casos cuentan con un seguimiento mínimo de 6 meses. Se utiliza en todos los pacientes una pauta de 2+ PRN y como tratamiento se administra Bevacizumab, Ranibizumab o bien tratamiento combinado. Como conclusión los resultados obtenidos nos muestran que nuestra pauta utilizada de 2 inyecciones en la fase de carga presenta mayor número de recidivas y peores resultados visuales finales que las pautas de 3 inyecciones +mantenimiento usadas en la mayoría de series publicadas y que no hay diferencias entre los dos fármacos principales a estudio Ranibizumab y Bevacizumab a nivel de resultados anatómicos y funcionales finales, pero parece que el Ranibizumab es más efectivo a corto plazo. En cuanto al estudio de los factores de riesgo, se observa que la hipertensión arterial, el colesterol total y la edad son los factores que influyen de manera directa en el pronóstico funcional final.AMD is the leading cause of blindness in patients over 65 years. The investigation of this disease has gained considerable importance over the years by its high prevalence worldwide. Since the introduction of anti-VEGF drugs have substantially improved the prognosis of patients affected by the wet form of the disease. The purpose of this thesis is to evaluate our experience in a tertiary referral center with the use of anti-VEGF in clinical practice for the treatment of this disease. Specifically our objectives are to study the functional anatomical results with our treatment regimen based on 2 + PRN, comparing the main drugs used (Bevacizumab and Ranibizumab) and evaluate some general risk factors, local and macular to predict whether they can influence the final functional outcome. Initially we review the literature. It delves into the pathogenesis, epidemiology, risk factors and disease classification, to finish reviewing comprehensively the evolution of the different treatments used to treat neovascular AMD. The study design is prospective, interventional, nonrandomized comparative and includes a sample of 94 eyes, homogeneous level of baseline demographic and ocular, with mean values, in terms of population characteristics, that match those of the typical population used in most of large randomized studies, all cases have a follow up 6 months or more. It is used in all patients a pattern of 2 + PRN and as treatment is administered Bevacizumab, Ranibizumab or combination therapy. In conclusion the results show that our regimen of 2 injections used in the loading phase shows more relapses and worse final visual results than patterns of 3 injections + manteinance used in most published series. They also indicate that there is no difference between the two main drugs Lucentis and Avastin in late anatomical and functional results, but it seems that Ranibizumab is more effective the short-term. As for the study of risk factors, we observe that high blood pressure, total cholesterol and age are factors that directly influence the functional prognosis

Degeneración macular asociada a la edad : aspectos clínicos en el manejo de los anti-vegf /

La DMAE es la principal causa de ceguera en pacientes por encima de los 65 años. La investigación de esta enfermedad está adquiriendo gran importancia desde hace años por su alta prevalencia a nivel mundial. Desde la introducción de los fármacos anti-VEGF ha mejorado de manera sustancial el pronóstico de los pacientes afectos por la forma húmeda de esta enfermedad. El propósito de esta tesis es evaluar nuestra experiencia en un centro terciario de referencia con el uso de los anti- VEFG en la práctica clínica diaria para el tratamiento de esta enfermedad. En concreto nuestros objetivos son estudiar los resultados anatómico funcionales con nuestra pauta de tratamiento basada en 2+ PRN, comparar los principales fármacos utilizados ( Bevacizumab y Ranibizumab) y evaluar algunos factores de riesgo generales, locales y maculares para predecir si los mismos pueden influir en el resultado funcional final. Inicialmente se realiza una revisión de la literatura. Se profundiza en la etiopatogenia, epidemiología, factores de riesgo y clasificación de la enfermedad, para terminar revisando de manera amplia la evolución de los diferentes tratamientos utilizados para el tratamiento de la DMAE neovascular. El estudio diseñado es prospectivo, intervencional, comparativo y no randomizado y comprende una muestra de 94 ojos, homogénea a nivel de características demográficas y oculares basales, con valores medios en cuanto a las características poblacionales coincidentes con los de la típica población utilizada en la mayoría de los grandes estudios randomizados, todos los casos cuentan con un seguimiento mínimo de 6 meses. Se utiliza en todos los pacientes una pauta de 2+ PRN y como tratamiento se administra Bevacizumab, Ranibizumab o bien tratamiento combinado. Como conclusión los resultados obtenidos nos muestran que nuestra pauta utilizada de 2 inyecciones en la fase de carga presenta mayor número de recidivas y peores resultados visuales finales que las pautas de 3 inyecciones +mantenimiento usadas en la mayoría de series publicadas y que no hay diferencias entre los dos fármacos principales a estudio Ranibizumab y Bevacizumab a nivel de resultados anatómicos y funcionales finales, pero parece que el Ranibizumab es más efectivo a corto plazo. En cuanto al estudio de los factores de riesgo, se observa que la hipertensión arterial, el colesterol total y la edad son los factores que influyen de manera directa en el pronóstico funcional final.AMD is the leading cause of blindness in patients over 65 years. The investigation of this disease has gained considerable importance over the years by its high prevalence worldwide. Since the introduction of anti-VEGF drugs have substantially improved the prognosis of patients affected by the wet form of the disease. The purpose of this thesis is to evaluate our experience in a tertiary referral center with the use of anti-VEGF in clinical practice for the treatment of this disease. Specifically our objectives are to study the functional anatomical results with our treatment regimen based on 2 + PRN, comparing the main drugs used (Bevacizumab and Ranibizumab) and evaluate some general risk factors, local and macular to predict whether they can influence the final functional outcome. Initially we review the literature. It delves into the pathogenesis, epidemiology, risk factors and disease classification, to finish reviewing comprehensively the evolution of the different treatments used to treat neovascular AMD. The study design is prospective, interventional, nonrandomized comparative and includes a sample of 94 eyes, homogeneous level of baseline demographic and ocular, with mean values, in terms of population characteristics, that match those of the typical population used in most of large randomized studies, all cases have a follow up 6 months or more. It is used in all patients a pattern of 2 + PRN and as treatment is administered Bevacizumab, Ranibizumab or combination therapy. In conclusion the results show that our regimen of 2 injections used in the loading phase shows more relapses and worse final visual results than patterns of 3 injections + manteinance used in most published series. They also indicate that there is no difference between the two main drugs Lucentis and Avastin in late anatomical and functional results, but it seems that Ranibizumab is more effective the short-term. As for the study of risk factors, we observe that high blood pressure, total cholesterol and age are factors that directly influence the functional prognosis

Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

© 2020 Elsevier Ltd. All rights reserved.Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.info:eu-repo/semantics/publishedVersio

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Drug prescription and delirium in older inpatients: Results from the nationwide multicenter Italian Delirium Day 2015-2016

Objective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship