Concomitant renal insufficiency and diabetes mellitus as prognostic factors for acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Diabetes mellitus and renal dysfunction are prognostic factors after acute myocardial infarction (AMI). However, few studies have assessed the effects of renal insufficiency in association with diabetes in the context of AMI. Here, we investigated the clinical outcomes according to the concomitance of renal dysfunction and diabetes mellitus in patients with AMI.</p> <p>Methods</p> <p>From November 2005 to August 2008, 9905 patients (63 ± 13 years; 70% men) with AMI were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) and were categorized into 4 groups: Group I (n = 5700) had neither diabetes nor renal insufficiency (glomerular filtration rate [GFR] ≥ 60 ml/min/1.73 m²), Group II (n = 1730) had diabetes but no renal insufficiency, Group III (n = 1431) had no diabetes but renal insufficiency, and Group IV (n = 1044) had both diabetes and renal insufficiency. The primary endpoints were major adverse cardiac events (MACE), including a composite of all cause-of-death, myocardial infarction, target lesion revascularization, and coronary artery bypass graft after 1-year clinical follow-up.</p> <p>Results</p> <p>Primary endpoints occurred in 1804 (18.2%) patients. There were significant differences in composite MACE among the 4 groups (Group I, 12.5%; Group II, 15.7%; Group III, 30.5%; Group IV, 36.5%; <it>p </it>< 0.001). In a Cox proportional hazards model, after adjusting for multiple covariates, the 1-year mortality increased stepwise from Group III to IV as compared with Group I (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.34-2.86; <it>p </it>= 0.001; and HR, 2.42; 95% CI, 1.62-3.62; <it>p </it>< 0.001, respectively). However, Kaplan-Meier analysis showed no significant difference in probability of death at 1 year between Group III and IV (p = 0.288).</p> <p>Conclusions</p> <p>Renal insufficiency, especially in association with diabetes, is associated with the occurrence of composite MACE and indicates poor prognosis in patients with AMI. Categorization of patients with diabetes and/or renal insufficiency provides valuable information for early-risk stratification of AMI patients.</p

The Ship Detection Using Airborne and In-situ Measurements Based on Hyperspectral Remote Sensing

International audienceMaritime accidents around the Korean Peninsula are increasing, and the ship detection research using remote sensing data is consequently becoming increasingly important. This study presented a new ship detection algorithm using hyperspectral images that provide the spectral information of several hundred channels in the ship detection field, which depends on high resolution optical imagery. We applied a spectral matching algorithm between the reflection spectrum of the ship deck obtained from two field observations and the ship and seawater spectrum of the hyperspectral sensor of an airborne visible/infrared imaging spectrometer. A total of five detection algorithms were used, namely spectral distance similarity (SDS), spectral correlation similarity (SCS), spectral similarity value (SSV), spectral angle mapper (SAM), and spectral information divergence (SID). SDS showed an error in the detection of seawater inside the ship, and SAM showed a clear classification result with a difference between ship and seawater of approximately 1.8 times. Additionally, the present study classified the vessels included in hyperspectral images by presenting the adaptive thresholds of each technique. As a result, SAM and SID showed superior ship detection abilities compared to those of other detection algorithms

Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons

Background. The adjuvanted RSV prefusion F protein–based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post–dose 1. Methods. In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre–season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre–season 2; participants who received placebo pre–season 1 received placebo pre–season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%). Results. The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2–80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6–92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1–80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5–92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1. Conclusions. One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post–dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population. Clinical Trials Registration. ClinicalTrials.gov: NCT04886596

Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions

Background Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in &amp; GE;60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest").Methods Medically stable &amp; GE;60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups.Results In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had &amp; GE;1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with &amp; GE;1 condition of interest (94.6%), &amp; GE;1 cardiorespiratory (92.1%), &amp; GE;1 endocrine/metabolic (100%), and &amp; GE;2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with &amp; GE;1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with &amp; GE;2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with &amp; GE;1 condition of interest as in those without.Conclusions RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease.Clinical Trials Registration ClinicalTrials.gov: NCT04886596.Graphical Abstrac

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

© 2018 The Author(s). Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling

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&nbsp;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&nbsp;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&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 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&nbsp;= 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&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P &lt; 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.</p

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Background Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20–29?years to 70–79?years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results In 2005–16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P &lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age