ABSTRACT
The COVID-19 pandemic, a transformative event in modern society, has disrupted routine, work, behavior, and human relationships. Organizations, amidst the chaos, have innovatively adapted to the evolving situation. However, many countries were unprepared for the magnitude of the challenge, revealing the fragility of health responses due to inadequate leadership, insufficient resources, and poor information system integration. Structural changes in health systems are imperative, particularly in leadership, governance, human resources, financing, information systems, technology, and health service provision. This research utilizes the Technological Roadmapping method to analyze the health sector, focusing on public health, drawing on articles from SCOPUS and PubMed databases, and creating a roadmap extending to 2050. The research presents three long-term scenarios based on the literature-derived roadmap and explores various alternatives, including integrated care, telemedicine, Big Data utilization, nanotechnology, and Big Tech's AI services. The results underscore the anticipation of post-pandemic public health with high expectations, emphasizing the importance of integrating health history access, encouraging self-care, and leveraging technology for streamlined treatment. Practical implications include insights for decision makers and stakeholders to inform strategic planning and adapt to evolving industry demands, recognizing the significance of preventive services and the humanizing potential of technology.
ABSTRACT
The use of piezoelectric transducers for internal dynamic pressure measurements in ammunition testing provides a significant advantage in the development and performance analysis of weapons and ammunition. Knowledge of the electrical characteristics of the dynamic pressure measurement chain, which includes the piezoelectric transducer and the charge amplifier, is a relevant condition for the design of interior ballistics pressure measurement systems. Thus, this study aims to characterize and model a piezoelectric transducer and its associated charge amplifier. First, the piezoelectric transducer was characterized using impedance analysis and modeled using a least squares curve-fitting tool, according to the Butterworth-Van Dyke model. Next, the charge amplifier was characterized through response analysis based on known inputs and modeled using LTSpice simulation techniques and the least squares curve-fit tool. Consequently, a measurement chain model is presented and simulated for two cases with different impulse signals. The first impulse signal was obtained from an interior ballistics computer simulation, and in the second case, it was considered the negative step signal characteristic of the calibration of piezoelectric transducers by means of dead weight. From the simulations, it was possible to verify the effectiveness of the model, which provided results with a low error in relation to the original pressure curve, and its applicability is demonstrated by the result of the simulation of the pressure variation in the calibration, where the attenuation of the signal can be visualized as the characteristic of the input curve changes.
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The aim of this retrospective cross-sectional study was to verify the association between salivary flow rates (SFR) and the histopathologic aspects of labial salivary glands (LSG) in patients with rheumatoid arthritis (RA). Patients presenting rheumatologic diseases referred for oral evaluation were included in the study if they had RA and had SFR measured and LSG biopsy performed. Patients were excluded if they had systemic conditions that affect SFR or if they were being treated for hyposalivation. Cases without enough material for histopathologic analysis were also excluded. Data were collected through questionnaires, oral examination, resting and stimulated SFR, and LSG biopsies. A histopathologic reevaluation was carried out in order to seek for additional histopathologic aspects. Fifty-one patients met the inclusion criteria. The mean age was 53.5 years (25-77), and 94.1% were women. The median resting and stimulated SFRs were 0.24 mL/min and 1.02 mL/min, respectively. The presence of lymphocytic focus and fibrosis were significantly associated with stimulated SFR, but not with resting SFR. The odds ratio of patients who had hyposalivation for presenting a positive lymphocytic focus was 7.33 (confidence interval CI: 1.53-35.23) by the stimulated technique, and 2.56 (CI: 0.57-11.40) in resting SFR. In the medical records, 14 (31.80%) patients had been diagnosed with secondary Sjögren's syndrome. In conclusion, stimulated SFR represent a good screening test to predict lymphocytic focus in LSG in patients with RA, which represents the most specific test to diagnose Sjögren's syndrome.
Subject(s)
Arthritis, Rheumatoid , Salivary Glands , Xerostomia , Arthritis, Rheumatoid/complications , Biopsy , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Salivary Glands/pathology , Sjogren's Syndrome/complications , Xerostomia/etiologyABSTRACT
Smart manufacturing comprises fully integrated manufacturing systems that respond in real time to meet the changing demands and conditions in industrial activities, supply networks and customer needs. A smart manufacturing environment will face new challenges, including those concerning metrological issues, i.e., analysis of large quantities of data; communication systems for digitalization; measurement standards for automated process control; digital transformation of metrological services; and simulations and virtual measurement processes for the automatic assessment of measured data. Based on the assumption that the interplay between smart manufacturing and digitalization of metrology is an emerging research field, this paper aims to present a systematic literature review (SLR) based on a bibliographic data collection of 160 scientific articles retrieved from the Web of Science and Scopus databases over the 2016-2022 time frame. The findings presented in this review and recommendations for building a research agenda can help policy makers, researchers and practitioners by providing directions for the evolution of digital metrology and its role in the digitalization of the economy and society.
ABSTRACT
Increasing attention has been directed to cytotoxic CD4+ T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite Trypanosoma cruzi. CD4CTLs display parallel kinetics to Th1 cells in the spleen, mediate specific cytotoxicity against cells presenting pathogen-derived antigens and express immunoregulatory and/or exhaustion markers. We demonstrate that CD4CTL absolute numbers and activity are severely reduced in both Myd88-/- and Il18ra-/- mice. Of note, the infection of mixed-bone marrow chimeras revealed that wild-type (WT) but not Myd88-/- cells transcribe the CD4CTL gene signature and that Il18ra-/- and Myd88-/- CD4+ T cells phenocopy each other. Moreover, adoptive transfer of WT CD4+GzB+ T cells to infected Il18ra-/- mice extended their survival. Importantly, cells expressing the CD4CTL phenotype predominate among CD4+ T cells infiltrating the infected mouse cardiac tissue and are increased in the blood of Chagas patients, in which the frequency of CD4CTLs correlates with the severity of cardiomyopathy. Our findings describe CD4CTLs as a major player in immunity to a relevant human pathogen and disclose T-cell intrinsic IL-18R/MyD88 signaling as a key pathway controlling the magnitude of the CD4CTL response.
Subject(s)
Chagas Disease , Trypanosoma cruzi , Animals , CD4-Positive T-Lymphocytes , Humans , Mice , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Signal Transduction , Th1 CellsABSTRACT
Abstract The aim of this retrospective cross-sectional study was to verify the association between salivary flow rates (SFR) and the histopathologic aspects of labial salivary glands (LSG) in patients with rheumatoid arthritis (RA). Patients presenting rheumatologic diseases referred for oral evaluation were included in the study if they had RA and had SFR measured and LSG biopsy performed. Patients were excluded if they had systemic conditions that affect SFR or if they were being treated for hyposalivation. Cases without enough material for histopathologic analysis were also excluded. Data were collected through questionnaires, oral examination, resting and stimulated SFR, and LSG biopsies. A histopathologic reevaluation was carried out in order to seek for additional histopathologic aspects. Fifty-one patients met the inclusion criteria. The mean age was 53.5 years (25-77), and 94.1% were women. The median resting and stimulated SFRs were 0.24 mL/min and 1.02 mL/min, respectively. The presence of lymphocytic focus and fibrosis were significantly associated with stimulated SFR, but not with resting SFR. The odds ratio of patients who had hyposalivation for presenting a positive lymphocytic focus was 7.33 (confidence interval CI: 1.53-35.23) by the stimulated technique, and 2.56 (CI: 0.57-11.40) in resting SFR. In the medical records, 14 (31.80%) patients had been diagnosed with secondary Sjögren's syndrome. In conclusion, stimulated SFR represent a good screening test to predict lymphocytic focus in LSG in patients with RA, which represents the most specific test to diagnose Sjögren's syndrome.
ABSTRACT
BACKGROUND: Aedes aegypti is a vector for the transmission of diseases such as dengue fever, chikungunya, Zika fever, and yellow fever. In 2016, over 1 million cases of these diseases were reported in Brazil, which is an alarming public health issue. One of the ways of controlling this disease is by inspecting and neutralizing the places where A. aegypti lays its eggs. The Ministry of Planning, Development, and Administration of Brazil maintains the inspection statistics. OBJECTIVE: We propose a multi-criteria analysis to create an index for A. aegypti inspections reported through the Ministry of Planning, Development, and Administration system of Brazil. METHODS: Based on the repository from urban cleaning services combined with data on inspections conducted by government agencies in several Brazilian cities and municipalities, we selected and combined metrics, which we further ranked using the analytic hierarchy process methodology. We also developed risk maps based on the analytic hierarchy process ranking of the A. aegypti breeding sites. RESULTS: Based on our analysis and the available data, the priority for inspections should consider the number of sick people (weight 0.350), medical evaluations (weight 0.239), inspections (weight 0.201), mosquito breeding sites (weight 0.126), and days of absence from work (weight 0.096). CONCLUSIONS: The proposed index could aid public health practitioners in preventing the appearance of new A. aegypti breeding sites. This information technology application can help solve such public health challenges.
Subject(s)
Aedes , Dengue , Zika Virus Infection , Zika Virus , Animals , Brazil/epidemiology , Breeding , Dengue/epidemiology , Dengue/prevention & control , Humans , Mosquito Vectors , Zika Virus Infection/epidemiology , Zika Virus Infection/prevention & controlABSTRACT
BACKGROUND: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications. OBJECTIVES: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding. METHODS: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units). RESULTS: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003). CONCLUSIONS: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267).
Subject(s)
Acute Coronary Syndrome/drug therapy , Blood Coagulation Tests/instrumentation , Coronary Artery Bypass/statistics & numerical data , Purinergic P2Y Receptor Antagonists/administration & dosage , Time-to-Treatment/statistics & numerical data , Acute Coronary Syndrome/economics , Acute Coronary Syndrome/surgery , Aged , Aspirin/administration & dosage , Aspirin/adverse effects , Blood Transfusion/statistics & numerical data , Female , Hospital Costs/statistics & numerical data , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Postoperative Hemorrhage/chemically induced , Postoperative Hemorrhage/prevention & control , Preoperative Care/instrumentation , Purinergic P2Y Receptor Antagonists/adverse effectsABSTRACT
Three-dimensional (3D) imaging technologies have been increasingly explored in academia and the industrial sector, especially the ones yielding point clouds. However, obtaining these data can still be expensive and time-consuming, reducing the efficiency of procedures dependent on large datasets, such as the generation of data for machine learning training, forest canopy calculation, and subsea survey. A trending solution is developing simulators for imaging systems, performing the virtual scanning of the digital world, and generating synthetic point clouds from the targets. This work presents a guideline for the development of modular Light Detection and Ranging (LiDAR) system simulators based on parallel raycasting algorithms, with its sensor modeled by metrological parameters and error models. A procedure for calibrating the sensor is also presented, based on comparing with the measurements made by a commercial LiDAR sensor. The sensor simulator developed as a case study resulted in a robust generation of synthetic point clouds in different scenarios, enabling the creation of datasets for use in concept tests, combining real and virtual data, among other applications.
ABSTRACT
Several three-dimensional scanning methods have been developed and improved over the past 40 years. The peculiarities of each technique, associated with the computational advances of the period, allowed the increasing application and diffusion of the technology in several sectors, among them those related to metrology in ballistics and the testing of protective materials. The specific goal of such ballistic tests is to estimate the depth of indentation caused by projectiles. In particular, this study presents a comparative analysis between two three-dimensional optical scanning methods, taking into account the same object of interest. The comparative analysis was based on reference planes detected by Random Sample Consensus methodology in each cloud. By comparing the results of the different techniques, it was found for this case that three-dimensional reconstruction by stereo images estimated values closer to the real ones in comparison to those estimated by the structured light scanner, mainly due to the fact that, for three-dimensional reconstruction, the image acquisition was conducted statically.
ABSTRACT
INTRODUCTION: Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. METHODS: Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen-epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. RESULTS: Overall, 294 (74.2%) individuals had Lp(a) < 50 mg/dL [median (IQR) 13.2 (5.8-27.9) mg/dL] and 102 (25.8%) had Lp(a) ≥ 50 mg/dL [82.5 (67.6-114.5) mg/dL], P < 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp(a) ≥ 50 mg/dL (249.4 ± 43.8 PRU) versus Lp(a) < 50 mg/dL (243.1 ± 52.2 PRU), P = 0.277. Similar findings were present in individuals with (P = 0.228) and without (P = 0.669) CAD, and regardless of the agonist used or method of analysis (all P > 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99-1.01), P = 0.590]. CONCLUSION: In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity.
Subject(s)
Coronary Artery Disease , Blood Platelets , Humans , Lipoprotein(a) , Platelet Aggregation Inhibitors/therapeutic use , Platelet Function TestsABSTRACT
ABSTRACT Objective: To describe the oral health status of patients with multiple myeloma and compare to a control group. Materials and methods: The medical history of the studied subjects was obtained from the medical records and through interviews. Trained examiners evaluated the oral mucosa, teeth, periodontium and imaging aspects. The dental status was evaluated by the decayed, missing and filled teeth index. The presence of bone lesions was investigated with cone beam computer tomography images of the jaws. Results: The most common oral mucosa features were paleness (31%) and coated tongue (14.3%) in the multiple myeloma group (N = 42); and coated (21.4%) and fissured tongue (10.7%) in the control group (N = 28). The mean DMFT index of patients with multiple myeloma was high, but not significantly different from controls (14.57 versus 19.69, p = 0.975). Hypodense lesions suggestive of multiple myeloma were observed in the jaws of 73.8% of the patients. Hypodense lesions related to teeth were detected in 33.3% of the patients and in 53.6% of the controls (p = 0.832). Conclusions: The studied population of multiple myeloma patients presented many oral health issues that needed attention. Thus, oral care should be included in the routine treatment to improve the quality of the oral status in these patients.
Subject(s)
Humans , Male , Female , Middle Aged , Oral Manifestations , Dental Caries , Mouth , Multiple MyelomaABSTRACT
OBJECTIVE: To describe the oral health status of patients with multiple myeloma and compare to a control group. MATERIALS AND METHODS: The medical history of the studied subjects was obtained from the medical records and through interviews. Trained examiners evaluated the oral mucosa, teeth, periodontium and imaging aspects. The dental status was evaluated by the decayed, missing and filled teeth index. The presence of bone lesions was investigated with cone beam computer tomography images of the jaws. RESULTS: The most common oral mucosa features were paleness (31%) and coated tongue (14.3%) in the multiple myeloma group (N=42); and coated (21.4%) and fissured tongue (10.7%) in the control group (N=28). The mean DMFT index of patients with multiple myeloma was high, but not significantly different from controls (14.57 versus 19.69, p=0.975). Hypodense lesions suggestive of multiple myeloma were observed in the jaws of 73.8% of the patients. Hypodense lesions related to teeth were detected in 33.3% of the patients and in 53.6% of the controls (p=0.832). CONCLUSIONS: The studied population of multiple myeloma patients presented many oral health issues that needed attention. Thus, oral care should be included in the routine treatment to improve the quality of the oral status in these patients.
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INTRODUCTION: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. METHODS: This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). RESULTS: Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs - 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. CONCLUSIONS: DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02389582.
Subject(s)
Antithrombins/therapeutic use , Coronary Artery Disease/drug therapy , Dabigatran/therapeutic use , Enoxaparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Platelet Aggregation/drug effects , Aged , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). CONCLUSION: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.
Subject(s)
Blood Coagulation/physiology , Coronary Artery Disease/blood , Fibrinolysis/physiology , Ischemic Attack, Transient/blood , Platelet Aggregation/physiology , Stroke/blood , Aged , Blood Coagulation Tests , Case-Control Studies , Coronary Artery Disease/physiopathology , Female , Humans , Ischemic Attack, Transient/physiopathology , Male , Middle Aged , Platelet Function Tests , Prospective Studies , Stroke/physiopathologyABSTRACT
BACKGROUND: Patients with coronary artery disease (CAD) and previous ischemic cerebrovascular events (ICVE, ischemic stroke, or transitory ischemic attack) constitute a high-risk subgroup for cardiovascular outcomes. High-density lipoprotein cholesterol (HDL-C) levels are correlated with cardiovascular events. Lipid transfer to HDL affects structure size and HDL subclass profile. Impairment of this transfer could influence ischemic risk seen in patients with CAD + ICVE. The objective was to evaluate the HDL ability to receive the lipids in patients with CAD with or without ICVE. METHODS: Patients with CAD + ICVE (n = 60) and patients with CAD only (n = 60) were matched by age, sex, acute coronary syndromes (ACS) event type, and time elapsed between the ACS event and inclusion in the study. Lipid transfer to HDL was evaluated by incubating donor lipid nanoparticles labeled with radioactive unesterified cholesterol (UC) and esterified cholesterol (EC), phospholipid (PL), and triglyceride (TG) with whole plasma. After the chemical precipitation of non-HDL fractions and nanoparticles, the supernatant was counted for HDL radioactivity. RESULTS: CAD + ICVE group presented with impaired lipid transfer to HDL for PL (CAD + ICVE: 21.14 ± 2.7% vs CAD: 21.67 ± 3.1%, P = .03), TG (CAD + ICVE: 4.88 ± 0.97% vs CAD: 5.63 ± 0.92%, P = .002), and UC (CAD + ICVE: 5.55 ± 1.19% vs CAD: 6.16 ± 1.14%, P = .009). Lipid transfer to HDL was similar in both groups for EC. Adjusted models showed similar results. CONCLUSION: Patients with CAD and ICVE have reduced lipid transfer to HDL compared to those with CAD only. Dysfunctional HDL may account for the higher incidence of ischemic outcomes observed in this population.
Subject(s)
Brain Ischemia/complications , Carrier Proteins/blood , Coronary Artery Disease/blood , Lipid Metabolism , Lipoproteins, HDL/blood , Aged , Biomarkers/blood , Brain Ischemia/blood , Coronary Artery Disease/complications , Female , Follow-Up Studies , Humans , Male , Nanoparticles , Retrospective StudiesABSTRACT
Recent reports have suggested that aspirin effect might be influenced by bodyweight, with decreased efficacy in heavier individuals. We investigated the influence of bodyweight on aspirin pharmacodynamics in two independent datasets of patients taking non-enteric coated aspirin 100 mg QD for coronary artery disease (CAD). In the first dataset, 368 patients had their platelet aggregation assessed using VerifyNow Aspirin and measured in Aspirin Reaction Units (ARU). In the second dataset, 70 patients had serum thromboxane B2 (TXB2) dosage assessed by an ELISA assay and measured in pg/mL. Platelet aggregation was independently associated with bodyweight, with 8.41 (95% CI 1.86-14.97; adjusted p-value = 0.012) increase in ARU for every 10 kg. Furthermore, the rate of non-response to aspirin (defined as ARU ≥ 550) was significantly associated with increased bodyweight (adjusted p-value = 0.007), with OR = 1.23 (95% CI 1.06-1.42) for every 10 kg. Similar results were found considering body mass index (in kg/m2), with 15.5 (95% CI 5.0 to 25.9; adjusted p-value = 0.004) increase in ARU for every 10 kg and non-response OR = 1.43 (95% CI 1.13 to 1.81, adjusted p-value = 0.003) for every 5 kg/m2. Moreover, serum TXB2 was higher in patients weighting more than 70 kg (222.6 ± 62.9 versus 194.9 ± 61.9 pg/mL; adjusted p-value = 0.018). In two different datasets of patients with CAD on non-enteric coated aspirin 100 mg QD, increased bodyweight was independently associated with impaired response to aspirin.
Subject(s)
Aspirin/pharmacokinetics , Coronary Artery Disease/drug therapy , Weight Gain , Adult , Aged , Body Mass Index , Coronary Artery Disease/blood , Databases, Factual , Datasets as Topic , Female , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Platelet Aggregation/physiology , Thromboxane B2/administration & dosageABSTRACT
OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). CONCLUSION: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.