472 research outputs found
Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples
Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample procedure for TDM. TDM was found to be an important component of clinical care for many (but not all) pulmonary infections. For gentamicin, linezolid, voriconazole and posaconazole dried blood spot methods and their use in TDM were already evident in literature. For glycopeptides, beta-lactam antibiotics and fluoroquinolones it was determined that development of a dried blood spot (DBS) method could be useful. This review identifies specific antibiotics for which development of DBS methods could support the optimization of treatment of pulmonary infections
A many-analysts approach to the relation between religiosity and well-being
The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported beta = 0.120). For the second research question, this was the case for 65% of the teams (median reported beta = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates
Myocardial extracellular volume fraction to differentiate healthy from cardiomyopathic myocardium using dual-source dual-energy CT
Objective: To evaluate the feasibility of dual-energy CT (DECT)-based iodine quantification to estimate myocardial extracellular volume (ECV) fraction in patients with and without cardiomyopathy (CM), as well as to assess its ability to distinguish healthy myocardial tissue from cardiomyopathic, with the goal of defining a threshold ECV value for disease detection. Methods: Ten subjects free of heart disease and 60 patients with CM (mean age 66.4 ± 9.4; 59 males and 11 females; 40 ischemic and 20 non-ischemic CM) underwent late iodine enhanced DECT imaging. Myocardial iodine maps were obtained using 3-material decomposition. ECV of the left ventricle was estimated from hematocrit levels and the iodine maps using the AHA 16-segment model. Receiver operating characteristic curve analysis was performed, with corresponding area under the curve, along with Youden's index assessment, to establish a threshold for CM detection. Results: The median ECV for healthy myocardium, non-ischemic CM, and ischemic CM were 25.4% (22.9â27.3), 38.3% (33.7â43.0), and 36.9% (32.4â41.1), respectively. Healthy myocardium showed significantly lower ECV values compared to ischemic and non-ischemic CM (p 29.5% would indicate the presence of CM in the myocardium (sensitivity = 90.3; specificity = 90.3); the AUC for this criterion was 0.950 (p < 0.001). Conclusion: The findings of this study resulted in a statistically significant distinction between healthy myocardium and CM ECVs. This led to the establishment of a promising threshold ECV value that could facilitate the differentiation between healthy and diseased myocardium, and highlights the potential of this DECT methodology to detect cardiomyopathic tissue
Rhodococcus equi Infection after Alemtuzumab Therapy for T-cell Prolymphocytic Leukemia
Rhodococcus equi, mainly known from veterinary medicine as a pathogen in domestic animals, can also cause infections in immunocompromised humans, especially in those with defects in cellular immunity. Alemtuzumab, an anti-CD52 monoclonal antibody, causes lymphocytopenia by eliminating CD52-positive cells. We report a patient in whom Rhodococcus equi infection developed after alemtuzumab therapy
Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus:No association with subclinical viral reactivations or lupus disease activity
Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia
Moral imagination as an instrument for ethics education for biomedical researchers
Moral sensitivity and moral reasoning are essential competencies biomedical researchers have to develop to make ethical decisions in their daily practices. Previous research has shown that these competencies can be developed through ethics education. However, it is unclear which underlying mechanisms best support the development of these competencies. In this article we argue that the development of moral sensitivity and moral reasoning can be fostered through teaching strategies that tap into studentsâ moral imagination. We describe how moral imagination can stimulate the development of these competencies through three different merits of moral imagination. Moral imagination can help students to 1) transfer and apply abstract moral concepts to concrete situations and contexts, 2) explore the perspective of others, 3) explore and foresee the moral consequences of different decisions and actions. We explain these three merits of moral imagination in the context of biomedical research and present a theoretical model for how these merits can be used to stimulate the development of moral sensitivity and moral reasoning. Furthermore, we describe multiple teaching strategies for biomedical curricula that tap into the three merits of moral imagination. These teaching strategies can inspire teachers to design ethics education that activates studentsâ moral imagination for the development of moral sensitivity and moral reasoning
Automatic coronary calcium scoring in chest CT using a deep neural network in direct comparison with non-contrast cardiac CT:A validation study
Purpose: To evaluate deep-learning based calcium quantification on Chest CT scans compared with manual evaluation, and to enable interpretation in terms of the traditional Agatston score on dedicated Cardiac CT. Methods: Automated calcium quantification was performed using a combination of deep-learning convolution neural networks with a ResNet-architecture for image features and a fully connected neural network for spatial coordinate features. Calcifications were identified automatically, after which the algorithm automatically excluded all non-coronary calcifications using coronary probability maps and aortic segmentation. The algorithm was first trained on cardiac-CTs and refined on non-triggered chest-CTs. This study used on 95 patients (cohort 1), who underwent both dedicated calcium scoring and chest-CT acquisitions using the Agatston score as reference standard and 168 patients (cohort 2) who underwent chest-CT only using qualitative expert assessment for external validation. Results from the deep-learning model were compared to Agatston-scores(cardiac-CTs) and manually determined calcium volumes(chest-CTs) and risk classifications. Results: In cohort 1, the Agatston score and AI determined calcium volume shows high correlation with a correlation coefficient of 0.921(p < 0.001) and R-2 of 0.91. According to the Agatston categories, a total of 67(70 %) were correctly classified with a sensitivity of 91 % and specificity of 92 % in detecting presence of coronary calcifications. Manual determined calcium volume on chest-CT showed excellent correlation with the AI volumes with a correlation coefficient of 0.923(p < 0.001) and R-2 of 0.96, no significant difference was found (p = 0.247). According to qualitative risk classifications in cohort 2, 138(82 %) cases were correctly classified with a k-coefficient of 0.74, representing good agreement. All wrongly classified scans (30(18 %)) were attributed to an adjacent category. Conclusion: Artificial intelligence based calcium quantification on chest-CTs shows good correlation compared to reference standards. Fully automating this process may reduce evaluation time and potentially optimize clinical calcium scoring without additional acquisitions
Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA)
Background: Patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions.<p></p>
Objectives: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide.<p></p>
Methods Study design: international, cross-sectional. Patients: consecutive RA patients. Data collected: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders).<p></p>
Results: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13â
years; disease duration, 10±9â
years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)âerythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%.<p></p>
Conclusions: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.<p></p>
Ensuring the quality and specificity of preregistrations
Researchers face many, often seemingly arbitrary, choices in formulating hypotheses, designing protocols, collecting data, analyzing data, and reporting results. Opportunistic use of âresearcher degrees of freedomâ aimed at obtaining statistical significance increases the likelihood of obtaining and publishing false-positive results and overestimated effect sizes. Preregistration is a mechanism for reducing such degrees of freedom by specifying designs and analysis plans before observing the research outcomes. The effectiveness of preregistration may depend, in part, on whether the process facilitates sufficiently specific articulation of such plans. In this preregistered study, we compared 2 formats of preregistration available on the OSF: Standard Pre-Data Collection Registration and Prereg Challenge Registration (now called âOSF Preregistration,â http://osf.io/prereg/). The Prereg Challenge format was a âstructuredâ workflow with detailed instructions and an independent review to confirm completeness; the âStandardâ format was âunstructuredâ with minimal direct guidance to give researchers flexibility for what to prespecify. Results of comparing random samples of 53 preregistrations from each format indicate that the âstructuredâ format restricted the opportunistic use of researcher degrees of freedom better (Cliffâs Delta = 0.49) than the âunstructuredâ format, but neither eliminated all researcher degrees of freedom. We also observed very low concordance among coders about the number of hypotheses (14%), indicating that they are often not clearly stated. We conclude that effective preregistration is challenging, and registration formats that provide effective guidance may improve the quality of research
Characterization of ascending aortic flow in patients with degenerative aneurysms a 4D flow magnetic resonance study
Objectives Degenerative thoracic aortic aneurysm (TAA) patients are known to be at risk of life-threatening acute aortic events. Guidelines recommend preemptive surgery at diameters of greater than 55 mm, although many patients with small aneurysms show only mild growth rates and more than half of complications occur in aneurysms below this threshold. Thus, assessment of hemodynamics using 4-dimensional flow magnetic resonance has been of interest to obtain more insights in aneurysm development. Nonetheless, the role of aberrant flow patterns in TAA patients is not yet fully understood. Materials and Methods A total of 25 TAA patients and 22 controls underwent time-resolved 3-dimensional phase contrast magnetic resonance imaging with 3-directional velocity encoding (ie, 4-dimensional flow magnetic resonance imaging). Hemodynamic parameters such as vorticity, helicity, and wall shear stress (WSS) were calculated from velocity data in 3 anatomical segments of the ascending aorta (root, proximal, and distal). Regional WSS distribution was assessed for the full cardiac cycle. Results Flow vorticity and helicity were significantly lower for TAA patients in all segments. The proximal ascending aorta showed a significant increase in peak WSS in the outer curvature in TAA patients, whereas WSS values at the inner curvature were significantly lower as compared with controls. Furthermore, positive WSS gradients from sinotubular junction to midascending aorta were most prominent in the outer curvature, whereas from midascending aorta to brachiocephalic trunk, the outer curvature showed negative WSS gradients in the TAA group. Controls solely showed a positive gradient at the inner curvature for both segments. Conclusions Degenerative TAA patients show a decrease in flow vorticity and helicity, which is likely to cause perturbations in physiological flow patterns. The subsequent differing distribution of WSS might be a contributor to vessel wall remodeling and aneurysm formation.Cardiolog
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