Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment to target strategy

Objective: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early rheumatoid arthritis (RA), achieved with treat-to-target management in clinical practice. Methods: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by disease activity score (DAS28-CRP<2.6). Twelve month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on ultrasound (US) of 26 joints (total PDA score=0 or ≤1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes. Results: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Amongst patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42%, 44% and 40%, respectively; absent/minimal PDA was detected in 62%, 66% and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of osteoarthritis predicted absence of PDA and lower total baseline PDA predicted absent/minimal PDA. Conclusion: DAS28-CRP remission and absence of PDA were observed in almost half of patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target

Bayesian hierarchical modeling of longitudinal glaucomatous visual fields using a two-stage approach

The Bayesian approach has become increasingly popular because it allows to fit quite complex models to data via Markov chain Monte Carlo sampling. However, it is also recognized nowadays that Markov chain Monte Carlo sampling can become computationally prohibitive when applied to a large data set. We encountered serious computational difficulties when fitting an hierarchical model to longitudinal glaucoma data of patients who participate in an ongoing Dutch study. To overcome this problem, we applied and extended a recently proposed two-stage approach to model these data. Glaucoma is one of the leading causes of blindness in the world. In order to detect deterioration at an early stage, a model for predicting visual fields (VFs) in time is needed. Hence, the true underlying VF progression can be determined, and treatment strategies can then be optimized to prevent further VF loss. Because we were unable to fit these data with the classical one-stage approach upon which the current popular Bayesian software is based, we made use of the two-stage Bayesian approach. The considered hierarchical longitudinal model involves estimating a large number of random effects and deals with censoring and high measurement variability. In addition, we extended the approach with tools for model evaluation. Copyrigh

Implementation of the Diagnostic Pathfinder, an Internet-Based Tool to Teach Clinical Pathology in Diverse Educational Settings

Those of us who teach clinical pathology to veterinary students are continually exploring more effective ways to help students master the application of laboratory medicine to the solution of clinical problems. We not only must teach students the pathophysiologic basis of disease as applied to clinical laboratory data, but we also must instill a diagnostic reasoning process that is consistent and reliable. This reasoning process must be successful when applied to both common and uncommon diseases in multiple species, and also must be suitable for characterizing emerging diseases. Many of us have successfully used mechanism-based instruction to teach diagnostic reasoning, rather than presenting lists of facts and relying upon students to rote memorize

An approach to the use of indices-based analysis subject to money laundering and terrorist financing national risk assessment

The core aim of this study is to propose an approach to quantitate estimation of indices-based information subject to necessities of the National Risk Assessment (NRA) of money laundering and terrorist financing (ML/TF) risks. Mathematical formalization analysis for Ukraine based on 11 indices and indicators for years 2011-2015 subject to core areas of the overall situation in a country considered within its National Risk Assessment was carried out. Authors’ contribution covers scientific novelty that is a first-time analysis of a general situation in a jurisdiction in light of the National Risk Assessment’s requirements based on joint consideration of various indices and setting priority to areas of the overall country’s situation in the framework of conducted calculations. It was concluded that proposed approach is a valuable instrument for assessing priority of areas of the overall situation in the country for the National Risk Assessment’s purposes through a formalized mechanism ensuring high objectiveness. Practical significance of this study is a possibility to reach higher efficiency in allocation of available resources for the participants of the National Risk Assessment, to reduce some costs considering flexibility of the approach allowing consideration of significant volumes of information, its updating and comparison. This research could become a starting point for further research. Considering complexity of existing indices, there is a necessity to study a mechanism of their correlation and mutual influence, analyze elasticity and joint behavior, and discover the areas of preferable influence on large range of purposes not only limited to the MRA of ML/TF risks

Osteocalcin binds tightly to the γ-glutamylcarboxylase at a site distinct from that of the other known vitamin K-dependent proteins

Vitamin K-dependent proteins contain a propeptide that is required for recognition by the enzyme gamma-glutamylcarboxylase. Substrates used in vitro for carboxylation studies lacking a prosequence are characterized by Km values in the millimolar range, whereas the Km for peptides containing a prosequence is three or four orders of magnitude smaller. Here we report that descarboxy-osteocalcin is an exception in this respect. With descarboxy-osteocalcin in purified propeptide-free recombinant carboxylase, the Km was 1.8 microM. Furthermore, osteocalcin was an inhibitor of descarboxy-osteocalcin carboxylation with a Ki of 76 microM. In contrast with the other vitamin K-dependent proteins, free propeptides do not inhibit descarboxy-osteocalcin carboxylation. Moreover, propeptide-containing substrates were inhibited neither by osteocalcin nor by its propeptide. From our studies we conclude that descarboxy-osteocalcin must have an internal recognition sequence that binds to gamma-glutamylcarboxylase at a site different from the propeptide-recognition site

Observational Dutch Young Symptomatic StrokE studY (ODYSSEY): Study rationale and protocol of a multicentre prospective cohort study

Background: The proportion of strokes occurring in younger adults has been rising over the past decade. Due to the far longer life expectancy in the young, stroke in this group has an even larger socio-economic impact. However, information on etiology and prognosis remains scarce.Methods/design: ODYSSEY is a multicentre prospective cohort study on the prognosis and risk factors of patients with a first-ever TIA, ischemic stroke or intracerebral hemorrhage aged 18 to 49 years. Our aim is to include 1500 patients. Primary outcome will be all cause mortality and risk of recurrent vascular events. Secondary outcome will be the risk of post-stroke epilepsy and cognitive impairment. Patients will complete structured questionnaires on outcome measures and risk factors. Both well-documented and less well-documented risk factors and potentially acute trigger factors will be investigated. Patients will be followed every 6 months for at least 3 years. In addition, an extensive neuropsychological assessment will be administered both at baseline and 1 year after the stroke/TIA. Furthermore we will include 250 stroke-free controls, who will complete baseline assessment and one neuropsychological assessment.Discussion: ODYSSEY is designed to prospectively determine prognosis after a young stroke and get more insight into etiology of patients with a TIA, ischemic stroke and intracerebral hemorrhage in patients aged 18 to 49 years old in a large sample size

Continuously improving the practice of cardiology

Guidelines for the management of patients with cardiovascular disease are designed to assist cardiologists and other physicans in their practice. Surveys are conducted to assess whether guidelines are followed in practice. The results of surveys on acute coronary syndromes, coronary revascularisation, secondary prevention, valvular heart disease and heart failure are presented. Comparing surveys conducted between 1995 and 2002, a gradual improvement in use ofsecondary preventive therapy is observed. Nevertheless, important deviations from established guidelines are noted, with a significant variation among different hospitals in the Netherlands and in other European countries. Measures for fiuther improvement of clinical practice indude more rapid treatment of patients with evolving myocardial infarction, more frequent use of clopidogrel and glycoprotein IIb/IIIa receptor blockers in patients with acute coronary syndromes, more frequent use of 5-blockers in patients with heart failure and more intense measures to encourage patients to stop smoking. Targets for the proportion ofpatients who might receive specific therapies are presented