Risk of recurrence after a first unprovoked venous thromboembolism : external validation of the Vienna Prediction Model with pooled individual patient data

Background: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. Objective: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Patients/Methods: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. Results: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P\ua0=\ua00.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12\ua0months. Conclusions: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence

Reference materials (RMs) for analysis of the human factor II (prothrombin) gene G20210A mutation

The Scientific Committee of Molecular Biology Techniques (C-MbT) in Clinical Chemistry of the IFCC has initiated a joint project in co-operation with the European Commission, Joint Research Centre, Institute of Reference Materials and Measurements to develop and produce plasmid-type reference materials (RMs), for the analysis of the human prothrombin gene G20210A mutation. Although DNA tests have a high impact on clinical decision-making and the number of tests performed in diagnostic laboratories is high, issues of quality and quality assurance exist, and currently only a few RMs for clinical genetic testing are available. A gene fragment chosen was produced that spans all primer annealing sites published to date. Both the wild-type and mutant alleles of this gene fragment were cloned into a pUC18 plasmid and two plasmid RMs were produced. In addition, a mixture of both plasmids was produced to mimic the heterozygous genotype. The present study describes the performance of these reference materials in a commutability study, in which they were tested by nine different methods in 13 expert laboratories.. This series of plasmid RMs are, to the best of our knowledge, the first plasmid-type clinical genetic RMs introduced worldwide

The progression from obesity to type 2 diabetes in Alström syndrome.

Rapporten är en studie av åtgärder mot kemiska hälsorisker inom kemisk industri.Rapporten är en studie av åtgärder mot kemiska hälsorisker inom kemisk industri

Effect of growth hormone replacement therapy in a boy with Dent's disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Dent's disease is an X-linked recessive proximal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis and progressive renal failure. To the best of our knowledge, this is only the third report on the use of growth hormone therapy in a child with poor growth associated with Dent's disease.</p> <p>Case presentation</p> <p>We report on a 7-year-old Montenegrin boy with proteinuria, hypercalciuria, nephrocalcinosis, rickets and short stature with unimpaired growth hormone secretion. A molecular genetic analysis showed S244L substitution on the CLCN5 gene. After two years of conventional treatment with hydrochlorothiazide, laboratory tests revealed more prominent proteinuria, mild hypophosphatemia, increased values of alkaline phosphatase and features of rickets. Phosphate salts, calcitriol, potassium citrate and growth hormone were included in the therapy. After three years of therapy, his adjusted parental stature was 1.53 standard deviations higher than at the initiation of growth hormone therapy. His global kidney functions and levels of proteinuria and calciuria remained relatively stable. In spite of the growth hormone therapy, his tubular reabsorption of phosphate deteriorated.</p> <p>Conclusion</p> <p>Treatment with recombinant human growth hormone may have a positive effect on final height in poorly growing children with Dent's disease and hypophosphatemic rickets. However, it is not possible to reach definite conclusions due to the small sample within the literature and the brief duration of the therapy.</p

Diversidade de mamíferos em fragmentos florestais urbanos na Bacia Hidrográfica do Rio Cachoeira, Joinville, SC

Na mata atlântica, reduzida a cerca de 12% de sua cobertura original, é inevitável que a riqueza mastofaunística esteja pressionada pelas atividades antrópicas. A Bacia Hidrográfica do Rio Cachoeira, inserida na malha urbana, possui fragmentos de floresta ainda pouco conhecidos em relação à sua diversidade. O objetivo deste trabalho foi analisar a ocorrência de mamíferos nos fragmentos florestais urbanos da Bacia Hidrográfica do Rio Cachoeira. A amostragem foi realizada em cinco fragmentos de floresta ombrófila densa, combinando diversos métodos: armadilhas de contenção viva, armadilhas fotográficas, redes de neblina, transecções para procura de vestígios, entrevistas e revisão na literatura. Foram registradas 32 espécies de 13 famílias e sete ordens, sendo duas espécies exóticas. Três espécies foram registradas nos cinco sítios: Dasypus novemcinctus, Carollia perspicillata e Canis familiaris. Cinco espécies foram registradas em quatro sítios: Didelphis aurita, Artibeus lituratus, Nasua nasua, Procyon cancrivorus e Dasyprocta azarae. Catorze espécies foram registradas somente em um dos cinco sítios. Do total de espécies, 56,3% são onívoras. A diversidade nos sítios não está relacionada ao tamanho dos fragmentos. Sugerem-se programas de monitoramento, controle de espécies exóticas, construção de corredores, enriquecimento e translocações

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohort

von Willebrand disease: proposing definitions for future research

Thrombosis and Hemostasi