Risk of recurrent venous thromboembolism after discontinuation of vitamin K antagonist treatment: a nested case-control study.

UNLABELLED: Essentials Vitamin K antagonists (VKA) in venous thromboembolism (VTE) lower the risk of recurrences. 41 841 VKA-treated VTE patients had 1242 recurrent VTEs on therapy or early after cessation. An increased risk of recurrence was found in the first 120 days after VKA cessation. Patient education for the early detection of recurrent VTE after VKA cessation is recommended. SUMMARY: Background The standard treatment for venous thromboembolism (VTE) and the prevention of recurrent VTE (rVTE) consists of anticoagulant therapy. The optimal duration of anticoagulation depends on the presence of risk factors for rVTE. Objectives To estimate the risk of rVTE in association with time since discontinuation of vitamin K antagonist (VKA) treatment. Methods From the UK Clinical Practice Research Datalink with linked information on hospitalization and cause of death, a cohort of patients with a first VTE receiving initial VKA treatment between 2001 and 2013 was formed. With a nested case-control approach, patients with incident rVTE (cases) were matched to patients with VTE but without rVTE (controls). Adjusted rate ratios (RRs) of rVTE associated with time since VKA discontinuation relative to current VKA use were estimated from conditional logistic regression. Results The VTE cohort comprised 41 841 patients with 1242 rVTEs and 6205 matched controls. The RR of rVTE was increased within 60 days following VKA discontinuation (RR 2.23, 95% confidence interval [CI] 1.71-2.91) and within 61-120 days following VKA discontinuation (RR 1.49, 95% CI 1.08-2.05) relative to current VKA use. The increased RR corresponded to excess incidence rates of 6.72 (95% CI 3.90-10.06) rVTE cases per 100 person-years within 60 days, and of 2.68 (95% CI 0.42-5.58) rVTE cases per 100 person-years within 61-120 days after VKA discontinuation. Conclusions VKA discontinuation results in a transient increased risk of rVTE, which peaks within 60 days and lasts for up to 120 days after VKA discontinuation. Specific patient education for increased vigilance for signs and symptoms of recurrences is recommended in this period.

Cost-effectiveness impact of rivaroxaban versus new and existing prophylaxis for the prevention of venous thromboembolism after total hip or knee replacement surgery in France, Italy and Spain.

Venous thromboembolism (VTE) has a significant impact on healthcare costs but is largely preventable with anticoagulant prophylaxis using low-molecular-weight heparins (LMWHs), such as enoxaparin or dalteparin. Rivaroxaban and dabigatran etexilate are two new oral anticoagulants (NOACs) both compared with enoxaparin in separate trials. A decision analytic model with a healthcare and national payer perspective over a five-year time horizon was used to evaluate the cost-effectiveness of the NOACs for VTE prophylaxis after total hip replacement (THR) or total knee replacement (TKR) in France, Italy and Spain. Efficacy and safety data were obtained from randomised controlled trials of rivaroxaban vs enoxaparin and an indirect statistical comparison for rivaroxaban vs dabigatran. Rivaroxaban demonstrated dominance across all comparisons, indications and countries. In THR, total per-patient costs were reduced by up to €160 in the enoxaparin comparison and €115 in the dabigatran comparison, respectively. In addition, quality-adjusted life-years (QALYs) were increased by up to 0.0011 and 0.0012 in each comparison, respectively. Similarly, total costs were reduced in TKR by up to €137 and €28 in the enoxaparin and dabigatran comparisons, respectively. The total number of QALYs was increased by up to 0.0014 in the enoxaparin comparison and 0.0005 in the dabigatran comparison. The results were driven by costs since the incremental benefits were minimal. Rivaroxaban use could result in substantial healthcare cost savings and improved quality of life. The results are applicable across three European countries with differing healthcare systems so, potentially, could be generalised to a much wider population.

[Radiation exposure of health personnel and patients in the heart catheterization laboratory in during vascular brachytherapy]. / Untersuchungen zur Strahlenexposition von Beschäftigten und Patienten im Herzkatheterlabor und bei der vaskulären Brachytherapie.

Interventional radiological measures can lead to high radiation exposures for medical staff. In order to determine the radiation exposure to staff and patients, the resulting radiation exposures were directly measured for 52 measures at an cardiac catheterization laboratory with a new dosimetry system DIS (Direct Ion Storage). Beside the measurement of body dose behind the lead apron, measurements of radiation doses were performed in front of the lead apron and at the wrist of the physician. These measurements were taken as an approximation of the radiation exposure of the non-shielded body parts. The patients dose was estimated by placing a dosemeter close to the head of the patient and from the dose-area product. The mean value of body dose from 52 measurements for the physician behind the lead apron was 1.9 microSv per procedure with a range of 0-9 microSv. In front of the lead apron, a mean value of 53.9 microSv (3-233 microSv) per procedure was obtained. The mean value of partial body dose at the physician's wrist was determined to be 163.2 microSv (12-603 microSv) per procedure. It could be shown that measures combined with interventions lead to higher exposures compared with measures without interventions. For the medical technician, the mean value behind the lead apron was 3.9 microSv (0-58 microSv) per procedure. For the patient, a mean value of 800 microSv (119-8642 microSv) was measured close to the head. The mean dose to the skin of the patient at radiation entrance was determined to be 307 mGy (70-1190 mGy). From this data, the radiation dose per year for the physician performing 1000 measures, was determined to be 1.9 mSv/year. This is below the new dose limit of 20 mSv/year. Also the estimations for the dose to the eye lens and the hands of the physician show no conflicts with actual dose limits when obeying all radiation regulations. The results for vascular brachytherapy did not show significantly higher exposures, compared with conventional measures including interventions.

[Estimation of radiation exposure and radiation risk for employees of a heart catheterization laboratory]. / Abschätzung der Strahlenexposition und des Strahlenrisikos für Beschäftigte im Herzkatheterlabor.

The staff at interventional radiological procedures is exposed to high levels of ionizing radiation. This applies especially to measures at cardiac catheterization laboratories. In this study the annual radiation exposure to the staff was estimated by measuring the dose rate under characteristic conditions. It could be shown that the resulting radiation exposure was strongly dependent on the radiation protection measures and is also dependent on the operation conditions of the x-ray-tube. The effective dose for the physician wearing a lead apron and thyroid shield was determined to about 1.7 mSv/a. Without a thyroid shield an effective dose of about 3.5 mSv/a resulted. This corresponds to approximately the natural background radiation of about 2.4 mSv/a in the Federal Republic of Germany. From the number of procedures performed we could derive an effective dose of approximately 1-2 microSv per application for the physician, averaged over all types of procedures. Further, it could be shown that the readings of the film badges, usually worn by the staff, underestimate the effective dose by approximately a factor of two. This is because the film badges do not include the contribution of the unshielded parts of the body to effective dose. From the estimated annual effective dose, a lifetime dose of 68 mSv was estimated for a 40-year working career. The corresponding lifetime risk for induced fatal cancer due to radiation exposure was determined to 0.3% applying the ICRP risk factor of 4 x 10(-2) Sv-1. Considering the NCRP recommendations for a safe occupation, working in a cardiac catheterization laboratory can be considered as safe when applying all radiation protection measures. However, changing the protection measures and modifying the parameters of the x-ray-tube can lead to strong changes of the radiation exposure and the resulting risk estimation.

A novel anther-expressed adh-homologous gene in Lycopersicon esculentum.

Two novel tandemly-oriented open reading frames (ORFs) with homology to alcohol dehydrogenase (ADH) were isolated from tomato. The predicted amino acid composition for each of the two tandem adh genes indicates the presence of 22 and 21, respectively, of 22 amino acids conserved in ADH proteins from plants and animals. However, comparison to known plant adh genes reveals a significantly lower similarity indicating that they belong to a novel class of ADHs. According to mapping data, the adh-homologous ORFs do not represent either of the previously studied adh1 or adh2 genes of tomato. The tandem genes, termed adh3a and adh3b, mapped to a distal region of the long arm of chromosome 4, unlike adh1, which maps closer to the centromere. Adh3a and adh3b have over 90% similarity to each other at the nucleotide and putative peptide levels. The adh3a gene has ten exons and nine introns with the transcription initiation site 57 bp upstream of the translation start. A putative TATA box and polyadenylation site have been identified. Adh3a is transcribed and, according to cDNA sequence analysis, fully processed in the late stages of anther development. According to transformation analysis, tissue-specific regulatory elements reside within the -448 to +724 region. The termination codon of adh3a is separated from the putative adh3b translation start site by 789 bp of intervening sequence. The 5' untranscribed sequences of each gene contain a stretch of 68 bp with 78% similarity. Within this stretch are sequences which are homologous to sequences found in anaerobically-induced or pollen-expressed genes from various plant species.

Discussing possible standards of natural radioactivity in building materials.

This paper discusses different possibilities of deriving reference values for the natural radioactivity concentrations in building materials to estimate possible additional radiation exposure for the population. Based on comprehensive experimental and theoretical investigations the consequences of the resulting hypothetical reference activity concentrations in building materials, applying different dose limits, were examined. The calculation of the activity concentration standards was performed for standard conditions obtained by earlier studies on exhalation of Radon-222 and Radon-220 from building materials.

Radon-222 concentrations and decay-product equilibrium in dwellings and in the open air.

Results are presented of measurements of the activity concentrations of 222Rn and its short-lived decay products and the 212Pb/212Bi concentrations in more than 200 dwellings in West Germany and in the open air. For more than 130 measurements of the equilibrium factor F in dwellings the median value was found to be 0.3. Measurements of F in the open air under various conditions resulted in a mean value of about 0.4. The results of the investigations showed that indoors F depends only slightly on ventilation, indoor 222Rn concentration and other parameters. The equilibrium factor F in the open air, however, was found to depend on meteorological conditions. Empirical correlations from the data obtained for the daughter/222Rn concentration ratios were derived to provide relations for the prediction of the individual daughter product concentrations at a measured 222Rn level. It was established that the daughter/222Rn concentration ratios for indoor air do not change within the range of 222Rn concentrations investigated (1-370 Bq X m-3). These relations, however, are not valid for the daughter/222Rn concentration ratios in outdoor air. The correlations derived further suggest that the individual daughter product concentrations may be assessed with sufficient accuracy by only measuring the 222Rn concentrations. Thus the daughter ratios obtained in this way should enable good estimates of the lung dose for members of the public due to inhalation of the short-lived 222Rn daughters and the dose contribution of the individual 222Rn-daughter products.

Activity concentrations of 222Rn, 220Rn, and their decay products in german dwellings, dose calculations and estimate of risk.

Measurements of the concentrations of 222Rn, its short-lived decay products and of 212Pb - 212Bi were performed in 150 dwellings and in the open air in the Federal Republic of Germany. The concentrations of 222Rn was measured by electrostatic deposition of 218Po. The concentration of the short-lived decay products were measured by air sampling and alpha-spectroscopy. It was found that inside dwellings the average potential alpha-energy concentration of the short-lived daughters is about three times higher than in the open air. The total potential alpha-energy concentration indoors amounts to 2.6 . 10(-3) Working Level (W.L.). Direct measurements of the equilibrium factor inside dwellings gave a mean value of 0.3. A strong dependence of the potential alpha energy concentration on the ventilation rate in dwellings has been observed. These ventilation effects exceed the effects caused by differences in the activity concentrations due to different building materials. The dose calculation results in an average dose to the whole lung due to the inhalation of short-lived radon daughters of about 0.05-0.2 m/Gy/a. An estimate of risk - based on the risk factors for uranium miners - shows an average lifetime risk of about 6 . 10(-4) for the incidence of lung cancer caused by inhalation of radon and thoron daughters in dwellings in the Federal Republic of Germany.