Background: Warfarin is the most widely used oral anticoagulant worldwide, but it has a narrow therapeutic index which necessitates constant monitoring of anticoagulation response. Previous genome-wide studies have fo...
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Background: Warfarin is the most widely used oral anticoagulant worldwide, but it has a narrow therapeutic index which necessitates constant monitoring of anticoagulation response. Previous genome-wide studies have focused on identifying factors explaining variance in stable dose, but have not explored the initial patient response to warfarin, and a wider range of clinical and biochemical factors affecting both initial and stable dosing with warfarin. Methods: A prospective cohort of 711 patients starting warfarin was followed up for 6 months with analyses focusing on both non-genetic and genetic factors. The outcome measures used were mean weekly warfarin dose (MWD), stable mean weekly dose (SMWD) and international normalised ratio (INR) > 4 during the first week. Samples were genotyped on the Illumina Human610-Quad chip. Statistical analyses were performed using Plink and R. Results: VKORC1 and CYP2C9 were the major genetic determinants of warfarin MWD and SMWD, with CYP4F2 having a smaller effect. Age, height, weight, cigarette smoking and interacting medications accounted for less than 20 % of the variance. Our multifactorial analysis explained 57.89 % and 56.97 % of the variation for MWD and SMWD, respectively. Genotypes for VKORC1 and CYP2C9*3, age, height and weight, as well as other clinical factors such as alcohol consumption, loading dose and concomitant drugs were important for the initial INR response to warfarin. In a small subset of patients for whom data were available, levels of the coagulation factors VII and IX (highly correlated) also played a role. Conclusion: Our multifactorial analysis in a prospectively recruited cohort has shown that multiple factors, genetic and clinical, are important in determining the response to warfarin. VKORC1 and CYP2C9 genetic polymorphisms are the most important determinants of warfarin dosing, and it is highly unlikely that other common variants of clinical importance influencing warfarin dosage will be found. Both
We have designed a simple benchmark test for the user of a treatment planning system to check the calculation algorithm's ability to model the build up effect beyond an air/tissue interface. The expected result is...
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We have designed a simple benchmark test for the user of a treatment planning system to check the calculation algorithm's ability to model the build up effect beyond an air/tissue interface. The expected result is expressed as an inhomogeneity correction factor CF derived from measurements and from Monte Carlo calculations for a full range of photon beam qualities. The Linear regression lines obtained from plotting CF as a function of beam quality index form the basis for a quantitative check of the algorithm performance. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Wireless phones (both mobile and cordless) emit not only radiofrequency (RF) electromagnetic fields (EMF) but also extremely low frequency (ELF) magnetic fields, both of which should be considered in epidemiological s...
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Wireless phones (both mobile and cordless) emit not only radiofrequency (RF) electromagnetic fields (EMF) but also extremely low frequency (ELF) magnetic fields, both of which should be considered in epidemiological studies of the possible adverse health effects of use of such devices. This paper describes a unique algorithm, developed for the multinational case-control MOBI-Kids study, that estimates the cumulative specific energy (CSE) and the cumulative induced current density (CICD) in the brain from RF and ELF fields, respectively, for each subject in the study (aged 10-24 years old). Factors such as age, tumour location, self-reported phone models and usage patterns (laterality, call frequency/duration and hands-free use) were considered, as was the prevalence of different communication systems over time. Median CSE and CICD were substantially higher in GSM than 3G systems and varied considerably with location in the brain. Agreement between RF CSE and mobile phone use variables was moderate to null, depending on the communication system. Agreement between mobile phone use variables and ELF CICD was higher overall but also strongly dependent on communication system. Despite ELF dose distribution across the brain being more diffuse than that of RF, high correlation was observed between RF , ELF dose. The algorithm was used to systematically estimate the localised RF and ELF doses in the brain from wireless phones, which were found to be strongly dependent on location and communication system. Analysis of car-tographies showed high correlation across phone models and across ages, however diagonal agreement between these cartographies suggest these factors do affect dose distribution to some level. Overall, duration and number of calls may not be adequate proxies of dose, particularly as communication systems available for voice calls tend to become more complex with time.
Purpose: This postmarketing surveillance survey was conducted to investigate the utility of the CONsistency in r-FSH Starting doses for individualized tReatmenT (CONSORT) calculator for individualizing recombinant hum...
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Purpose: This postmarketing surveillance survey was conducted to investigate the utility of the CONsistency in r-FSH Starting doses for individualized tReatmenT (CONSORT) calculator for individualizing recombinant human follicle-stimulating hormone (r-hFSH) starting doses for controlled ovarian stimulation (COS) in routine clinical practice. Methods: This was a 3-year, open-label, observational study evaluating data from women undergoing COS for assisted reproductive technology at 31 German fertility centers. Physicians stated their recommended r-hFSH starting dose, then generated a CONSORT-recommended r-hFSH starting dose. Physicians could prescribe any r-hFSH starting dose. The primary objective was to compare the r-hFSH starting dose recommended by the physician with the CONSORTcalculated dose and that prescribed. Statistical analyses were conducted post hoc. Results: Data were collected from 2,579 patients;the mean (standard deviation [SD]) age was 30.5 (2.93) years (range: 19-40 years). The mean (SD) CONSORT-calculated r-hFSH starting dose was significantly lower than the physician-recommended dose (134.5 [38.0] IU versus 164.6 [47.1] IU;P, 0.0001);the mean (SD) starting dose prescribed was 162.2 (48.4) IU. CONSORT-calculated doses were prescribed for 27.3% (number [n] = 677) of patients, and non-CONSORT-calculated doses prescribed for 72.7% (n= 1,800). The mean (SD) number of oocytes retrieved per patient was 10.6 (6.15) and 11.4 (6.66) in the CONSORT and non-CONSORT groups, respectively;the mean (SD) number of embryos transferred per patient was 1.98 (0.41) and 2.03 (0.45), respectively. Clinical pregnancy rates per COS cycle were 38.8% (CONSORT) and 34.8% (non-CONSORT) (P= 0.142);clinical pregnancy rates per embryos transferred were 45.0% and 39.5%, respectively (P= 0.049). Miscarriage occurred in 14.8% of all clinical pregnancies (CONSORT: 12.5%;non-CONSORT: 15.3%). The rate of grade 3 ovarian hyperstimulation syndrome (OHSS) was 0.3% (n= 2) in the CONSORT
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