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Background Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value. Methods A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed. Results Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents. Conclusions The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer. [ABSTRACT FROM AUTHOR]

Initiation of phenprocoumon therapy is associated with a variable individual response. The CYP2C9 genotype has been shown to influence the response to warfarin therapy, but such an effect on phenprocoumon therapy remains uncertain. Two hundred sixty hospital patients started on phenprocoumon were recruited for this study. Body mass index (BMI), waist and hip circumference, dietary habits, comorbidity, and comedication were initially assessed. A 5′ exonuclease assay (TaqManR) was used to analyze the presence of five polymorphisms of the CYP2C9 gene in each of the study patients. Study endpoints included the time necessary to achieve the international normalized ratio (INR) target (INR >2) and the total drug amount required to attain target INR. For 250 of 260 patients, the subsequent required daily maintenance dose of phenprocoumon was also recorded. Both the necessary time and total dose required to attain target INR correlated significantly with BMI. The leaner the patient, the shorter the required time interval [BMI <22 ( n=31), 5.48±2.49 days; BMI 22–25 ( n=70), 6.09±2.40; BMI 25–30 ( n=113), 6.76±3.61; BMI >30 ( n=46), 8.50±5.75; p=0.001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 ( n=31), 23.8±12.1 mg; BMI 22–25 ( n=70), 25.9±11.4 mg; BMI 25–30 ( n=113), 29.6±25.2; BMI >30 ( n=46), 35.8±19.7; p=0.027]. Overweight and waist circumference as a surrogate marker for abdominal fat were also associated significantly with these two parameters. Moreover, obesity was associated with a lower body-weight-adjusted maintenance dosage. All CYP2C9 genotypes that were tested failed to reveal an association with individual response variability. Patient obesity appears to directly correspond to the amount of phenprocoumon required during initiation of therapy. The CYP2C9 genotype was not shown to influence the necessary therapeutic dosage. [ABSTRACT FROM AUTHOR]

Background and Aim of the Study: The study aim was to evaluate the relationship between serum calcium levels and the degree of calcification found in stenotic aortic valves., Methods: Using atomic absorption spectroscopy, the hydroxyapatite content of 228 excised human stenotic aortic valves was determined and expressed as a percentage of valve mass. Left heart catheterization preceded valve replacement. In addition, serum levels of calcium and creatinine were determined before native calcific aortic valve excision., Results: Valves from male patients contained more hydroxyapatite than those of female patients (26 +/- 9 versus 22 +/- 9 mass%; p < 0.001). Patients presenting with lower serum calcium levels showed a slight trend towards higher levels of valve calcification (r = -0.15, p = 0.026), but this association appeared only within the subgroup of male patients. Male patients with lowest serum calcium levels displayed greatest valvular hydroxyapatite deposition (1st calcium tertiary: 29.5 +/- 8.9 mass% versus 2nd calcium tertiary 26.4 +/- 7.8 mass% versus 3rd calcium tertiary 21.4 +/- 8.9 mass%; n = 122; p = 0.001; r = -0.25; p = 0.006). This association was even more distinct in male patients with normal serum creatinine levels. Furthermore, serum calcium was inversely and significantly associated with serum C-reactive protein in male patients (r = - 0.34; p < 0.001)., Conclusion: Serum calcium levels appear to be inversely related to valve calcification in patients with severe calcific aortic stenosis (AS). This finding indicates the importance of systemic calcium metabolism in calcific AS, independent of manifest disorders of calcium metabolism or renal function. Interestingly, this association was evident only in male patients, suggesting a gender-dependent pathogenesis.