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Patients with venous thromboembolism who had received initial anticoagulant therapy were studied in two trials of dabigatran. Dabigatran was effective in preventing recurrent venous thromboembolism and carried a lower risk of bleeding than warfarin but a higher risk than placebo. Anticoagulant treatment with vitamin K antagonists is recommended for patients with venous thromboembolism. 1 Most patients receive at least 3 months of treatment. Long-term treatment is recommended if there are risk factors for recurrence, such as multiple thrombotic episodes. 1 In the absence of clear contraindications to anticoagulant therapy, the risk of major bleeding is approximately 1% per year with extended vitamin K antagonist therapy after venous thromboembolism. 2 The risk of major bleeding, together with the need for frequent laboratory monitoring and dose adjustments, makes long-term treatment problematic. Dabigatran, a direct thrombin inhibitor, does not require frequent monitoring and dose adjustments. At . . .

In this comparative-effectiveness trial, the oral direct thrombin inhibitor dabigatran was shown to be as effective as warfarin in the prevention of recurrent venous thromboembolism. Bleeding complications were similar. Dabigatran therapy offers the advantage that monitoring of anticoagulation is not necessary. In this comparative-effectiveness trial, the oral direct thrombin inhibitor dabigatran was shown to be as effective as warfarin in the prevention of recurrent venous thromboembolism. Dabigatran therapy offers the advantage that monitoring of anticoagulation is not necessary. Venous thromboembolism affects 1 to 2 adults per 1000 annually and is the third most common cause of vascular death after myocardial infarction and stroke. 1 , 2 The current standard treatment is rapidly acting parenteral anticoagulation for 5 to 7 days followed by at least 3 months of treatment with a vitamin K antagonist. 3 Treatment with a vitamin K antagonist requires frequent monitoring of the international normalized ratio (INR), and multiple interactions of vitamin K antagonists with foods and other drugs have been reported. 4 Dabigatran etexilate (hereafter termed dabigatran) is an orally available, potent, direct inhibitor of thrombin. It is rapidly . . .

To study age and sex specific prevalence of 30 symptoms in random samples from the general population and to analyze possible secular trends across time. The study was based on data from eight on-going Swedish cohort studies, with baseline investigations performed between 1973 and 2003. Samples were drawn from the general population of the cities of Gothenburg and Eskilstuna, and of Uppsala County. Overall, 20,160 subjects were sampled, 14,470 (71.8%) responded, of whom 12.000 were unique subjects, and 2548 were part of more than one sample. The Complaint score sub-scale of the Gothenburg Quality of Life instrument, listing 30 general symptoms was used. Responders were asked to indicate which symptoms they had experienced during the last three months. Women reported on average 7.8 symptoms, and men 5.3 (p<0.0001). Women reported higher prevalence than men for 24 of the 30 symptoms. In multivariate analyses four patterns of prevalence across age were identified in both men and women; increasing prevalence, decreasing, stable and biphasic prevalence. The symptoms in the various pattern groups differed somewhat between men and women. However, symptoms related to strain were prominent among symptoms decreasing with age. Moreover, there were secular trends. Across all symptoms reporting prevalence increased over time in men (p<0.001) as well as in women (p<0.0001). Women reported higher total symptom prevalence than men. Symptoms related to health generally increased with age, while symptoms related to stress decreased markedly. Significant secular trends across time regarding symptom prevalence were found.

Background A number of previous studies have investigated various predictors for being granted a disability pension. The aim of this study was to test the efficacy of sick-leave track record as a predictor of being granted a disability pension in a large dataset based on subjects sampled from the general population and followed for a long time. Methods Data from five ongoing population-based Swedish studies was used, supplemented with data on all compensated sick leave periods, disability pensions granted, and vital status, obtained from official registers. The data set included 8,218 men and women followed for 16 years, generated 109,369 person years of observation and 97,160 sickness spells. Various measures of days of sick leave during follow up were used as independent variables and disability pension grant was used as outcome. Results There was a strong relationship between individual sickness spell duration and annual cumulative days of sick leave on the one hand and being granted a disability pension on the other, among both men and women, after adjustment for the effects of marital status, education, household size, smoking habits, geographical area and calendar time period, a proxy for position in the business cycle. The interval between sickness spells showed a corresponding inverse relationship. Of all the variables studied, the number of days of sick leave per year was the most powerful predictor of a disability pension. For both men and women 245 annual sick leave days were needed to reach a 50% probability of transition to disability. The independent variables, taken together, explained 96% of the variation in disability pension grantings. Conclusion The sick-leave track record was the most important predictor of the probability of being granted a disability pension in this study, even when the influences of other variables affecting the outcome were taken into account.

In this clinical trial, rivaroxaban, an oral factor Xa inhibitor, was effective in the initial and continued treatment of symptomatic venous thromboembolism; it may become part of the treatment armamentarium for this common clinical problem. Acute venous thromboembolism (i.e., deep-vein thrombosis [DVT] or pulmonary embolism) is a common disorder with an annual incidence of approximately 1 or 2 cases per 1000 persons in the general population. 1 , 2 Short-term treatment is effective, with the risk of recurrent disease — the major complication — reduced from an estimated 25% to about 3% during the first 6 to 12 months of therapy. 3 The risk of recurrence remains after treatment ends and can reach 5 to 10% during the first year. 4 , 5 Standard treatment for acute venous thromboembolism is limited by the need for parenteral heparin initially, with overlapping . . .

Ximelagatran, a direct inhibitor of thrombin, is administered orally, and its use does not necessitate monitoring of coagulation. In this study, patients treated for venous thromboembolism with warfarin for six months were randomly assigned to receive ximelagatran or placebo. During the subsequent 18 months, the patients in the ximelagatran group had many fewer episodes of recurrent thromboembolism than those in the placebo group, without an increase in the frequency of bleeding. Ximelagatran to prevent recurrent thromboembolism. Despite progress in diagnosis and treatment, venous thromboembolism continues to be associated with high morbidity and mortality. 1 Previous studies have shown a risk of recurrence after six months of anticoagulant therapy of 5 to 7 percent per year. 2 , 3 The rate of recurrence can be reduced with the use of vitamin K antagonists such as warfarin, 4 – 7 but such therapy is associated with an annual risk of major hemorrhage of 3 to 4 percent. 4 – 6 Treatment with lower-intensity anticoagulants for a longer period may reduce the risk of hemorrhage, 7 although this hypothesis is controversial. 8 Routine monitoring of coagulation and frequent . . .

Background Simple global self-ratings of health (SRH) have become increasingly used in national and international public health monitoring, and in recent decades recommended as a standard part of health surveys. Monitoring developments in population health requires identification and use of health measures, valid in relation to targets for population health. The aim of the present study was to investigate associations between SRH and sick leave, disability pension, hospital admissions, and mortality, adjusted for effects of significant covariates, in a large population-based cohort. Methods The analyses were based on screening data from eight population-based cohorts in southern and central Sweden, and on official register data regarding sick-leave, disability pension, hospital admissions, and death, with little or no data loss. Sampling was performed 1973–2003. The study population consisted of 11,880 women and men, age 25–99 years, providing 14,470 observations. Information on SRH, socio-demographic data, lifestyle variables and somatic and psychological symptoms were obtained from questionnaires. Results There was a significant negative association between SRH and sick leave (Beta −13.2, p<0.0001, and −9.5, p<0.01, in women and men, respectively), disability pension (Hazard ratio 0.77, p<0.0001 and 0.76, p<0.0001, in women and men, respectively), and mortality, adjusted for covariates. SRH was also significantly associated with hospital admissions in men (Hazard ratio 0.87, p<0.0001), but not in women (Hazard ratio 0.96, p0.20). Associations between SRH on the one hand, and sick leave, disability pension, hospital admission, and mortality, on the other, were robust during the follow-up period. Conclusions SRH had strong predictive validity in relation to use of social insurance facilities and health care services, and to mortality. Associations were strong and robust during follow-up.

The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain.

The phosphatidylinositol 3-kinases (PI3Ks) regulate cell growth, proliferation and survival, and are frequently affected in human cancer. PI3K is composed of a catalytic subunit, p110, and a regulatory subunit, p85. The PI3K catalytic subunit p110δ is encoded by PIK3CD and contains p85- and RAS-binding domains, and a kinase domain. Here we present an alternatively spliced PIK3CD transcript encoding a previously unknown protein, p37δ, and demonstrate that this protein is expressed in human ovarian and colorectal tumors. p37δ retains the p85-binding domain and a fraction of the RAS-binding domain, lacks the catalytic domain, and has a unique carboxyl-terminal region. In contrast to p110δ, which stabilizes p85, p37δ promoted p85 sequestering. Despite the truncated RAS-binding domain, p37δ bound to RAS and we found a strong positive correlation between the protein levels of p37δ and RAS. Overexpressing p37δ, but not p110δ, increased the proliferation and invasive properties of HEK-293 cells and mouse embryonic fibroblasts. Cells overexpressing p37δ showed a quicker phosphorylation response of AKT and ERK1/2 following serum stimulation. Ubiquitous expression of human p37δ in the fruit fly increased body size, DNA content and phosphorylated ERK1/2 levels. Thus, p37δ appears to be a new tumor-specific isoform of p110δ with growth-promoting properties.

The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2.0–3.0]. Patients (≥18 years old) had symptomatic proximal deep vein thrombosis and/or pulmonary embolism. NCB was the composite of cardiovascular endpoints (non-fatal events of recurrent VTE, myocardial infarction, stroke or systemic embolism), all-cause death, and bleeding outcomes, all weighted equally. A broad definition of NCB included major bleeding events (MBE) and clinically relevant non-major bleeding events as bleeding outcomes, while a narrow definition included just MBE. The pooled dataset totalled 5107 patients from RE-COVER/RE-COVER II and 2856 patients from RE-MEDY. When NCB was narrowly defined, NCB was similar between DE and warfarin. When broadly defined, NCB was superior with DE vs. warfarin [RE-COVER/RE-COVER II, hazard ratio (HR) 0.80; 95% confidence interval (CI), 0.68–0.95 and RE-MEDY, HR 0.73; 95% CI 0.59–0.91]. These findings were unaffected by warfarin time in therapeutic range. The NCB of DE was similar or superior to warfarin, depending on the NCB definition used, regardless of the quality of INR control.