Abstract Background Venous thromboembolism prophylaxis is suboptimal in the US despite long-standing evidence-based recommendations. The aim of this subset analysis of the Epidemiologic International ...Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study was to identify characteristics of hospitals with high guideline-recommended prophylaxis use. Methods Between September and November 2006, charts from eligible patients aged ≥40 years with an acute medical illness or age ≥18 years and undergoing a surgical procedure were reviewed from randomly selected US acute-care hospitals. Hospitals were ranked based on the proportion of at-risk patients who received American College of Chest Physicians–recommended types of prophylaxis. Hospital characteristics were compared to determine factors related to more frequent prophylaxis use. Hospitals were followed up 1 year after the chart audit. Results Overall, 9257 patients were evaluated from 81 hospitals. Appropriate types of prophylaxis were prescribed to more at-risk patients in hospitals in the highest quartile compared with the lowest quartile of prophylaxis use (74% vs 36%). All quartiles had a similar percentage of at-risk patients (61%-65%). Significantly more hospitals in the highest quartile had residency training programs (43% vs 5%), a larger median number of beds (277 vs 140), and had adopted hospital-wide prophylaxis protocols (76% vs 40%). In the follow-up survey, more hospitals overall had adopted hospital-wide written guidelines for venous thromboembolism prevention. Conclusions These findings support the value of hospital-wide protocols and local audits for VTE prevention, as recommended by several national quality-of-care groups.
A growing health problem, venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), requires refined diagnostic and therapeutic approaches. Neutrophils ...contribute to thrombus initiation and development in experimental DVT. Recent animal studies recognized neutrophil extracellular traps (NETs) as an important scaffold supporting thrombus stability. However, the hypothesis that human venous thrombi involve NETs has not undergone rigorous testing.
To explore the cellular composition and the presence of NETs within human venous thrombi at different stages of development.
We examined 16 thrombi obtained from 11 patients during surgery or at autopsy using histomorphological, immunohistochemical and immunofluorescence analyses.
We classified thrombus regions as unorganized, organizing and organized according to their morphological characteristics. We then evaluated them, focusing on neutrophil and platelet deposition as well as micro-vascularization of the thrombus body. We observed evidence of NET accumulation, including the presence of citrullinated histone H3 (H3Cit)-positive cells. NETs, defined as extracellular diffuse H3Cit areas associated with myeloperoxidase and DNA, localized predominantly during the phase of organization in human venous thrombi.
NETs are present in organizing thrombi in patients with VTE. They are associated with thrombus maturation in humans. Dissolution of NETs might thus facilitate thrombolysis. This finding provides new insights into the clinical development and pathology of thrombosis and provides new perspectives for therapeutic advances.
Abstract Background Inferior vena caval filters (IVCFs) may prevent recurrent pulmonary embolism (PE). Despite uncertainty about their net benefit, patterns of use and outcomes of these devices in ...contemporary practice are unknown. Objectives The authors determined the trends in utilization rates and outcomes of IVCF placement in patients with PE and explored regional variations in use in the United States. Methods In a national cohort study of all Medicare fee-for-service beneficiaries ≥65 years of age with principal discharge diagnoses of PE between 1999 and 2010, rates of IVCF placement per 100,000 beneficiary-years and per 1,000 patients with PE were determined. The 30-day and 1-year mortality rates after IVCF placement were also investigated. Results Among 556,658 patients hospitalized with PE, 94,427 underwent IVCF placement. Between 1999 and 2010, the number of PE hospitalizations with IVCF placement increased from 5,003 to 8,928, representing an increase in the rate per 100,000 beneficiary-years from 19.0 to 32.5 (p < 0.001 for both). As the total number of PE hospitalizations increased (from 31,746 in 1999 to 54,392 in 2010), the rate of IVCF placement per 1,000 PE hospitalizations did not change significantly (from 157.6 to 164.1, p = 0.11). Results were consistent across demographic subgroups, although IVCF use was higher in blacks and patients ≥85 years of age. IVCF utilization varied widely across regions, with the highest rate in the South Atlantic region and the lowest rate in the Mountain region. Conclusions In a period of increasing PE hospitalizations among Medicare fee-for-service beneficiaries, IVCF placement increased as utilization rates in patients with PE remained greater than 15%. Mortality associated with PE hospitalizations is declining, regardless of IVCF use.
Treatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low-molecular-weight heparin (LMWH) for at least 3-6 ...months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting treatment with LMWH beyond 6 months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12 months in cancer-associated VTE.
Patients with active cancer and newly diagnosed VTE were enrolled in a prospective, multicenter study and received subcutaneous dalteparin for 12 months. The rates of bleeding and recurrent VTE were evaluated at months 1, 2-6 and 7-12.
Of 334 patients enrolled, 185 and 109 completed 6 and 12 months of therapy; 49.1% had deep vein thrombosis (DVT); 38.9% had pulmonary embolism (PE); and 12.0% had both on presentation. The overall frequency of major bleeding was 10.2% (34/334). Major bleeding occurred in 3.6% (12/334) in the first month, and 1.1% (14/1237) and 0.7% (8/1086) per patient-month during months 2-6 and 7-12, respectively. Recurrent VTE occurred in 11.1% (37/334); the incidence rate was 5.7% (19/334) for month 1, 3.4% (10/296) during months 2-6, and 4.1% (8/194) during months 7-12. One hundred and sixteen patients died, four due to recurrent VTE and two due to bleeding.
Major bleeding was less frequent during dalteparin therapy beyond 6 months. The risk of developing major bleeding complications or VTE recurrence was greatest in the first month of therapy and lower over the subsequent 11 months.
An integrated collaborative care intervention was used to treat primary care patients with comorbid obesity and depression in a randomized clinical trial. To increase wider uptake and dissemination, ...information is needed on translational potential.
The trial collected longitudinal, qualitative data at baseline, 6 months (end of intensive treatment), 12 months (end of maintenance treatment), and 24 months (end of follow-up). Semi-structured interviews (n = 142) were conducted with 54 out of 409 randomly selected trial participants and 37 other stakeholders, such as recruitment staff, intervention staff, and clinicians. Using a Framework Analysis approach, we examined themes across time and stakeholder groups according to the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework.
At baseline, participants and other stakeholders reported being skeptical of the collaborative care approach related to some RE-AIM dimensions. However, over time they indicated greater confidence regarding the potential for future public health impact. They also provided information on barriers and actionable information to enhance program reach, effectiveness, adoption, implementation, and maintenance.
RE-AIM provided a useful framework for understanding how to increase the impact of a collaborative and integrative approach for treating comorbid obesity and depression. It also demonstrates the utility of using the framework as a planning tool early in the evidence-generation pipeline.
Transposition of bacteriophage Mu uses two DNA cleavage sites and six transposase recognition sites, with each recognition site divided into two half-sites. The recognition sites can activate ...transposition of non-Mu DNA sequences if a complete set of Mu sequences is not available. We have analyzed 18 sequences from a non-Mu DNA molecule, selected in a functional assay for the ability to be transposed by MuA transposase. These sequences are remarkably diverse. Nonetheless, when viewed as a group they resemble a Mu DNA end, with a cleavage site and a single recognition site. Analysis of these “pseudo-Mu ends” indicates that most positions in the cleavage and recognition sites contribute sequence-specific information that helps drive transposition, though only the strongest contributors are apparent from mutagenesis data. The sequence analysis also suggests variability in the alignment of recognition half-sites. Transposition assays of specifically designed DNA substrates support the conclusion that the transposition machinery is flexible enough to permit variability in half-site spacing and also perhaps variability in the placement of the recognition site with respect to the cleavage site. This variability causes only local perturbations in the protein-DNA complex, as indicated by experiments in which altered and unaltered DNA substrates are paired.
The efficacy and safety of dabigatran for treatment of venous thromboembolism (VTE) were demonstrated in two trials. It is unclear if the results pertain to patients with cancer and VTE. Data from ...two randomised trials comparing dabigatran and warfarin for acute VTE were pooled. Primary efficacy outcome was symptomatic recurrent VTE and related death from randomisation to the end of the treatment period. Safety outcomes were major, major and clinically relevant non-major, and any bleeding during the oral-only treatment period. Patients with active cancer (=within 5 years) at baseline or diagnosed during the study were analysed. Compared with 4,772 patients without cancer, recurrent VTE occurred more frequently in 335 patients with cancer at any time (hazard ratio HR 3.3; 95 % confidence interval CI, 2.1-5.3) and more often in 114 with cancer diagnosed during the study compared to 221 with cancer at baseline (HR 2.6; 95 % CI, 1.1-6.2). There was no significant difference in efficacy between dabigatran and warfarin for cancer at baseline (HR 0.75; 95 % CI, 0.20-2.8) or diagnosed during the study (HR 0.63; 95 % CI, 0.20-2.0). Major bleeding (HR 4.1; 95 % CI, 2.2-7.5) and any bleeding (HR 1.5; 95 % CI, 1.2-2.0) were more frequent in patients with cancer than without, but with similar incidence in cancer with dabigatran or warfarin. In conclusion, in cancer patients, dabigatran provided similar clinical benefit as warfarin. VTE recurrence or bleeding were similar in patients on dabigatran or warfarin. The efficacy of dabigatran has not been assessed in comparison with low-molecular-weight heparin.
Background
In the USA, chronic kidney disease (CKD) affects 1 in 7 adults and costs $100 billion annually. The DAPA-CKD trial found dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, ...to be effective in reducing CKD progression and mortality in patients with diabetic and non-diabetic CKD. Currently, SGLT2 inhibitors are not considered standard of care for patients with non-diabetic CKD.
Objective
Determine the cost-effectiveness of adding dapagliflozin to standard management of patients with non-diabetic CKD.
Design
Markov model with lifetime time horizon and US healthcare sector perspective.
Patients
Patients with non-diabetic CKD
Intervention
Dapagliflozin plus standard care versus standard care only.
Main Measures
Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), all discounted at 3% annually; total incidence of kidney failure on kidney replacement therapy; average years on kidney replacement therapy.
Key Results
Adding dapagliflozin to standard care improved life expectancy by 2 years, increased discounted QALYS (from 6.75 to 8.06), and reduced the total incidence of kidney failure on kidney replacement therapy (KRT) (from 17.4 to 11.0%) and average years on KRT (from 0.77 to 0.43) over the lifetime of the cohort. Dapagliflozin plus standard care was more effective than standard care alone while increasing lifetime costs (from $245,900 to $324,8900, or $60,000 per QALY gained). Results were robust to variations in assumptions about dapagliflozin’s efficacy over time and by CKD stage, added costs of kidney replacement therapy, and expected population annual CKD progression rates and sensitive to the cost of dapagliflozin. The net 1-year budgetary implication of treating all US patients with non-diabetic CKD could be up to $21 billion.
Conclusions
Dapagliflozin improved life expectancy and reduced progression of CKD, the proportion of patients requiring kidney replacement therapy, and time on kidney replacement therapy in patients with non-diabetic CKD. Use of dapagliflozin meets conventional criteria for cost-effectiveness.
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