Indications for Catheter-Directed Thrombolysis in the Management of Acute Proximal Deep Venous Thrombosis

Deep vein thromboses (DVTs) cause significant morbidity and mortality in the general population. Oral anticoagulation therapy may reduce thrombus propagation but does not cause clot lysis and therefore does not prevent postthrombotic syndrome (PTS). Catheter-directed thrombolysis (CDT) can be used to treat DVTs as an adjunct to medical therapy, but there is no consensus defining exact indications. Current evidence suggests that CDT can reduce clot burden and DVT recurrence and consequently prevents the formation of PTS compared with systemic anticoagulation. Appropriate indications include younger individuals with acute proximal thromboses, a long life expectancy, and relatively few comorbidities. Limb-threatening thromboses may also be treated with CDT, although the subsequent mortality remains high. A number of randomized controlled trials are currently under way comparing the longer-term outcomes of CDT compared with anticoagulation alone. Initial reports suggest that venous patency and valvular function are better maintained after CDT. The effectiveness of combined pharmacomechanical thrombectomy and the role of vena cava filters need to be investigated further before strong recommendations can be made. The reported short-term outcomes following catheter-based intervention for DVT are encouraging in selected patients. Further evidence is required to establish long-term benefits and cost-effectiveness

Effect of Endovascular Aneurysm Repair on the Volume-Outcome Relationship in Aneurysm Repair

Background— We aim to quantify the relationship between the annual caseload (volume) and outcome from elective endovascular (EVR) or open repair of abdominal aortic aneurysms (AAAs) in England between 2005 and 2007. Methods and Results— Individual patient data were obtained from the Hospital Episode Statistics. Statistical methods included multiple logistic regression models, mortality control charts, and safety plots to determine the nature of any relationship between volume and outcome. The case-mix between hospitals of different sizes was examined using observed and expected values for in-hospital mortality. Outcome measures included in-hospital mortality and hospital length of stay. Between 2005 and 2007, a total of 57 587 patients were admitted to hospitals in England with a diagnosis of AAA, and 11 574 underwent AAA repair. There were 7313 elective AAA repairs, of which 5668 (78%) were open and 1645 (22%) were EVR. In-hospital mortality rates were 5.63% for all elective AAA repairs with rates of 6.18% for open repair and 3.77% for EVR (odds ratio, 0.676; 95% CI, 0.501 to 0.913; P=0.011). High-volume aneurysm services were associated with significantly lower mortality rates overall (0.991; 0.988 to 0.994; P<0.0001), for open repairs (0.994; 0.991 to 0.998; P=0.0008), and EVR (0.989; 0.982 to 0.995; P=0.0007). Large endovascular units had low mortality rates for open repairs. Conclusion— A strong relationship existed between the volume of surgery performed and outcome from both open and endovascular aneurysm repairs. These data support the concept that abdominal aortic surgery should be performed in specialized units that meet a minimum volume threshold

Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach.

Finasteride taken for 7 years in the Prostate Cancer Prevention Trial (PCPT) reduced the risk of prostate cancer by 25%, but with an apparent increased risk of high-grade disease. Subsequent analyses found that finasteride biases toward improved prostate cancer detection and accuracy in prostate cancer grading at biopsy. In our first analysis of the present study, we accounted for these biases in estimating the effect of finasteride on the risk of overall and high-grade prostate cancer. This analysis used PCPT data that included 3-month longer collection of endpoints than in the original report with observed prostate cancer rates of 22.9% (4.8% with high grade; placebo) versus 16.6% (5.8% with high grade; finasteride). Based on these updated results, the bias-adjusted prostate cancer rates are estimated to be 21.1% (4.2% high grade; placebo) and 14.7% (4.8% high grade; finasteride), a 30% risk reduction in prostate cancer [relative risk (RR), 0.70; 95% confidence interval (95% CI), 0.64-0.76; P < 0.0001] and a nonsignificant 14% increase in high-grade cancer (RR, 1.14; 95% CI, 0.96-1.35; P = 0.12) with finasteride. We then estimated rates of high-grade prostate cancer based on an analysis that incorporated grading information from radical prostatectomies in 500 subjects diagnosed with cancer. The resulting estimates were high-grade cancer rates of 8.2% (placebo) versus 6.0% (finasteride), a 27% risk reduction (RR, 0.73; 95% CI, 0.56-0.96; P = 0.02) with finasteride. Our third analysis examined the impact of biopsy sensitivity on the relative risk of high-grade prostate cancer and found that differential sensitivity of biopsy between the treatment arms can have a significant impact on risk ratio estimates. These collective results suggest that the observed, unadjusted higher risk of high-grade disease with finasteride seems to have been due to facilitated diagnosis resulting primarily from increased biopsy sensitivity with finasteride. Therefore, men undergoing regular prostate cancer screening or who express an interest in cancer prevention should be informed of the opportunity to take finasteride for preventing prostate cancer

Measuring Accuracy of Automated Parsing and Categorization Tools and Processes in Digital Investigations

This work presents a method for the measurement of the accuracy of evidential artifact extraction and categorization tasks in digital forensic investigations. Instead of focusing on the measurement of accuracy and errors in the functions of digital forensic tools, this work proposes the application of information retrieval measurement techniques that allow the incorporation of errors introduced by tools and analysis processes. This method uses a `gold standard' that is the collection of evidential objects determined by a digital investigator from suspect data with an unknown ground truth. This work proposes that the accuracy of tools and investigation processes can be evaluated compared to the derived gold standard using common precision and recall values. Two example case studies are presented showing the measurement of the accuracy of automated analysis tools as compared to an in-depth analysis by an expert. It is shown that such measurement can allow investigators to determine changes in accuracy of their processes over time, and determine if such a change is caused by their tools or knowledge.Comment: 17 pages, 2 appendices, 1 figure, 5th International Conference on Digital Forensics and Cyber Crime; Digital Forensics and Cyber Crime, pp. 147-169, 201

Individual, social and environmental determinants of sleep among women : protocol for a systematic review and meta-analysis

Introduction: Sleep is important to promote optimal health and avoid negative health outcomes. Short-duration and low-quality sleep may be more common and more detrimental among women compared with men. Identifying the determinants of behaviour is one of the first steps in designing effective interventions. To our knowledge, no systematic review has identified the individual, social and environmental determinants of sleep among adult women. Methods and analysis: Studies reporting data on adult women from 18 to 64 years of age will be included. On the basis of ecological models of health behaviour and sleep, the types of determinants that will be included in the review are individual (eg, demographic, psychological and behavioural), social (eg, family) and environmental (eg, physical environment and policies) determinants. Observational (cross-sectional and longitudinal) and experimental studies will be included. MEDLINE/PubMed, PsycINFO, CINAHL, EMBASE and Proquest Dissertations and Theses will be investigated. Data will be extracted independently by two reviewers using a standardised data extraction form. The quality of observational studies will be assessed using the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and the quality of experimental studies will be assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Study. If there is a sufficient number of studies reporting data on a similar determinant among a similar population (k>5), a meta-analysis of the results will be performed with a random-effects model. If between-study heterogeneity is high (I² ≥75%), it will be investigated through sensitivity analyses and meta-regression. Ethics and dissemination: Formal ethical approval is not required as no primary data will be collected. The results will be published in a peer-reviewed journal. This review will provide valuable information to those interested in developing empirically based sleep interventions among women

Thresholds for Abdominal Aortic Aneurysm Repair in England and the United States.

Background Thresholds for repair of abdominal aortic aneurysms vary considerably among countries. Methods We examined differences between England and the United States in the frequency of aneurysm repair, the mean aneurysm diameter at the time of the procedure, and rates of aneurysm rupture and aneurysm-related death. Data on the frequency of repair of intact (nonruptured) abdominal aortic aneurysms, in-hospital mortality among patients who had undergone aneurysm repair, and rates of aneurysm rupture during the period from 2005 through 2012 were extracted from the Hospital Episode Statistics database in England and the U.S. Nationwide Inpatient Sample. Data on the aneurysm diameter at the time of repair were extracted from the U.K. National Vascular Registry (2014 data) and from the U.S. National Surgical Quality Improvement Program (2013 data). Aneurysm-related mortality during the period from 2005 through 2012 was determined from data obtained from the Centers for Disease Control and Prevention and the U.K. Office of National Statistics. Data were adjusted with the use of direct standardization or conditional logistic regression for differences between England and the United States with respect to population age and sex. Results During the period from 2005 through 2012, a total of 29,300 patients in England and 278,921 patients in the United States underwent repair of intact abdominal aortic aneurysms. Aneurysm repair was less common in England than in the United States (odds ratio, 0.49; 95% confidence interval [CI], 0.48 to 0.49; P<0.001), and aneurysm-related death was more common in England than in the United States (odds ratio, 3.60; 95% CI, 3.55 to 3.64; P<0.001). Hospitalization due to an aneurysm rupture occurred more frequently in England than in the United States (odds ratio, 2.23; 95% CI, 2.19 to 2.27; P<0.001), and the mean aneurysm diameter at the time of repair was larger in England (63.7 mm vs. 58.3 mm, P<0.001). Conclusions We found a lower rate of repair of abdominal aortic aneurysms and a larger mean aneurysm diameter at the time of repair in England than in the United States and lower rates of aneurysm rupture and aneurysm-related death in the United States than in England. (Funded by the Circulation Foundation and others.)

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Endovascular aneurysm sealing for the treatment of ruptured abdominal aortic aneurysms.

PURPOSE: To assess the feasibility and report preliminary results of ruptured abdominal aortic aneurysm (rAAA) repair with endovascular aneurysm sealing (EVAS), a novel therapeutic alternative whose feasibility has not been established in rAAAs due to the unknown effects of the rupture site on the ability to achieve sealing. CASE REPORT: Between December 2013 and April 2014, 5 patients (median age 71 years, range 57-90; 3 men) with rAAAs were treated with the Nellix EVAS system at a single institution. Median aneurysm diameter was 70 mm (range 67-91). Aneurysm morphology in 4 of the 5 patients was noncompliant with instructions for use (IFU) for both EVAS and standard stent-grafts; the remaining patient was outside the IFU for standard stent-grafts but treated with EVAS under standard IFU for the Nellix system. Median Hardman index was 2 (range 0-3). Two patients died of multiorgan failure after re-laparotomy and intraoperative cardiac arrest, respectively. Among survivors, all devices were patent with no signs of endoleak or failed aneurysm sac sealing at 6 months (median follow-up 9.2 months). CONCLUSION: EVAS for the management of infrarenal rAAAs appears feasible. The use of EVAS in emergency repairs may broaden the selection criteria of the current endovascular strategy to include patients with more complex aneurysm morphology

Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy