The morbidity and mortality following a diagnosis of peripheral arterial disease: Long-term follow-up of a large database

BACKGROUND: Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. METHODS: Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. CONCLUSION: A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased

Simplified tabu search with random-based searches for bound constrained global optimization

This paper proposes a simplified version of the tabu search algorithm that solely uses randomly generated direction vectors in the exploration and intensification search procedures, in order to define a set of trial points while searching in the neighborhood of a given point. In the diversification procedure, points that are inside any already visited region with a relative small visited frequency may be accepted, apart from those that are outside the visited regions. The produced numerical results show the robustness of the proposed method. Its efficiency when compared to other known metaheuristics available in the literature is encouraging.FCT - Fundação para a Ciência e a Tecnologia(UIDB/00013/2020); FCT – Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020, UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM

Cost of Dry Eye Treatment in an Asian Clinic Setting

10.1371/journal.pone.0037711PLoS ONE76

Mortality in Peripheral Arterial Disease: A Comparison of Patients Managed by Vascular Specialists and General Practitioners

BACKGROUND: Peripheral arterial disease (PAD) is undertreated by general practitioners (GPs). However, the impact of the suboptimal clinical management is unknown. OBJECTIVE: To assess the mortality rate of PAD patients in relation to the type of physician who provides their care (GP or vascular specialist). DESIGN: Prospective study. SETTING: Primary care practice and academic vascular laboratory. PARTICIPANTS: GP patients (n = 60) were those of the Peripheral Arteriopathy and Cardiovascular Events study (PACE). Patients managed by specialists (n = 82) were consecutive subjects with established PAD who were referred to our vascular laboratory during the enrolment period of the PACE study. MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: After 32 months of follow-up, specialist management was associated with a lower rate of all-cause mortality (RR = 0.04; 95% CI 0.01–0.34; p = .003) and cardiovascular mortality (RR = 0.07; 95% CI 0.01–0.65; p = .020), after adjustment for patients’ characteristics. Specialists were more likely to use antiplatelet agents (93% vs 73%, p < .001), statins (62% vs 25%, p < .001) and beta blockers (28% vs 3%, p < .001). Survival differences between specialists and GPs disappeared once the use of pharmacotherapies was added to the proportional hazard model. The fully adjusted model showed that the use of statins was significantly associated with a reduced risk of all-cause mortality (RR = 0.02; 95% CI 0.01–0.73, p = .034) and cardiovascular mortality (RR = 0.02; 95% CI 0.01–0.71, p = .033). CONCLUSIONS: Specialist management of patients with symptomatic PAD resulted in better survival than generalist management. This effect appears to be mainly caused by the more frequent use of effective medicines by specialists

Discrimination of low missing energy look-alikes at the LHC

The problem of discriminating possible scenarios of TeV scale new physics with large missing energy signature at the Large Hadron Collider (LHC) has received some attention in the recent past. We consider the complementary, and yet unexplored, case of theories predicting much softer missing energy spectra. As there is enough scope for such models to fake each other by having similar final states at the LHC, we have outlined a systematic method based on a combination of different kinematic features which can be used to distinguish among different possibilities. These features often trace back to the underlying mass spectrum and the spins of the new particles present in these models. As examples of "low missing energy look-alikes", we consider Supersymmetry with R-parity violation, Universal Extra Dimensions with both KK-parity conserved and KK-parity violated and the Littlest Higgs model with T-parity violated by the Wess-Zumino-Witten anomaly term. Through detailed Monte Carlo analysis of the four and higher lepton final states predicted by these models, we show that the models in their minimal forms may be distinguished at the LHC, while non-minimal variations can always leave scope for further confusion. We find that, for strongly interacting new particle mass-scale ~600 GeV (1 TeV), the simplest versions of the different theories can be discriminated at the LHC running at sqrt{s}=14 TeV within an integrated luminosity of 5 (30) fb^{-1}.Comment: 40 pages, 10 figures; v2: Further discussions, analysis and one figure added, ordering of certain sections changed, minor modifications in the abstract, version as published in JHE

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Peripheral artery disease assessed by ankle-brachial index in patients with established cardiovascular disease or at least one risk factor for atherothrombosis - CAREFUL Study: A national, multi-center, cross-sectional observational study

<p>Abstract</p> <p>Background</p> <p>To investigate the presence of peripheral artery disease (PAD) via the ankle brachial index (ABI) in patients with known cardiovascular and/or cerebrovascular diseases or with at least one risk factor for atherothrombosis.</p> <p>Methods</p> <p>Patients with a history of atherothrombotic events, or aged 50-69 years with at least one cardiovascular risk factor, or > = 70 years of age were included in this multicenter, cross-sectional, non-interventional study (DIREGL04074). Demographics, medical history, physical examination findings, and physician awareness of PAD were analyzed. The number of patients with low ABI (< = 0.90) was analyzed.</p> <p>Results</p> <p>A total of 530 patients (mean age, 63.4 ± 8.7 years; 50.2% female) were enrolled. Hypertension and dyslipidemia were present in 88.7% and 65.5% of patients, respectively. PAD-related symptoms were evident in about one-third of the patients, and at least one of the pedal pulses was negative in 6.5% of patients. The frequency of low ABI was 20.0% in the whole study population and 30% for patients older than 70 years. Older age, greater number of total risk factors, and presence of PAD-related physical findings were associated with increased likelihood of low ABI (<it>p </it>< 0.001). There was no gender difference in the prevalence of low ABI, PAD symptoms, or total number of risk factors. Exercise (33.6%) was the most common non-pharmacological option recommended by physicians, and acetylsalicylic acid (ASA) (45.4%) was the most frequently prescribed medication for PAD.</p> <p>Conclusion</p> <p>Our results indicate that advanced age, greater number of total risk factors and presence of PAD-related physical findings were associated with increased likelihood of low ABI. These findings are similar to those reported in similar studies of different populations, and document a fairly high prevalence of PAD in a Mediterranean country.</p

Long-term survival after initial hospital admission for peripheral arterial disease in the lower extremities

ABSTRACT: Background As the population ages, peripheral arterial disease (PAD) in the lower extremities will become a larger public health problem. Awareness in patients as well clinicians of the high risk of morbidity and mortality is important but seems currently low. Insights in absolute mortality risks following admission for PAD in the lower extremities can be useful to improve awareness as they are easy to interpret. Methods A nationwide cohort of 4,158 patients with an initial admission for PAD in the lower extremities was identified through linkage of the national hospital and population register in 1997 and 2000. Results Over 60% of 4,158 patients were men. 28 days, 1 year and 5 year mortality risk were 2.4%, 10.3% and 31.0% for men and 3.5%, 10.4% and 27.4% for women. Coronary heart disease and stroke were frequent cause of death. Five years mortality risk was higher for men compared to women (HR 1.36, 95% CI 1.21-1.53). Conclusions Our findings demonstrate that, 5 year mortality risk is high, especially in men and comparable to that of patients admitted for acute myocardial infarction or ischemic stroke. Though, in general population the awareness of the severity of PAD in the lower extremities is significantly lower than that for any other cardiovascular disease and it seems that cardiovascular risk factor management for prevention in PAD patients is very modes

Management of venous thrombosis in fibular free osseomusculocutaneous flaps used for mandibular reconstruction: clinical techniques and treatment considerations

<p>Abstract</p> <p>Background</p> <p>Mandibular reconstruction by means of fibula transplants is the standard therapy for severe bone loss after subtotal mandibulectomy. Venous failure still represents the most common complication in free flap surgery. We present the injection of heparine into the arterial pedicle as modification of the revising both anastomoses in these cases and illustrate the application with a clinical case example.</p> <p>Methods</p> <p>Methods consist of immediate revision surgery with clot removal, heparin perfusion by direct injection in the arterial vessel of the pedicle, subsequent high dose low-molecular weight heparin therapy, and leeches. After 6 hours postoperatively, images of early flap recovery show first sings of recovery by fading livid skin color.</p> <p>Results</p> <p>The application of this technique in a patient with venous thrombosis resulted in the complete recovery of the flap 60 hours postoperatively. Other cases achieved similar success without additional lysis Therapy or revision of the arterial anastomosis.</p> <p>Conclusion</p> <p>Rescue of fibular flaps is possible even in patients with massive thrombosis if surgical revision is done quickly.</p