Reconsidering low-dose aspirin therapy for cardiovascular disease: a study protocol for physician and patient behavioral change

<p>Abstract</p> <p>Background</p> <p>There are often disparities between current evidence and current practice. Decreasing the gap between desired practice outcomes and observed practice outcomes in the healthcare system is not always easy. Stopping previously recommended or variably recommended interventions may be even harder to achieve than increasing the use of a desired but under-performed activity. For over a decade, aspirin has been prescribed for primary prevention of cardiovascular disease and for patients with the coronary artery disease risk equivalents; yet, there is no substantial evidence of an appropriate risk-benefit ratio to support this practice. This paper describes the protocol of a randomized trial being conducted in six primary care practices in the Denver metropolitan area to examine the effectiveness of three interventional strategies to change physician behavior regarding prescription of low-dose aspirin.</p> <p>Methods</p> <p>All practices received academic detailing, one arm received clinician reminders to reconsider aspirin, a second arm received both clinician and patient messages to reconsider aspirin. The intervention will run for 15 to 18 months. Data collected at baseline and for outcomes from an electronic health record will be used to assess pre- and post-interventional prescribing, as well as to explore any inappropriate decrease in aspirin use by patients with known cardiovascular disease.</p> <p>Discussion</p> <p>This study was designed to investigate effective methods of changing physician behavior to decrease the use of aspirin for primary cardiovascular disease prevention. The results of this study will contribute to the small pool of knowledge currently available on the topic of ceasing previously supported practices.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01247454">NCT01247454</a></p

Fabrication of periodic microstructures on flexible polyimide membranes

Periodic metallic microstructures were fabricated on polyimide membranes. Techniques were developed to maintain flatness of the membrane during processing while still allowing for flexibility in the final structure. For proper functionality of the structures, it was necessary to first fabricate a continuous metallic film and a continuous dielectric layer on top of the flexible substrate, which underlaid the periodic microstructure. Flexibility of the overall structure was maintained by using a polymer as the dielectric layer, which was constrained to have high optical transmission over the infrared wavelength range of 6-14 mu m. Three candidate polymers were evaluated, and their measured optical properties are presented. Benzocyclobutene was found to be the best choice for this application. The final structure fully populated a 10 cm (4 in.) diameter flexible membrane with microstructures of excellent uniformity. (C) 2007 American Vacuum Society

Normalization factors for magnetic relaxation of small particle systems in non-zero magnetic field

We critically discuss relaxation experiments in magnetic systems that can be characterized in terms of an energy barrier distribution, showing that proper normalization of the relaxation data is needed whenever curves corresponding to different temperatures are to be compared. We show how these normalization factors can be obtained from experimental data by using the $T \ln(t/\tau_0)$ scaling method without making any assumptions about the nature of the energy barrier distribution. The validity of the procedure is tested using a ferrofluid of Fe_3O_4 particles.Comment: 5 pages, 6 eps figures added in April 22, to be published in Phys. Rev. B 55 (1 April 1997

Growth, structural and magnetic properties of high coercivity Co/Pt multilayers

Co/Pt multilayer films ([Co (tCo nm)/Pt(1 nm)]10, 0.2 250 degrees C show fine-grained MFM features on the sub-100 nm length scale and hysteresis studies indicate reversal dominated by localized switching of small clusters. The hysteresis curves for the highest coercivity films are sheared with a hysteresis slope alpha=4(pi)dM/dH|Hc approximately equal 1.5, which is close to the ideal value for completely decoupled grains of alpha =1. High resolution cross-sectional TEM with elemental analysis shows columnar grains extending throughout the multilayer stack. Sharp Co/Pt interfaces are found from TEM and grazing incidence X-ray diffraction. At higher TG, Co depletion and structural defects at the grain boundaries provide a mechanism for exchange decoupling of adjacent grains, which may result in the high coercivities observed. Anisotropy and magnetization values are estimated as Ku {approx} 8x106 erg/cc and MS {approx} 450 emu/cc (per total volume), hence Hk = 2Ku/MS {approx} 17.5 kOe for the highest coercivity Hc {approx} 15 kOe films

Differential Response of Primary and Immortalized CD4+ T Cells to Neisseria gonorrhoeae-Induced Cytokines Determines the Effect on HIV-1 Replication

To compare the effect of gonococcal co-infection on immortalized versus primary CD4+ T cells the Jurkat cell line or freshly isolated human CD4+ T cells were infected with the HIV-1 X4 strain NL4-3. These cells were exposed to whole gonococci, supernatants from gonococcal-infected PBMCs, or N. gonorrhoeae-induced cytokines at varying levels. Supernatants from gonococcal-infected PBMCs stimulated HIV-1 replication in Jurkat cells while effectively inhibiting HIV-1 replication in primary CD4+ T cells. ELISA-based analyses revealed that the gonococcal-induced supernatants contained high levels of proinflammatory cytokines that promote HIV-1 replication, as well as the HIV-inhibitory IFNα. While all the T cells responded to the HIV-stimulatory cytokines, albeit to differing degrees, the Jurkat cells were refractory to IFNα. Combined, these results indicate that N. gonorrhoeae elicits immune-modulating cytokines that both activate and inhibit HIV-production; the outcome of co-infection depending upon the balance between these opposing signals

Does psychological status influence clinical outcomes in patients with inflammatory bowel disease (IBD) and other chronic gastroenterological diseases: An observational cohort prospective study

Background: Whether there is a temporal relationship between psychological problems and clinical outcomes in patients with diseases of the digestive tract has not been widely researched. Thus, our aims were 1) To observe and compare prospectively clinical outcomes in relation to psychological co-morbidity in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) and, 2) To test the hypothesis that patients with psychological co-morbidities are less likely to have a satisfactory response to standard treatment at 12 months. Methods: Overall, 139 patients were enrolled in this observational cohort prospective study. Over the ensuing year, physical and psychological measures were made at baseline and after 12 months (HADS, SCL90, SF-12 and disease activity measures). A logistic regression was conducted to observe any relationship between baseline characteristics and patients' clinical outcomes after 12 months. Results: Overall, there was no relationship between psychological status and quality of life at baseline and relapse at 12 months (p &gt; 0.05). However, patients with inactive disease at baseline were at lower risk of relapse after 12 months (OR = 0.046, CI: 0.012–0.178). No significant relationship was found between psychological problems such as depression/anxiety and a total number of relapses in the IBD group. However, interestingly, patients with an active disease at baseline tended to have a greater number of relapses (OR = 3.07, CI: 1.650–5.738) and CD participants were found at lower risk of relapse than UC participants (OR = 0.382, CI: 0.198–0.736). Conclusion: In contrast to previous investigations, this study suggests that there is no temporal relationship between psychological problems at baseline and clinical outcomes over time. Longer and larger prospective studies are needed to better understand this result.Antonina A Mikocka-Walus, Deborah A Turnbull, Nicole T Moulding, Ian G Wilson, Gerald J Holtmann and Jane M Andrew

HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges

Historically, HIV vaccines specifically designed to raise cellular immunity resulted in protection from disease progression but not infection when tested in monkeys challenged with a single high virus exposure. An alternative approach, more analogous to human sexual exposures, is to repetitively challenge immunized monkeys with a much lower dose of virus until systemic infection is documented. Using these conditions to mimic human sexual transmission, we found that a multi-protein DNA/MVA HIV-1 vaccine is indeed capable of protecting rhesus monkeys against systemic infection when repeatedly challenged with a highly heterologous immunodeficiency virus (SHIV). Furthermore, this repetitive challenge approach allowed us to calculate per-exposure probability of infection, an observed vaccine efficacy of 64%, and undertake a systematic analysis for correlates of protection based on exposures needed to achieve infection. Therefore, improved non-human primate models for vaccine efficacy can provide novel insight and perhaps renew expectations for positive outcomes of human HIV clinical trials

Interferon-Alpha Mediates Restriction of Human Immunodeficiency Virus Type-1 Replication in Primary Human Macrophages at an Early Stage of Replication

Type I interferons (IFNα and β) are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα