ObjectiveTo evaluate the public health and economic benefits of adherence to a fixed-dose combination polypill for the secondary prevention of cardiovascular (CV) events in adults with a history of myocardial infarction (MI) in the UK.DesignMarkov-model-based cost-effectiveness analysis, informed by systematic reviews, which identified efficacy, utilities and adherence data inputs.SettingGeneral practice in the UK.ParticipantsPatients with a mean age of 64.7 years, most of whom are men with a recent or non-recent diagnosis of MI and for whom secondary preventive medication is indicated and well tolerated.InterventionFixed-dose combination polypill (100 mg aspirin, 20 mg atorvastatin and 2.5, 5, or 10 mg ramipril) compared with multiple monotherapy.Primary and secondary outcome measuresCV events prevented per 1000 patients; cost per life-year gained; and cost per quality-adjusted life-year (QALY) gained.ResultsThe model estimates that for each 10% increase in adherence, an additional 6.7% fatal and non-fatal CV events can be prevented. In the base case, over 10 years, the polypill would improve adherence by ∼20% and thereby prevent 47 of 323 (15%) fatal and non-fatal CV events per 1000 patients compared with multiple monotherapy, with an incremental cost-effectiveness ratio (ICER) of £8200 per QALY gained. Probabilistic sensitivity analyses for the base-case assumptions showed an 81.5% chance of the polypill being cost-effective at a willingness-to-pay threshold of £20 000 per QALY gained compared with multiple monotherapy. In scenario analyses that varied structural assumptions, ICERs ranged between cost saving and £21 430 per QALY gained.ConclusionsAssuming that some 450 000 adults are at risk of MI, a 10 percentage point uptake of the polypill could prevent 3260 CV events and 590 CV deaths over a decade.The polypill appears to be a cost-effective strategy to prevent fatal and non-fatal CV events in the UK.

IMPORTANCE Ozenoxacin, a novel topical antibacterial agent with potent bactericidal activity against gram-positive bacteria, has been developed as a cream with 1% active drug for the treatment of impetigo, a highly contagious bacterial skin infection. OBJECTIVES To evaluate the efficacy, safety, and tolerability of ozenoxacin cream, 1%, after 5-day twice-daily topical treatment in patients with impetigo. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, vehicle-controlled clinical trial included patients 2 months or older with impetigo who were enrolled at centers in 6 countries from June 2, 2014, through May 30, 2015. Data were analyzed based on intention to treat from July 9 through July 22, 2015. INTERVENTIONS Patients were randomized 1:1 to receive topical ozenoxacin or placebo control. MAIN OUTCOMES AND MEASURES Efficacy was measured using the Skin Infection Rating Scale and microbiological culture. Safety and tolerability were also evaluated. RESULTS Among the 411 patients who received treatment (210 males [51.1%]; mean [SD] age, 18.6 [18.3] years), ozenoxacin demonstrated superior clinical success compared with placebo, which was evident after 5 days of therapy (112 of 206 [54.4%] vs 78 of 206 [37.9%]; P = .001). Ozenoxacin also demonstrated superior microbiological success compared with placebo after 2 days of therapy (109 of 125 [87.2%] vs 76 of 119 [63.9%]; P = .002). Ozenoxacin was well tolerated, with 8 of 206 patients experiencing adverse effects, with only 1 of these potentially related to the study treatment; none were serious. CONCLUSIONS AND RELEVANCE Topical ozenoxacin is effective and well tolerated in the treatment of impetigo in patients 2 months and older. This effect is demonstrated by rapid onset of response and superior clinical and microbiological response compared with placebo. Topical ozenoxacin represents a novel option for the treatment of impetigo.

Trogocytosis modulates immune responses, with still unclear underlying molecular mechanisms. Using leukemia mouse models, we found that lymphocytes perform trogocytosis at high rates with tumor cells. While performing trogocytosis, both Natural Killer (NK) and CD8 + T cells acquire the checkpoint receptor PD-1 from leukemia cells. In vitro and in vivo investigation revealed that PD-1 on the surface of NK cells, rather than being endogenously expressed, was derived entirely from leukemia cells in a SLAM receptor–dependent fashion. PD-1 acquired via trogocytosis actively suppressed NK cell antitumor immunity. PD-1 trogocytosis was corroborated in patients with clonal plasma cell disorders, where NK cells that stained for PD-1 also stained for tumor cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on NK and cytotoxic T cells, reveal the immunoregulatory effect of membrane transfer occurring when immune cells contact tumor cells.

Estimating the social benefits of barrier-free building has always required indirect solutions, such as calculating the savings in social services, hospitalization or adaptations made possible by the increase in accessibility. This research uses the contingent valuation method to gain a direct appraisal of the benefits from barrier-free housing. When comparing two similar dwellings, with the only difference being their accessibility conditions, the 1,007 randomly chosen households that answered the direct survey would pay, on average, 12.5 per cent more for being barrier-free. None of the different appraisals made on accessibility costs reaches 5 per cent. This confirms the social profitability of building without barriers and shows the potential size of the private market for those housing developers that meet the demand. Accessibility is a general concern, an economic good or attribute that most households value, irrespective of the physical conditions of their members.Adaptable Housing, Contingent Valuation Method, Benefits Of Accessibility,

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With extensive use of herbicides in agricultural areas, the risk of contamination of groundwater and surface water by these products has become a worldwide concern. Practices of application or maintenance of soil organic residues that have begun to be used in agriculture for soil nutrition have demonstrated other benefits besides nutrient supplementation, such as reduced mobility and increased soil degradation of herbicides. Because it is the final destination of herbicides, soil and its constituents, especially organic matter in tropical soils, play a prominent role in processes that encompass the dynamics of herbicide molecules. In this context, it is necessary to know the influence of the organic matter and its constituents on the behavior of the herbicides. This review discusses the main relationships of organic matter in the retention, transport, and transformation processes of herbicides in the soil, as well as the interference in the weed control effectiveness of these products. Because of this, knowing the influence of organic matter in the various processes related to the behavior of herbicides in the soil allows us to adopt more appropriate management practices regarding both weed control and remediation of contaminated areas. However, despite the wide range of information on the subject in the literature, each situation is distinct due to the wide variation in the behavioral response of the products to the different types of organic material present in the soil.

NK cells are key effectors of cancer immunosurveillance and immunotherapy and yet, much is still unknown about how cancer evades NK cell responses. Recent studies showed that checkpoint receptors, including PD-1, inhibit NK cell functions, but the mechanisms underlying the expression of these receptors remains unknown. Here, using two mouse models of leukemia, we show that NK cells, rather than intrinsically expressing the protein, are decorated with exogenous PD-1 by acquisition of membrane fragments from tumor cells. PD-1 acquisition, both ex vivo and in vivo, was a feature not only of NK cells, but also of CD8+ T cells. PD-1 acquisition occurred with a mechanism consistent with trogocytosis and did not require engagement of PD-1-ligands on NK cells. In vivo results were corroborated in humans, where PD-1+ NK cells from multiple myeloma patients also stained for cancer cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on NK and T cells, reveal the immuno-regulatory effect of membrane transfer occurring when immune cells contact tumor cells.