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101.
《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2022,42(5):519-530
Hypertension mediated organ damage (HMOD) refers to structural or functional changes in arteries or target organs that can be present in long-standing hypertension, but it can be also found in naïve never treated patients. Traditionally, cardiovascular risk is stratified with charts or calculators that tend to underestimate the real cardiovascular risk. The diagnosis of HMOD automatically reclassifies patients to the highest level of cardiovascular risk. Subclinical HMOD can be present already at the diagnosis of hypertension and more than 25% of hypertensives are misclassified with the routine tests recommended by hypertension guidelines. Whether HMOD regression improves cardiovascular outcomes has never been investigated in randomized clinical trials and remains controversial. However, different drugs have been probed with promising results in high cardiovascular risk patients, such as the new antidiabetic or the novel non-steroid mineralocorticoid antagonists. Accordingly, trials have shown that lowering blood pressure reduces cardiovascular events. In this narrative review, we will discuss the role of HMOD in cardiovascular risk stratification, the different types of organ damage, and the evidence available to define whether HMOD can be used as a therapeutic target. 相似文献
102.
103.
Exploring immunological mechanisms of the whole sporozoite vaccination against P. falciparum malaria
《Vaccine》2015,33(25):2851-2857
Great progress has been made in the development of whole sporozoite vaccines including the manufacturing of cryopreserved Plasmodium falciparum sporozoites (PfSPZ) suitable for clinical application. Such whole sporozoites are being used for clinical studies of controlled human malaria infection (CHMI) as well as for evaluation of candidate vaccine approaches (both attenuated sporozoites and infectious sporozoites administered with chemoprophylaxis) and as reagents for immunology and cell biology assays. CHMI studies with whole sporozoites provide a great opportunity to better understand the intrinsic mechanisms of resistance to P. falciparum (e.g. due to sickle cell trait and other hemoglobinopathies) as well as host responses to an initial P. falciparum infection. High-level protective efficacy has been demonstrated in a small number of volunteers after intravenous (IV) inoculation of radiation-attenuated PfSPZ or in those who were exposed to live PfSPZ while on malaria chemoprophylaxis. These advances and data warrant further investigations of the immunological mechanism(s) whereby whole sporozoite inoculation elicits protective immunity in order to facilitate whole sporozoite vaccine development. The National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on Sept. 2–3, 2014 involving participation of international experts in the field of malaria vaccine development, and in basic and clinical immunology research. The workshop discussed the current understanding of host immune responses to whole malaria sporozoite inoculation, identified gaps in knowledge, resources to facilitate progress, and applicable new technologies and approaches to accelerate immunologic and vaccinologic studies and biomarker identification. This report summarizes the discussions and major conclusions from the workshop participants. 相似文献
104.
《Vaccine》2015,33(13):1527-1540
BackgroundEconomic evaluations have routinely understated the net benefits of vaccination by not including the full range of economic benefits that accrue over the lifetime of a vaccinated person. Broader approaches for evaluating benefits of vaccination can be used to more accurately calculate the value of vaccination.MethodologyThis paper reflects on the methodology of one such approach – the health investment life course approach – that looks at the impact of vaccine investment on lifetime returns. The role of this approach on vaccine decision-making will be assessed using the malaria health investment life course model example.ResultsWe describe a framework that measures the impact of a health policy decision on government accounts over many generations. The methodological issues emerging from this approach are illustrated with an example from a recently completed health investment life course analysis of malaria vaccination in Ghana. Beyond the results, various conceptual and practical challenges of applying this framework to Ghana are discussed in this paper.Discussion and conclusionsThe current framework seeks to understand how disease and available technologies can impact a range of economic parameters such as labour force participation, education, healthcare consumption, productivity, wages or economic growth, and taxation following their introduction. The framework is unique amongst previous economic models in malaria because it considers future tax revenue for governments. The framework is complementary to cost-effectiveness and budget impact analysis. The intent of this paper is to stimulate discussion on how existing and new methodology can add to knowledge regarding the benefits from investing in new and underutilized vaccines. 相似文献
105.
Patients often respond differently to a treatment because of individual heterogeneity. Failures of clinical trials can be substantially reduced if, prior to an investigational treatment, patients are stratified into responders and nonresponders based on biological or demographic characteristics. These characteristics are captured by a predictive signature. In this paper, we propose a procedure to search for predictive signatures based on the approach of patient rule induction method. Specifically, we discuss selection of a proper objective function for the search, present its algorithm, and describe a resampling scheme that can enhance search performance. Through simulations, we characterize conditions under which the procedure works well. To demonstrate practical uses of the procedure, we apply it to two real‐world data sets. We also compare the results with those obtained from a recent regression‐based approach, Adaptive Index Models, and discuss their respective advantages. In this study, we focus on oncology applications with survival responses. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. 相似文献
106.
A principal stratification approach for evaluating natural direct and indirect effects in the presence of treatment‐induced intermediate confounding 下载免费PDF全文
Recently, several authors have shown that natural direct and indirect effects (NDEs and NIEs) can be identified under the sequential ignorability assumptions, as long as there is no mediator–outcome confounder that is affected by the treatment. However, if such a confounder exists, NDEs and NIEs will generally not be identified without making additional identifying assumptions. In this article, we propose novel identification assumptions and estimators for evaluating NDEs and NIEs under the usual sequential ignorability assumptions, using the principal stratification framework. It is assumed that the treatment and the mediator are dichotomous. We must impose strong assumptions for identification. However, even if these assumptions were violated, the bias of our estimator would be small under typical conditions, which can be easily evaluated from the observed data. This conjecture is confirmed for binary outcomes by deriving the bounds of the bias terms. In addition, the advantage of our estimator is illustrated through a simulation study. We also propose a method of sensitivity analysis that examines what happens when our assumptions are violated. We apply the proposed method to data from the National Center for Health Statistics. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
107.
This study investigates the reasons for the gaps in educational attainment between children from married biological parents and alternative families. Socioeconomic resources and parental behaviors are well‐established reasons, but these factors do not explain the entire relationship between family structure and educational outcomes. We argue that these parental‐level factors influence children's academic socialization and thus indirectly contribute to differential educational outcomes. Hence, this study considers whether children's academic characteristics are a complementary explanation for the effect of family structure on education. The logistic regression analysis demonstrates that these characteristics represent an important explanation for the lower educational attainment of children from alternative families. The decomposition analysis shows that academic characteristics are the predominant reason for the gaps in postsecondary educational attainment between children from married biological parents and alternative families. These characteristics account for a relatively higher proportion of these gaps than the combined direct effects of parental socioeconomic status and parental behaviors. 相似文献
108.
Population stratification has long been recognized as an issue in genetic association studies because unrecognized population stratification can lead to both false‐positive and false‐negative findings and can obscure true association signals if not appropriately corrected. This issue can be even worse in rare variant association analyses because rare variants often demonstrate stronger and potentially different patterns of stratification than common variants. To correct for population stratification in genetic association studies, we proposed a novel method to Test the effect of an Optimally Weighted combination of variants in Admixed populations (TOWA) in which the analytically derived optimal weights can be calculated from existing phenotype and genotype data. TOWA up weights rare variants and those variants that have strong associations with the phenotype. Additionally, it can adjust for the direction of the association, and allows for local ancestry difference among study subjects. Extensive simulations show that the type I error rate of TOWA is under control in the presence of population stratification and it is more powerful than existing methods. We have also applied TOWA to a real sequencing data. Our simulation studies as well as real data analysis results indicate that TOWA is a useful tool for rare variant association analyses in admixed populations. 相似文献
109.
Gregory Gafni-Pappas Susanne D. DeMeester Michael A. Boyd Arun Ganti Adam M. Nicholson Jeremy Albright Juan Wu 《The American journal of emergency medicine》2018,36(10):1825-1831
Objective
The HAS-Choice pathway utilizes the HEART Score, an accelerated diagnostic protocol (ADP), and shared decision-making using a visual aid in the evaluation of chest pain patients. We seek to determine if our intervention can improve resource utilization in a community emergency department (ED) setting while maintaining safe patient care.Methods
This was a single-center prospective cohort study with historical that included ED patients ≥21 years old presenting with a primary complaint of chest pain in two time periods. The primary outcome was patient disposition. Secondary outcomes focused on 30-day ED bounce back and major adverse cardiac events (MACE). We used multivariate logistic regression to estimate the odds ratio (OR) and its 95% confidence interval (CI).Results
In the pre-implementation period, the unadjusted disposition to inpatient, observation and discharge was 6.5%, 49.1% and 44.4%, respectively, whereas in the post period, the disposition was 4.8%, 41.5% and 53.7%, respectively (chi-square p < 0.001). The adjusted odds of a patient being discharged was 40% higher (OR = 1.40; 95% CI, 1.30, 1.51; p < 0.001) in the post-implementation period. The adjusted odds of patient admission was 30% lower (OR = 0.70; 95% CI, 0.60, 0.82; p < 0.001) in the post-implementation period. The odds of 30-day ED bounce back did not statistically differ between the two periods. MACE rates were <1% in both periods, with a significant decrease in mortality in the post-implementation period.Conclusion
Our study suggests that implementation of a shared decision-making tool that integrates an ADP and the HEART score can safely decrease hospital admissions without an increase in MACE. 相似文献110.