The impact on risk-factor analysis of different mortality outcomes in COPD patients

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Socioeconomic differences in one-year survival after ischemic stroke: the effect of acute and post-acute care-pathways in a cohort study

Abstract Background The reasons for socioeconomic inequity in stroke mortality are not well understood. The aim of this study was to explore the role of ischemic stroke care-pathways on the association between education level and one-year survival after hospital admission. Methods Hospitalizations for ischemic stroke during 2011/12 were selected from Lazio health data. Patients’ clinical history was defined by retrieving previous hospitalizations and drugs prescriptions. The association between education level and mortality after stroke was studied for acute and post-acute phases using multilevel logistic models (Odds Ratio (OR)). Different scenarios of quality care-pathways were identified considering hospital performance, access to rehabilitation and drug treatment post-discharge. The probability to survive to acute and post-acute phases according to education level and care-pathway scenarios was estimated for a “mean-severity” patient. One-year survival probability was calculated as the product of two probabilities. For each scenario, the 1-year survival probability ratio, university versus elementary education, and its Bootstrap Confidence Intervals (95 % BCI) were calculated. Results We identified 9,958 patients with ischemic stroke, 53.3 % with elementary education level and 3.2 % with university. The mortality was 14.9 % in acute phase and 14.3 % in post-acute phase among survived to the acute phase. The adjusted mortality in acute and post-acute phases decreased with an increase in educational level (OR = 0.90 p-trend < 0.001; OR = 0.85 p-trend < 0.001). For the best care-pathway, the one-year survival probability ratio was 1.06 (95 % BCI = 1.03–1.10), while it was 1.17 (95 % BCI = 1.09–1.25) for the worst. Conclusions Education level was inversely associated with mortality both in acute and post-acute phases. The care-pathway reduces but does not eliminate 1-year survival inequity

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION: FROM PALIVIZUMAB TO NIRSEVIMAB, WHAT EVIDENCE?

The Respiratory Syncytial Virus (RSV) is considered the leading cause of lower respiratory tract infections (LRTI) in children aged &lt; 2 years. In high-risk children, including preterm infants, or in children with bronchopulmonary dysplasia (BPD) and infants with congenital heart diseases (CHD), RSV infections may lead to severe consequences that often require hospitalizations. The typical seasonality of RSV is going through some changes and as consequence the healthcare management of serious infections is facing some difficulties. In this context and in light of the worldwide economic, political and healthcare debate around treatment of RSV infections, this article aims to inform physicians and healthcare professionals about evidence regarding the two drugs licensed for passive prophylaxis against RSV, namely palivizumab and nirsevimab. According to the 1998 IMpact study, palivizumab administration (5 monthly doses) was able to reduce the incidence of RSV hospitalizations in infants born preterm and in those with BPD. However, over the years, several studies found questionable cost-effectiveness evidence regarding the use of palivizumab in preterm infants born at ≥ 29 weeks of gestation. Differently from palivizumab, one single dose of nirsevimab is able to protect over an entire RSV season. This drug was able to reduce hospitalizations and medically attended RSV-associated LRTI in infants born preterm and without comorbidities, but none similar efficacy was found in reducing hospitalizations in healthy infants born at term (born at ≥ 35 weeks of gestation). As such, while future interventions in the clinical management of RSV infections and related consequences are warranted, new evidence about nirsevimab and palivizumab use will be essential to define which population will benefit the most from passive prophylaxis