Validation of a novel framework defining the acceptable standard of care for heart failure with reduced ejection fraction

Background In heart failure with reduced ejection fraction (HFrEF), uptitration of neurohormonal antagonists to trial-proven doses shown to reduce mortality is challenging and seldomly achieved in clinical practice. A major reason for underdosing of these agents is the lack of a clear description of what constitutes an acceptable standard of care in HFrEF. To address this limitation, a novel framework for describing the physician adherence to evidence-based treatment was recently proposed. The aim of our study was to evaluate and validate the proposed framework in a real-world population of patients with HFrEF. Methods A cohort of patients with HFrEF, defined as left ventricular ejection fraction (LVEF) <40%, under treatment with neurohormonal antagonists for at least 3 months were retrospectively identified at a tertiary hospital's Heart Failure Clinic. Demographic, clinical, echocardiographic and treatment data were assessed. Patients were divided in three strata for each neurohormonal antagonist, according to the proposed framework: Status I – patients receiving target doses or the highest tolerated dose; Status II – use of subtarget doses for reasons unrelated to clinically important intolerance; and Status III – not receiving the drug at any dose. The prognostic value of each strata was assessed for all-cause mortality. Results A total of 408 patients (mean age 68±12 years, 78% male, 63% ischemic etiology) were included. The median LVEF was 31% (IQR 25–36) and most patients were in NYHA class II or III [210 (51.5%) and 163 (40%), respectively]. Medical therapy is described in Table 1. During a median follow-up of 3.3 years (IQR 1.4–5.6), 210 patients died. On univariable analysis, achieving Status I of beta-blocker (BB) therapy (HR: 0.50; 95% CI: 0.32–0.81; P=0.004) or ACEi/ARB (HR: 0.56; 95% CI: 0.36–0.86; P=0.012) was associated with reduced all-cause mortality. The mortality of patients in Status II of BB or ACEi/ARB was similar to the mortality of those not receiving the drug (HR for BB: 0.90; 95% CI: 0.53–1.52; P=0.69 and HR for ACEi/ARB: 0.71; 95% CI: 0.42–1.18; P=0.182) – figure 1. Achieving Status I of BB remained independently associated with reduced mortality after adjustment for several clinical and echocardiographic confounders (n=13) (adjusted HR: 0.59; 95% CI: 0.35–0.98; P=0.041). Conclusions In this real-world population of patients with HFrEF, the vast majority of patients were in Status I of BB and ACEi/ARB therapy. Achieving Status I of BB therapy seems to be associated with reduced mortality, even after adjustment for several markers of disease severity, highlighting the need for uptitration of medical therapy to maximal tolerated doses according to trial-proven regimens. FUNDunding Acknowledgement Type of funding sources: None.

A Scholarly Glance at Theoretical and Practical Aspects of Housing Urbanites

This paper has been rigorously reviewed and finally it has been checked with internationally acceptable standard so that SAGE recognized it with moderate review which yet need to be further undergo peer review process. The theme on which the paper was built has been found to be practically and theoretically relevant. In the coming academic discussion this paper is expected to be more refined with critical comments and scholarly detection.

A Scholarly Glance at Theoretical and Practical Aspects of Housing Urbanites

This paper has been rigorously reviewed and finally it has been checked with internationally acceptable standard so that SAGE recognized it with moderate review which yet need to be further undergo peer review process. The theme on which the paper was built has been found to be practically and theoretically relevant. In the coming academic discussion this paper is expected to be more refined with critical comments and scholarly detection.

Losing Sight of Women's Rights (again): A Response to Cowan et al.

This article responds to Cowan et al.'s critique of our article ‘Losing sight of women's rights: the unregulated introduction of gender self-identification as a case study of policy capture in Scotland’, published by Scottish Affairs 28(3) in August 2019. Cowan et al. make a series of strong criticisms, including of our accuracy, diligence and adherence to scholarly norms. We reject these as unreasonable. In our view, they misunderstand and misrepresent the fundamental purpose of our article, fail to engage with our core thesis of policy capture, and implausibly seek to place our view of the law beyond academic respectability. Their own strongly-asserted view of the law appears at least open to question. We argue that the problem is not with our scholarship falling below any normal acceptable standard, but rather that Cowan et al. appear to be uncomfortable with others holding and expressing any different view to theirs on this topic. They have therefore reached too quickly for assertions of incompetence or worse. We discuss the climate in which our original article was produced and in which we are now defending it. Describing our own experiences as well of those of other academics, we question how the scholarship needed to help shape policy and law in this area can take place under such conditions.

Cancer Risk Assessment for Workers Exposed to Pollution Source, a Petrochemical Company, Iran

Background: Air pollution have led to severe problem of adverse health effect in the world. This study aimed to conduct the health risk assessment, cancer risk analysis, and non-cancer risk for exposure to volatile organic compounds (VOCs) and hydrogen sulfide (H2S) in petrochemical industry. Methods: In this cross-sectional research, 123 samples were collected in the ambient air in Iran during winter 2016. For sampling and analysis of VOCs and H2S, 3 methods (numbers 1500, 1501, and 6013) presented by the National Institute of Occupational Safety and Health (NIOSH) were used. For determination of risk assessment of chemical pollutants, semi-quantitative method presented by the Occupational Safety and Health Division, Singapore was used. Finally, for calculation of cancer risk analysis, Chronic Daily Intake (CDI) and calculation of non-cancer risk, Exposure Concentration (EC) were used. Results: Average concentration of benzene (2.12±0.95) in breathing zone of workers were higher than the Threshold Limit Values-Time Weighted Average (TLV-TWA) (P<0.05). Among chemical substance, benzene had very high rank of risk in petrochemical industry. Rank of risk for H2S, toluene, and xylene present in the breathing zone of workers was low. The mean cancer risk for workers exposed to benzene was estimated 8.78×10-3, in other words, 8.7 cancer per 1000 i.e. higher than the acceptable standard of 10-6 . In our study, non-cancer risk for BTX was higher than the acceptable standard of 1. Conclusion: In particular, overall cancer and toxic risk can be associated with long term exposure to benzene.

Assessing Study Quality in Meta-Analysis

An assumption of meta-analyses is made with regard to the quality of the primary studies included for analysis. Specifically, the process assumes each study is a valid estimation of a hypothesized relationship of interest. In instances when a primary study's quality is below an acceptable standard, one option is for the study be excluded from further analyses. Alternatively, studies of acceptable merit could be further investigated through moderator analyses in an attempt to explain heterogeneity among effect sizes due to quality elements. The current essay discusses methods for evaluating study quality before proposing guidelines for their assessment. It is recommended that future meta-analyses in communication include a dedicated section detailing how study quality is addressed when reviewing studies for inclusion.

‘He Wasn’t Able to Understand What I Was Saying’: The Experiences of Returnees’ Speaking Western Armenian in ‘Eastern’ Armenia

Since Armenia’s independence in 1991, thousands of diasporans have made the decision to return and settle in the ancestral homeland. The returnees, who speak Western Armenian, one of the two standardised forms of modern Armenian, are switching to the use of Eastern Armenian, the official variant of the homeland. Using two determinants of language perception—standardisation and vitality—this paper analyses the reactions received by thirty returnees who emigrated from nine countries, when speaking Western Armenian to an Eastern Armenian-speaking society. The vitality of the language shows signs of increasing through an encouragement by locals aware of the language’s historical significance, and an admiration of its ‘beauty’ and terminology. A heightened vitality has led returnees to feel confident about its use during social interactions and the possibility of the standard being incorporated into the nation’s linguistic narrative. However, confusion and ridicule due to a differing pronunciation, vocabulary, terminology, and the inability to be understood by some in Armenian society, has led to discomfort by returnees who are shifting to the usage of Eastern Armenian. At present, the use of Western Armenian in the homeland remains within the confines of family, friends and returnee circles. Despite the changing status of Western Armenian through a notable welcoming of the language into the linguistic narrative of the country, some segments of Armenian society do not perceive Western Armenian as an acceptable standard for broader use in Armenian society and national institutions. The homeland’s inconsistent, and at times questionable, acceptance of the language perpetuates the status quo that Western Armenian remains an unacceptable standard within the homeland and for use only in the diaspora.

Trade Commitments and Data Flows: The National Security Wildcard

This paper poses a hypothetical WTO challenge to the Passenger Name Records (PNR) Transfer Agreements the European Union has signed with the United States (as well as Australia and Canada). The focus will be on a possible citation of GATS Article XIV National Security Exception by the EU, and the viability of such a defense. Because of the absence of case law, this paper will also attempt to synthesize an acceptable standard for assessing GATS National Security Exception citations.