Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.     

Severe bradyarrhythmia linked to left atrial dysfunction in Fabry disease—A cross‐sectional study

Background

Fabry disease (FD) is a lysosomal storage disorder caused by an enzymatic deficiency. Conduction abnormalities and bradyarrhythmias are common and can occur prior to the onset of left ventricular (LV) hypertrophy. We aimed to describe the clinical, electrocardiographic and echocardiographic, including left atrial (LA) function, determinants of bradyarrhythmic events in FD.

Hypothesis

Bradyarrhythmic events are frequent in patients with FD and are associated with LA dysfunction.

Methods

We designed a cross‐sectional study that includes 53 FD patients (mean age, 45 years; 42% male). Clinical characteristics and electrocardiographic and echocardiographic data were collected. LA function was measured using biplane volumes and 2D speckle‐tracking echocardiography. Bradyarrhythmic events were defined as pause of more than 2 seconds (sinus pause or atrioventricular block) recorded on Holter, severe bradycardia (≤ 40 bpm on ECG) or implantation of a permanent pacemaker.

Results

Six (11%) patients had installation of a pacemaker, 4 (8%) patients had cardiac pause and 2 (4%) patients had an episode of severe bradycardia. Patients with bradyarrhythmic events were older and had a lower resting heart rate. On echocardiography, a significantly higher LV mass, a lower LV ejection fraction, and a more affected LA reservoir function were found in those with bradyarrhythmic events. Patients also experienced tachyarrhythmias frequently. Atrial fibrillation occurred in 11 (21%) patients and ventricular tachycardia in 4 (8%) patients.

Conclusions

Bradyarrhythmia are common manifestations of cardiac involvement in FD. Age, LV mass, LV ejection fraction and LA reservoir dysfunction can be useful markers associated with bradyarrhythmia.     

Clinical outcomes of primary arterial embolization in severe hepatic trauma: A systematic review

Purpose

This purpose of this systematic review was to determine the safety and efficacy of arterial embolization as the primary treatment for grade III-V liver trauma, excluding the postoperative use of arterial embolization.

Beta-Blockers and Ivabradine in Chronic Heart Failure: From Clinical Trials to Clinical Practice

Beta-blockers have become one of the cornerstones of treatment of patients with heart failure (HF) and depressed left ventricular function, but in clinical practice only 30–35 % of patients achieve the therapeutic target dose as established in randomized clinical trials. Moreover, high resting heart rate (HR) has emerged as a simple but relevant risk factor for cardiovascular events, including coronary artery disease and HF; also, it was found to have an independent prognostic value in patients with HF. Evidence that HR could be considered a good parameter to evaluate the quality of treatment in patients with HF has been suggested; of note, many patients maintain a resting HR ≥70 beats per minute despite optimal beta-blocker therapy. In recent years, a new drug able to reduce HR, ivabradine, has been introduced in clinical practice, and its use in the clinical setting of HF patients has been recommended by current European Society of Cardiology (ESC) guidelines. Here we review the evidence of the prognostic role of HR in systolic HF and the potential relationship between HR lowering and the beneficial effects of beta-blockers; we will also analyze the reasons why an appropriate use of these drugs is seldom achieved in clinical practice, and review the evidence for the use of ivabradine in systolic HF in the clinical setting.     

国际康复政策架构与核心内容研究：基于世界卫生组织康复政策文件的内容分析

目的 运用世界卫生组织(WHO)健康服务构成要素的理论,从健康服务体系视域,对WHO有关康复服务的政策架构与行动战略进行系统的内容分析,探讨WHO国际康复政策的理论基础与方法、康复政策架构以及行动战略的核心内容。方法 WHO发布的康复相关政策文件包括《健康服务体系中的康复》《健康服务体系中的康复：行动指南》《康复指标清单：康复监测和评估架构配套的工具》和《康复现状系统评估配套工具(STARS)：康复信息收集模板(TRIC)》,形成国际康复政策体系。本研究运用内容分析方法,根据WHO健康服务构成的六大要素,即领导力和治理能力、筹资、健康人力资源、服务提供、医药技术、健康信息系统,详细分析国际康复政策的理论基础与方法、政策架构以及行动战略的核心内容与康复服务优先发展领域。结果 现代康复服务政策核心依据WHO有关构建以人为本的健康服务、关注健康的社会决定因素的理论,依据《国际功能、残疾与健康分类》的功能、残疾和健康理论,明确发展康复是实现联合国可持续发展目标三,确保健康的生活方式,促进各年龄段人群的福祉,即“全民健康覆盖”的重要路径。系统分析了领导力和治理能力、筹资、健康人力资源、服务提供、医药技术、健康信息系统六大领域,WHO的国际政策架构、行动战略以及发展内容与优先领域。WHO倡导制定国家康复规划,建立与完善康复治理结构并发展康复治理能力,采取多种途径为发展康复服务筹资。将康复融入现代健康服务体系,在健康服务连续体中提供不同层次的康复服务,在健康服务体系中构建康复服务体系,培训专业人员,建立服务信息网络,提升服务质量和服务覆盖率,关注重点领域和优先项目,以满足不同人群的多样化需求,实现全民健康覆盖。将辅助技术作为医药技术领域纳入康复服务体系。在健康信息系统中,收集有关功能和康复需求的信息以及康复服务结果和影响的数据,并开展基于循证的康复政策系统研究。结论 基于健康服务体系六大构成要素,从宏观、中观和微观三个层面,系统研究了国际康复政策架构。现代康复发展的理念是要实现全民健康覆盖。发展康复必须建立以人为中心的现代健康服务体系,并且关注社会决定因素。发展康复是实现联合国2030年可持续发展目标的重要举措。国际康复的政策体系围绕康复领导力和治理、康复筹资、康复人力资源、康复服务提供、康复相关医药技术以及康复与健康信息六大领域,从理论与政策、政策行动、实施工具和路径(评价指标体系和实施效果评估)三个层级,构建了康复发展的政策和行动战略以及具体的实施方法与工具的体系。实施WHO康复政策,需要采取如下行动：加强康复服务领导力、治理、规划和协调能力;构建合理的康复筹资机制,为康复筹措必要资金;健全康复人力资源培养与保障机制;提升康复人员专业能力,提升康复服务提供能力并改善服务质量;提高辅助产品和辅助技术服务的质量与可及性;建立涵盖功能、残疾和康复的健康信息系统并开展康复科学研究。