Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

Purpose

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.

Methods

We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.

Results

Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P?=?0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P?=?0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P?=?0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher V_T.

Conclusions

Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

     

Cost-Effectiveness of Primary Prevention with Statin Treatment for Chinese Patients with Type 2 Diabetes

Introduction

Statins can reduce the risk of cardiovascular events in patients with diabetes. The objective of this analysis was to evaluate whether primary prevention with statin treatment is cost-effective for newly diagnosed type 2 diabetes mellitus (T2DM) patients in the Chinese context.

Methods

An economic analysis of primary prevention with statin treatment was conducted using the Chinese Outcomes Model for T2DM with a time horizon of a lifetime, which was developed and validated based on the Chinese population. Clinical costs and utility inputs were gathered from published sources. Lifetime discounted quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER) were measured. The uncertainty was evaluated by one-way and probabilistic sensitivity analyses.

Results

Statin treatment with atorvastatin 10 mg could add 0.08 QALYs with an additional $1676 compared with that of no statin management (control strategy) over a lifetime horizon, which led to an ICER of $21,924 per QALY gained. At a willingness-to-pay threshold of $27,351 per QALY gained, there was an approximately 80% probability of statin treatment being cost-effective compared with the control strategy. The model outcomes were most sensitive to the length of the expected life and age at the T2DM diagnosis.

Conclusions

Statin treatment with atorvastatin is most likely cost-effective for primary prevention in Chinese patients newly diagnosed with type 2 diabetes.

Funding

Partially funded by Pfizer Inc.

     

Perioperative Management of Patients with Inflammatory Rheumatic Diseases Undergoing Major Orthopaedic Surgery: A Practical Overview

Patients with inflammatory rheumatic diseases often need orthopaedic surgery due to joint involvement. Total hip replacement and total knee replacement are frequent surgical procedures in these patients. Due to the complexity of the inflammatory rheumatic diseases, the perioperative management of these patients must envisage a multidisciplinary approach. The frequent association with extraarticular comorbidities must be considered when evaluating perioperative risk of the patient and should guide the clinician in the decision-making process. However, guidelines of different medical societies may vary and are sometimes contradictory. Orthopaedics should collaborate with rheumatologists, anaesthesiologists and, when needed, cardiologists and haematologists with the common aim of minimising perioperative risk in patients with inflammatory rheumatic diseases. The aim of this review is to provide the reader with simple practical recommendations regarding perioperative management of drugs such as disease-modifying anti-rheumatic drugs, corticosteroids, non-steroidal anti-inflammatory drugs and tools for a risk stratification for cardiovascular and thromboembolic risk based on current evidence for patients with inflammatory rheumatic diseases.     

The Proteolytic Fraction from Latex of <Emphasis Type="Italic">Vasconcellea cundinamarcensis</Emphasis> (P1G10) Enhances Wound Healing of Diabetic Foot Ulcers: A Double-Blind Randomized Pilot Study

Introduction

The aim of the study was to investigate the role of the proteolytic fraction from Vasconcellea cundinamarcensis, designated as P1G10, on the healing of chronic foot ulcers in neuropathic patients with diabetes 2.

Methods

Fifty patients were enrolled in a prospective, randomized, double-blind trial, to verify the efficacy and safety of a topical dressing formulated with 0.1% P1G10, intended for wound healing, versus a hydrogel (control) protocol. Upon completion of the intervention, the outcome evaluated the number of patients attaining full epithelization (100%), or at least 80% healing. Statistical analysis compared the data on each group for the significance of the differences.

Results

Collection of data was finished in week 16, and the results were analyzed by intention to treat. The results showed that, in the control group, 5 patients attained 100% ulcer healing, 3 patients?≥?80% healing and 11 experienced ulcer changes?≤?80%, and the remainder showed no changes or their wounds became worse. Meanwhile, in the P1G10 group, 11 patients experienced full healing, 4 had healing?≥?80% and 5 had ulcer changes?≤?lower than 80%, and the remainder showed no changes or their wounds became worse. The healing incidence for the first endpoint (100% healing) showed that the P1G10 group was 2.95-fold more efficacious than the control group (CI 95%) and 2.52-fold (CI, 95%) higher than its control for the second endpoint (80% healing).

Conclusions

These data support the hypothesis that topical application of the proteolytic fraction identified as P1G10 significantly enhances foot ulcer healing compared to hydrogel treatment.

     

Recognizing Gynecological Cancer in Primary Care: Risk Factors,Red Flags,and Referrals

Early diagnosis of symptomatic gynecological cancer is likely to improve patient outcomes, including survival. The primary care practitioner has a key role to play in this—they must recognize the symptoms and signs of gynecological cancer and make prompt evidence-based decisions regarding further investigation and referral. However, this is often difficult as many of the symptoms of gynecological cancers are nonspecific and are more likely to be caused by benign rather than malignant disease. As primary care is generally the first point of patient contact, those working in this setting usually encounter cancer patients at an earlier, and possibly less symptomatic, stage than practitioners in secondary care. Despite these challenges, research has improved our understanding of the symptoms patients present to primary care with, and a range of tests and referral pathways now exist in the UK and other countries to aid early diagnosis. Primary care practitioners can also play a key role in gynecological cancer prevention. A significant proportion of gynecological cancer is preventable either through lifestyle changes such as weight loss, or, for cervical cancer, vaccination and/or engagement with screening programs. Primary care provides an excellent opportunity to discuss cancer risk with patients and to promote risk reduction strategies and lifestyle change. In this article, the first in a series discussing cancer detection in primary care, we concentrate on gynecological cancer and focus on the three most common forms that a primary care practitioner is likely to encounter: ovarian, endometrial, and cervical cancer. We outline key risk factors, briefly discuss prevention and screening strategies, and offer practical guidance on the recognition of symptoms and signs and the investigation and referral of women with suspected cancer. While this article is written from a UK primary care perspective, much of what is discussed will be of relevance to those working in other healthcare systems.