Evaluation of a new equation for LDL-c estimation and prediction of death by cardiovascular related events in a German population-based study cohort

A simple equation established by Cordova &; Cordova (LDL-COR) was developed to provide an improved estimation of LDL-cholesterol in a large Brazilian laboratory database. We evaluated this new equation in a general population cohort in Pomerania, north-eastern Germany (SHIP Study) compared to other existing formulas (Anandaraja, Teerakanchana, Chen, Hattori, Martin, Friedewald and Ahmadi), and its power in the prediction of death by atherosclerosis related events as the primary outcome. Analysis was conducted on a cohort of 4075 individuals considering age, gender, use of lipid lowering therapy and associated co-morbidities such as diabetes, hepatic, kidney and thyroid disease. LDL-COR values had a lower standard deviation compared to the previously published equations: 0.92 versus 1.02, 1.02, 1.03, 1.04, 1.09, 1.10 and 1.74?mmol/L, respectively. All of the factors known to affect the results obtained by the Friedewald’s equation (LDL-FW), except fibrate use, were associated with the difference between LDL-COR and LDL-FW (p?p?=?.06). LDL-COR determined a higher hazard ratio (1.23 versus 1.12, 1.19, 1.21, 1.19, 1.21 and 1.19) for cardiovascular disease related mortality, incident stroke or myocardial infarction compared to the other evaluated formulas, except for Ahmadi’s (1.24), and the same adjusted predictive power considering all confounding factors. The proposed simple equation was demonstrated to be suitable for a more precise LDL-c estimation in the studied population. Since LDL-c is a parameter frequently requested by medical laboratories in clinical routine, and will probably remain so, precise methods for its estimation are needed when direct measurement is not available.     

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).

     

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.     

How physical therapists instruct patients with stroke: an observational study on attentional focus during gait rehabilitation after stroke

Purpose: People without neurological impairments show superior motor learning when they focus on movement effects (external focus) rather than on movement execution itself (internal focus). Despite its potential for neurorehabilitation, it remains unclear to what extent external focus strategies are currently incorporated in rehabilitation post-stroke. Therefore, we observed how physical therapists use attentional focus when treating gait of rehabilitating patients with stroke.

Methods: Twenty physical therapist-patient couples from six rehabilitation centers participated. Per couple, one regular gait-training session was video-recorded. Therapists’ statements were classified using a standardized scoring method to determine the relative proportion of internally and externally focused instructions/feedback. Also, we explored associations between therapists’ use of external/internal focus strategies and patients’ focus preference, length of stay, mobility, and cognition.

Results: Therapists’ instructions were generally more external while feedback was more internal. Therapists used relatively more externally focused statements for patients with a longer length of stay (B?=??0.239, p?=?0.013) and for patients who had a stronger internal focus preference (B?=??0.930, p?=?0.035).

Conclusions: Physical therapists used more external focus instructions, but more internally focused feedback. Also, they seem to adapt their attentional focus use to patients’ focus preference and rehabilitation phase. Future research may determine how these factors influence the effectiveness of different attentional foci for motor learning post-stroke.

• IMPLICATIONS FOR REHABILITATION

• Physical therapists use a balanced mix of internal focus and external focus instructions and feedback when treating gait of stroke patients.

• Therapists predominantly used an external focus for patients in later rehabilitation phases, and for patients with stronger internal focus preferences, possibly in an attempt to stimulate more automatic control of movement in these patients.

• Future research should further explore how a patients’ focus preference and rehabilitation phase influence the effectiveness of different focus strategies.

• Awaiting further research, we recommend that therapists use both attentional focus strategies, and explore per patient which focus works best on a trial-and-error basis.

     

Carbon monoxide and the CNS: challenges and achievements

Haem oxygenase (HO) and its product carbon monoxide (CO) are associated with cytoprotection and maintenance of homeostasis in several different organs and tissues. This review focuses upon the role of exogenous and endogenous CO (via HO activity and expression) in various CNS pathologies, based upon data from experimental models, as well as from some clinical data on human patients. The pathophysiological conditions reviewed are cerebral ischaemia, chronic neurodegenerative diseases (Alzheimer''s and Parkinson''s diseases), multiple sclerosis and pain. Among these pathophysiological conditions, a variety of cellular mechanisms and processes are considered, namely cytoprotection, cell death, inflammation, cell metabolism, cellular redox responses and vasomodulation, as well as the different targeted neural cells. Finally, novel potential methods and strategies for delivering exogenous CO as a drug are discussed, particularly approaches based upon CO-releasing molecules, their limitations and challenges. The diagnostic and prognostic value of HO expression in clinical use for brain pathologies is also addressed.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6