Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.

The limits of medicine and the social consequences for sufferers of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) appears to be made up of several clusters of illness categories acting alone or in tandem to cause the decline of health through; fatigue/exhaustion, sensitivity/allergies, pain, general muscle and joint pains, cognitive impairment and gastrointestinal problems. This study investigated how patients interpret, evaluate and respond to the complex and varied symptoms of chronic fatigue syndrome. Data were collected from persons with CFS using a survey (n=90) and an interview (n=45). The researchers investigated how chronic fatigue syndrome is diagnosed by medical practitioners, how the label of CFS is determined and the social consequences for the patient. The results confirm the limited ability of the biomedical paradigm to diagnose adequately and treat effectively 'socially constructed' and medically ambiguous illnesses like CFS. In the absence of a legitimated regime of medical treatment for CFS, a range of often expensive treatments are employed by CFS sufferers, from formal use of pharmaceutical drugs through to 'alternative' therapies, including herbal, vitamin, homeopathic, esoteric meditative techniques, spiritual healing and general counselling are taken in no particular order.

Single vs. two steroid injections for carpal tunnel syndrome: a randomised clinical trial

We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome (CTS) in a randomised double-blind controlled trial. Patients with idiopathic CTS were randomised into (i) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and (ii) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks. The primary outcome was the Global Symptom Score (GSS). Forty patients were recruited. By 40 weeks, the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group, but there was no significant difference in GSS between the two groups (p = 0.26). There were also no significant differences in terms of electrophysiological and functional outcomes. The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief.

Overweight, obesity and metabolic syndrome in rural south-eastern Australia

Aims & rationale/Objectives : To measure the prevalence of overweight, obesity and the metabolic syndrome in rural Australia.</p>

Methods :Two cross-sectional population surveys of chronic disease risk factors were carried out in rural Victoria (Corangamite Shire) and South Australia (Limestone Coast) in 2004-05. For both surveys, a stratified random sample of the population aged 25 to 74 years was drawn from the electoral roll. The surveys comprised a self-administered questionnaire, physical measurements and laboratory tests.</p>

Principal findings : A total of 841 individuals had complete questionnaire, health check and measured MetS data. The prevalence of overweight and obesity was 75% in males and 64.7% in females defined by BMI. Using waist circumference, the prevalence of overweight and obesity was higher in females (72.9%) than in males (63.2%). The overall prevalence of obesity of was 30.1% when defined by BMI, but 44.8% when defined by waist circumference. The prevalence of metabolic syndrome according to NCEP ATP III 2005 criteria was 29.0% in males and 28.5% in females. According to IDF criteria, the prevalence for males and females were 30.5% and 36.3%, respectively. The prevalence of metabolic syndrome and central (abdominal) obesity, hyperglycaemia, hypertension, and hypertriglyceridaemia increased with age.

Discussion : The prevalence of overweight and obesity, in particular central obesity, in rural Australia is very high as is the prevalence of metabolic syndrome.

Implications : Urgent population wide action is required to turn this trend around and regular monitoring of the trends in response to such action is essential.

Muscle p70S6K phosphorylation in response to soy and dairy rich meals in middle aged men with metabolic syndrome: a randomised crossover trial

The mammalian target of rapamycin (mTOR) pathway is the primary regulator of muscle protein synthesis. Metabolic syndrome (MetS) is characterized by central obesity and insulin resistance; little is known about how MetS affects the sensitivity of the mTOR pathway to feeding.

Efficacy and safety of thrombin-receptor antagonist (atopaxar and vorapaxar) in patients with acute coronary syndrome or coronary artery disease-a meta-analysis of randomized controlled trials

Background: Meta-analysis for the efficacy and safety data of thrombin-receptor antagonist (TRA) based on patients with acute coronary syndrome (ACS) or coronary artery disease (CAD) and indirect comparisons between TRAs were not available. Objectives: We intended to synthesize the primary end points based on different patient populations (ACS or CAD) as well as perform indirect comparison between two newly invented antiplatelet agents atopaxar and vorapaxar. Methods: A literature search was performed in MEDLINE, Embase, and Cochrane Library. Incidences of major adverse cardiovascular events (MACEs) and bleeding events according to thrombolysis in myocardial infarction were selected as primary outcomes, whereas adverse effects were considered as secondary outcomes. Corresponding results were synthesized using Revman 5.1 according to ACS or CAD cohorts. Results: Among the seven included randomized controlled trials, the efficacy end points in the TRA treatment group were favorable compared with placebo. Specifically, the odds ratio (OR) of MACEs was 0.80 (95% confidence interval [CI] 0.52-1.22) for patients with ACS and 0.74 (95% CI 0.53-1.05) for the cohort with CAD. The events of bleeding were unanimously superior in the placebo arm for both cohorts. The indirect comparison showed a superior trend in favor of atopaxar over vorapaxar in occurrences of MACEs (OR 0.93; 95% CI 0.38-1.32), myocardial infarction (OR 0.52; 95% CI 0.13-0.95), and cardiovascular death (OR 0.82; 95% CI 0.12-4.24) and caused less incidence of bleeding. Conclusions: Besides being more effective than placebo in improving the incidence of MACEs but with a higher risk of bleeding, TRAs may exert different effects in patients with ACS and CAD. Indirect comparisons also suggested that atopaxar might be better than vorapaxar in lowering the incidence of MACEs, myocardial infarction, and cardiovascular death and at the same time with lower risks of bleeding.