The global burden of musculoskeletal conditions for 2010: an overview of methods.

The objective of this paper is to provide an overview of methods used for estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Diseases 2010 study. It should be read in conjunction with the disease-specific MSK papers published in Annals of Rheumatic Diseases. Burden estimates (disability-adjusted life years (DALYs)) were made for five specific MSK conditions: hip and/or knee osteoarthritis (OA), low back pain (LBP), rheumatoid arthritis (RA), gout and neck pain, and an 'other MSK conditions' category. For each condition, the main disabling sequelae were identified and disability weights (DW) were derived based on short lay descriptions. Mortality (years of life lost (YLLs)) was estimated for RA and the rest category of 'other MSK', which includes a wide range of conditions such as systemic lupus erythematosus, other autoimmune diseases and osteomyelitis. A series of systematic reviews were conducted to determine the prevalence, incidence, remission, duration and mortality risk of each condition. A Bayesian meta-regression method was used to pool available data and to predict prevalence values for regions with no or scarce data. The DWs were applied to prevalence values for 1990, 2005 and 2010 to derive years lived with disability. These were added to YLLs to quantify overall burden (DALYs) for each condition. To estimate the burden of MSK disease arising from risk factors, population attributable fractions were determined for bone mineral density as a risk factor for fractures, the occupational risk of LBP and elevated body mass index as a risk factor for LBP and OA. Burden of Disease studies provide pivotal guidance for governments when determining health priority areas and allocating resources. Rigorous methods were used to derive the increasing global burden of MSK conditions.

Oleocanthal, a phenolic derived from virgin olive oil: a review of the beneficial effects on inflammatory disease

Virgin olive oil (VOO) is credited as being one of many healthful components of the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday dietary pattern. A phenolic compound contained in VOO, named oleocanthal, shares unique perceptual and anti-inflammatory characteristics with Ibuprofen. Over recent years oleocanthal has become a compound of interest in the search for naturally occurring compounds with pharmacological qualities. Subsequent to its discovery and identification, oleocanthal has been reported to exhibit various modes of action in reducing inflammatory related disease, including joint-degenerative disease, neuro-degenerative disease and specific cancers. Therefore, it is postulated that long term consumption of VOO containing oleocanthal may contribute to the health benefits associated with the Mediterranean dietary pattern. The following paper summarizes the current literature on oleocanthal, in terms of its sensory and pharmacological properties, and also discusses the beneficial, health promoting activities of oleocanthal, in the context of the molecular mechanisms within various models of disease.

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.

Auranofin: repurposing an old drug for a golden new age

Drug discovery, development and registration is an expensive and time-consuming process associated with a high failure rate [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013), Woodcock and Woosley (Annu Rev Med 59:1-12, 2008)]. Drug 'repurposing' is the identification of new therapeutic purposes for already approved drugs and is more affordable and achievable than novel drug discovery [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013)]. Auranofin is a drug that is approved for the treatment of rheumatoid arthritis but is being investigated for potential therapeutic application in a number of other diseases including cancer, neurodegenerative disorders, HIV/AIDS, parasitic infections and bacterial infections [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029-2035, 2013)]. The main mechanism of action of auranofin is through the inhibition of reduction/oxidation (redox) enzymes that are essential for maintaining intracellular levels of reactive oxygen species. Inhibition of these enzymes leads to cellular oxidative stress and intrinsic apoptosis [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013), Fan et al. (Cell Death Dis 5:e1191, 2014), Fiskus et al. (Cancer Res 74:2520-2532, 2014), Marzano et al. (Free Radic Biol Med 42:872-881, 2007)]. Drugs such as auranofin that have already been approved for human use [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029-2035, 2013)] can be brought into clinical use for other diseases relatively quickly and for a fraction of the cost of new drugs.

The neuro-immune pathophysiology of central and peripheral fatigue in systemic immune-inflammatory and neuro-immune diseases

Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

Prescription and over-the-counter pain medication in arthritis: awareness of active ingredients and attitudes to medication borrowing and sharing

Background:
Many Australians with arthritis self-manage their pain with prescription and/or over-the-counter pain medications, containing paracetamol. If taken appropriately, these medications are relatively safe; however, if mismanaged through patients' iinability to understand medication labels and instructions, these medications may cause adverse drug events and/or toxicities.
Aim:
This study explored the prescription and over-the-counter pain medications most commonly used by people with arthritis and the ability of these patients to correctly identify paracetamol as an active ingredient in commonly available preparations. The study also investigated the functional health literacy of these patients and their inclination to borrow and/or share pain medications.
Method:
Adult participants diagnosed with arthritis were invited to complete an anonymous survey which included questions about their prescription and over-the-counter pain medications; their medication borrowing and sharing behaviours; their functional health literacy; and their knowledge about preparations containing paracetamol as an active ingredient.
Results:
Most of the 254 participants used analgesic agents containing paracetamol, as combination tablets (paracetamol 500 mg and codeine 30 mg) or paracetamol-only tablets (paracetamol 665 mg) to self-manage their pain. Respondents with low functional health literacy scores were significantly less likely to identify paracetamol as an active ingredient in both combination and paracetamol-only pharmaceutical products, and were more likely to guess or did not know how to identify that paracetamol was an active ingredient in these products. Almost 30% of the respondents indicated that they had and/or intended to borrow/share their over-the-counter
pain medications whereas less than 10% suggested that they had and/or intended to borrow/share their prescription pain medication.
Conclusion:
Australians with arthritis, especially those with low functional health literacy scores, self-managing their pain with paracetamol-containing products, do not always recognise paracetamol as an active ingredient in combination products, and may risk potential paracetamol-related adverse effects and/or toxicities.

Statistically modelling the relationships between Type D personality and social support, health behaviors and symptom severity in chronic illness groups

OBJECTIVE: The study aimed to develop a predictive model of how Type D personality influences health behaviours, social support and symptom severity and assess its generalisability to a range of chronic illnesses.

DESIGN: Participants were classified as either healthy (n = 182) or having a chronic illness (n = 207). Participants completed an online survey measuring Type D and a range of health-related variables. Chronic illness participants were classified as having either a functional somatic syndrome (i.e. chronic fatigue syndrome or fibromyalgia), where the underlying pathological processes were unclear, or illnesses such as type 2 diabetes, osteoarthritis or rheumatoid arthritis, where the causes are well understood.

MAIN OUTCOME MEASURES: Outcome measures were health behaviours, social support and both physical and psychological symptoms.

RESULTS: The rate of Type D was higher in chronic illness participants (53%) than in healthy controls (39%). Negative affectivity (NA) and social inhibition (SI) both correlated with outcome measures, although NA was generally the stronger predictor. Using NA and SI as independent subscales led to superior prediction of health outcomes than using categorical or continuous representations.

CONCLUSION: Findings suggest that the relationship between Type D and health outcomes may generalise across different chronic illnesses.