Improving the communication between care providers of individuals who may require joint replacement surgery (JRS) a framework for referral

Aims & rationale/Objectives : The objective of the project was to specify the information required in referrals to public hospital orthopaedic outpatient departments in order to streamline the care and prioritisation of individuals who may require JRS. It was envisaged that an evidence-based GP-Orthopaedic derived referral system would assist in ensuring that the right person accessed the right care at the right time.

Methods : In collaboration with the RACGP and the Commonwealth Department of Health and Ageing, a national stakeholder working group was convened. A scoping document was prepared with input from key stakeholders. A review of primary research was undertaken as well as a review of relevant guidelines. Information on the implementation and evaluation of similar programs in Australia and overseas also informed the referral specification.

Principal findings : The initial scoping processes with key stakeholders provided clear information on core components of the referral. These were the use of standardised and respected assessment tools to determine the severity of arthritis, fitness for surgery and willingness of affected individuals to undergo surgery.

Discussion : About 20,000 JRS occur each year in public hospitals which emanate from 5 to 10 fold number of referrals. Arthritis and musculoskeletal diseases are a national health priority area reflecting the high burden of disease associated with these conditions. Various initiatives are being undertaken to address the quality of life of affected individuals. This project has revealed areas of potential improvement in the communication between care providers of individuals who may need JRS.

Implications : The project will result in the development of a standard referral form and guidelines to assist referring practitioners to communicate more effectively with the multidisciplinary care team, in particular orthopaedic care providers. The guidelines will be piloted in a large rural setting.

Recent advances on the roles of NO in cancer and chronic inflammatory disorders

Nitric oxide (NO) is a short-life molecule produced by the enzyme known as the nitric oxide synthase (NOS), in a reaction that converts arginine and oxygen into citrulline and NO. There are three isoforms of the enzyme: neuronal NOS (nNOS, also called NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3). It is now known that each of these isoforms may be expressed in a variety of tissues and cell types. This paper is a review of the current knowledge of various functions of NO in diseases. We discuss in more detail its role in Cancer, the role of NO in myocardial pathophysiology, in central nervous system (CNS) pathologies. Other diseases such as inflammation, asthma, in chronic liver diseases, inflammatory bowel disease (IBD), arthritis, are also discussed. This review also covers the role of NO in cardiovascular, central nervous, pancreas, lung, gut, kidney, myoskeletal and chronic liver diseases (CLD). The ubiquitous role that the simple gas nitric oxide plays in the body, from maintaining vascular homeostasis and fighting infections to acting as a neurotransmitter and its role in cancer, has spurred a lot of interest among researchers all over the world. Nitric oxide plays an important role in the physiologic modulation of coronary artery tone and myocardial function. Nitric oxide from iNOS appears to be a key mediator of such glial-induced neuronal death. The high sensitivity of neurons to NO is partly due to NO causing inhibition of respiration, rapid glutamate release from both astrocytes and neurons, and subsequent excitotoxic death of the neurons.

Anti-inflammatory immunotherapy for multiple sclerosis/experimental autoimmune encephalomyelitis (EAE) disease

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory diseases of the central nervous system (CNS) characterized by localized areas with demyelination. Disease is believed to be an autoimmune disorder mediated by activated immune cells such as T- and B-lymphocytes and macrophages/microglia. Lymphocytes are primed in the peripheral tissues by antigens, and clonally expanded cells infiltrate the CNS. They produce large amounts of inflammatory cytokines, nitric oxide (NO) that lead to demyelination and axonal degeneration. Although several studies have shown that oligodendrocytes (OLGs), the myelin-forming glial cells in the CNS, are sensitive to cell death stimuli, such as cytotoxic cytokines, anti-myelin antibodies, NO, and oxidative stress, in vitro, the mechanisms underlying injury to the OLGs in MS/EAE remain unclear. The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy, trauma and MS has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic ionotropic and metabotropic receptors. Inflammation can be blocked with anti-cell adhesion molecules MAb, simultaneously protected oligodendrocytes and neurons against glutamate-mediated damage with the AMPA/kainate antagonist NBQX, and the NMDA receptor antagonist GPE, could thus be effective therapies for multiple sclerosis.

Promises of nanotechnology for drug delivery to brain in neurodegenerative diseases

Brain is a delicate organ, isolated from general circulation and characterized by the presence of relatively impermeable endothelial cells with tight junctions, enzymatic activity and the presence of active efflux transporter mechanisms. These formidable obstacles often block drug delivery to the brain across the blood-brain barrier (BBB). Although several promising molecules have the potential in the in vitro settings but lack of in vivo response is probably because the molecule cannot reach the brain in a sufficient concentration. Drug delivery across the BBB is a major limitation in the treatment of central nervous system (CNS) disorders and CNS infections. This review deals with the role of nanobiotechnology in CNS drug delivery, in which three categories of carbon nanotubes, nanowires and nanoparticles (NPs) are explained. The small size of the NPs makes them an ideal choice to penetrate the BBB. Several mechanisms are involved in this process and various strategies are used. There are some concerns about the safety of NP entry in the brain that need to be resolved before human use. Although there is no approved nanotechnology-based CNS drug available the future for such neuro-nanobiotechnology based delivery system developments is promising.

Oleocanthal, a natural anti-Inflammatory compound in extra virgin olive oil

Recent research on the olive oil phenolic, oleo canthal has led to speculation that it may confer some of the health benefits associated with a traditional Mediterranean diet. Oleocanthal produces a peppery, stinging sensation at the back of the throat similar to that of the non-steroidal anti-inflammatory drug (NSAID), ibuprofen. This led to the hypothesis that the perceptual similarity between oleocanthal and ibuprofen may indicate similar pharmacological properties. Subsequent studies have proved the hypothesis and oleocanthal was shown not only to inhibit inflammation in the same way as ibuprofen does, but it was found to be substantially more potent than this NSAID. It is important to note that inflammation has been demonstrated to playa significant role in the development of a number of chronic diseases, such as cardiovascular disease (CVD) and certain types of cancers. Therefore, as a result of dietary feeding with olive oil as a part of the traditional Mediterranean diet, a reduction in inflammation produced by oleocanthal is speculated to be the potential mechanism that is partially responsible for the health benefits associated with this dietary pattern. This review summarizes the current knowledge on oleocanthal, in tenns of its physiological and sensory properties, as well as a discussion on the factors that have the ability to affect oleocanthal concentrations in extra virgin olive oils (EVOOs).

Recent advances on the possible neuroprotective activities of Epstein-Barr virus oncogene BARF1 protein in chronic inflammatory disorders of central nervous system

Multiple sclerosis and neurodegenerative diseases in which cells of the central nervous system (CNS) are lost or damaged are rapidly increasing in frequency, and there is neither effective treatment nor cure to impede or arrest their destructive course. The Epstein-Barr virus is a human gamma-herpesvirus that infects more than 90% of the human population worldwide and persisting for the lifetime of the host. It is associated with numerous epithelial cancers, principally undifferentiated nasopharyngeal carcinoma and gastric carcinoma. Individuals with a history of symptomatic primary EBV infection, called infectious mononucleosis, carry a moderately higher risk of developing multiple sclerosis (MS). It is not known how EBV infection potentially promotes autoimmunity and central nervous system (CNS) tissue damage in MS. Recently it has been found that EBV isolates from different geographic regions have highly conserved BARF1 epitopes. BARF1 protein has the neuroprotective and mitogenic activity, thus may be useful to combat and overcome neurodegenerative disease. BARF1 protein therapy can potentially be used to enhance the neuroprotective activities by combinational treatment with anti-inflammatory antagonists and neuroprotectors in neural disorders.

Antimicrobial, antioxidant and anti-inflammatory phenolic activities in extra virgin olive oil

The Mediterranean diet is associated with a lower incidence of chronic degenerative diseases and higher life expectancy. These health benefits have been partially attributed to the dietary consumption of extra virgin olive oil (EVOO) by Mediterranean populations, and more specifically the phenolic compounds naturally present in EVOO. Studies involving humans and animals (in vivo and in vitro) have demonstrated that olive oil phenolic compounds have potentially beneficial biological effects resulting from their antimicrobial, antioxidant and anti-inflammatory activities. This paper summarizes current knowledge on the biological activities of specific olive oil phenolic compounds together with information on their concentration in EVOO, bioavailability and stability over time.

Nano-lactoferrin in diagnostic, imaging and targeted delivery for cancer and infectious diseases

Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and inflammatory diseases and the recent nanotechnology based strategies.

Anti-inflammatory and chondroprotectivity of dominant-negative survivan and nutraceuticals, lactoferrin and herbs

Osteoarthritis is a highly problematic and debilitating medical issues affecting over 630 million people worldwide. Current treatments include anti-inflammatory drugs and joint injections which are painful and cause systemic side effects. The present study, investigates the activity of nanoformulated bioactive proteins and herbals as potential therapeutics for chronic inflammatory arthritis.

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.

Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

Venous thromboembolism and underutilisation of anticoagulant thromboprophylaxis in hospitalised patients with inflammatory bowel disease

Background: Venous thromboembolism (VTE) is a well-recognised extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite the widespread support for anticoagulant prophylaxis in hospitalised IBD patients, the utilisation and efficacy in clinical practice are unknown. Aims: The aim of this study was to assess the prevalence and clinical features of VTE among hospitalised IBD patients and ascertain whether appropriate thromboprophylaxis had been administered. Methods: All patients with a discharge diagnosis of Crohn disease or ulcerative colitis and VTE were retrospectively identified using International Classification of Diseases, tenth revision codes from medical records at our institution from July 1998 to December 2009. Medical records were then reviewed for clinical history and utilisation of thromboprophylaxis. Statistical analysis was performed by Mann-Whitney test and either χ2 tests or Fisher's exact tests. Results: Twenty-nine of 3758 (0.8%) IBD admissions suffered VTE, 13 preadmission and 16 during admission. Of these 29 admissions (in 25 patients), 24% required intensive care unit and 10% died. Of the 16 venous thrombotic events that occurred during an admission, eight (50%) did not receive anticoagulant thromboprophylaxis and eight (50%) occurred despite thromboprophylaxis. Most thromboembolism despite prophylaxis occurred post-intestinal resection (n = 5, 63%). Conclusion: Thromboprophylaxis is underutilised in half of IBD patients suffering VTE. Prescription of thromboprophylaxis for all hospitalised IBD patients, including dual pharmacological and mechanical prophylaxis in postoperative patients, may lead to a reduction in this preventable complication of IBD. © 2014 Royal Australasian College of Physicians.

The impact of sleep restriction and simulated physical firefighting work on acute inflammatory stress responses

OBJECTIVES: This study investigated the effect restricted sleep has on wildland firefighters' acute cytokine levels during 3 days and 2 nights of simulated physical wildfire suppression work. METHODS: Firefighters completed multiple days of physical firefighting work separated by either an 8-h (Control condition; n = 18) or 4-h (Sleep restriction condition; n = 17) sleep opportunity each night. Blood samples were collected 4 times a day (i.e., 06:15, 11:30, 18:15, 21:30) from which plasma cytokine levels (IL-6, IL-8, IL-1β, TNF-α, IL-4, IL-10) were measured. RESULTS: The primary findings for cytokine levels revealed a fixed effect for condition that showed higher IL-8 levels among firefighters who received an 8-h sleep each night. An interaction effect demonstrated differing increases in IL-6 over successive days of work for the SR and CON conditions. Fixed effects for time indicated that IL-6 and IL-4 levels increased, while IL-1β, TNF-α and IL-8 levels decreased. There were no significant effects for IL-10 observed. CONCLUSION: Findings demonstrate increased IL-8 levels among firefighters who received an 8-h sleep when compared to those who had a restricted 4-h sleep. Firefighters' IL-6 levels increased in both conditions which may indicate that a 4-h sleep restriction duration and/or period (i.e., 2 nights) was not a significant enough stressor to affect this cytokine. Considering the immunomodulatory properties of IL-6 and IL-4 that inhibit pro-inflammatory cytokines, the rise in IL-6 and IL-4, independent of increases in IL-1β and TNF-α, could indicate a non-damaging response to the stress of simulated physical firefighting work. However, given the link between chronically elevated cytokine levels and several diseases, further research is needed to determine if firefighters' IL-8 and IL-6 levels are elevated following repeated firefighting deployments across a fire season and over multiple fire seasons.

Physical activity habits, limitations, and predictors in people with inflammatory bowel disease: a large cross-sectional online survey

BACKGROUND: Limited evidence suggests that physical activity has beneficial effects in people with inflammatory bowel disease (IBD). This study aimed to determine the physical activity habits of adults with IBD, the limitations to physical activity they experience because of their disease, and the extent to which their physical activity is affected by various demographic, clinical, and psychological factors. METHODS: Data were collected on 859 adult participants (52% with Crohn's disease, 75% women) through an online survey conducted between May and June 2016. Measures included physical activity (International Physical Activity Questionnaire), psychological symptoms (Hospital Anxiety and Depression Scale), fatigue (subitems of IBD fatigue scale), exercise perceptions (Exercise Benefits/Barriers Scale), and disease activity. Regression analyses were used to identify predictors of physical activity. RESULTS: Only 17% of respondents were categorized as "high active." Self-reported physical activity levels decreased, and fatigue and psychological scores increased, with increasing disease activity. Walking was the most common activity performed (57% of respondents) and running/jogging the most commonly avoided (34%). Many participants (n = 677) reported that IBD limited their physical activity, for reasons including abdominal/joint pain (70%), fatigue/tiredness (69%), disease flare-up (63%), and increased toilet urgency (61%). Physical activity was independently associated with depression, disease activity, and perceived barriers to exercise in people with Crohn's disease, and depression and age in people with ulcerative or indeterminate colitis (all P ≤ 0.038). CONCLUSIONS: This survey highlights several important factors that should be considered by designers of future physical activity interventions for people with IBD.