Baseline comorbidities in a population-bases cohort of rheumatoid arthritis patients receiving biological therapy: data from the Australian Rheumatology Association database

Aims: To describe the baseline characteristics of an Australian population-based cohort of rheumatoid arthritis (RA) patients commencing biological therapy.

Methods: Descriptive analysis from the Australian Rheumatology Association Database (ARAD).

Results: Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%) had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina). Self-reported infections within the previous 6 months were common (71.5%).

Conclusions: History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy.

Rheumatoid arthritis and incident fracture in women: a case-control study

Background:
To examine fracture incidence in women with rheumatoid arthritis (RA) for an entire geographical region of south-eastern Australia.

Methods:
Women aged 35 years and older, resident in the Barwon Statistical Division (BSD) and clinically diagnosed with RA 1994–2001 were eligible for inclusion as cases (n =1,008). The control population (n = 172,422) comprised the entire female BSD population aged 35 years and older, excluding those individuals identified as cases. Incident fractures were extracted from the prospective Geelong Osteoporosis Study Fracture Grid. We calculated rate ratios (RR) and 95% confidence intervals (CI) to compare the age- adjusted rate of fracture between the RA and non-RA populations, and used a chi-square test to compare proportions of fractures between women with and without RA, and a two-sided Mann–Whitney U-test to examine age-differences.

Results:
Among 1,008 women with RA, 19 (1.9%) sustained a fracture, compared to 1,981 fractures sustained by the 172,422 women without RA (1.2%). Fracture rates showed a trend for being greater among women diagnosed with RA (age-adjusted RR 1.43, 95%CI 0.98-2.09, p= 0.08). Women with RA sustained vertebral fractures at twice the expected frequency, whereas hip fractures were underrepresented in the RA population (p< 0.001). RA status was not associated with the likelihood of sustaining a fracture at sites adjacent to joints most commonly affected by RA (p= 0.22).

Conclusion:
Given that women with RA have a greater risk of fracture compared to women without RA, these patients may be a suitable target population for anti-resorptive agents; however, larger studies are warranted.

Improving treatment with methotrexate in rheumatoid arthritis-development of a multimedia patient education program and the MiRAK, a new instrument to evaluate methotrexate-related knowledge

To develop and test an evidence-based, multimedia patient education program (MPEP) about methotrexate (MTX) treatment for rheumatoid arthritis (RA) and a new measure of patient knowledge [Methotrexate in Rheumatoid Arthritis Knowledge test (MiRAK)].

Measuring the impact of arthritis on worker productivity : perspectives, methodologic issues and contextual factors

Leading up to the Outcome Measures in Rheumatology (OMERACT) 10 meeting, the goal of the Worker Productivity Special Interest Group (WP-SIG) was to make progress on 3 key issues that relate to the application and interpretation of worker productivity outcomes in arthritis: (1) to review existing conceptual frameworks to help consolidate our intended target and scope of measurement; (2) to examine the methodologic issues associated with our goal of combining multiple indicators of worker productivity loss (e.g., absenteeism <—> presenteeism) into a single comprehensive outcome; and (3) to examine the relevant contextual factors of work and potential implications for the interpretation of scores derived from existing outcome measures. Progress was made on all 3 issues at OMERACT 10. We identified 3 theoretical frameworks that offered unique but converging perspectives on worker productivity loss and/or work disability to provide guidance with classification, selection, and future recommendation of outcomes. Several measurement and analytic approaches to combine absenteeism and presenteeism outcomes were proposed, and the need for further validation of such approaches was also recognized. Finally, participants at the WP-SIG were engaged to brainstorm and provide preliminary endorsements to support key contextual factors of worker productivity through an anonymous “dot voting” exercise. A total of 24 specific factors were identified, with 16 receiving ≥ 1 vote among members, reflecting highly diverse views on specific factors that were considered most important. Moving forward, further progress on these issues remains a priority to help inform the best application of worker productivity outcomes in arthritis research.

Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis

Arthritis is a multifactorial disease for which current therapeutic intervention with high efficacy remains challenging. Arthritis predominately affects articular joints, and cartilage deterioration and inflammation are key characteristics. Current therapeutics targeting inflammatory responses often cause severe side effects in patients because of the systemic inhibition of cytokines or other global immunosuppressive activities. Furthermore, a lack of primary response or failure to sustain a response to treatment through acquired drug resistance is an ongoing concern. Nevertheless, treatments such as disease-modifying anti-rheumatic drugs, biological agents, and corticosteroids have revealed promising outcomes by decreasing pain and inflammation in patients and in some cases reducing radiographic progression of the disease. Emerging and anecdotal therapeutics with anti-inflammatory activity, alongside specific inhibitors of the A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 repeats (ADAMTS) cartilage-degrading aggrecanases, provide promising additions to current arthritis treatment strategies. Thus, it is paramount that treatment strategies be optimized to increase efficacy, reduce debilitating side effects, and improve the quality of life of patients with arthritis. Here, we review the current strategies that attempt to slow or halt the progression of osteoarthritis and rheumatoid arthritis, providing an up-to-date summary of pharmaceutical treatment strategies and side effects. Importantly, we highlight their potential to indirectly regulate ADAMTS aggrecanase activity through their targeting of inflammatory mediators, thus providing insight into a mechanism by which they might inhibit cartilage destruction to slow or halt radiographic progression of the disease. We also contrast these with anecdotal or experimental administration of statins that could equally regulate ADAMTS aggrecanase activity and are available to arthritis sufferers worldwide. Finally, we review the current literature regarding the development of synthetic inhibitors directed toward the aggrecanases ADAMTS4 and ADAMTS5, a strategy that might directly inhibit cartilage destruction and restore joint function in both rheumatoid arthritis and osteoarthritis.

Molecular targets in arthritis and recent trends in nanotherapy

Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

Quality of life and sense of coherence in people with arthritis

This study investigated the physical and psychological impact of arthritis on people's quality of life. A range of variables were examined in a sample of 375 participants who comprised three groups: people with arthritis receiving a support-based service from the Arthritis Foundation of Victoria, people with arthritis receiving standard treatment, and a group of people from the general population. The results revealed that the two arthritis groups reported a significantly higher level of functional impairment, pain, and negative affectivity, and lowered mood, positive affect, and Sense of Coherence, compared to the general population group. They also reported normal levels of importance, but lower levels of satisfaction on various life domains. After statistically controlling for pain however, group differences were eliminated on all variables except for functional impairment and for all satisfaction domains except health. These data are interpreted as evidence that the combination of low domain satisfaction coupled with high domain importance yields a negative psychological state. This, then suggests the possibility of a therapy based on reducing the perceived importance of health.

What about the men? Gender differences in utilisation of arthritis self-management services

As self-management programs for chronic illness increasingly become the domain of primary health care providers, it is important to consider gender inequities in access to these services and gender differences in patterns of use to inform the development and delivery of services. This study explores gender differences in levels and patterns of access to arthritis elf-management services by analyzing data collected from the Telephone Information Service of Arthritis Victoria, Contingency tables were analyzed and odds-ratios calculated to confirm gender differences in levels and patterns of service utilisation. Men were found to be significantly under-represented as users of the service, even after taking into account gender differences in prevalence of arthritis in the population. Women were more likely than men to contact the service on their own behalf. Men were more likely to have a family member or friend contact the services for them. Women showed more interest in learning about their condition while men focused more on symptom management. These gender differences in rates and patterns of services use indicate that services providers of self-management services for conditions such as arthritis need to take into account the interaction between gender and service utilisation.

Protein kinase C isozymes as potential therapeutic targets in immune disorders

Background: Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases. Objective: To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy. Methods: A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs. Results/conclusion: There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical efficacy.

Role of age, sex, and obesity in the higher prevalence of arthritis among lower socioeconomic groups: a population-based survey

Objective: To compare the prevalence of arthritis among population groups based on demographic, socioeconomic, and body mass index (BMI) characteristics; to investigate the combined influence of these factors on arthritis; and to assess the relationship between self-reported health and psychological distress and arthritis.

Methods: Data from the Victorian Population Health Survey (n = 7,500) were used in the study. Psychological distress was assessed using the Kessler Psychological Distress scale, and self-reported health was assessed by a single item. Multiple logistic regression was used to investigate the combined influence of demographic and socioeconomic factors and BMI on arthritis.

Results: Overall, 23% of Victorian adults (20% men and 26% women) reported having arthritis. The presence of arthritis was associated with high psychological distress (odds ratio [OR] 1.2; 95% confidence interval [95% CI] 1.1-1.4) and poor self-reported health (OR 1.9; 95% CI 1.7-2.1). Increased prevalence of arthritis was found in older age groups, lower education and income groups, and in people who were overweight or obese. Women had higher risk of arthritis, even after adjustment for age, residence, education, occupation, income, and BMI. Age and BMI independently predicted arthritis for men and women. For men, higher risk of arthritis was also associated with lower income.

Conclusion: Arthritis is a highly prevalent condition associated with poor health and high psychological distress. Prevalence of arthritis is disproportionately high among women and individuals from lower socioeconomic backgrounds. As the prevalence of arthritis is predicted to increase, careful consideration of causal factors, and setting priorities for resource allocation for the treatment and prevention of arthritis are required.

Does self-management lead to sustainable health benefits in people with arthritis? A 2-year transition study of 452 Australians.

Objective: To evaluate the Arthritis Self-Management Course (ASMC) when applied in a nationwide context.

Methods: Four hundred fifty-two people who participated in the ASMC across Australian states took part in a longitudinal followup study. ASMC is a 6 week, 2 h group educational program designed to assist people with chronic illness to better manage their condition. Measures of program effectiveness included health status and service utilization. Data were collected on 3 occasions: before intervention (baseline) and 6 months and 2 years after the program.

Results: Several indicators of health status showed improvement at 6 months following the ASMC. These included reduction in pain (4%; p < 0.001), fatigue (3%; p < 0.01), and health distress (12%; p < 0.001) as well as increase in self-efficacy (6%; p < 0.001). Increased self-efficacy was a significant predictor of positive change in health status. Health-related behaviors such as aerobic exercise also increased, with the proportion of people who did little or no exercise decreasing by up to 8%. These changes were sustained at 2 years. There was an increase in use of analgesics at 6 months and an increase in use of nonsteroidal antiinflammatory drugs at 2 years. No changes in healthcare utilization (physician visits, allied health visits, and hospitalizations) were observed.

Conclusion: The ASMC is a widely applied program in which participants benefit through a reduction in pain, fatigue, and health distress. Although the absolute changes in health status are small, the low cost and wide application of the intervention suggests the program may have a substantial public health effect.

A critical look at the role of self-management for people with arthritis and other chronic diseases

Most patients with chronic conditions, such as osteoarthritis, only have contact with healthcare professionals for a few hours over the course of a year. Good self-management programs are, therefore, critical for patients to cope with their conditions on a daily basis. Drs Osborne, Jordan and Rogers discuss the importance of engaging patients, clinicians and policymakers in the development and implementation of self-management programs.

Guideline for the non-surgical management of hip and knee osteoarthritis

Introduction: Chronic disease is a major public health burden on Australian society. An increasing proportion of the population has risk factors for, or at least one, chronic disease, leading to increasing public health costs. Health service policy and delivery must not only address acute conditions, it must also effectively respond to the wide range of health and public service requirements of people with chronic illness.^1,2 Strong primary health care policy is an important foundation for a successful national health delivery system and long term management of public health, and is linked to practical outcomes including lower mortality, decreased hospitalisation and improved health outcomes.¹ National strategic health policy has recently given increased recognition to the importance of chronic disease management, with the Australian Federal Government endorsement of a number of initiatives for the prevention (or delay in onset), early detection and evidence based management of chronic disease, including osteoarthritis.^1,3
Chronic musculoskeletal conditions, including arthritis, account for over 4% of the national disease burden in terms of disability adjusted life years. Over 6 million Australians (almost one-third of the population) are estimated to have a chronic musculoskeletal disease; chronic musculoskeletal disease represents the main cause of long term pain and physical disability. In Australia, osteoarthritis is self reported by more than 1.4 million people (7.3% of the population4) and is the tenth most commonly managed problem in general practice.5 This number is set to rise as the elderly population grows. Osteoarthritis exerts a significant burden on the individual and the community through reduction in quality of life, diminished employment capacity and an increase in health care costs. For further details, refer to the Evidence to support the National Action Plan for Osteoarthritis, Rheumatoid Arthritis and Osteoporosis: Opportunities to improve health-related quality of life and reduce the burden of disease and disability (2004).⁶
As such, federal government health policy has identified arthritis as a National Health Priority Area and adopted a number of initiatives aimed at decreasing the burden of chronic disease and disability; raising awareness of preventive disease factors; providing access to evidence based knowledge; and improving the overall management of arthritis within the community.4 In 2002, all Australian health ministers designated arthritis and musculoskeletal conditions as Australia’s seventh National Health Priority Area. In response, a National Action Plan was developed in 2004 by the National Arthritis and Musculoskeletal Conditions Advisory Group (NAMSCAG).6 The aim of this document was to provide a blueprint for national initiatives to improve the health related quality of life of people living with osteoarthritis, rheumatoid arthritis and osteoporosis; reduce the cost and prevalence of these conditions; and reduce the impact on individuals, their carers and their communities within Australia. The National Action Plan was developed to complement both the National Chronic Disease Strategy – which is broader – and the National Service Improvement Framework for Osteoarthritis, Rheumatoid Arthritis and Osteoporosis, in addition to other national and state/ territory structures.

A systematic grounded approach to the development of complex interventions : The Australian WorkHealth Program – Arthritis as a case study

Despite demands for evidence-based research and practice, little attention has been given to systematic approaches to the development of complex interventions to tackle workplace health problems. This paper outlines an approach to the initial stages of a workplace program development which integrates health promotion and disease management. The approach commences with systematic and genuine processes of obtaining information from key stakeholders with broad experience of these interventions. This information is constructed into a program framework in which practice-based and research-informed elements are both valued. We used this approach to develop a workplace education program to reduce the onset and impact of a common chronic disease – osteoarthritis.

To gain information systematically at a national level, a structured concept mapping workshop with 47 participants from across Australia was undertaken. Participants were selected to maximise the whole-of-workplace perspective and included health education providers, academics, clinicians and policymakers. Participants generated statements in response to a seeding statement: Thinking as broadly as possible, what changes in education and support should occur in the workplace to help in the prevention and management of arthritis? Participants grouped the resulting statements into conceptually coherent groups and a computer program was used to generate a ‘cluster map’ along with a list of statements sorted according to cluster membership.

In combination with research-based evidence, the concept map informed the development of a program logic model incorporating the program's guiding principles, possible service providers, services, training modes, program elements and the causal processes by which participants might benefit. The program logic model components were further validated through research findings from diverse fields, including health education, coaching, organisational learning, workplace interventions, workforce development and osteoarthritis disability prevention.

In summary, wide and genuine consultation, concept mapping, and evidence-based program logic development were integrated to develop a whole-of-system complex intervention in which potential effectiveness and assimilation into the workplace for which optimised.