Gene-Siew Ngian

Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study

IntroductionPulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy.MethodsPatients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data.ResultsAmong 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective.ConclusionsIn this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.

Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis

Objectives To determine the prevalence of coronary heart disease (CHD) and cardiovascular risk factors in a well-characterised cohort of systemic sclerosis (SSc) patients, and to compare this with the general population. Methods A cross-sectional study of the prevalence of CHD and cardiovascular risk factors in participants in the Australian Scleroderma Cohort Study was performed. Controls were drawn from the 2007–8 National Health Survey (NHS) and the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). OR and 95% CI were calculated to determine the prevalence of CHD and cardiovascular risk factors in SSc patients compared with controls. Results Data were available for 850 SSc patients (86% female), 15 787 NHS participants (53% female) and 8802 AusDiab participants (56% female). Adjusted for age and gender, the OR of CHD in SSc patients was 1.9 (95% CI 1.4 to 2.4) compared with controls from AusDiab and 2.0 (95% CI 1.5 to 2.5) compared with controls from the NHS. The OR of CHD increased to 3.2 (95% CI 2.3 to 4.5) for SSc patients compared with controls from AusDiab after further adjustment for cardiovascular risk factors. Hypercholesterolaemia, diabetes mellitus and obesity were significantly less prevalent in the SSc cohort than in AusDiab. Within the SSc cohort, the presence of pulmonary arterial hypertension was associated with CHD. Conclusions This is the first report of an increased prevalence of CHD in SSc patients. Further studies are required to determine the relative contribution of scleroderma-specific factors such as microvascular disease to the development of CHD.

Cardiovascular disease in systemic sclerosis - an emerging association?

Microvascular disease is a prominent feature of systemic sclerosis (SSc) and leads to Raynauds phenomenon, pulmonary arterial hypertension, and scleroderma renal crisis. The presence of macrovascular disease is less well established, and, in particular, it is not known whether the prevalence of coronary heart disease in SSc is increased. Furthermore, in terms of cardiac involvement in SSc, there remains conjecture about the relative contributions of atherosclerotic macrovascular disease and myocardial microvascular disease. In this review, we summarize the literature describing cardiovascular disease in SSc, discuss the pathophysiological mechanisms common to SSc and atherosclerosis, and review the surrogate markers of cardiovascular disease which have been examined in SSc. Proposed mediators of the vasculopathy of SSc which have also been implicated in atherosclerosis include endothelial dysfunction, a reduced number of circulating endothelial progenitor cells, and an increased number of microparticles. Excess cardiovascular risk in SSc is suggested by increased arterial stiffness and carotid intima thickening and reduced flow-mediated dilatation. Cohort studies of adequate size are required to resolve whether this translates into an increased incidence of cardiovascular events in patients with SSc.

Safety of anti-rheumatic drugs for rheumatoid arthritis in pregnancy and lactation.

Women with rheumatoid arthritis (RA) are often of childbearing age and therefore questions regarding reproductive health and the use of medications, including disease‐modifying anti‐rheumatic drugs (DMARDs) may arise during the clinical consultation. Each patient requires individual assessment in order to effectively manage the disease while minimizing any treatment‐associated risks to the fetus. Although good‐quality controlled trials are lacking, there is an increasing volume of evidence surrounding the use of immunosuppressive therapies in pregnancy and lactation. This review summarizes the currently available information which can be of benefit to clinicians guiding patients and their families through the risks and benefits of continuing RA therapy during pregnancy and lactation. Further studies and ongoing surveillance of drug safety in pregnancy are required to resolve the uncertainties that remain regarding synthetic and biologic DMARDs.

Management of pregnancy in women with rheumatoid arthritis

Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease‐modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal–fetal medicine specialist for risk assessment and advice.

Is DISH Painful

Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory condition characterized by new bone growth affecting cancellous and cortical bone and particularly targeting the enthesis, that region where ligament, tendon, annulus fibrosis, and similar structures insert into cortical bone. Criteria for diagnosis are based on the radiological presence of entheseal ossification1,2, principally in the spine, where the new bone growth of DISH is ubiquitous. DISH is a common condition with prevalence rates that vary depending on the criteria applied and the population studied. Estimates range from 3.8% of men and 2.6% of women in a Finnish population-based study3, to 22.4% of men and 13.4% of women in an Israeli hospital-based study4. Its prevalence increases with age and hence with the aging population DISH will become more prevalent than before. There is a 2:1 male predominance in DISH, with severe radiological changes reported more commonly in males4. An association with obesity has been noted since the early description of the condition by Forestier and Rotes-Querol5, and over time, type 2 diabetes and the metabolic syndrome have also been identified as comorbid conditions6,7. The metabolic factors associated with DISH, despite decades of inquiry, still likely relate to insulin-associated growth factors and the effect of those factors on bone and entheseal growth plates8,9. As the population ages and as the proportion of metabolically vulnerable persons increases, so will the prevalence of DISH increase. Will this emerging epidemic of DISH increase the musculoskeletal health burden? In particular, will there be more pain and disability due to this disorder? Symptoms traditionally attributed to DISH include restriction in movement of spinal joints and entheseal-related …

Long-term efficacy and tolerability of mycophenolate mofetil therapy in diffuse scleroderma skin disease

To assess the long‐term efficacy and tolerability of mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic sclerosis (dcSSc).

Closing the pregnancy-related information gap for women with rheumatoid arthritis

Although RA affects women across their lifespan, it has particular implications for women who are planning a family, given the physical and psychosocial impacts of this disease and the potential adverse effects of RA drugs. Conception (and contraception), pregnancy and breastfeeding must all be planned and managed carefully, with appropriate clinical guidance [1]. There is a clear need for accurate, evidence-based and freely accessible information to support shared decision-making between women with RA, their families and the treating health-care professionals during this key stage of life. For families living in rural and remote areas or lowand middle-income countries where access to rheumatology care is limited, this is particularly important [2]. Given the recent evidence around unmet educational needs and limited evidence for the effectiveness of educational interventions, it is clear that more needs to be done to support women with RA across the pregnancy and post-natal continuum. Several qualitative studies from Australia and The Netherlands have highlighted key pregnancy-related educational needs and concerns among this patient group. Our recent study investigated the specific educational needs of women with RA who were pregnant, planning a pregnancy or who had been pregnant in the past 5 years [3]. Participants cited a lack of accessible and relevant information (particularly around the safety and toxicity of RA medications) and expressed a strong desire for practical strategies from peers to assist them in meeting the daily challenges of caring for a young baby. Another study found that women with RA experienced considerable uncertainty about the impact of RA medications on their unborn child and the effect of ceasing medications on their disease status [4]. In a study involving men and women with inflammatory arthritis (88% had RA), Nota et al. [5] reported that younger patients worried about the effect of DMARDs on fertility and pregnancy when deciding whether to commence therapy. These perspectives and others [6] suggest that contemporary arthritis education should incorporate pregnancy-related information for people with RA during their reproductive years and include a focus on both knowledge and practical skills. Patient education that is targeted to an individual’s information needs and life stage should form a fundamental component of routine care for people with inflammatory arthritis, as emphasized by recent EULAR recommendations [7]. However, with regard to the provision of pregnancy and post-natal education in the context of RA, the evidence about effective interventions is extremely limited. We recently completed a systematic literature review to determine the effectiveness of interventions designed to improve knowledge or self-management skills concerning contraception, pregnancy and breastfeeding in people with RA [8]. Of the 68 studies eligible for inclusion in our review, only one specifically evaluated pregnancy-focused education or self-management support for people with RA [9]. That particular randomized controlled trial evaluated a motherhood choices decision aid for RA, which was developed to assist women with RA in making informed choices about having children (or having additional children). The 45-page decision aid resource is publicly available and includes information on RA, pregnancy and the post-natal period, personal narratives, decision-making tasks and links to online resources and telephone helplines in several countries. The study found that participants who were given the motherhood decision aid had a greater increase in knowledge around RA and pregnancy-related topics and a greater reduction in decisional conflict compared with a no-intervention control group; however, the study did have some methodological limitations (e.g. participant follow-up beyond the immediate post-intervention period was not undertaken, and an intention-to-treat analysis was not reported). A further eight studies identified in our systematic review described interventions containing only minor components that could be considered relevant to conception, contraception, pregnancy or breastfeeding, within broader RA educational or self-management programmes. Despite the prevalence of RA among women of childbearing age, it is clear that published models of disease education do not adequately cater to this important stage of life. In the proceedings of the 2014 ACR Reproductive Health Summit [10], Kavanaugh et al. acknowledged the need for improved interdisciplinary communication among medical specialists who care for people with inflammatory and autoimmune conditions during pregnancy, and we agree that this is an important path to pursue. Conflicting advice from health professionals regarding pregnancy issues can be frustrating and confusing for women with RA [3]. To address this issue, our research group is currently undertaking a national e-Delphi study involving experienced rheumatologists, obstetricians and clinical pharmacists. The study is designed to establish cross-discipline consensus on key messages that should be delivered to women with RA by health professionals on contraception, pregnancy,

Early Accrual of Organ Damage in Systemic Sclerosis: Rationale for Development of a Disease Damage Index

Introduction Systemic sclerosis (SSc) is characterized by irreversible organ damage rather than fluctuating disease activity. However, there is no validated measure of damage in SSc. We aimed to quantify the accrual of organ damage in patients with early SSc. Methods Patients enrolled in the Australian Scleroderma Cohort Study with less than 2 years of SSc since the onset of the first non-Raynauds symptom were included. Organ damage was defined by a group of six experts as substantial and permanent loss of organ function due to SSc. Results We identified 278 patients with early SSc. Among these, 38% had diffuse SSc. Damage was more common in the diffuse than in the limited disease subtype in the skin/musculoskeletal (75% vs. 25.2%, p<0.001) and lung (31.4% vs. 19.9%, p = 0.035) domains at year seven. The rates of damage accrual were highest in the skin/musculoskeletal, gastrointestinal and respiratory systems at year two (29.1%, 18.7%, 14.4%), increasing at year five (41.4%, 30.6%, 21.2%) and declining thereafter to year seven (43.9%, 32.7%, 23.0%). In particular, there was early accrual of damage due to joint contracture (22.3%), gastrointestinal dysmotility (11.5%) and pulmonary fibrosis with forced vital capacity <70% predicted (9.7%) at year two. The highest accrual rate of organ-specific damage from years two to seven was seen in fecal incontinence followed by proximal muscle weakness and pulmonary fibrosis. Conclusions Substantial accrual of organ damage occurs early in the course of disease, particularly in diffuse SSc. This provides the rationale for the development of a SSc damage index.

Is there a role for opioids in the treatment of fibromyalgia

The use of opioids for chronic pain has increased significantly due to a combination of the high patient burden of pain and the more widespread availability of a range of long-acting opioid preparations. This increased opioid use has translated into the care of many patients with fibromyalgia. The pain mechanism in fibromyalgia is complex but does not seem to involve disturbance of opioid analgesic functions. Hence, there is general concern about the harms in the absence of benefits of opioids in this setting. There is no evidence that pure opioids are effective in fibromyalgia but there is some evidence that opioids with additional actions on the norepinephrine-related pain modulatory pathways, such as tramadol, can be clinically useful in some patients. Novel actions of low-dose opioid antagonists may lead to better understanding of the role of opioid function in fibromyalgia.