All-cause, cause-specific and age-specific standardised mortality ratios of patients with systemic lupus erythematosus in Ontario, Canada over 43 years (1971-2013).

BACKGROUND: Survival in systemic lupus erythematosus (SLE) has improved substantially in the last 50 years. The aim of the present study was to assess the evolution of the all-cause, cause-specific and age-specific standardised mortality ratios (SMRs) of patients with lupus in Ontario, Canada. PATIENTS AND METHODS: Between 1971 and 2013, 1732 patients were followed in the Toronto Lupus Clinic. Causes of death were retrieved from death certificates, autopsy reports, hospital records or the records of the family physicians. They were categorised as atherosclerotic, infectious, malignancy, active lupus and others. For the calculation of the SMR (indirect standardisation method), data from the general population of Ontario, Canada were used (Statistics Canada). RESULTS: Two hundred and forty-nine patients (205 women) died (infections 24.5%, atherosclerosis 15.7%, active lupus 13.3%, malignancy 9.6%); mean age was 53.2±16.6 years and mean disease duration 15.2±11.7 years. The all-cause SMR was substantially decreased from the 1970s (13.5, 95% CI 8.6 to 18.5) to recent years (2.2, 95% CI 1.4 to 3.1). Similar trends were observed for atherosclerosis, infections and malignancies over time. The all-cause age-specific SMR was particularly high in younger (19-39 years old) patients (SMR=12.4, 95% CI 9.7 to 15.1) as compared with individuals older than 40 years (SMR=3.1, 95% CI 2.6 to 3.6). The cause-specific SMR was also higher in younger patients, particularly for infections and malignancies. CONCLUSIONS: The all-cause and cause-specific SMR significantly decreased over time, likely reflecting the advances in the management of SLE and certain comorbidities. The all-cause and cause-specific SMR was particularly high for younger patients (<40 years old).

Magnetic Resonance Imaging in Psoriatic Arthritis: A Descriptive Study of Indications, Features and Effect on Treatment Change.

OBJECTIVE: The aims of this study were to describe the indications for, and features of, axial/peripheral joint magnetic resonance imaging (MRI) in psoriatic arthritis (PsA) and to examine the influence of MRI findings on clinical practice. METHODS: All axial and peripheral (hand and/or foot) MRI scans on patients attending the Toronto PsA clinic l between 2003 and 2014 were included. Scan details were garnered from the radiologist's official report. A chart review was performed to determine if MRI findings contributed to a change of treatment. RESULTS: One hundred sixty-eight scans were performed on 125 patients (135 axial and 33 peripheral). The mean age was 50.5 (SD, 11.5) years, with 51.2% being female. Mean duration of PsA was 11.2 (SD, 10.9) years. Of the axial scans, the majority were performed on the whole spine (excluding the sacrum) (27.4%) or the sacroiliac joints and spine together (45.2%). The predominant indications were for suspected inflammatory (51.1%) or degenerative (24.4%) disease. Magnetic resonance imaging revealed inflammatory and/or structural change in 34.1% versus 54.8% with degenerative changes. In MRI axial inflammation (n = 25), the majority (48%) had sacroiliac joint involvement, whereas 28% had inflammation at 2 or more sites.Of the periphery, 60.6% of scans were on hands and 21.2% were on feet alone. The main indications were for suspected subclinical synovitis (78.8%). Inflammatory arthritis was the MRI diagnosis in 72.7%. Magnetic resonance imaging findings influenced treatment change (n = 32) in 56.3%, but were insufficient to effect treatment change without clinical findings (100%). CONCLUSIONS: Magnetic resonance imaging is useful in evaluating patients with active PsA, particularly when suspecting inflammation and radiographic findings are unhelpful. In some cases, it can be used as an adjunct to clinical examination in determining treatment change.

Disease Outcomes in Glucocorticosteroid-Naive Patients With Systemic Lupus Erythematosus.

OBJECTIVE: The phenotype of patients who remain naive of glucocorticosteroids has not been described, and the type and rate of their damage accrual remains largely unknown. The objective of this study was to compare the type, amount, rate, and nature of organ damage accrual, mortality, and atherosclerotic comorbidities in glucocorticosteroid-naive and glucocorticosteroid-exposed patients with systemic lupus erythematosus (SLE). METHODS: Inception patients from the University of Toronto Lupus Clinic who had never taken glucocorticosteroids and had a minimum of 3 years of followup were compared to patients who received glucocorticosteroids within the first 6 months of SLE diagnosis and for at least 3 years. All patients had no damage at inception. RESULTS: A total of 86 glucocorticosteroid-naive and 173 glucocorticosteroid-exposed patients were included. There were more females and whites among the glucocorticosteroid-naive patients, whereas the glucocorticosteroid-exposed patients had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores on first examination. Overall mortality was higher in the glucocorticosteroid-exposed group, but the deaths occurred late. There was no difference in the frequency of coronary artery disease overall or at each of the time points. Damage accrual was higher in glucocorticosteroid-exposed patients overall and at 5 and 8 years. Individual damage items that were higher in glucocorticosteroid-exposed patients included ocular (cataracts) and musculoskeletal (osteoporosis with fragility fractures, and osteonecrosis) components. CONCLUSION: Mortality is more frequent in patients taking glucocorticosteroids for at least the first 3 years of their lupus compared to patients who are glucocorticosteroid-naive. In addition, patients taking glucocorticosteroids accumulate more damage by 5 years of disease, and damage tends to be glucocorticosteroid related, including cataracts and musculoskeletal components.

Attainment of Minimal Disease Activity Using Methotrexate in Psoriatic Arthritis.

OBJECTIVE: An international task force has recommended that disease remission or minimal disease activity (MDA) be the target of treatment for psoriatic arthritis (PsA) and that remission or MDA should be attained within 6 months of initiating medication. The aim of this study was to establish the proportion of patients with PsA who achieve MDA after 6 months of methotrexate (MTX) treatment. METHODS: Patients who initiated MTX and were naive to biologics between 2004 and 2014 were included. The primary outcome was the achievement of MDA after 6 months of MTX, defined as the presence of at least 5 out of the following 7: tender joint count ≤ 1, swollen joint count (SJC) ≤ 1, Psoriasis Area Severity Index (PASI) ≤ 1 or body surface area ≤ 3%, tender entheseal points ≤ 1, Health Assessment Questionnaire score ≤ 0.5, patient global disease activity visual analog scale (VAS) score ≤ 20, and patient pain VAS ≤ 15. Of 204 patients identified, 167 were treated with MTX for at least 3 months and had sufficient data for analysis at 6 months. RESULTS: At 6 months, 29 patients (17.4%) achieved MDA; 97 patients (58.1%) achieved an SJC ≤ 1 and 138 (82.6%) a PASI ≤ 1. Only 22 (13.2%) achieved the patient global disease activity criterion. Lower back pain and dactylitis were associated with a lower probability of achieving MDA. CONCLUSION: MTX use achieves MDA by 6 months in < 20% of patients. This compares unfavorably with data for tumor necrosis factor inhibitor use.

Optimal Monitoring For Coronary Heart Disease Risk in Patients with Systemic Lupus Erythematosus: A Systematic Review.

OBJECTIVE: Premature coronary heart disease (CHD) significantly affects morbidity and mortality in systemic lupus erythematosus (SLE). Several studies have detected factors influencing the atherosclerotic process, as well as methods to quantify the atherosclerotic burden in subclinical stages. The aim of this systematic review was to identify the minimum investigations to optimally monitor CHD risk in SLE. METHODS: English-restricted literature review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines through Ovid Medline, Embase, and Cochrane Central databases, from inception until May 2014 (Medline until October 2014). Specific search terms included, among others, "SLE," "atherosclerosis," "CHD," "myocardial ischemia," "acute coronary syndrome," "myocardial infarction," and "angina pectoris." We identified 101 eligible articles, 23 with cardiovascular events (CVE) as endpoints and 78 with measures of subclinical atherosclerosis. The Newcastle-Ottawa scale was used for quality assessment. RESULTS: Certain traditional and disease-specific factors were identified as independent predictors for CHD. Among the former were age (particularly postmenopausal state), male sex, arterial hypertension, dyslipidemia, and smoking. Disease activity and duration, cumulative damage, antiphospholipid antibodies, high sensitivity C-reactive protein, and renal disease were the most consistent disease-related factors. Corticosteroids were linked to increased CHD risk whereas antimalarials were protective. Concerning imaging techniques, carotid ultrasonography (intima-media thickness and plaque) was shown to independently predict CVE. CONCLUSION: Premature CHD in SLE is multifactorial; modifiable variables should be monitored at frequent intervals to ensure prompt management. Disease-specific factors also affect the atherogenic process and should be evaluated regularly. Carotid ultrasonography may hold promise in predicting CVE in selected high-risk patients.

An Association between MicroRNA-21 Expression and Vitamin D Deficiency in Coronary Artery Disease.

BACKGROUND: Atherosclerosis-related cardiovascular disease and osteoporosis (OP) occur concurrently and may share a common pathogenesis. Aberrant expression of miR-21 and vitamin D deficiency have been independently linked to the pathogenesis of atherosclerosis and OP. OBJECTIVES: To examine the relationship between miR-21 expression and vitamin D in aorta and bone in atherosclerotic disease. METHODS: Aorta, internal mammary artery (IMA) and sternal bone samples were collected from patients undergoing coronary artery bypass graft (CABG) surgery. Bone density was measured by dual x-ray absorbtiometry (DXA). MiR-21 was quantified using a two-step reverse transcription-polymerase chain reaction. RESULTS: Ten patients were included for analysis; 5 were vitamin D deficient (<25nmol/L). MiR-21 was expressed at a greater level in aorta compared with the IMA (p = 0.003), and sternal bone (p = 0.002). Expression of miR-21 between the IMA and bone was similar (p = 0.7). A positive correlation between the magnitude of difference (fold-difference) of miR-21 expression between aorta and IMA and CRP (correlation coefficient 0.9, p = 0.009) was found. Vitamin D deficient patients had greater expression of miR-21 in aorta compared with non-deficient patients (p = 0.03). Increasing CRP and vitamin D deficiency were independent predictors of miR-21 expression in aorta. The lower the difference in miR-21 expression between aorta and bone, the lower the bone density. CONCLUSION: In atherosclerosis, miR-21 is increased in the aorta and associated with vitamin D deficiency. Vitamin D deficiency may influence aberrant miR-21 expression in vasculature and bone contributing to the concurrent development of atherosclerosis and osteoporosis.

Investigational drugs for treating psoriatic arthritis.

INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory arthritis occurring in up to 30% of patients with psoriasis and can lead to progressive joint damage and disability. The emergence of 'biological' treatments, typified by the TNF inhibitors, has significantly advanced treatment of psoriatic disease over the last two decades and has led to an expanding field of drugs designed to target specific pathways identified in the pathogenesis of the disease. AREAS COVERED: This review article describes current knowledge pertaining to genetic susceptibility and that gleaned from animal models. It discusses putative drug targets and drugs in development, up to Phase II, while acknowledging that many of these drugs are being investigated in rheumatoid arthritis and psoriasis rather than PsA alone. EXPERT OPINION: Ongoing trials of some of these drugs, such as the JAK inhibitors, appear particularly promising, while the evolution of dual-targeting therapies affords the aspiration of enhanced efficacy, safety and remission. Paramount to the future of drug discovery and development is the affordability of these agents to the healthcare purchaser as well as their accessibility to the patient.

Attitudes towards exercise in patients with chronic disease: the influence of comorbid factors on motivation and ability to exercise.

BACKGROUND: Exercise is an integral part of a healthy lifestyle. It has a well defined role in maintaining health in chronic illness. This study was undertaken to determine attitudes towards exercise in patients admitted to hospital with medical illnesses. METHODS: A questionnaire on attitudes to and extent of exercise was devised and administered to patients admitted to an acute medical unit of a large university teaching hospital in 2008. Data were analysed using SPSS. RESULTS: 107 patients participated, mean age 57 years (range 20-92): 79% had at least one chronic disease, 60% were overweight, 42% did little or no exercise, while 81% did not achieve moderate physical activity. Factors associated with reduced activity included increasing age, alcohol excess, lower education level, and unemployment. Approximately 50% of the patients blamed health problems while the other half cited lack of time or motivation as reasons for not exercising. Only 3% were aware of national or international exercise recommendations. CONCLUSIONS: Much greater awareness of the importance of exercise and its impact on health and longevity is needed. Healthcare providers have an important role in exercise education in patients with acute and chronic disease.

Targeted ultrasound of the fifth metatarsophalangeal joint in an early inflammatory arthritis cohort.

OBJECTIVE: To determine whether targeted ultrasonographic (US) imaging of the fifth metatarsophalangeal (MTP) joint, compared with radiographs, could aid in the early diagnosis of rheumatoid arthritis (RA) by identifying erosions sooner in early inflammatory arthritis. Radiographic erosion in RA is a late indication of poor prognosis. The earlier detection of erosion may facilitate the timely initiation of disease-modifying antirheumatic drug therapy, particularly in patients with undifferentiated synovitis. METHODS: Patients presenting with synovitis for the first time were invited to participate. Each patient underwent laboratory tests, radiographs of the hands and feet, and US imaging of both fifth MTP joints. RESULTS: Thirty patients (22 women) took part in the study. Seventeen patients (57%) had RA, and 13 (43%) had undifferentiated arthritis (UA). The mean +/- SD time taken to scan both fifth MTP joints was 10.9 +/- 4.4 minutes. Ten patients (33%) had US evidence of synovitis associated with a positive power Doppler (PD) signal (P = 0.04). Seven patients (23%) had radiographic erosions of the fifth MTP joint, and 17 patients (57%) had US evidence of fifth MTP joint erosions (P = 0.01). A positive PD signal at the fifth MTP joint was seen in 9 of 17 patients with RA and 1 of 13 patients with UA (P = 0.02). Patients with a definite diagnosis of RA were more likely to have fifth MTP joint erosions (11 [65%] of 17) compared with UA (6 [46%] of 13). CONCLUSION: Targeted US is a rapid and useful tool in detecting erosive disease in early inflammatory arthritis. It gives a better indication of disease severity and prognosis compared with routinely available laboratory tests, even in the absence of a definite diagnosis.

Greater focus on clinical rheumatology is required for training in internal medicine.

Early intervention for rheumatic disease has been shown to improve prognosis, but is dependent on the recognition of pertinent symptoms and signs. This study was undertaken to identify the attitudes of junior doctors toward musculoskeletal assessment. The charts of 100 randomly selected medical patients admitted via the Emergency Department were reviewed for documentation of the musculoskeletal system. In addition, junior doctors were interviewed regarding their views on musculoskeletal assessment. Only 16% of medical admission notes contained a reference to the musculoskeletal system and the recording of joint examinations was incomplete in all cases. Prior training in musculoskeletal assessment depended on the joint area involved (hand, 100%; foot, 36.2%). Most doctors felt competent in hand assessment (68.8%) but only 12.5% could examine the foot. More than one third could not confidently diagnose common rheumatic conditions, while 75% felt unable to diagnose a connective tissue disorder. The majority (88.7%) regarded the musculoskeletal assessment as difficult/challenging and 61.3% thought that it should not be included as part of a general medical examination. However, 80% of doctors felt that they had not received adequate teaching in musculoskeletal assessment and would welcome further training. The omission of the musculoskeletal assessment for medical patients admitted to hospital is reflected in the fact that doctors lack training in this area. Furthermore, doctors lack confidence in their ability to recognise both common and rare rheumatic diagnoses, a problem likely to impact adversely on the outcome of patients with these conditions.

Sub-optimal pain control in patients with rheumatic disease.

The visual analog scale (VAS) of pain is a ubiquitous clinical and research tool with widespread application in the rheumatic diseases. The objectives of this study were to assess if patients report pain differently to doctors or nurses, to determine reproducibility of this test for diagnosis, age, gender, and treatment, and to ascertain the level of pain in patients attending general rheumatology clinics. Using a standardized line of exactly 100 mm and instructions with identical wording, consecutive patients attending general rheumatology clinics were asked to score their perceived level of pain in the preceding week. Two assessments were carried out, one before and one after the clinic visit, and each patient was questioned by both a doctor and a nurse. Differences between the first and second VAS scores (VAS1 and VAS2) were recorded. One hundred and eight patients completed the study (69 female). VAS1 and VAS2 scores were administered by a similar number of doctors and nurses. There was no significant difference between mean VAS1 and VAS2 scores (41.1 vs. 41.4 mm, p = 0.78). VAS1 and VAS2 differed by <4 mm in 59% of patients. Age, gender, or diagnosis did not influence VAS1 or VAS2. Differences in scores were independent of which health professional administered the scale (p = 0.19). Patients taking painkillers had higher mean VAS scores (49 mm) compared with those not on analgesia (27 mm; p < 0.001). Anti-rheumatic treatment did not influence pain scores (p = 0.13). The VAS is a reliable and effective method of pain assessment. Results are independent of which health professional administers the scale. Patients with rheumatic disease report their pain similarly regardless of diagnosis. However, pain control is sub-optimal in patients taking analgesia. Specific assessment of pain is, thus, important in patients attending rheumatology clinics.