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  • The importance of the disease process and disease-modifying antirheumatic drug treatment in the development of septic arthritis in patients with rheumatoid arthritis.

    18 September 2018

    OBJECTIVE: To evaluate the effect of disease-modifying antirheumatic drugs (DMARDs) on the likelihood of patients with rheumatoid arthritis (RA) developing septic arthritis (SA). METHODS: The United Kingdom General Practice Research Database (GPRD) was used to identify adults with RA, and age-, sex-, and practice-matched control subjects. Subjects were studied between 1987 and 2002. The risk of developing SA (excluding infected joint replacements) for individuals with RA was calculated and the effect of DMARD use determined. RESULTS: A total of 136,977 subjects (34,250 patients with RA, 102,747 controls) were identified. SA was identified in 345 subjects, of which 321 (236 in patients with RA, 85 in controls) cases occurred during the study period. The incidence rate of SA was 12.9 times higher in subjects with RA than in those without (95% confidence interval [95% CI] 10.1-16.5, P < 0.001). The incident rate ratios (IRRs) for developing SA while receiving DMARDs compared with receiving no DMARDs were different for different medications. Penicillamine (adjusted IRR 2.51, 95% CI 1.29-4.89, P = 0.004), sulfasalazine (adjusted IRR 1.74, 95% CI 1.04-2.91, P = 0.03), and prednisolone (adjusted IRR 2.94, 95% CI 1.93-4.46, P < 0.001) were associated with an increased incidence of SA when compared with not receiving any DMARD. The use of other DMARDs including methotrexate showed no such effect. CONCLUSION: Individuals with RA have an increased risk of developing SA. This increased risk can be attributed to both the disease process and the use of DMARDs.

  • Knee pain, knee osteoarthritis, and the risk of fracture.

    18 September 2018

    OBJECTIVE: Patients with osteoarthritis (OA) have increased bone mineral density; however, the association between knee OA and fracture is controversial. Few data exist on the association between knee pain and fracture. We examined the association of knee OA and knee pain with fracture and falls in elderly men and women. METHODS: The study group comprised 6,641 men and women ages > or =75 years who participated in a 3-year randomized controlled trial of intramuscular vitamin D therapy. Patients completed a questionnaire about knee pain and OA. Fracture and fall data were collected prospectively every 6 months. RESULTS: Knee pain prevalence and a clinician diagnosis of knee OA were 35.2% and 6.8%, respectively. A total of 436 incident nonvertebral fractures were reported, and 3,992 patients sustained a fall. Prevalent knee pain was associated with an increased risk of falls (hazard ratio [HR] 1.26, 95% confidence interval [95% CI] 1.17-1.36) and hip fracture (HR 2.0, 95% CI 1.18-3.37). Increasing severity of knee pain was associated with a greater risk of falls and hip fracture. Clinician diagnosis of knee OA was associated with an increased risk of nonvertebral fractures (HR 1.61, 95% CI 1.09-2.36). The increased risk of fracture was not substantially reduced by adjusting for falls, but was attenuated by adjustment for the use of walking aids. CONCLUSION: Patients with a clinical diagnosis of knee OA and with knee pain have an increased risk of nonvertebral and hip fracture. This is not explained by the increased risk of falls, but is more likely to be due to the severity of falls sustained. Knee pain and OA should be regarded as independent risk factors for fracture.

  • Laboratory markers predict bone loss in Crohn's disease: relationship to blood mononuclear cell function and nutritional status.

    18 September 2018

    BACKGROUND: Crohn's disease is associated with reduced bone density. The power of simple markers of systemic inflammation to identify higher rates of bone loss, in Crohn's disease, is uncertain. This relationship and the role of circulating (peripheral blood) mononuclear cells were investigated in a case-control study. METHODS: Urinary deoxypyridinoline/creatinine and serum osteocalcin concentrations were compared in male and premenopausal females with "active" Crohn's disease (C-reactive protein > or = 10 and/or erythrocyte sedimentation rate > or = 20) (n = 22) and controls with "quiescent" Crohn's disease (C-reactive protein < 10 and erythrocyte sedimentation rate < 20) (n = 21). No patients were receiving corticosteroid therapy. Production of tumour necrosis factor-alpha, interferon-gamma and prostaglandin E(2) by peripheral blood mononuclear cells were measured. RESULTS: Active Crohn's disease was associated with a higher deoxypyridinoline/creatinine (P = 0.02) and deoxypyridinoline/creatinine:osteocalcin ratio (P =0.01) compared with quiescent Crohn's disease, but similar osteocalcin (P = 0.24). These were not explained by vitamin D status, dietary intake or nutritional status. However, production of interferon-gamma by concanavalin A-stimulated peripheral blood mononuclear cells was lower in active Crohn's disease (P = 0.02) and correlated negatively with the deoxypyridinoline/creatinine:osteocalcin ratio (r = -0.40, P = 0.004). CONCLUSION: In Crohn's disease, raised C-reactive protein and erythrocyte sedimentation rate may indicate higher rates of bone loss and, if persistent, the need to assess bone mass even where disease symptoms are mild. This may be partly explained by altered production of interferon-gamma by peripheral blood mononuclear cells.

  • Incidence of shoulder dislocations in the UK, 1995-2015: a population-based cohort study.

    18 September 2018

    OBJECTIVE: This cohort study evaluates the unknown age-specific and gender-specific incidence of primary shoulder dislocations in the UK. SETTING: UK primary care data from the Clinical Practice Research Datalink (CPRD) were used to identify patients aged 16-70 years with a shoulder dislocation during 1995-2015. Coding of primary shoulder dislocations was validated using the CPRD general practitioner questionnaire service. PARTICIPANTS: A cohort of 16 763 patients with shoulder dislocation aged 16-70 years during 1995-2015 were identified. PRIMARY OUTCOME MEASURE: Incidence rates per 100 000 person-years and 95% CIs were calculated. RESULTS: Correct coding of shoulder dislocation within CPRD was 89% (95% CI 83% to 95%), and confirmation that the dislocation was a 'primary' was 76% (95% CI 67% to 85%). Seventy-two percent of shoulder dislocations occurred in men. The overall incidence rate in men was 40.4 per 100 000 person-years (95% CI 40.4 to 40.4), and in women was 15.5 per 100 000 person-years (95% CI 15.5 to 15.5). The highest incidence was observed in men aged 16-20 years (80.5 per 100 000 person-years; 95% CI 80.5 to 80.6). Incidence in women increased with age to a peak of 28.6 per 100 000 person-years among those aged 61-70 years. CONCLUSIONS: This is the first time the incidence of shoulder dislocations has been studied using primary care data from a national database, and the first time the results for the UK have been produced. While most primary dislocations occurred in young men, an unexpected finding was that the incidence increased in women aged over 50 years, but not in men. The reasons for this are unknown. Further work is commissioned by the National Institute for Health Research to examine treatments and predictors for recurrent shoulder dislocation. STUDY REGISTRATION: The design of this study was approved by the Independent Scientific Advisory Committee (15_260) for the Medicines & Healthcare products Regulatory Agency.

  • Osteoarthritis.

    18 September 2018

    Osteoarthritis (OA) is the most common joint disorder, is associated with an increasing socioeconomic impact owing to the ageing population and mainly affects the diarthrodial joints. Primary OA results from a combination of risk factors, with increasing age and obesity being the most prominent. The concept of the pathophysiology is still evolving, from being viewed as cartilage-limited to a multifactorial disease that affects the whole joint. An intricate relationship between local and systemic factors modulates its clinical and structural presentations, leading to a common final pathway of joint destruction. Pharmacological treatments are mostly related to relief of symptoms and there is no disease-modifying OA drug (that is, treatment that will reduce symptoms in addition to slowing or stopping the disease progression) yet approved by the regulatory agencies. Identifying phenotypes of patients will enable the detection of the disease in its early stages as well as distinguish individuals who are at higher risk of progression, which in turn could be used to guide clinical decision making and allow more effective and specific therapeutic interventions to be designed. This Primer is an update on the progress made in the field of OA epidemiology, quality of life, pathophysiological mechanisms, diagnosis, screening, prevention and disease management.

  • Epidemiological aspects of osteoporosis

    18 September 2018

    Osteoporosis is an increasing social and economic burden as the age of populations throughout the world increases. The purpose of this review is to highlight some of the key epidemiological aspects of osteoporosis. First, the definition is explored, examining its origins, implications and limitations. The clinical significance of osteoporosis lies in its predisposition to fracture, but once fracture has occurred, intervention is already late. As a result, methods of noninvasive assessment have been developed which can be used to identify 'at risk' subjects. An overview is given of the densitometric WHO criteria which are used to define these high risk populations, and their limitations are explored, including: significant overlap between normal and fracture-prone groups; applicability in individuals; variations between populations; and inaccuracies which are inherent in measurement with any equipment. These variations are summarized for the sites which are most frequently affected by osteoporotic fractures, particularly at the hip, spine and wrist. Finally, using current epidemiological knowledge, and estimates of likely demographic changes, future projections for fracture are estimated.