A J Silman

The University of Manchester, Manchester, England, United Kingdom

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Publications (594)3453.86 Total impact

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    ABSTRACT: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8 % in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8 % with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.
    Osteoporosis International 05/2015; DOI:10.1007/s00198-015-3170-6 · 4.17 Impact Factor
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    Journal of Neurology Neurosurgery & Psychiatry 09/2014; 85(10):e4-e4. DOI:10.1136/jnnp-2014-309236.160 · 5.58 Impact Factor
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    ABSTRACT: BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.
    Postgraduate medical journal 04/2013; 89(1050):231-240. DOI:10.1136/postgradmedj-2011-201063rep · 1.55 Impact Factor
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    ABSTRACT: The aim of this report was to propose a definition for erosive disease in the context of inflammatory arthritis in light of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) criteria for use in clinical practice and studies. A EULAR task force was formed including 16 rheumatologists and one rheumatology fellow. The process was both evidence based and consensus based, and included, between March 2010 and April 2012, analyses of data from two cohorts, two face-to-face meetings, one online voting and one teleconference. The Leiden Early Arthritis Cohort and the French ESPOIR cohort were used for the evidence-based part. The outcome measures, which were initiation of methotrexate therapy, or any disease-modifying antirheumatic drug therapy within the first year of disease and arthritis persistency over 5 years, were studied with the aim to give the best definition of erosive disease. A decision was made to select a definition with a high specificity and focus on patients who did not otherwise fulfil the 2010 ACR/EULAR RA criteria (<6 points). By a unanimous vote the following definition was selected: erosive disease for use in the 2010 ACR/EULAR RA classification criteria is defined when an erosion (defined as a cortical break) is seen in at least three separate joints at any of the following sites: the proximal interphalangeal, the metacarpophalangeal, the wrist (counted as one joint) and the metatarsophalangeal joints on radiographs of both hands and feet. A highly specific definition for erosive disease has thus been formulated.
    Annals of the rheumatic diseases 02/2013; DOI:10.1136/annrheumdis-2012-202779 · 9.27 Impact Factor
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    ABSTRACT: OBJECTIVE: It has been suggested that elevated levels of C-reactive protein (CRP) might interfere with leptin signalling and contribute to leptin resistance. Our aim was to assess whether plasma levels of CRP influence leptin resistance in humans; and our hypothesis was that CRP levels would modify the cross-sectional relationships between leptin and measures of adiposity. DESIGN AND METHODS: We assessed 4 measures of adiposity: body mass index, waist circumference, fat mass, and % body fat in 2113 British Regional Heart Study (BRHS) men (mean (SD) age 69 (5) years), with replication in 760 (age 69 (6) years) European Male Aging Study (EMAS) subjects. RESULTS: In BRHS subjects leptin correlated with CRP (Spearman's r=0.22, p<0.0001). Leptin and CRP correlated with all 4 measures of adiposity (r-value range: 0.22 to 0.57, all p<0.0001). Age-adjusted mean levels for adiposity measures increased in relation to leptin levels; but CRP level did not consistently influence the β coefficients of the regression lines in a CRP-stratified analysis. In BRHS subjects, the BMI vs. leptin relationship demonstrated a weak statistical interaction with CRP (p=0.04). We observed no similar interaction in EMAS subjects, and no significant interactions with other measures of adiposity in BRHS or EMAS cohorts. CONCLUSION: We have shown that plasma CRP has little influence on the relationship between measures of adiposity and serum leptin levels in these middle-aged and elderly male European cohorts. This study provides epidemiological evidence against CRP having a significant role in causing leptin resistance.
    European Journal of Endocrinology 10/2012; DOI:10.1530/EJE-12-0348 · 3.69 Impact Factor
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    ABSTRACT: There are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements. Men and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors. 139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = -10.0; 95% confidence interval (CI) -17.4, -2.6) though BUA was similar (difference = -1.2; 95% CI -4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS. In this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.
    BMC Musculoskeletal Disorders 07/2012; 13:133. DOI:10.1186/1471-2474-13-133 · 1.90 Impact Factor
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    ABSTRACT: BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment.OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce.METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature.RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems.CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.
    Annals of the rheumatic diseases 04/2012; 72(1). DOI:10.1136/annrheumdis-2011-201063 · 9.27 Impact Factor
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    ABSTRACT: The limitations of serum testosterone and estradiol (E(2)) measurements using non-extraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. We compared serum testosterone and E(2) measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (n=3174; age 40-79 years), peripheral serum testosterone and E(2) were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC-MS methods. Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (R=0.93, P<0.001), which was less robust in the hypogonadal range (<11 nmol/l; R=0.72, P<0.001). The IA/MS correlation was weaker in E(2) measurements (R=0.32, P<0.001, at E(2) <40.8 pmol/l, and R=0.74, P<0.001, at E(2) >40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (<11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E(2) (<40.7 pmol/l) were 13.3 and 99.3%, and for high E(2) (>120 pmol/l) 88.4 and 88.6%. A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E(2) measurements showed poor correlation with MS and may only be suitable for the detection of high E(2) in men.
    European Journal of Endocrinology 03/2012; 166(6):983-91. DOI:10.1530/EJE-11-1051 · 3.69 Impact Factor
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    ABSTRACT: The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance.
    International Journal of Epidemiology 02/2012; 42(2). DOI:10.1093/ije/dyr234 · 9.20 Impact Factor
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    ABSTRACT: Previously, active shape modelling (ASM) of the proximal femur was shown to identify those individuals at highest risk of developing radiographic OA. Here we determine whether ASM predicts the need for total hip replacement (THR) independent of Kellgren-Lawrence grade (KLG) and other known risk factors. A retrospective cohort study of 141 subjects consulting primary care with new hip pain was conducted. Pelvic radiographs taken on recruitment were assessed for KLG, centre-edge angle, acetabular depth and femoral head migration. Clinical factors (duration of pain, use of a stick and physical function) were collected by self-completed questionnaires. ASM differences between shape mode scores at baseline for individuals who underwent THR during the 5-year follow-up (n = 27) and those whose OA did not progress radiographically (n = 75) were compared. A 1 s.d. reduction in baseline ASM mode 2 score was associated with an 81% reduction in odds of THR (OR = 0.19, 95% CI 0.52, 0.70) after adjustment for KLG, radiographic and clinical factors. A similar reduction in odds of THR was associated with a 1 s.d. reduction in mode 3 (OR = 0.45, 95% CI 0.28, 0.71) and a 1 s.d. increase in mode 4 score (OR = 2.8, 95% CI 1.7, 4.7), although these associations were no longer significant after adjustment for KLG and clinical factors. ASM of the hip joint is a reliable early biomarker of radiographic OA severity, which can improve the ability to identify patients at higher risk of rapid progression and poor outcome even when KLG and clinical risk factors are taken into account.
    Rheumatology (Oxford, England) 12/2011; 51(3):562-70. DOI:10.1093/rheumatology/ker382 · 4.44 Impact Factor
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    ABSTRACT: We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r2 ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40–79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm3) and cross-sectional area (mm2) at the 4% site and cortical vBMD (mg/mm3); total, cortical, and medullary area (mm2); cortical thickness (mm); and stress strain index (SSI) (mm3) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12–16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10–9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03–0.13], P = 0.002), and medullary area (β [95% CI] = −2.90 [−4.94 to −0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = −4.30 [−7.78 to −0.82], P = 0.015) and cortical thickness (β [95% CI] = −0.08 [−0.13 to −0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = −7.58 [−14.01 to −1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92–16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men. Electronic supplementary material The online version of this article (doi:10.1007/s00223-011-9532-y) contains supplementary material, which is available to authorized users.
    Calcified Tissue International 10/2011; 89(6):446-55. DOI:10.1007/s00223-011-9532-y · 2.75 Impact Factor
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    ABSTRACT: Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) levels have been linked with depressive symptoms among adults in various clinical settings. Data in generally healthy, community-dwelling individuals remain inconclusive. We investigated whether depression was associated with 25(OH)D and/or PTH in a sample of middle-aged and older men (n = 3369; mean age 60 ± 11) participating in the European Male Ageing Study, and whether any associations were explained by lifestyle and health factors. The Beck Depression Inventory-II (BDI-II) was used to screen for depression, and serum 25(OH)D and PTH levels measured by radioimmunoassay. Univariate analysis revealed that 25(OH)D levels were lower (p < 0.001) and PTH higher (p = 0.004) in people with depression. In age- and centre-adjusted linear regressions a higher BDI-II score was significantly associated with lower levels of 25(OH)D (p = 0.004). After adjustment for lifestyle and health factors this relationship was attenuated but remained significant (p = 0.01). Using multivariable logistic regression the odds for depression increased approximately 70% across decreasing 25(OH)D quartiles (p (trend) = 0.04). There was no independent association between PTH and depression in any of the multivariable regressions. Our results reveal an inverse association between 25(OH)D levels and depression, largely independent of several lifestyle and health factors. Further studies are required to determine whether higher levels of vitamin D have an antidepressant effect in older adults.
    Journal of Psychopharmacology 10/2011; 25(10):1320-8. DOI:10.1177/0269881110379287 · 2.81 Impact Factor
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    ABSTRACT: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. A cross-sectional population-based survey. Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β C-terminal cross-linked telopeptide (β-cTX)), total testosterone, total oestradiol (E(2)), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres. A total of 3120, mean age 59.9 years (s.d.=11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E(2) were negatively associated with β-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both β-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. E(2), SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.
    European Journal of Endocrinology 09/2011; 165(6):977-86. DOI:10.1530/EJE-11-0353 · 3.69 Impact Factor
  • Alan J Silman, Anthony E Ades
    Rheumatology (Oxford, England) 09/2011; 50 Suppl 4:iv1-2. DOI:10.1093/rheumatology/ker238 · 4.44 Impact Factor
  • Alan J Silman
    Rheumatology (Oxford, England) 09/2011; 50 Suppl 4:iv3-4. DOI:10.1093/rheumatology/ker239 · 4.44 Impact Factor
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    ABSTRACT: Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe. The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men. Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry. We conducted a community-based population survey in eight European centers. Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau. These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.
    The Journal of Clinical Endocrinology and Metabolism 08/2011; 96(10):E1577-87. DOI:10.1210/jc.2010-2216 · 6.31 Impact Factor
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    ABSTRACT: Our aim was to describe clinical features and pattern of care in children with localized scleroderma presenting to secondary care during a 25-month incidence study. Eighty-seven patients were identified, and clinical features, serum autoantibodies, current treatment and outcome at 12 months were documented. Fifty-eight (67%) had linear scleroderma, 25 (29%) non-linear morphoea and 4 (4%) a mixed pattern. Of the 58 patients with linear scleroderma, 29 (50%) presented with lesions of the trunk and/or limbs only, 26 (45%) with face-head localization only and 3 (5%) with both. Thirteen (15%) had extracutaneous features and 16 (43%) out of 37 were ANA positive. At 12 months, 59% were on MTX. At 12 months, 51 (65%) were improved/resolved, 14 (18%) were unchanged and 13 (17%) had deteriorated. Key findings included the high prevalence of face-head involvement in those with linear disease, and the high prevalence of extracutaneous disease and of ANA positivity. After 12 months, most patients improved according to clinician's opinion.
    Rheumatology (Oxford, England) 07/2011; 50(10):1865-8. DOI:10.1093/rheumatology/ker142 · 4.44 Impact Factor
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    ABSTRACT: The aim of this study was to determine the influence of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, and IGF-I on calcaneal ultrasound parameters in middle-aged and elderly European men. Men aged 40-79 years were recruited from population registers for participation in the European Male Ageing Study (EMAS). Subjects were invited by letter to complete a postal questionnaire and to attend for an interviewer-assisted questionnaire, quantitative ultrasound (QUS) of the calcaneus, and a fasting blood sample from which serum levels of IGFBP-1, IGFBP-3, IGF-I, estradiol (E(2)), and SHBG were assayed. The questionnaires included the Physical Activity Scale for the Elderly (PASE) and questions about smoking and alcohol consumption. Estimated bone mineral density (eBMD) was derived as a function of the QUS parameters speed of sound and broadband ultrasound attenuation. Height and weight were measured in all subjects. 3057 men, mean age 59.7 years (standard deviation 11.0) were included in the analysis. After adjusting for age, center, and BMI, higher levels of IGFBP-1 were associated with lower eBMD. Higher levels of both IGFBP-3 and IGF-I were associated with higher eBMD. After further adjustment for PASE score, current smoking, alcohol consumption, free E(2), and SHBG, IGFBP-3 and IGF-I, though not IGFBP-1, remained significantly associated with eBMD. IGFBP-1 was associated with bone health, though the effect could be explained by other factors. IGFBP-3 and IGF-I were independent determinants of bone health in middle-aged and elderly European men.
    Calcified Tissue International 06/2011; 88(6):503-10. DOI:10.1007/s00223-011-9484-2 · 2.75 Impact Factor
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    ABSTRACT: To explore the associations between frailty and reproductive axis hormones (as an important regulatory system) in middle aged and older men. Cross-sectional. The European Male Aging Study. Three thousand two hundred nineteen community-dwelling European men aged 40 to 79. Interviewer-assisted questionnaires to assess physical activity, health status, and mood were administered. Testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured in a fasting morning blood sample. Frailty was assessed as an index (FI) according to the number (out of 43 possible) of health deficits (symptoms, signs, and functional impairments). Relationships between FI and hormone levels (as outcomes) were explored using regression models. Mean FI was 0.12 ± 0.11 (range 0-0.67) was highest in the oldest group. After adjustment for confounders, higher levels of FI were significantly associated with lower levels of total T, free T, and DHEAS and higher levels of gonadotropins and SHBG; a 1-standard deviation cross-sectional increase in FI was associated with a regression coefficient of -0.30 nmol/L (95% confidence interval (CI)=-0.53 to -0.07) decrease in total T and 0.66 U/L (95% CI=0.48-0.83) increase in LH. The associations between high FI, high gonadotropins, and well-maintained circulating T suggest that these changes are markers of aging-related disruptions of multiple physiological regulation, of which alterations in pituitary-testicular function represent a sensitive marker rather than an underlying pathogenic mechanism for frailty.
    Journal of the American Geriatrics Society 05/2011; 59(5):814-21. DOI:10.1111/j.1532-5415.2011.03398.x · 4.22 Impact Factor
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    ABSTRACT: Few published data link overweight and obesity with measures of quality of life (QoL) including sexual health in men. To assess the association of overweight/obesity with impairment of physical and psychological QoL and sexual functions in men. Cross-sectional, multicentre survey of 3369 community-dwelling men aged 40-79 (mean±s.d., 60±11) years randomly selected from eight European centres. Adiposity was assessed by body mass index (BMI) and waist circumference (WC), QoL and functional impairments by physical and psychological function domains of the Short Form-36 questionnaire, Beck's Depression Inventory and the European Male Ageing Study sexual function questionnaire. Complete data on sexual activities and erectile function were available in 2734 (92%) and 3193 (95%) of the participants respectively. From the population studied, 814 men were obese (BMI ≥30 kg/m(2)) and 1171 had WC ≥102 cm, 25% of all men were unable to do vigorous activity and 2-13% reported depressive symptoms. Symptoms of sexual dysfunction ranged between 22% (low sexual desire) and 40% (infrequent morning erections) of the participants. Among obese men with both BMI ≥30 kg/m(2) and WC ≥102 cm, at least one symptom of impaired physical, psychological and sexual function was reported by 41, 43 and 73% of the participants respectively. Compared with the reference group of non-obese men (BMI <30 kg/m(2) and WC <102 cm), men with BMI ≥30 kg/m(2) and WC ≥102 cm more frequently reported at least one symptom of impaired physical function (odds ratio (OR)=2.67; confidence interval (CI): 2.07-3.45, P<0.001), impaired psychological function (OR=1.48; CI: 1.14-1.90, P<0.01) and impaired sexual function (OR=1.45; CI: 1.14-1.85, P<0.01). These functional impairments were also more prevalent in men who had WC ≥102 cm even with BMI <30 kg/m(2), but those with BMI ≥30 kg/m(2) and WC <102 cm generally did not suffer from increased impaired physical or sexual health. Men with high BMI and WC were at even greater likelihood of having a composite of two or more or three or more symptoms compared with those with normal BMI and WC. Men with high WC, including those who are 'non-obese' with BMI <30 kg/m(2), have poor QoL with symptoms of impaired physical, psychological and sexual functions. Health promotion to improve QoL should focus on prevention of obesity and central fat accumulation.
    European Journal of Endocrinology 04/2011; 164(6):1003-11. DOI:10.1530/EJE-10-1129 · 3.69 Impact Factor

Publication Stats

37k Citations
3,453.86 Total Impact Points

Institutions

  • 1989–2014
    • The University of Manchester
      • • School of Nursing, Midwifery and Social Work
      • • Centre for Integrated Genomic Medical Research (CIGMR)
      • • Manchester Medical School
      • • School of Biomedicine
      Manchester, England, United Kingdom
  • 2008–2013
    • Arthritis Research UK
      Chesterfield, England, United Kingdom
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 1993–2013
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 2012
    • Imperial College London
      • Department of Surgery and Cancer
      London, ENG, United Kingdom
  • 2006–2011
    • University of Aberdeen
      Aberdeen, Scotland, United Kingdom
  • 2000–2011
    • University of Toronto
      Toronto, Ontario, Canada
    • The University of Western Ontario
      London, Ontario, Canada
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2010
    • Indian Broiler (IB) Group India
      Bhānpuri, Chhattisgarh, India
  • 2003–2006
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 1996–2006
    • Keele University
      • School of Medicine
      Newcastle-under-Lyme, England, United Kingdom
  • 2005
    • Belgian Scientific Institute for Public Health
      Bruxelles, Brussels Capital Region, Belgium
  • 2004
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 1996–2004
    • University of Cambridge
      • • Cambridge Institute of Public Health
      • • Department of Medicine
      Cambridge, England, United Kingdom
  • 2002
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 2001
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 1993–1999
    • University of Leeds
      Leeds, England, United Kingdom
  • 1998
    • Staffordshire and Stoke-On-Trent Partnership NHS Trust
      Newcastle-under-Lyme, England, United Kingdom
  • 1997
    • Lancaster University
      • Lancaster Law School
      Lancaster, England, United Kingdom
  • 1995–1996
    • University of Maiduguri
      • Department of Medicine
      Maidugari, Borno, Nigeria
    • Garvan Institute of Medical Research
      Darlinghurst, New South Wales, Australia
  • 1994
    • Cambridge Institute for Medical Research
      Cambridge, England, United Kingdom
    • Cornell University
      Ithaca, New York, United States
  • 1992
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
    • Navy Environmental & Preventive Medicine Unit Five
      San Diego, California, United States
  • 1990
    • Royal National Hospital For Rheumatic Diseases NHS Foundation Trust
      Bath, England, United Kingdom
  • 1989–1990
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 1987
    • London College of Clinical Hypnosis
      Londinium, England, United Kingdom