K R Muir

Publications of K R Muir

• Reply: 'Hand pattern indicates risk of prostate cancer'.

  Authors: A A Rahman, A Lophatananon, S Stewart-Brown, D Harriss, J Anderson, T Parker, D Easton, Z Kote-Jarai, R Pocock, D Dearnaley, M Guy, L O'Brien, R A Wilkinson, A L Hall, E Sawyer, E Page, J F Liu, R A Eeles, K R Muir

  British journal of cancer. 07/2011; 105(3):467.

• Incident knee pain in the Nottingham community: a 12-year retrospective cohort study.

  Authors: S L Ingham, W Zhang, S A Doherty, D F McWilliams, K R Muir, M Doherty

  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 04/2011; 19(7):847-52.

  To determine the community incidence of knee pain and associated risk factors over a 12-year period in people over the age of 40 years. A cohort study of knee pain was undertaken in 2156 people fromTo determine the community incidence of knee pain and associated risk factors over a 12-year period in people over the age of 40 years. A cohort study of knee pain was undertaken in 2156 people from four general practices in North Nottinghamshire, UK. Knee pain was defined as 'pain around the knee for most days of at least a month'. Cumulative incidence over 12 years and person-year incidence rate of knee pain were estimated. Survival analysis was undertaken for time to the onset of knee pain. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for relative risk between exposure and non-exposure. Cox regression model was used to adjust for confounding factors. The 12-year cumulative incidence of knee pain was 34.4% (32% for men and 35% for women), corresponding to an average incidence rate of 32 (31 for men and 34 for women)/1000 person-years. Incident knee pain was associated with female gender (HR 1.27, 95% CI 1.08, 1.49), obesity (1.80; 95% CI 1.37, 2.38), varus (1.68, 95% CI 1.15, 2.47) and valgus (1.83, 95% CI 1.05, 3.20) mal-alignment, and knee injury (2.37, 95% CI 2.98, 2.85). For people over age 40, one in three will develop knee pain within 12 years. On average, the risk of knee pain was 32/1000 person-years. This risk is associated with a variety of constitutional and environmental biomechanical insults to the knee. Some of these could be modified to possibly reduce the incidence of the condition.

• Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis.

  Authors: H J M Kerkhof, M Doherty, N K Arden, S B Abramson, M Attur, S D Bos, C Cooper, E M Dennison, S A Doherty, E Evangelou [......] E Slagboom, A J P Smith, T D Spector, A Tamm, A G Uitterlinden, M Wheeler, G Zhai, W Zhang, J B J van Meurs, A M Valdes

  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 12/2010; 19(3):265-71.

  To clarify the role of common genetic variation in the Interleukin-1β (IL1B) and Interleukin-1R antagonist (IL1RN) genes on risk of knee and hip osteoarthritis (OA) and severity of knee OA by meansTo clarify the role of common genetic variation in the Interleukin-1β (IL1B) and Interleukin-1R antagonist (IL1RN) genes on risk of knee and hip osteoarthritis (OA) and severity of knee OA by means of large-scale meta-analyses. We searched PubMed for articles assessing the role of IL1B and IL1RN polymorphisms/haplotypes on the risk of hip and/or knee OA. Novel data were included from eight unpublished studies. Meta-analyses were performed using fixed- and random-effects models with a total of 3595 hip OA and 5013 knee OA cases, and 6559 and 9132 controls respectively. The role of ILRN haplotypes on radiographic severity of knee OA was tested in 1918 cases with Kellgren-Lawrence (K/L) 1 or 2 compared to 199 cases with K/L 3 or 4. The meta-analysis of six published studies retrieved from the literature search and eight unpublished studies showed no evidence of association between common genetic variation in the IL1B or IL1RN genes and risk of hip OA or knee OA (P>0.05 for rs16944, rs1143634, rs419598 and haplotype C-G-C (rs1143634, rs16944 and rs419598) previously implicated in risk of hip OA). The C-T-A haplotype formed by rs419598, rs315952 and rs9005, previously implicated in radiographic severity of knee OA, was associated with reduced severity of knee OA (odds ratio (OR)=0.71 95%CI 0.56-0.91; P=0.006, I(2)=74%), and achieved borderline statistical significance in a random-effects model (OR=0.61 95%CI 0.35-1.06 P=0.08). Common genetic variation in the Interleukin-1 region is not associated with prevalence of hip or knee OA but our data suggest that IL1RN might have a role in severity of knee OA.

• Attempt to replicate published genetic associations in a large, well-defined osteoarthritis case-control population (the GOAL study).

  Authors: K L Limer, K Tosh, S R Bujac, R McConnell, S Doherty, F Nyberg, W Zhang, M Doherty, K R Muir, R A Maciewicz

  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 12/2008;

  OBJECTIVE: Published studies have tested over 90 genes for association with osteoarthritis (OA), but few positives reported have been independently replicated. Using a new case-control study, our aimOBJECTIVE: Published studies have tested over 90 genes for association with osteoarthritis (OA), but few positives reported have been independently replicated. Using a new case-control study, our aim was to attempt the replication of findings from 12 genes reported to have significant genetic association with OA and to further examine the role of genetic variation in six of these genes. METHODS: A case-control study was undertaken in Nottingham, UK. Hospital-referred index cases with symptomatic, radiographic OA (ROA) of the knee (n=1040) or hip (n=1004) were recruited. Asymptomatic controls (n=1123) were recruited from intravenous urography waiting lists and screened for radiographic hip and knee OA. Sixty-eight polymorphisms were genotyped in IL1A, IL1B, IL1RN, IL4R, IL6, COL2A1, ADAM12, ASPN, IGF1, TGFB1, ESR1 and VDR. Statistical analysis compared allele or genotype frequencies of these polymorphisms in all asymptomatic controls and the subset of controls without ROA vs all OA, knee OA and hip OA. The analyses were adjusted for age, gender and body mass index. RESULTS: We were unable to replicate any of the published genetic associations investigated. Our extended exploratory analyses identified some associations between polymorphisms in TGFB1, IGF1 and IL1RN and OA; but the strength of evidence varied with the control group used. CONCLUSION: Lack of replication is common and could be due to differences in study design, phenotype, populations examined or the occurrence of false positives in the initial study. Variants within TGFB1, IGF1 and IL1RN could have a role in OA susceptibility; however, replication of these findings is required in an independent study.

• Dietary zinc intake and brain cancer in adults: a case-control study.

  Authors: P Dimitropoulou, S Nayee, J F Liu, L Demetriou, M van Tongeren, S J Hepworth, K R Muir

  The British journal of nutrition. 04/2008; 99(3):667-73.

  Little is known about the aetiology of brain tumours. One putative factor suggested from animal models is a protective effect of dietary Zn. We tested the hypothesis that increased compared with lowLittle is known about the aetiology of brain tumours. One putative factor suggested from animal models is a protective effect of dietary Zn. We tested the hypothesis that increased compared with low dietary Zn intake is protective against brain tumour development. We conducted a population-based case-control study in the UK, of adults aged 18-69 years, between 2001 and 2004 aiming to identify possible risk factors. Dietary information was collected from 637 cases diagnosed with a glioma or meningioma, and 876 controls. Data were obtained from a self-completed FFQ. Multivariate logistic regression analysis was conducted, adjusting for socio-demographic factors, season of questionnaire return, multivitamin supplementation and energy intake. Although a weak protective effect was observed for the third quartile of intake (normal compared with low intake) in the meningioma group, this was limited to the specific brain tumour subtype and quartile, and was not significant after also adjusting for intake of other elements. Overall there was no significant effect of Zn intake. No association or dose-response relationship was observed between increased compared with low Zn intake and risk of glioma or meningioma.

• Index to ring finger length ratio and the risk of osteoarthritis.

  Authors: W Zhang, J Robertson, S Doherty, J J Liu, R A Maciewicz, K R Muir, M Doherty

  Arthritis and rheumatism. 02/2008; 58(1):137-44.

  OBJECTIVE: To determine the relationship between the index to ring finger (2D:4D) length ratio and the risk of knee and hip osteoarthritis (OA). METHODS: We conducted a case-control study, in whichOBJECTIVE: To determine the relationship between the index to ring finger (2D:4D) length ratio and the risk of knee and hip osteoarthritis (OA). METHODS: We conducted a case-control study, in which cases with persistent symptoms and radiographic evidence of knee or hip OA were compared with controls with no symptoms and no radiographic evidence of knee or hip OA. Hand radiographs were visually classified as type 1 (index finger longer than the ring finger), type 2 (index finger equal to the ring finger), or type 3 (index finger shorter than the ring finger). The 2D:4D phalangeal and metacarpal length ratios were measured separately. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated and adjusted for possible confounding factors using a logistic regression model. RESULTS: Of 2,049 cases, 1,013 had radiographic evidence of knee OA and 995 had hip OA. Of 1,123 controls, 836 had no knee OA and 1,050 had no hip OA. The type 3 finger pattern was associated with knee OA (OR 1.94, 95% CI 1.54-2.44), and the risk was greater in women (OR 3.05, 95% CI 2.08-4.47) than in men (OR 1.45, 95% CI 1.08-1.95). There was a dose-response relationship between both 2D:4D phalangeal and metacarpal length ratios and the risk of knee OA. The risk of hip OA was inconsistent. CONCLUSION: Compared with types 1 and 2, the type 3 "male" pattern 2D:4D length ratio is associated with OA, especially knee OA. The risk is independent of other major OA risk factors.

• Radiographic assessment of the index to ring finger ratio (2D:4D) in adults.

  Authors: J Robertson, W Zhang, J J Liu, K R Muir, R A Maciewicz, M Doherty

  Journal of anatomy. 01/2008; 212(1):42-8.

  The smaller index to ring finger (2D:4D) ratio has been considered as a 'male finger pattern' and is associated with sporting ability and a number of conditions. However, the ratio may vary accordingThe smaller index to ring finger (2D:4D) ratio has been considered as a 'male finger pattern' and is associated with sporting ability and a number of conditions. However, the ratio may vary according to what is measured, the hand selected and the method used. This study aimed to determine: (1) which bones (phalanges, metacarpals or both) account for variation in the 2D:4D ratio; (2) whether the ratio shows right-left symmetry or relates to hand dominance; and (3) the correlation between visual classification and measured determinations of the ratio based on radiographs. Hand radiographs obtained as part of a large osteoarthritis genetic study were examined. Each hand was classified visually into three types according to the relative length of the index and ring finger: Type 1 (index longer than ring), Type 2 (index = ring) and Type 3 (index shorter than ring). For both index and ring fingers we measured (1) from base of proximal to tip of distal phalanx and (2) metacarpal length. Reproducibility of the classification and measurements were examined using kappa and intraclass correlation coefficient; symmetry between left and right hands was examined using Bland and Altman's agreement analysis; and correlation between visual classification and 2D:4D ratio data was analysed using the anova linearity test. Data were obtained from 3172 radiographs (1636 men, 1536 women; mean age 67 +/- 7.9 years, range 45-86 years). Prevalence of Type 3 hand was 61% in men and 37% in women (P < 0.001). Men had smaller 2D:4D ratios than women for phalanges (0.908 versus 0.922, P < 0.01), metacarpals (1.152 versus 1.157, P < 0.01) and the sum of phalanges plus metacarpals (1.005 versus 1.015, P < 0.01). The mean difference between right and left was -0.001 (95% limit of agreement -0.035, 0.032) for the phalangeal ratio and 0.003 (95% limit of agreement -0.051 to 0.057) for the metacarpal ratio. The 2D:4D ratio did not associate with handedness or age. There was a linear trend between the visual classification of hand type and the 2D:4D ratio data (P < 0.001). More technical difficulties (due to positioning, finger trauma, osteoarthritis) were encountered with the phalangeal ratio and visual categorization than with the metacarpal ratio: the latter could be measured in 98.7% of the study population. We concluded that measured 2D:4D ratios and visual categorization can be derived from hand radiographs. The phalanges and metacarpals both contribute to the variation in 2D:4D ratio with smaller ratios observed in men than in women. The ratio is symmetrical with only very small differences between right and left hands. Visual classification may be a useful simple tool for future epidemiological studies but is more prone to bias from positioning than direct measurement. If radiographs are used for this purpose, we recommend the metacarpal ratio with measurement of a single index hand or an average of both as it is least affected by bias from malpositioning, trauma or common joint disease.

• Thymidylate synthase polymorphisms, folate and B-vitamin intake, and risk of colorectal adenoma.

  Authors: R A Hubner, J F Liu, G S Sellick, R F A Logan, R S Houlston, K R Muir

  British journal of cancer. 11/2007; 97(10):1449-56.

  The effects of polymorphisms in genes coding for key folate metabolism enzymes such as thymidylate synthetase (TS) on colorectal neoplasia risk are likely to be influenced by gene-gene andThe effects of polymorphisms in genes coding for key folate metabolism enzymes such as thymidylate synthetase (TS) on colorectal neoplasia risk are likely to be influenced by gene-gene and gene-nutrient interactions. We investigated the combined effects of three polymorphisms in the TS gene region, TSER, TS 3R G>C, and TS 1494del6, dietary intakes of folate and other B vitamins, and genotype for other folate metabolism variants, in a colorectal adenoma (CRA) case-control study. Individuals homozygous for TS 1494del6 del/del were at significantly reduced CRA risk compared to those with either ins/del or ins/ins genotypes (odds ratio 0.52; 95% confidence interval: 0.31-0.85, P=0.009). We also observed evidence of interactions between TS 1494del6 genotype and intake of folate, and vitamins B6 and B12, and MTHFR C677T genotype, with the reduction in risk in del/del homozygotes being largely confined to individuals with high nutrient intakes and MTHFR 677CC genotype (P interaction=0.01, 0.006, 0.03, and 0.07, respectively). TSER genotype, when considered either alone or in combination with TS 3R G>C genotype, did not significantly influence CRA risk. These findings support a role for TS in colorectal carcinogenesis, and provide further evidence that functional polymorphisms in folate metabolism genes act as low-risk alleles for colorectal neoplasia and participate in complex gene-gene and gene-nutrient interactions.

• History of allergic disease and risk of meningioma.

  Authors: M J Schoemaker, A J Swerdlow, S J Hepworth, M van Tongeren, K R Muir, P A McKinney

  American journal of epidemiology. 03/2007; 165(5):477-85.

  Epidemiologic studies have consistently shown inverse associations of allergic disease with risk of glioma, but it is unclear whether this association also applies to meningioma. The authorsEpidemiologic studies have consistently shown inverse associations of allergic disease with risk of glioma, but it is unclear whether this association also applies to meningioma. The authors conducted a pooled analysis of meningioma risk in relation to a history of allergic disease based on data from two population-based, case-control studies with 475 cases and 1,716 controls in the United Kingdom (2001-2004). Meningioma risk was significantly reduced in relation to self-reported, physician-diagnosed allergic disease (odds ratio = 0.76, 95% confidence interval (CI): 0.61, 0.96) but was nonsignificantly reduced for individual conditions: asthma (odds ratio = 0.85, 95% CI: 0.61, 1.18), hay fever (odds ratio = 0.81, 95% CI: 0.62, 1.06), and eczema (odds ratio = 0.72, 95% CI: 0.51, 1.02). Risk reductions were greatest for asthma (odds ratio = 0.43, 95% CI: 0.21, 0.89) and hay fever (odds ratio = 0.50, 95% CI: 0.25, 1.00) with an early age at onset (<10 years) and for eczema (odds ratio = 0.46, 95% CI: 0.21, 1.07) with an onset at ages 10-19 years; they were near unity for onset in adulthood. This study suggests an inverse association between a history of allergies and meningioma risk, but with smaller risk reductions than for glioma. The reasons for this association need clarification, as well as an etiologic explanation. Consideration also needs to be given to confounding or bias.

• The relationship between body mass index and health-related quality of life: comparing the EQ-5D, EuroQol VAS and SF-6D.

  Authors: T H Sach, G.R. Barton, M Doherty, K R Muir, C Jenkinson, A J Avery

  International journal of obesity (2005). 02/2007; 31(1):189-96.

  BACKGROUND: No other studies have compared the relationship between body mass index (BMI) and health-related quality of life (HRQL) on more than one utility measure. Estimating the HRQL effects ofBACKGROUND: No other studies have compared the relationship between body mass index (BMI) and health-related quality of life (HRQL) on more than one utility measure. Estimating the HRQL effects of obesity on a (common) utility scale enables the relative cost-effectiveness of interventions designed to alleviate obesity to be estimated. OBJECTIVE: To examine the relationship between BMI and HRQL according to the EQ-5D, EuroQol visual analogue scale (EQ-VAS) and SF-6D. METHODS: Patients aged >/=45 years at one UK general practice were asked to complete the EQ-5D, EQ-VAS, SF-36 questionnaire (used to derive the SF-6D), and information on their characteristics and co-morbidity. Body mass index was categorized according to the World Health Organization (WHO) recommendations. Regression analysis was used to compare the HRQL of normal BMI patients to the HRQL of patients in other BMI categories, while controlling for patient characteristics and co-morbidity. RESULTS: A total of 1865 patients responded (67%), mean BMI 26.0 kg/m(2), 16% obese (BMI>/=30). Patients with back pain, hip pain, knee pain, asthma, diabetes or osteoarthritis were also significantly more likely to be obese. After controlling for other factors, compared to normal BMI patients, obese patients had a lower HRQL according to the EQ-5D (P<0.01), EQ-VAS (P<0.001) and SF-6D (P<0.001). Pre-obese patients were not estimated to have a significantly lower HRQL, and underweight patients were only estimated to have a significantly lower HRQL according to the SF-6D. These results arose because, on the EQ-5D, obese patients were found to have significantly more problems with mobility and pain, compared to physical functioning, social functioning and role limitations on the SF-6D. Whereas, according to the SF-6D, underweight patients had significantly more problems on the dimension of role limitation. CONCLUSION: The EQ-5D, EQ-VAS and SF-6D were in agreement that, relative to a normal BMI, obesity is associated with a lower HRQL, even after controlling for patient characteristics and co-morbidity. These three measures are thereby sensitive to the HRQL effects of obesity and can be used to estimate the cost-effectiveness of interventions designed to alleviate obesity.

• Assigning exposure to pesticides and solvents from self-reports collected by a computer assisted personal interview and expert assessment of job codes: the UK Adult Brain Tumour Study.

  Authors: S J Hepworth, A Bolton, R C Parslow, M van Tongeren, K R Muir, P A McKinney

  Occupational and environmental medicine. 05/2006; 63(4):267-72.

  OBJECTIVES: To compare assignment of occupational pesticide and solvent exposure using self-reported data collected by a computer assisted personal interview (CAPI) with exposure based on expertOBJECTIVES: To compare assignment of occupational pesticide and solvent exposure using self-reported data collected by a computer assisted personal interview (CAPI) with exposure based on expert assessment of job codes. To discuss the advantages and disadvantages of using a CAPI to collect individual occupational exposure data. METHODS: Between 2001 and 2004, 1495 participants were interviewed using a CAPI for a case-control study of adult brain tumours and acoustic neuromas. Two types of occupational data were collected: (1) a full history, including job title from which a job code was assigned from the Standard Occupational Classification; and (2) specific details on pesticide and solvent exposure reported by participants. Study members' experiences of using the CAPI were recorded and advantages and disadvantages summarised. RESULTS: Of 7192 jobs recorded, the prevalence of self-reported exposure was 1.3% for pesticides and 11.5% for solvents. Comparing this with exposure expertly assessed from job titles showed 53.6% and 45.8% concordance for pesticides and solvents respectively. Advantages of the CAPI include no data entry stage, automatic input validation, and a reduction in interviewer bias. Disadvantages include an adverse effect on study implementation as a consequence of resources required for programming and difficulties encountered with data management prior to analysis. CONCLUSIONS: Different methods of exposure assessment derive different exposure levels for pesticide and solvent exposure at work. Agreement between self-reported and expert assessment of exposure was greater for pesticides compared to solvents. The advantages of using a CAPI for the collection of complex data outweigh the disadvantages for interviewers and data quality but using such a method requires extra resources at the study outset.

• Cost effectiveness of a two-year home exercise program for the treatment of knee pain.

  Authors: K S Thomas, P Miller, M Doherty, K R Muir, A C Jones, S C O'Reilly

  Arthritis and rheumatism. 06/2005; 53(3):388-94.

  OBJECTIVE: To assess the cost effectiveness of a 2-year home exercise program for the treatment of knee pain. METHODS: A total of 759 adults aged > or = 45 years were randomized to receive exerciseOBJECTIVE: To assess the cost effectiveness of a 2-year home exercise program for the treatment of knee pain. METHODS: A total of 759 adults aged > or = 45 years were randomized to receive exercise therapy, monthly telephone contact, exercise therapy and telephone contact, or no intervention. Efficacy was measured using self-reported knee pain at 2 years. Costs to both the National Health Service and to the patient were included. RESULTS: Exercise therapy was associated with higher costs and better effectiveness. Direct costs for the interventions were pound 112 for the exercise program and pound 61 for the monthly telephone support. Participants allocated to receive exercise therapy were significantly more likely to incur higher medical costs than those in the no-exercise groups (mean difference pound 225; 95% confidence interval pound 218, pound 232; P < 0.001). CONCLUSION: Exercise therapy is associated with improvements in knee pain, but the cost of delivering the exercise program is unlikely to be offset by any reduction in medical resource use.

• The role of occupational and environmental exposures in the aetiology of acquired severe aplastic anaemia: a case control investigation.

  Authors: K R Muir, C E D Chilvers, C Harriss, L Coulson, M Grainge, P Darbyshire, C Geary, J Hows, J Marsh, T Rutherford, M Taylor, E C Gordon-Smith

  British journal of haematology. 12/2003; 123(5):906-14.

  Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplasticAplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview-based case-control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged < or =75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age- and sex-matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2.51, 95% confidence interval (CI) 1.02-12.01], particularly for woodworm treatment (OR = 5.1, 95% CI 1.5-17.4). This study identified significant risks associated with self-reported exposure to solvents, radiation and pesticides in the workplace. Self-reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature.

• Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial.

  Authors: K S Thomas, K R Muir, M Doherty, A C Jones, S C O'Reilly, E J Bassey

  BMJ (Clinical research ed.). 10/2002; 325(7367):752.

  OBJECTIVES: To determine whether a home based exercise programme can improve outcomes in patients with knee pain. DESIGN: Pragmatic, factorial randomised controlled trial of two years' duration.OBJECTIVES: To determine whether a home based exercise programme can improve outcomes in patients with knee pain. DESIGN: Pragmatic, factorial randomised controlled trial of two years' duration. SETTING: Two general practices in Nottingham. PARTICIPANTS: 786 men and women aged >/=45 years with self reported knee pain. Interventions: Participants were randomised to four groups to receive exercise therapy, monthly telephone contact, exercise therapy plus telephone contact, or no intervention. Patients in the no intervention and combined exercise and telephone groups were randomised to receive or not receive a placebo health food tablet. MAIN OUTCOME MEASURES: Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities (WOMAC) osteoarthritis index at two years. Secondary outcomes included knee specific physical function and stiffness (scored on WOMAC index), general physical function (scored on SF-36 questionnaire), psychological outlook (scored on hospital anxiety and depression scale), and isometric muscle strength. RESULTS: 600 (76.3%) participants completed the study. At 24 months, highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups (mean difference -0.82, 95% confidence interval -1.3 to -0.3). Similar improvements were observed at 6, 12, and 18 months. Regular telephone contact alone did not reduce pain. The reduction in pain was greater the closer patients adhered to the exercise plan. CONCLUSIONS: A simple home based exercise programme can significantly reduce knee pain. The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist.

• Long-term outcome after tibial shaft fracture: is malunion important?

  Authors: S A Milner, T R C Davis, K R Muir, D C Greenwood, M Doherty

  The Journal of bone and joint surgery. American volume. 06/2002; 84-A(6):971-80.

  BACKGROUND: Fractures of the shaft of the tibia often heal with some angulation. Although there is biomechanical evidence that such angulation alters load transmission through the joints of the lowerBACKGROUND: Fractures of the shaft of the tibia often heal with some angulation. Although there is biomechanical evidence that such angulation alters load transmission through the joints of the lower limb, it is not clear whether it can eventually lead to osteoarthritis. METHODS: One hundred and sixty-four individuals who had sustained a tibial shaft fracture were assessed in a research clinic thirty to forty-three years after the injury. The subjects were evaluated with regard to self-reported lower limb joint pain, stiffness, and disability (assessed with the Western Ontario and McMaster Universities [WOMAC] osteoarthritis questionnaire); clinical signs of osteoarthritis; and radiographic evidence of osteophytes and joint-space narrowing in the knees, ankles, and subtalar joints. RESULTS: Twenty-two (15%) of the 151 subjects who reported no other knee injury reported at least moderate knee pain, and eight (6%) of the 145 subjects who reported no other ankle injury reported at least moderate ankle pain. Seventeen (13%) of the 135 subjects who reported no other knee or ankle injury reported at least moderate disability. The ipsilateral side demonstrated a higher prevalence than the contralateral side in terms of pain with passive ankle movement (nineteen versus nine subjects, p = 0.02), pain with passive subtalar movement (fifteen versus four subjects, p = 0.01), and radiographic signs of ankle joint space narrowing (twelve subjects versus one subject, p = 0.0055). Knee osteoarthritis was frequently bilateral. Forty-seven fractures (29%) healed with coronal angulation of > or = 5 degrees. Apart from an association between shortening of > or = 10 mm and self-reported knee pain (p = 0.016), there were no significant univariate associations between these malunions and the development of osteoarthritis. Seventeen (15%) of 114 eligible subjects had overall malalignment of the lower limb, defined as a hip-knee-ankle angle outside the normal range of 6.25 degrees of varus to 4.75 degrees of valgus. This malalignment was due to the fracture malunion in nine subjects and predated the fracture in eight. In limbs with varus or valgus malalignment, there was an excess of subtalar stiffness (p = 0.04) and a nonsignificant trend toward more frequent knee pain. In limbs with varus malalignment, there was a nonsignificant trend toward more frequent radiographic evidence of osteoarthritis in the medial compartment of the knee joint. Most of the subjects in whom osteoarthritis was observed had normal overall alignment of the lower limb. CONCLUSIONS: The thirty-year outcome after a tibial shaft fracture is usually good, although mild osteoarthritis is common. Fracture malunion is not the cause of the higher prevalence of symptomatic ankle and subtalar osteoarthritis on the side of the fracture. Although varus malalignment of the lower limb occurs occasionally and may cause osteoarthritis in the medial compartment of the knee, other factors are more important in causing osteoarthritis after a tibial shaft fracture.

• A case-control study to investigate the relation between low and moderate levels of physical activity and osteoarthritis of the knee using data collected as part of the Allied Dunbar National Fitness Survey.

  Authors: A J Sutton, K R Muir, S Mockett, P Fentem

  Annals of the rheumatic diseases. 09/2001; 60(8):756-64.

  BACKGROUND: Physical activity is being recommended as an intervention for seemingly almost universal improvements to health. A potential concern with this recommendation for increased exercise isBACKGROUND: Physical activity is being recommended as an intervention for seemingly almost universal improvements to health. A potential concern with this recommendation for increased exercise is that some believe increased levels of activity may lead to increased incidence of osteoarthritis of the knee (knee OA), as a result of accelerated "wear and tear" of the major joints. OBJECTIVE: To investigate the hypothesis that the occurrence of knee OA may be related to the duration of participation in some forms of sport and active recreation. METHODS: The relation between habitual exercise, reported by a cross section of people surveyed in England, and self reported knee OA was investigated. Data were derived from the Allied Dunbar National Fitness Survey (1990-91). A matched retrospective case-control design was used and a new exposure classification system which categorised different grades of activities for different time periods for each subject's lifetime participation in regular physical activities was developed. Additional data on knee injuries sustained and bodily composition were also included in a multivariate analysis. RESULTS: From 4316 people originally interviewed, 216 eligible cases (66 men, 150 women) were identified (mean age 57.1). Each case was matched to four controls. When habitual sport/exercise participation were examined during a subject's life, only exposure to regular long walks and being physically active between the ages of 20 and 24 suggested any association with developing knee OA later in life. The only strong association found was a greatly increased risk of knee OA having previously sustained a knee injury (p<0.01, odds ratio 8.0 (95% confidence interval 2.0 to 32.0)). CONCLUSIONS: There was little evidence to suggest that increased levels of regular physical activity throughout life lead to an increased risk of knee OA later in life. Previous knee injury was associated with an increased risk of knee OA. Additionally, most injuries were caused through participation in physical activities. Hence, when deciding on participation in activities, it is worth taking the likelihood of joint injury into consideration, as the chance of injury is greater in some activities than others.

• Occupation and knee pain: a community study.

  Authors: S C O'Reilly, K R Muir, M Doherty

  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 04/2000; 8(2):78-81.

  OBJECTIVE: To examine the relationship between knee pain and occupation in a community setting. DESIGN: A postal survey was sent to 4057 men and women aged 40-80. Subjects were asked about chronicOBJECTIVE: To examine the relationship between knee pain and occupation in a community setting. DESIGN: A postal survey was sent to 4057 men and women aged 40-80. Subjects were asked about chronic knee pain. A question concerning job title and industry was included in addition to demographic details. Prevalence of knee pain and odds ratios for pain were calculated for the most common occupational groups. RESULTS: Response was 82% and overall prevalence of knee pain was 28%. Highest prevalence of pain was seen in carpenters and miners. Increased odds for pain (adjusted for age, gender, body mass index, social class, smoking history and psychological distress) were apparent in carpenters (4.6, 95% confidence intervals 1.9-11.1), miners (1.9, 95%CI 1.3-2.8) and construction workers (2.4, 95%CI 1.4-4.1). CONCLUSIONS: Increased risk of knee pain is apparent in miners, construction workers and carpenters; occupations which are likely to involve knee bending and possibly heavy lifting.

• Racial group, socioeconomic status, and the development of persistent proteinuria in systemic lupus erythematosus.

  Authors: N D Hopkinson, C Jenkinson, K R Muir, M Doherty, R J Powell

  Annals of the rheumatic diseases. 02/2000; 59(2):116-9.

  OBJECTIVES: Systemic lupus erythematosus (SLE) patients of Afro-Caribbean and Asian origin living in the United Kingdom have a more severe spectrum of disease compared with the white population butOBJECTIVES: Systemic lupus erythematosus (SLE) patients of Afro-Caribbean and Asian origin living in the United Kingdom have a more severe spectrum of disease compared with the white population but whether this is attributable to genetic host factors or environmental factors is unclear. This study examines time from first symptom to onset of persistent proteinuria, as a marker of renal disease, to assess which factors are important. METHODS: The 189 patients studied were ascertained using multiple methods and included 161 white, 22 Afro-Caribbean and six Asian patients. Time of first observation of persistent proteinuria (>/=0.5 g/day) was taken as onset of renal SLE. Initial univariate analysis to determine which factors are associated with onset of renal disease was followed by using a Cox's proportional hazards regression model enabling analysis of several prognostic factors at the same time. Variables included three measures of socioeconomic status, ethnic group and the presence or absence of different autoantibodies. RESULTS: There was no effect from any socioeconomic variable. Using forwards stepwise selection, the following had independent effects (p<0.05) on the development of renal SLE: Afro-Caribbean race (hazard rate ratio 4.4 (1.9-10.2), compared with white population); and the presence of IgG anti-cardiolipin antibodies (hazard rate ratio 2.6 (1.2-5.7)). CONCLUSION: Differing socioeconomic factors do not explain the increased frequency of lupus nephritis in Afro-Caribbean patients with SLE, but rather there are important genetic or other host differences. The independent effect of IgG anti-cardiolipin antibodies warrants further investigation.

• Aspirin, NSAIDs and colorectal cancer--what do the epidemiological studies show and what do they tell us about the modus operandi?

  Authors: K R Muir, R F Logan

  Apoptosis : an international journal on programmed cell death. 11/1999; 4(5):389-96.

  A large number of observational epidemiological studies show that regular use of aspirin and other NSAID's is associated with a reduction in the risk of developing both colorectal adenomas andA large number of observational epidemiological studies show that regular use of aspirin and other NSAID's is associated with a reduction in the risk of developing both colorectal adenomas and cancer. Furthermore, the prodrug sulindac appears clinically to be able to reduce and reverse the growth of existing polyps in familial adenomatous polyposis (FAP). For aspirin and NSAID's the dose, duration of effect and length of protection seen after cessation remain to be fully established. The available data for aspirin suggest that doses higher than those needed for heart disease prevention are required. It is also likely that the drug needs to be taken continuously for a number of years. With regards to randomised controlled trials to evaluate chemopreventive strategies there are so far only limited data available. The only trial reported to date found no effect but employed a relatively low dose of 325 mg of aspirin every other day and the randomised intervention period was relatively short (5 years). Further trials of intermediate endpoints (adenomas) are currently underway in the UK and USA and are employing higher doses of aspirin. Randomised clinical studies of sulindac have been more encouraging demonstrating that it is a useful drug for therapeutic applications in FAP patients. Its relatively greater side effects, however, prevent its consideration for primary chemoprevention. The mechanisms by which NSAID's act are still sought. Strategies for possible primary and secondary chemoprevention in humans also require evaluation.

• Pregnancy outcome and family size in systemic lupus erythematosus: a case-control study.

  Authors: C J Hardy, B P Palmer, S J Morton, K R Muir, R J Powell

  Rheumatology (Oxford, England). 06/1999; 38(6):559-63.

  OBJECTIVE: To establish pregnancy outcomes and family size in a geographically defined population of systemic lupus erythematosus (SLE) patients. METHODS: One hundred and thirty-eight SLE patientsOBJECTIVE: To establish pregnancy outcomes and family size in a geographically defined population of systemic lupus erythematosus (SLE) patients. METHODS: One hundred and thirty-eight SLE patients (all women satisfying at least four American Rheumatism Association criteria) and 276 age-matched female controls, from the Nottingham area, were interviewed by a single investigator. Demographic details and maternity histories were obtained, and the data collected were analysed statistically to calculate odds ratios (ORs) for risk of fetal loss (through miscarriage, stillbirth and abortion). Family size was also determined in White and non-White cases and controls. RESULTS: Women with SLE are at greater risk of spontaneous fetal loss than their healthy counterparts (OR = 2.21, 95% CI 1.46-3.35, P < 0.01) and they are more likely than controls to have a surgical abortion (OR 2.44, 95%, CI 1.22-4.87, P = 0.01). The excess risk of both of these outcomes exists both before and after diagnosis of SLE. The median number of children in White and non-White families of cases and controls is the same, i.e. two. White women with SLE, however, appear less likely than controls to have more than two children, whereas non-White lupus women tend to retain their propensity to have larger families, i.e. more than two children. CONCLUSIONS: We confirm that lupus women who have, or later develop, SLE are at greater risk of pregnancy loss by spontaneous or surgical means. We have also shown that race, and the inherent differences in social and cultural influences, appears to be an important determinant of ultimate family size; White women with SLE have fewer children than controls, whilst non-White lupus women tend to have larger families.