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Biomedical subjects

K Muir

Publications and source records attributed to K Muir.

At least 19 recordsLinked to original sources

Mobile phone use and risk of acoustic neuroma: results of the Interphone case-control study in five North European countries.

There is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of the acoustic nerve to the handset. We conducted, to a shared protocol, six population-based case-control studies in four Nordic countries and the UK to assess the risk of acoustic neuroma in relation to mobile phone use. Data were collected by personal interview from 678 cases of acoustic neuroma and 3553 controls. The risk of acoustic neuroma in relation to regular mobile phone use in the pooled data set was not raised (odds ratio (OR) = 0.9, 95% confidence interval (CI): 0.7-1.1). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR = 1.8, 95% CI: 1.1-3.1). The study suggests that there is no substantial risk of acoustic neuroma in the first decade after starting mobile phone use. However, an increase in risk after longer term use or after a longer lag period could not be ruled out.

Case-Control Studies↗

ATM polymorphisms as risk factors for prostate cancer development.

The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17-3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk.

Adult↗

Breast cancer incidence and its possible spatial association with pesticide application in two counties of England.

BACKGROUND: This study examines the spatial distribution of breast cancer incidence in Lincolnshire and Leicestershire, and its association with the application of selected pesticides. METHODS: The Black-White (BW) join-count statistic and Moran I coefficient were used to investigate the localized distribution of breast cancer. Linear regression techniques were applied to examine the association between the breast cancer incidence rate and pesticide application. RESULTS: The results from the BW join-count test and the Moran I coefficient test showed no overall evidence of localized distribution, 'clusters', of breast cancer. The regression analyses showed no sign of spatial association between breast cancer and application of pesticides in the urban areas as expected. The findings, however, did reveal a spatial association between the breast cancer incidence rates and the application of three selected pesticides [Aldicarb, Atrazine and Lindane (thought to potentially mimic oestrogen)] in rural Leicestershire. No such association was seen in Lincolnshire. CONCLUSIONS: Pesticides vary significantly in their spatial application. Overall, consistent associations between breast cancer incidence rates and the selected pesticides were not found, although the ecological study design has limitations and these are discussed. This approach is able to rule out strong associations; assessment of smaller risk would require a large and expensive study in individuals. The results of this study, although derived in the UK, have significance to the debate concerning the possibility of environmental compounds that mimic oestrogen and their consequences for human health.

Aged↗

Influence of radiographic phenotype on risk of hip osteoarthritis within families.

OBJECTIVE: To determine whether the magnitude of the genetic influence on the development of hip osteoarthritis (OA) varies according to the radiographic phenotype within families. PARTICIPANTS AND METHODS: 331 families in which at least one sibling (index participant) had undergone total hip replacement for OA and whose preoperative x ray findings were available; 505 siblings of these index participants, who have high exposure to genetic risk of hip OA; and 1718 participants who had previously undergone intravenous urography, representative of the average general population exposure to genetic risk. Prevalence of hip OA was determined by individual radiographic features and minimum hip joint space. OA phenotype was partitioned according to pattern of femoral head migration and osteophyte bone response. Age adjusted odds ratios for hip OA in siblings, stratified according to phenotypic pattern in their index sibling, were assessed by unconditional logistic regression. RESULTS: The superior pattern of femoral head migration was more common in men, and the axial pattern more common in women. A poor bone response (absent osteophytosis) was associated with an indeterminate pattern of migration. The age adjusted odds ratios for definite hip OA were twofold higher in siblings of index participants who had no osteophyte response than in siblings whose index case had any degree of osteophyte (OR 2.05, 95% CI 1.12 to 3.76). The risk of the siblings from these families having undergone hip replacement themselves was threefold higher. Patterns of migration and bone response were not concordant within families, even among same sex siblings. CONCLUSION: Careful phenotypic characterisation is essential for genetic studies of hip OA. The results of these studies are likely to be influenced by the phenotypic pattern of hip disease, particularly osteophyte bone response.

Aged↗

Genetic risk of knee osteoarthritis: a sibling study.

OBJECTIVES: To determine whether there is a genetic contribution to knee osteoarthritis (OA) as defined by structural change on plain radiographs. DESIGN: Sibling study. Comparison of knee OA prevalence in the community with knee OA prevalence among siblings of index cases with knee OA. SUBJECTS: 490 knee OA index cases listed for total knee replacement and 737 of their siblings aged >40 years, 1729 community subjects aged >40 years. MAIN OUTCOME MEASURE: Odds ratio for radiographic knee OA in siblings v community participants. RESULTS: The age, sex, and knee pain adjusted odds ratios in siblings were 2.9 (95% confidence interval 2.3 to 3.7) for tibiofemoral OA and 1.7 (1.4 to 2.2) for patellofemoral OA. This difference remained after adjustment for important environmental risk factors. The heritability estimate for knee OA was 0.62. CONCLUSIONS: Siblings are at increased risk of knee OA in comparison with the general population. This is likely to be due to genetic factors.

Adult↗

UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte.

OBJECTIVES: (1) To estimate the prevalence of chondrocalcinosis (CC) in the community and to characterise its compartmental distribution within the knee. (2) To investigate the associations between CC and individual radiographic features of osteoarthritis (OA) at the tibiofemoral joint (TFJ) and patellofemoral joint (PFJ). METHODS: From three community questionnaire studies investigating the prevalence of knee pain, standing anteroposterior and skyline radiographs were obtained on 1727 subjects (1084 women, 643 men; mean age 63.7; 999 (58%) with knee pain). A single observer recorded the presence and site of CC and graded osteophyte and joint space narrowing (JSN) using a line atlas. "OA" was globally defined as the presence of definite osteophyte and definite JSN. Minimum joint space width (JSW) was measured to 0.1 mm with a metered dial caliper RESULTS: (1) The crude prevalence of CC was 7.0% (95% confidence interval (CI) 5.8 to 8.2). This showed a strong association with age. The age adjusted odds ratio (aOR) for CC in women v men was 0.79 (95% CI 0.52 to 1.12). The age, sex, and knee pain standardised estimate for those aged >40 in Nottingham, UK was 4.5%. Patellofemoral CC was seen in only nine cases, all with tibiofemoral CC. (2) The age-sex aOR for the association between CC and OA was 2.08 at the PFJ (1.38 to 3.12) and 2.00 (1.11 to 3.60) at the TFJ. There was no association between measured JSW and CC at either the PFJ or TFJ. Both total osteophyte score and total number of sites with osteophyte were positively associated with CC; aOR for the upper quartile was 2.40 (1.48 to 3.90) and 1.94 (1.15 to 3.26), respectively. An association between CC and diuretic use was also demonstrated (aOR=2.07, 1.02 to 4.19). CONCLUSIONS: In this large UK community study the age, sex, and knee pain adjusted prevalence of CC was 4.5%. There was a strong age association, but no sex predisposition. Patellofemoral CC was uncommon. An association between OA and CC was confirmed, but this appears to operate through an association with osteophyte rather than JSN. The new association between CC and diuretic use might theoretically be explained by diuretic induced hypomagnesaemia.

Age Distribution↗

Exposure to power frequency electric fields and the risk of childhood cancer in the UK.

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.

Adolescent↗

A nurse-delivered advice intervention can reduce chronic non-steroidal anti-inflammatory drug use in general practice: a randomized controlled trial.

OBJECTIVE: To find out whether a nurse-delivered educational package can reduce chronic oral non-steroidal anti-inflammatory drug (NSAID) usage in general practice. METHOD: A prospective randomized controlled trial with assessment of economic cost/benefits was carried out in five general practices in Nottinghamshire with computerized prescribing systems, representing a mix of rural/urban and fundholding/non-fundholding practices. Patients suffering from non-malignant, non-inflammatory musculoskeletal pain received repeat prescriptions for oral NSAIDs. Two hundred and twenty-two patients were randomized to a control group (simple advice regarding NSAID use) or an intervention group (asked to withdraw their NSAIDs and employ appropriate alternative drug and non-drug therapies). All advice was supported by patient literature and delivered by a nurse practitioner trained in musculoskeletal assessment. The primary outcome measure was change in NSAID use 6 months after the intervention. Secondary outcome measures were changes in health and quality of life (SF-36 and EQ-5D questionnaires) and drug, health service and patient costs. RESULTS: An extra 28% of patients in the intervention group either stopped taking oral NSAIDs or reduced dosage by > or =50% at 6 months compared with controls. There was no detrimental effect on health and well-being. Oral NSAID prescription costs were significantly lowered in the intervention group but not in the control group. A non-significant increase in total drug prescription costs occurred in both groups. CONCLUSIONS: Nurse-based intervention can reduce chronic NSAID usage and costs in primary care and would be cost-effective if maintained in the long term. This intervention package would be readily applicable in primary care.

Adult↗

Assessment of a genetic contribution to osteoarthritis of the hip: sibling study.

OBJECTIVES: To study the influence of genetics on the development of hip osteoarthritis as determined by structural change on plain radiographs. DESIGN: Sibling study. SETTING: Nottinghamshire, England. PARTICIPANTS: 392 index participants with hip osteoarthritis of sufficient severity to warrant total hip replacement, 604 siblings of the index participants, and 1718 participants who had undergone intravenous urography. MAIN OUTCOME MEASURE: Odds ratios for hip osteoarthritis in siblings. RESULTS: The age adjusted odds ratios in siblings were 4.9 (95% confidence interval, 3.9 to 6.4) for probable hip osteoarthritis and 6.4 (4.5 to 9.1) for definite hip osteoarthritis. These values were not significantly altered by adjusting for other risk factors. CONCLUSION: Siblings have a high risk of hip osteoarthritis as shown by structural changes on plain radiographs. One explanation is that hip osteoarthritis is under strong genetic influence.

Age Distribution↗

Screening for hand osteoarthritis (OA) using a postal survey.

OBJECTIVE: The aim of this study was to determine the feasibility of screening for hand osteoarthritis (OA) using a postal survey. METHODS: Men and women aged 40-79, selected at random from a general practice in Nottingham, were sent a postal survey concerning arm pain. Subjects were asked to identify presence of any nodes, based on a diagrammatic example, and to document specific distal (DIP) and proximal (PIP) nodes. One hundred and thirty-nine subjects were subsequently assessed by a nurse metrologist, blinded to the subjects assessment. Subject-observer agreement was measured by calculating unweighted kappa (kappa). In addition, sensitivity and specificity were calculated, taking observer-identified nodes as the 'gold standard'. Intraobserver reproducibility was assessed on 10 subjects with nodes. RESULTS: Intraobserver reproducibility was reasonable at all sites (kappa>/=0.59). Of the 56 subjects with observer-identified 'any nodes', 40 subjects had correctly identified them (sensitivity 71.4%); with three subjects incorrectly identifying nodes (specificity 96.4%). Corresponding kappa was 0.70. Subject-observer agreement was higher for presence/absence of any DIP nodes than PIP nodes (kappa=0.67 and 0.36 respectively). As with nodes overall, specificity was high (100% and 96.6% respectively). Agreement was generally poor for specific joint involvement. CONCLUSION: A postal survey is a useful screening tool for identifying subjects with nodes. Although sensitivity may not be sufficient to permit assessment of prevalence of hand OA in the community, it has potential applications in terms of identifying and defining cases for further study.

Adult↗

IgE and non-IgE mediated allergic disorders in systemic lupus erythematosus.

OBJECTIVE: To ascertain the prevalence of IgE and non-IgE mediated allergic disorders in patients with systemic lupus erythematosus (SLE). METHODS: 49 SLE cases (all satisfying at least four "Revised ARA Criteria") and 98 healthy, age, and sex matched controls (randomly selected through two urban general practices and one rural general practice) were interviewed by telephone to screen for a history of allergy. Subjects with a history of allergic rhinitis, asthma or atopic eczema then underwent skin prick testing to confirm underlying IgE mediated disease. RESULTS: Analysis of the data by conditional logistic regression revealed no significant difference in frequency of allergic disorders in SLE cases and controls (odds ratio (OR) 0.92, 95% confidence intervals (CI) 0.45, 1.86). In addition a subgroup analysis of subjects with IgE mediated/associated atopic disorders, showed that cases and controls were at a similar risk of having these conditions (OR 0.90, 95% CI 0.41, 1.96). CONCLUSIONS: This study suggests that people with SLE are not at an increased risk of IgE mediated/associated allergic disorders, in contrast with previous reports.

Adult↗

How do economic status and social support influence survival after initial recovery from acute myocardial infarction?

There is much interest in the influence of psychosocial factors and social deprivation on health. This study investigates the influence of economic status (as measured by car-ownership) and social support on survival after acute myocardial infarction (AMI). In addition, the possible influence of stressful life events and satisfaction with home, social and working/retirement life is also assessed. Cases with suspected AMI were identified through the Anglo-Scandinavian Study of Early Thrombolysis (ASSET). 1701 English patients completed a questionnaire. Patients were followed for between 4.7 and 6.3 years, with the single outcome measure being death from all causes. 1283 patients surviving 7 days were included in presented statistical analyses using Cox's regression. After adjusting for a broad range of clinical variables, patients with no car were at approximately 40% higher risk of dying following AMI than car-owners (hazard ratio 1.4, P = 0.007, 95% CI 1.1-1.8). Lack of social contacts or being unmarried were not significantly associated with survival after adjusting for car-ownership and clinical variables. Economic status and survival after AMI are associated. With the dominant psychosocial prognostic indicator in this study being economic status, attention focuses on the growing gap between the socially deprived and the more affluent, and its effects on health.

Aged↗

Urine neopterin: a new parameter for serial monitoring of disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the role of serial measurement of urine neopterin concentration in monitoring the progression of systemic lupus erythematosus (SLE) disease activity scored using the British Isles Lupus Assessment Group (BILAG) index. METHODS: We followed prospectively 68 unselected SLE patients for a total of 464 patient months during which 233 separate assessments were carried out. At each assessment, urine neopterin, determined by high performance liquid chromatography, together with erythrocyte sedimentation rate (ESR) and plasma C3, C4, and C3d were measured and the SLE disease activity scored by a single observer. Serial data sets were analysed using time series modelling techniques. RESULTS: Single time point analysis showed a significant increase in urine neopterin concentrations in 14 patients who suffered flares of their disease during the study period (p = 0.02). Thirty patients with active disease went into disease remission with significant decreases in their urine neopterin values (p = 0.02). In the time series analysis, a statistically significant association was found between serial concentrations of urine neopterin and BILAG score (r = 0.6, p < 0.05); no other study parameter (ESR and serum C3, C4, and C3d) mirrored SLE disease activity as effectively. CONCLUSIONS: This study provides initial evidence that changes in urine concentrations of neopterin are significantly correlated with fluctuations in disease activity over time, scored using the BILAG index, amongst individual patients with SLE. Consequently, serial urine neopterin measurements appear to be clinically useful for monitoring disease activity and may contribute substantially to therapeutic decision making in these patients.

Adult↗

Viral-associated haemophagocytosis with parvovirus-B19-related pancytopenia.

Viral-associated haemophagocyte syndrome in response to infection with human parvovirus B19 was seen in 2 patients with hereditary spherocytosis. Depressed reticulocyte response during acute parvovirus infection is a known cause of hypoproliferative crises in patients with reduced erythrocyte lifespan; the observation of parvovirus-associated haemophagocytosis could account for the pancytopenia that may accompany human parvovirus B19 infection.

Adult↗