The Associations Between Seven Different Types of Physical Activity and the Incidence of Fracture at Seven Sites in Healthy Postmenopausal UK Women.

There is a paucity of information on associations between specific types of physical activity and fracture risk at different sites in otherwise healthy postmenopausal women. Therefore, we examined risk of fracture at seven different sites associated with seven different types of physical activity in the population-based prospective UK Million Women Study. A total of 371,279 postmenopausal women (mean age 59.8 years), rating their health as good or excellent and reporting participation in walking, cycling, gardening, doing housework, yoga, dance, and sports club activities, were followed for site-specific incident fracture through record linkage to national databases on day-case and overnight hospital admissions. Cox regression yielded adjusted relative risks (RRs) and, because of the large number of statistical tests done, 99% confidence intervals (CIs) for fracture at seven different sites in relation to seven different physical activities. During an average follow-up of 12 years, numbers with a first site-specific fracture were as follows: humerus (2341), forearm (1238), wrist (7358), hip (4354), femur (not neck) (617), lower leg (1184), and ankle (3629). For upper limb fractures there was significant heterogeneity across the seven activity types (test for heterogeneity p = 0.004), with gardening more than 1 hour/week associated with a lower risk (RR = 0.91; 99% CI, 0.86 to 0.96; p < 0.0001), whereas cycling more than 1 hour/week was associated with an increased risk (RR = 1.11; 99% CI, 1.00 to 1.23; p = 0.008). For fractures of the lower limb (including hip) there was no significant heterogeneity by type of activity, with significant approximately 5% to 15% reductions in risk associated with most activities, except cycling. For hip fractures, there was no significant heterogeneity by type of activity, but with significant 15% to 20% reductions in risk associated with walking for 1 hour/day and participating in yoga and sporting activities. Physical activity is a modifiable risk factor for fracture, but the effects differ between different types of activities and different fracture sites. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Use of oral bisphosphonates and risk of hospital admission with osteonecrosis of the jaw: Large prospective cohort study in UK women.

About 1 in 10 postmenopausal UK women are currently prescribed oral bisphosphonates, but there are concerns about their adverse effects. Osteonecrosis of the jaw is a recognised uncommon but important side effect of intravenous bisphosphonates, but epidemiological evidence on risk of osteonecrosis of the jaw associated with oral bisphosphonate use is less conclusive. The incidence of hospital admission with osteonecrosis of the jaw was examined among 521,695 Million Women Study participants, aged 64.7 years at baseline. Cox proportional hazards regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) associated with use of oral bisphosphonates in postmenopausal women followed-up by record-linkage to National Health Service hospital admission databases. During mean follow-up of 8.2 years per woman, 100 women were admitted to hospital with first recorded osteonecrosis of the jaw, at mean age 72.4 years. Almost a third (29/100) of the cases had ever-used oral bisphosphonates. Ever-users had a six-fold increased risk of hospital admission for osteonecrosis of the jaw, when compared with never-users (adjusted RR = 6.09, 95% CI 3.83-9.66; p < 0.0001). The relative risk for osteonecrosis of the jaw in never-users of oral bisphosphonates was increased in women with prior cancer (RR = 3.40, 2.22-5.22, p < 0.0001). The estimated absolute risk of hospital admission for osteonecrosis of the jaw over a 5-year period from age 70 to 74 in women without prior cancer was 0.09 per 1000 in never-users and 0.69 per 1000 in ever-users of oral bisphosphonates. In this UK population of postmenopausal women, use of oral bisphosphonates was associated with a 6-fold increased risk of hospital admission with osteonecrosis of the jaw, accounting for around one-third of cases, with an excess risk of about 0.6/1000 users over 5 years.

Associations between specific autoimmune diseases and subsequent dementia: retrospective record-linkage cohort study, UK.

OBJECTIVE: To determine whether hospital admission for autoimmune disease is associated with an elevated risk of future admission for dementia. METHODS: Retrospective, record-linkage cohort study using national hospital care and mortality administrative data, 1999-2012. Cohorts of people admitted to hospital with a range of autoimmune diseases were constructed, along with a control cohort, and followed forward in time to see if they developed dementia. 1 833 827 people were admitted to hospital with an autoimmune disease; the number of people in cohorts for each autoimmune disease ranged from 1019 people in the Goodpasture's syndrome cohort, to 316 043 people in the rheumatoid arthritis cohort. RESULTS: The rate ratio for dementia after admission for an autoimmune disease, compared with the control cohort, was 1.20 (95% CI 1.19 to 1.21). Where dementia type was specified, the rate ratio was 1.06 (1.04 to 1.08) for Alzheimer's disease and 1.28 (1.26 to 1.31) for vascular dementia. Of 25 autoimmune diseases studied, 18 showed significant positive associations with dementia at p<0.05 (with 14 significant at p<0.001) including Addison's disease (1.48, 1.34 to 1.64), multiple sclerosis (1.97, 1.88 to 2.07), psoriasis (1.29, 1.25 to 1.34) and systemic lupus erythematosus (1.46, 1.32 to 1.61). CONCLUSIONS: The associations with vascular dementia may be one component of a broader association between autoimmune diseases and vascular damage. Though findings were significant, effect sizes were small. Clinicians should be aware of the possible coexistence of autoimmune disease and dementia in individuals. Further studies are needed to confirm or refute our findings and to explore possible mechanisms mediating any elevation of risk.

Coexistence of eating disorders and autoimmune diseases: Record linkage cohort study, UK.

OBJECTIVE: Recent research indicates that eating disorders (ED) are associated with type 1 diabetes and Crohn's disease. The aim of this study was to determine whether, in a hospitalized population, a range of autoimmune diseases (AIDs) occurred more often than expected in people with anorexia nervosa (AN) or bulimia nervosa (BN), and whether AIDs elevated the risk of ED. METHOD: Retrospective, record-linkage cohort study using national administrative statistical data on hospital care and mortality in England, 1999-2011. In people admitted when aged 10-44, cohorts of 8,700 females and 651 males with AN, and 4,783 females and 330 males with BN were constructed, along with a control cohort with the same age range. Results were expressed as risk ratios comparing each ED cohort with the control cohort. RESULTS: The overall rate ratio for an AID after admission for AN was 2.04 (95% confidence interval 1.81-2.28) in females, and 1.14 (0.37-2.67) in males; and, for BN, 1.83 (1.56-2.14) in females, and 4.41 (2.11-8.10) in males. Rate ratios for AN after admission for an AID were 3.34 (2.94-3.79) in females, 3.76 (2.06-6.53) in males; and those for BN were 2.57 (2.22-2.97) in females, and 3.10 (1.50-5.90) in males. There were significant associations between ED and several specific individual AIDs. DISCUSSION: Strong associations between ED and specific AIDs exist, although it is not possible from this study to determine if these are causal. Clinicians should be aware of the co-occurrence of these conditions. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:663-672).

Gender identity disorders and multiple sclerosis risk: A national record-linkage study.

BACKGROUND: An altered balance of gonadal hormones in males with gender identity disorders (GIDs) may increase multiple sclerosis (MS) risk both inherently and secondary to treatment in undergoing male-to-female conversion. OBJECTIVE: We investigated any association between GIDs and MS through analysis of record-linked hospital statistics. METHOD: Analysis of English Hospital Episode Statistics, 1999-2012. RESULTS: The adjusted rate ratio (RR) of MS following GIDs in males was 6.63 (95% confidence interval (95% CI) = 1.81-17.01, p = 0.0002). The RR of MS following GIDs in females was 1.44 (95% CI = 0.47-3.37, p = 0.58). CONCLUSION: We report a strong association between GIDs and MS in male-to-females, supporting a potential role for low testosterone and/or feminising hormones on MS risk in males.

Conversion from depression to bipolar disorder in a cohort of young people in England, 1999-2011: A national record linkage study.

OBJECTIVE: To estimate the conversion rate from unipolar depression (ICD10 codes F32-F33) to bipolar disorder (BP) (ICD10 codes F31) in an English national cohort. It was hypothesised that early-onset BP (age <18 years) is a more severe form of the disorder, with a more rapid, and higher rate of conversion from depression to BP. METHOD: This record linkage study used English national Hospital Episode Statistics (HES) covering all NHS inpatient and day case admissions between 1999 and 2011. RESULTS: The overall rate of conversion from depression to BP for all ages was 5.65% (95% CI: 5.48-5.83) over a minimum 4-year follow-up period. The conversion rate from depression to BP increased in a linear manner with age from 10-14 years - 2.21% (95% C: 1.16-4.22) to 30-34 years - 7.06% (95% CI: 6.44-7.55) (F1,23=77.6, p=0.001, R(2)=0.77). The time to conversion was constant across the age range. The rate of conversion was higher in females (6.77%; 95% CI: 6.53-7.02) compared to males, (4.17%; 95% CI: 3.95-4.40) (χ(2)=194, p<0.0001), and in those with psychotic depression 8.12% (95% CI: 7.65-8.62) compared to non-psychotic depression 5.65% (95% CI: 5.48-5.83) (χ(2)=97.0, p<0.0001). LIMITATIONS: The study was limited to hospital discharges and diagnoses were not standardised. CONCLUSIONS: Increasing conversion rate from depression to bipolar disorder with age, and constant time for conversion across the age range does not support the notion that early-onset BP is a more severe form of the disorder.

Risk of dementia in patients hospitalised with type 1 and type 2 diabetes in England, 1998-2011: a retrospective national record linkage cohort study.

AIMS/HYPOTHESIS: Type 2 diabetes increases the risk of subsequent dementia. Our objective was to determine whether a similar risk of subsequent dementia is associated with type 1 diabetes in a large defined population. METHODS: This retrospective cohort study examined national administrative record-linked statistical data on hospital care and mortality in England, 1998-2011. Cohorts of people admitted to hospital when aged 30 or over were constructed: 343,062 people with type 1 diabetes; 1,855,141 people with type 2 diabetes; and a reference cohort. Results were expressed as rate ratios (RR) comparing each diabetes cohort with the control cohort. RESULTS: The overall RR for dementia in people admitted to hospital with type 1 diabetes was 1.65 (95% CI 1.61, 1.68), and for people admitted to hospital with type 2 diabetes was 1.37 (1.35, 1.38). Young age at admission for diabetes appeared to confer a greater rate of subsequent dementia; the RR for dementia in people admitted to hospital with type 1 diabetes aged 30-39 years was 7.10 (4.65, 10.6), which reduced to 4.40 (3.55, 5.40) in those aged 40-49 at admission, and further reduced with increasing age to 1.16 (1.11, 1.20) in those aged 80 or over at admission. A similar pattern was seen with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Type 1 diabetes, as well as type 2 diabetes, may be associated with an elevated risk of subsequent dementia. The risk of dementia varies with age at admission to hospital with diabetes, and appears to be much greater in the young.

Age at obesity and association with subsequent dementia: record linkage study.

OBJECTIVE: Obesity in mid-life may increase the risk of subsequent dementia. Our objective was to study this risk, focusing on differences by age at the time of recording of obesity, in a large defined population. METHODS: A record linkage cohort study was undertaken using national administrative statistical data on hospital care and mortality in England, 1999-2011. A cohort of 451 232 people with obesity and a control cohort was constructed. Results were expressed as age-specific risk ratios comparing the two cohorts. RESULTS: The risk ratio for dementia in people admitted to hospital with obesity aged 30-39 years was significantly increased at 3.5 (95% CI 2.1 to 5.6). Risk ratios for dementia then gradually reduced with increasing age at obesity from 1.7 (95% CI 1.3 to 2.2) in people aged 40-49 years when obesity was first recorded to 1.4 (95% CI 1.3 to 1.5) in those aged 60-69 years. People in their 70s when obesity was recorded had neither an increased nor a reduced risk of subsequent dementia at 0.97 (95% CI 0.93 to 1.01), and those aged ≥80 years had a reduced risk of subsequent dementia at 0.78 (95% CI 0.74 to 0.82). CONCLUSIONS: Obesity is associated with a risk of dementia in a way that appears to vary with age. Investigation of the mechanisms mediating this association might give insights into the biology of both conditions.

Record-linkage studies of the coexistence of epilepsy and bipolar disorder.

PURPOSE: Interest is growing in a possible link between epilepsy and bipolar disorder (BPD). We used two large datasets of hospital admission data to determine whether epilepsy and BPD occur together in the same individuals more commonly than expected. METHODS: We undertook retrospective cohort studies using the Oxford Record Linkage Study (ORLS) and English national linked Hospital Episode Statistics. We constructed a cohort of people in each dataset admitted with epilepsy (without prior admission for BPD), and a control cohort (without prior admission for BPD), and compared their subsequent admission rates for BPD. Conversely, we constructed a cohort of people in each dataset admitted with BPD and a control cohort (both without prior admission for epilepsy), and compared their subsequent admission rates for epilepsy. RESULTS: In the epilepsy cohort, compared with the control cohort, the rate ratio (RR) for BPD was significantly high at 3.0 (95 % confidence interval 1.7-5.1) in the ORLS and 3.6 (3.3-3.9) in the all-England dataset. In the BPD cohort, the RR for epilepsy was 2.2 (1.2-3.7) in the ORLS and 4.2 (4.0-4.4) in the all-England cohort. We found no significant differences between RRs for males and females. CONCLUSIONS: Epilepsy and BPD occur together in individuals more frequently than expected by chance.

Association between cholecystectomy and intestinal cancer: a national record linkage study.

OBJECTIVE: To investigate the risk of intestinal cancer in a cohort of people who had undergone cholecystectomy for gallstones, and in a cohort of people who had been hospitalized for gallbladder disease but had not undergone cholecystectomy. BACKGROUND: Some investigators have suggested that cholecystectomy increases the risk of intestinal cancer. Despite extensive study, the evidence remains inconclusive. If there is doubt about safety, the question arises of whether patients considering the operation should be told of a possible risk. It is also increasingly clear that there are noncausal associations between gallstones and intestinal cancer. METHOD: Analysis of record-linked hospital admission and mortality statistics for England from 1998 to 2008; calculation of ratio of rates of cancers in the cholecystectomy cohort and the gallbladder disease cohort compared with a control cohort. RESULTS: : In the first year after cholecystectomy, the rate ratios for cancer of the small intestine, colon, and rectum were significantly high at, respectively, 4.6 (95% confidence interval 3.9-5.5), 2.0 (1.9-2.1), and 1.7 (1.6-1.9). Rates of these cancers were also significantly high in people with gallstones without cholecystectomy. By 8 to 10 years after cholecystectomy, rate ratios had declined to nonsignificant levels. CONCLUSIONS: These cancers are associated with gallstones. The highest elevation of risk of cancer after cholecystectomy was at the shortest time interval after operation. Thereafter, the level of risk in the cholecystectomy and control cohorts gradually converged. The association in this study, between cholecystectomy and intestinal cancer, is very unlikely to be causal. Intestinal cancers are, on occasion, initially misdiagnosed as gallbladder disease.

Risk of invasive pneumococcal disease in people admitted to hospital with selected immune-mediated diseases: record linkage cohort analyses.

BACKGROUND: Invasive pneumococcal disease is a serious infection, and it is an important cause of morbidity and mortality in certain groups of 'at-risk' people. Those considered 'at-risk' in the UK include very young children, people aged 65 years and older and people with certain serious chronic diseases, asplenia or immunosuppression. There is little evidence about whether people with immune-mediated diseases are at increased risk of pneumococcal disease and therefore may benefit from pneumococcal vaccination. METHODS: Retrospective cohort studies, using linked hospital data, from the longstanding Oxford Record Linkage Study (1963-2008) and from recent English national linked Hospital Episode Statistics (1999-2008); analysis of whether people with immune-mediated diseases are more likely than others to be admitted to hospital for pneumococcal disease; calculation of rate ratio for pneumococcal disease in cohorts with immune-mediated disease compared with control cohorts. RESULTS: There were elevated rate ratios for many of the immune-mediated diseases, for example, Addison's disease in England 3.8 (95% CI 3.4 to 4.2), autoimmune haemolytic anaemia 4.9 (4.4 to 5.3), Crohn's disease 2.2 (2.1 to 2.3), diabetes mellitus 3.7 (3.4 to 4.1), multiple sclerosis 3.7 (3.5 to 3.8), myxoedema 1.60 (1.58 to 1.63), pernicious anaemia 1.74 (1.66 to 1.83), primary biliary cirrhosis 3.3 (2.9 to 3.7), polyarteritis nodosa 5.0 (4.0 to 6.0), rheumatoid arthritis 2.47 (2.41 to 2.52), scleroderma 4.2 (3.8 to 4.7), Sjogren's syndrome 3.2 (2.9 to 3.5) and systemic lupus erythematosus 5.0 (4.6 to 5.4). Findings in the Oxford and all England data sets were similar. CONCLUSIONS: People admitted to hospital with immune-mediated diseases are at higher risk than those with invasive pneumococcal disease. Vaccination should be considered in this group of patients.

Risk of selected eye diseases in people admitted to hospital for hypertension or diabetes mellitus: record linkage studies.

AIMS: Associations among hypertension, diabetes mellitus and some ophthalmic diseases are well established; associations with others are more equivocal. The aim was to quantify associations accurately using large epidemiological datasets. METHODS: Analysis of the Oxford Record Linkage Study (ORLS), 1963-1998, and English linked hospital episode statistics (LHES), 1999-2010; calculation of rate ratios of eye disease in a hypertension cohort and a diabetes cohort, compared with a reference cohort as control. RESULTS: Risk of cataract following hypertension was marginally elevated (rate ratio ORLS 1.15, 95% CI 1.00 to 1.31; LHES 1.06, 1.01 to 1.10), as was risk of glaucoma (LHES 1.07, 1.00 to 1.14) and age-related macular degeneration (AMD) (LHES 1.14, 1.02 to 1.27). Risk of retinal vein or artery occlusion was elevated three- to fivefold in both populations. Risk of retinal detachment was elevated in LHES at 1.52 (1.43 to 1.73). Risk of cataract in diabetes was high in ORLS and LHES at, respectively, 2.95 (2.75 to 3.16) and 2.30 (2.24 to 2.35), as was risk of glaucoma: 2.47 (2.14 to 2.84) and 2.23 (2.15 to 2.30). Risks were high for AMD (10.3, 8.1 to 13.1, and 3.46, 3.35 to 3.58) and retinal detachment (3.41, 2.71 to 4.25, and 7.96, 7.63 to 8.30), and very high for retinal vein and artery occlusion. CONCLUSIONS: With the exception of retinal vascular occlusion, elevations of risk of the ophthalmic diseases studied in hypertension were modest. By contrast, there were significant and substantial increases of risk for each eye disease in people with diabetes.

Coexistence of schizophrenia and epilepsy: record-linkage studies.

For many years, there has been interest in a possible link between epilepsy and schizophrenia. A recent study found a strong, bidirectional link between the two conditions: people with one had a higher than average risk of having the other. Using two large data sets of hospital admission data, we investigated whether schizophrenia and epilepsy occur together in individuals more commonly than expected by chance. We undertook a retrospective cohort study using the Oxford Record Linkage Study (ORLS) and English national linked Hospital Episode Statistics to investigate the coexistence of these conditions. There was an elevated risk of epilepsy in people admitted to hospital with schizophrenia (ORLS rate ratio 2.1, 95% confidence interval 1.6-2.6; England 3.0, 2.9-3.1) and an elevated risk of schizophrenia in people admitted to hospital with epilepsy (ORLS 5.1, 4.1-6.2; England 4.5, 4.3-4.6). We found no consistent difference between male and female patients. Schizophrenia and epilepsy occur together in individuals more frequently than expected by chance.

Trends over time and geographical variation in rates of intravitreal injections in England.

AIMS: The recent emergence of antivascular endothelial growth factor (anti-VEGF) drugs has led to increased numbers of patients undergoing intravitreal injection for age-related macular degeneration (AMD). The aims of this study were to report on trends over time and geographical variation in intravitreal injection rates in England, and consider the implications for publicly funded health services of introducing new and expensive treatments. METHODS: Hospital episode statistics were analysed for annual treatment rates of intravitreal injection between the NHS financial years of 1989/1990 and 2008/1999. RESULTS: Annual injection rates increased from 0.4 episodes (95% CI 0.37 to 0.49) per 100,000 population in 1989/1990 to 10.7 (10.4-11.0) in 2006/2007. Rates then rose exponentially to 59.5 (58.8-60.2) in 2008/2009, with increasing use of multiple injections per person. The largest growth in injection rates was found in older people, and for AMD. Numbers of treatment episodes increased from 203 (1989/1990) to 30,458 (2008/2009). Geographical analysis showed a very wide variation across local authority areas in injection rates, from 0.9 (0.2-2.2) to 42.2 (38.9-45.7) people per 100,000 population in 2005-2008. CONCLUSION: Rates of intravitreal injection increased exponentially from 2006/2007. This followed the US Food and Drug Association licensing of ranibizumab for the treatment of neovascular AMD (2006), and its recommendation by National Institute for Health and Clinical Excellence (2008). This study demonstrates some of the major issues which arise with the emergence of expensive new treatments, including speed and cost of adoption, geographical variation in access, and implications for licensing, commissioning and health financing in an ageing society.

Perinatal and early life risk factors for inflammatory bowel disease.

AIM: To investigate associations between perinatal risk factors and subsequent inflammatory bowel disease (IBD) in children and young adults. METHODS: Record linked abstracts of birth registrations, maternity, day case and inpatient admissions in a defined population of southern England. Investigation of 20 perinatal factors relating to the maternity or the birth: maternal age, Crohn's disease (CD) or ulcerative colitis (UC) in the mother, maternal social class, marital status, smoking in pregnancy, ABO blood group and rhesus status, pre-eclampsia, parity, the infant's presentation at birth, caesarean delivery, forceps delivery, sex, number of babies delivered, gestational age, birthweight, head circumference, breastfeeding and Apgar scores at one and five minutes. RESULTS: Maternity records were present for 180 children who subsequently developed IBD. Univariate analysis showed increased risks of CD among children of mothers with CD (P = 0.011, based on two cases of CD in both mother and child) and children of mothers who smoked during pregnancy. Multivariate analysis confirmed increased risks of CD among children of mothers who smoked (odds ratio = 2.04, 95% CI = 1.06-3.92) and for older mothers aged 35+ years (4.81, 2.32-9.98). Multivariate analysis showed that there were no significant associations between CD and 17 other perinatal risk factors investigated. It also showed that, for UC, there were no significant associations with the perinatal factors studied. CONCLUSION: This study shows an association between CD in mother and child; and elevated risks of CD in children of older mothers and of mothers who smoked.

Maternal and perinatal factors associated with hospitalised infectious mononucleosis in children, adolescents and young adults: record linkage study.

BACKGROUND: There is current interest in the role of perinatal factors in the aetiology of diseases that occur later in life. Infectious mononucleosis (IM) can follow late primary infection with Epstein-Barr virus (EBV), and has been shown to increase the risk of multiple sclerosis and Hodgkin's disease. Little is known about maternal or perinatal factors associated with IM or its sequelae. METHODS: We investigated perinatal risk factors for hospitalised IM using a prospective record-linkage study in a population in the south of England. The dataset used, the Oxford record linkage study (ORLS), includes abstracts of birth registrations, maternities and in-patient hospital records, including day case care, for all subjects in a defined geographical area. From these sources, we identified cases of hospitalised IM up to the age of 30 years in people for whom the ORLS had a maternity record; and we compared perinatal factors in their pregnancy with those in the pregnancy of children who had no hospital record of IM. RESULTS: Our data showed a significant association between hospitalised IM and lower social class (p = 0.02), a higher risk of hospitalised IM in children of married rather than single mothers (p < 0.001), and, of marginal statistical significance, an association with singleton birth (p = 0.06). The ratio of observed to expected cases of hospitalised IM in each season was 0.95 in winter, 1.02 in spring, 1.02 in summer and 1.00 in autumn. The chi-square test for seasonality, with a value of 0.8, was not significant.Other factors studied, including low birth weight, short gestational age, maternal smoking, late age at motherhood, did not increase the risk of subsequent hospitalised IM. CONCLUSIONS: Because of the increasing tendency of women to postpone childbearing, it is useful to know that older age at motherhood is not associated with an increased risk of hospitalised IM in their children. We have no explanation for the finding that children of married women had a higher risk of IM than those of single mothers. Though highly significant, it may nonetheless be a chance finding. We found no evidence that such perinatal factors as birth weight and gestational age, or season of birth, were associated with the risk of hospitalised IM.

Epilepsy and the subsequent risk of cerebral tumour: record linkage retrospective cohort study.

BACKGROUND: Studies suggest that seizures may precede the detection of cerebral tumour by several years. Aim To quantify the risk of cerebral tumour after new onset seizures, with particular interest in long term risk. METHODS: Using the Oxford Record Linkage Study (ORLS, 1963-1998) and English national linked Hospital Episode Statistics (1999-2005), cohorts of people with a first admission for epilepsy were constructed. Subsequent admissions with cerebral tumour were identified. The rate of occurrence of subsequent cerebral tumour in each epilepsy cohort was compared with that in a comparison cohort and expressed as a rate ratio (RR). RESULTS: The RR for cerebral tumour after epilepsy, relative to the rate of cerebral tumour in the comparison cohort, was 19.9 (95% CI 17.2 to 22.9) in the ORLS cohort and 19.7 (18.3-21.1) in the England cohort. The RR for malignant tumours were, respectively, 25.6 (21.7 to 30.0) and 27.3 (25.2 to 29.6). The RR for benign tumours were 10.1 (7.38 to 13.6) and 10.4 (9.07 to 11.8), respectively. The risk was highest for those aged 15-44 years at initial admission for epilepsy both in Oxford (24.2, 18.5 to 31.5) and England (38.1, 32.8 to 44.2). The risk of cerebral tumour was still raised several years after initial admission for epilepsy: in the ORLS cohort at 15 years or more, the RR was 3.29 (1.39 to 6.66) and, in the England cohort 5-7 years after initial admission, the RR was 5.27 (3.87 to 7.06). CONCLUSIONS: Seizures may herald the development of cerebral tumour, remote in time as well as soon after onset, with implications for guidelines on continued surveillance of those with new onset seizures.

Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study.

BACKGROUND: Venous thromboembolism (VTE) is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in people admitted to hospital with a range of immune-mediated diseases. METHODS: We analysed databases of linked statistical records of hospital admissions and death certificates for the Oxford Record Linkage Study area (ORLS1:1968 to 1998 and ORLS2:1999 to 2008) and the whole of England (1999 to 2008). Rate ratios for VTE were determined, comparing immune-mediated disease cohorts with comparison cohorts. RESULTS: Significantly elevated risks of VTE were found, in all three populations studied, in people with a hospital record of admission for autoimmune haemolytic anaemia, chronic active hepatitis, dermatomyositis/polymyositis, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis, myxoedema, pemphigus/pemphigoid, polyarteritis nodosa, psoriasis, rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. Rate ratios were considerably higher for some of these diseases than others: for example, for systemic lupus erythematosus the rate ratios were 3.61 (2.36 to 5.31) in the ORLS1 population, 4.60 (3.19 to 6.43) in ORLS2 and 3.71 (3.43 to 4.02) in the England dataset. CONCLUSIONS: People admitted to hospital with immune-mediated diseases may be at an increased risk of subsequent VTE. Our findings need independent confirmation or refutation; but, if confirmed, there may be a role for thromboprophylaxis in some patients with these diseases.

Influence of maternal and perinatal factors on subsequent hospitalisation for asthma in children: evidence from the Oxford record linkage study.

BACKGROUND: There is much interest in the possibility that perinatal factors may influence the risk of disease in later life. We investigated the influence of maternal and perinatal factors on subsequent hospital admission for asthma in children. METHODS: Analysis of data from the Oxford record linkage study (ORLS) to generate a retrospective cohort of 248 612 records of births between 1970 and 1989, with follow-up to records of subsequent hospital admission for 4 017 children with asthma up to 1999. RESULTS: Univariate analysis showed significant associations between an increased risk of admission for asthma and later years of birth (reflecting the increase in asthma in the 1970s and 1980s), low social class, asthma in the mother, unmarried mothers, maternal smoking in pregnancy, subsequent births compared with first-born, male sex, low birth weight, short gestational age, caesarean delivery, forceps delivery and not being breastfed. Multivariate analysis, identifying each risk factor that had a significant effect independently of other risk factors, confirmed associations with maternal asthma (odds ratio (OR) 3.1, 95% confidence interval 2.7-3.6), male sex (versus female, 1.8, 1.7-2.0), low birth weight (1000-2999 g versus 3000-3999 g, 1.2, 1.1-1.3), maternal smoking (1.1, 1.0-1.3) and delivery by caesarean section (1.2; 1.0-1.3). In those first admitted with asthma under two years old, there were associations with having siblings (e.g. second child compared with first-born, OR 1.3, 1.0-1.7) and short gestational age (24-37 weeks versus 38-41 weeks, 1.6, 1.2-2.2). Multivariate analysis confined to those admitted with asthma aged six years or more, showed associations with maternal asthma (OR 3.8, 3.1-4.7), age of mother (under 25 versus 25-34 at birth, OR 1.16, 1.03-1.31; over 35 versus 25-34, OR 1.4, 1.1-1.7); high social class was protective (1 and 2, compared with 3, 0.72; 0.63-0.82). Hospital admission for asthma in people aged over six was more common in males than females (1.4; 1.2-1.5); but, by the teenage years, the sex ratio reversed and admission was more common in females than males. CONCLUSION: Several maternal characteristics and perinatal factors are associated with an elevated risk of hospital admission for asthma in the child in later life.