Clare J Wotton

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

BackgroundVenous 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.MethodsWe 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.ResultsSignificantly 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, Sjogrens 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.ConclusionsPeople 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.

Cancers and immune related diseases associated with Down’s syndrome: a record linkage study

Objective: To determine the risk of cancers and selected immune related diseases in people with Down’s syndrome, relative to risk in other people. Design: Cohort analysis of a linked dataset of abstracts of hospital and death records; results expressed as the ratios of rates of disease in people with and without Down’s syndrome. Setting: The former Oxford health region, England, 1963–1999. Subjects: Cohort of 1453 people with Down’s syndrome and cohort of 460 000 people with other conditions for comparison. Main outcomes: As expected, the rate ratio for leukaemia was substantially elevated in people with Down’s syndrome: it was 19-fold higher (95% confidence intervals 10.4 to 31.5) than the rate in the comparison cohort. For other cancers combined, excluding leukaemia, the rate ratio was not significantly elevated (1.2; 0.6 to 2.2). The risk of testicular cancer was increased (12.0; 2.5 to 35.6), although this was based on only three cases in the cohort of subjects with Down’s syndrome. Significantly elevated risks were found for coeliac disease (4.7; 1.3 to 12.2), acquired hypothyroidism (9.4; 3.4, 20.5), other thyroid disorders, and type 1 diabetes mellitus (2.8; 1.0 to 6.1). A decreased risk was found for asthma (0.4; 0.2 to 0.6). Conclusions: Our data add to the body of information on the risks of co-morbidity in people with Down’s syndrome. The finding on asthma needs to be confirmed or refuted by other studies.

Cancer in patients with motor neuron disease, multiple sclerosis and Parkinson's disease: record linkage studies

Objective To determine the risk of cancer before and after the diagnosis of motor neuron disease (MND), multiple sclerosis (MS) and Parkinsons disease (PD). Methods Analysis of statistical database of linked statistical abstracts of hospital and mortality data in an area in southern England. Results Only people with PD showed a significant difference in the overall incidence of cancer compared with controls (rate ratio (RR) 0.76, 95% CIs 0.70 to 0.82 before PD; RR 0.61, 0.53 to 0.70, after PD). RRs were close to 1 for cancer in patients after MND (0.98, 0.75 to 1.26) and after MS (0.96, 0.83 to 1.09). There were high rate ratios for malignant brain cancer (7.4, 2.4 to 17.5) and Hodgkins lymphoma (5.3, 1.1 to 15.6) in patients diagnosed with MND after cancer. In people with MS, malignant brain cancer also showed an increased RR both before hospital admission with a diagnosis of MS (3.2, 1.1 to 7.6) and after (2.4, 1.2 to 4.5). In people with PD, several specific cancers showed significantly and substantially reduced RRs for cancer, notably smoking related cancers, including lung cancer (0.5, 0.4 to 0.7, before PD; 0.5, 0.4 to 0.8, after PD) but also cancers that are not strongly smoking related, including colon cancer (0.7, 0.6 to 0.9, before PD; 0.5, 0.4 to 0.8, after PD). Conclusions People with MND, or MS, do not have an altered risk of cancer overall. There may sometimes be misdiagnosis between MND or MS and brain tumours. PD carries a reduced risk of cancer overall, of some smoking related cancers and of some cancers that are not smoking related.

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

BackgroundThere 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.MethodsAnalysis 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.ResultsUnivariate 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.ConclusionSeveral maternal characteristics and perinatal factors are associated with an elevated risk of hospital admission for asthma in the child in later life.

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, Addisons disease in England 3.8 (95% CI 3.4 to 4.2), autoimmune haemolytic anaemia 4.9 (4.4 to 5.3), Crohns 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), Sjogrens 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.

Cancer in patients with ulcerative colitis, Crohn's disease and coeliac disease: record linkage study.

Objective The objective of this study was to determine the risk of cancers in cohorts of patients with ulcerative colitis, Crohns disease, or coeliac disease, compared with the risk in a control cohort. Method The method used was the analysis of a linked statistical database of hospital and mortality data in an area in southern England. Results Rate ratios for cancer (excluding cases occurring within the first year of follow-up), compared with the value of 1 in the control cohort, were 1.25 [95% confidence interval (CI), 1.13–1.39] in patients with ulcerative colitis, 1.27 (95% CI, 1.11–1.45) with Crohns disease, and 1.16 (95% CI, 0.94–1.43) with coeliac disease. In patients with ulcerative colitis or Crohns disease, there was a significantly high risk of cancer of the colon [2.22 (95% CI, 1.71–2.83) and 1.64 (95% CI, 1.09–2.39), respectively]. In patients with ulcerative colitis there was a significantly high risk of cancer of the rectum [1.84 (95% CI, 1.27–2.58)]. In patients with ulcerative colitis or Crohns disease, who did not undergo partial or total colectomy for it, the rate ratios for colon cancer were, respectively, 5.52 (95% CI, 4.39–6.71) and 4.81 (95% CI, 3.52–6.47). In ulcerative colitis, there was an elevated risk of cancer of the rectum, liver and ovary. The rate ratio for lung cancer was low, but of borderline significance [0.72 (95% CI, 0.50–0.98)]. In Crohns disease, the rate ratio was high for cancer of the cervix [2.63 (95% CI, 1.12–5.29)]. In patients with coeliac disease, the high-risk cancer was non-Hodgkins lymphoma [rate ratio 3.28 (95% CI, 1.49–6.28)]. Conclusion All three diseases carry an increased risk of cancer overall when the first year cases are included, though fairly modest in scale, and the increased risk seen in coeliac disease reduces when first year cases are excluded. Each has a distinctive pattern of individual high-risk cancers.

Multiple sclerosis after infectious mononucleosis: record linkage study

Objective: To ascertain if infectious mononucleosis is a risk factor for the development of multiple sclerosis (MS); and, if it is, whether its effect is close to or remote in time from the onset of MS. Design: Analysis of database of linked abstracts of records of hospital admission and death. Setting: Health region in central southern England. Main outcome measure: Ratio of rate of MS in a cohort of people admitted to hospital with infectious mononucleosis to the rate in a comparison cohort. Results: Considering all time intervals from admission with infection to admission with MS, there was a non-significant increase of risk of MS in the infectious mononucleosis cohort (rate ratio 2.17, 95% confidence intervals 0.79 to 4.77). At the interval of 10 years or more, there was a significant increase in risk of MS (rate ratio 4.01, 1.48 to 8.93). The mean time from infectious mononucleosis to first admission with MS was 14 years. Conclusion: This study adds support to the evidence that Epstein-Barr virus, the cause of infectious mononucleosis, is associated with MS. Its role is probably as an initiator of the disease process of MS, or as a contributor to its early development, rather than as an activator of latent, existing disease.

Cardiovascular fitness as a risk factor for amyotrophic lateral sclerosis: indirect evidence from record linkage study

Background Amyotrophic lateral sclerosis (ALS) appears to be a sporadic disorder in 95% of cases. Although few personal characteristics associated with developing ALS are known, identification of those at risk is essential to any vision of early intervention. There is persistent anecdotal observation that those with ALS are premorbidly physically ‘fitter’, although such observations are susceptible to bias. Hospital admission for coronary heart disease (CHD) might serve as an objective marker of reduced cardiovascular fitness. Methods A record linkage study of two large databases of hospital admissions, the Oxford Record Linkage Study (ORLS) and an English national record linkage dataset of Hospital Episode Statistics was undertaken. The ratio of the rate of ALS in people without a record of CHD to that in those with a record of CHD was calculated, factoring out premature death in both cohorts. Similar analysis for Parkinsons disease (PD) and multiple sclerosis (MS) was undertaken. Results In the English population, the rate ratio for ALS in the non-CHD cohort, compared with the CHD cohort, was 1.14 (95% CI 1.05 to 1.22); for PD it was 0.95 (95% CI 0.93 to 0.98); and for MS 0.95 (95% CI 0.88 to 1.04). The ORLS data yielded similar findings. Conclusions Those without a record of CHD were at modestly higher risk of ALS, but not for PD or MS. This lends support to the assertion that ALS arises within a population who may have relatively higher levels of cardiovascular fitness.

Cancer in patients admitted to hospital with diabetes mellitus aged 30 years and over: record linkage studies

Aims/hypothesisThe aim of this study was to determine the risk of cancer in people admitted to hospital for diabetes mellitus when aged 30 or older.MethodsThis study involved the analysis of two statistical datasets of linked hospital and mortality data, in an area in southern England, between 1963 and 1998 (the Oxford Record Linkage Study, ORLS1) and between 1999 and 2008 (ORLS2). Rates of cancer in the diabetes cohorts were compared with rates of cancer in reference cohorts and expressed as rate ratios.ResultsThe rate ratio for all cancer in people admitted to hospital with diabetes was 1.01 (95% CI 0.95–1.06, based on 15,898 people with diabetes) for the years 1963–1998; and 1.09 (1.00–1.19, based on 7,771 people with diabetes) in the years 1999–2008. In both datasets, there were significantly high rate ratios for cancers of the liver (ORLS1 and ORLS2, respectively, 2.0 [95% CI 1.4–2.9]; 2.5 [95% CI 1.3–4.3]), pancreas (2.2 [95% CI 1.8–2.7]; 3.5 [95% CI 2.5–4.8]) and uterus (1.5 [95% CI 1.0–2.2]; 2.6 [95% CI 1.4–4.5]). There were significantly low rate ratios for cancer of the prostate (0.6 [95% CI 0.5–0.7]; 0.7 [95% CI 0.5–0.9]) and non-melanoma skin cancer (0.6 [95% CI 0.5–0.8]; 0.8 [95% CI 0.6–0.96]).Conclusions/interpretationDiabetes mellitus was associated with an elevated risk of some site-specific cancers and a reduction of risk of others. Considering the risk in diabetes of all cancers combined, the elevation of risk, if any, is likely to be small and numerically less important than other known complications of diabetes.

Pneumococcal infection in patients with coeliac disease

Objectives Some patients with coeliac disease are hyposplenic. Splenectomy is a risk factor for pneumococcal infection. Our objective was to determine the risk of invasive pneumococcal disease – septicaemia, pneumonia or meningitis – in patients with coeliac disease. Methods We analysed routinely collected, linked statistical records of hospital admission to study the risk of pneumococcal infection in patients with coeliac disease, in patients who underwent splenectomy and in a comparison cohort. The main outcome measure was the rate ratio for pneumococcal infection in the coeliac and splenectomized cohorts, compared with the comparison cohort. We undertook the study using linked records in two temporally and geographically distinct populations: the Oxford region (1963–1999) and the whole of England (1998–2003). Results The rate ratio of pneumococcal infection in patients with coeliac disease was 2.06 (95% confidence interval, 1.27–3.15) in the Oxford population and 1.61 (1.36–1.90) in England as a whole. As a comparison, the rate ratios in splenectomized patients were 3.40 (2.44–4.60) and 3.32 (2.80–3.90) in the Oxford and England populations, respectively. The increased rate ratio in coeliac patients persisted beyond the first year after diagnosis of the coeliac disease. The period covered by the Oxford study was mainly before the widespread availability of pneumococcal vaccination; but the availability of pneumococcal vaccine was widespread during the time of the English study. Conclusion Some patients with coeliac disease have an elevated risk of invasive pneumococcal disease.