Maternal and perinatal factors associated with subsequent meningococcal, Haemophilus or enteroviral meningitis in children: database study.

We used a database of 248 659 births, with follow-up to subsequent disease, in the Oxford record linkage archive (1979-1999) to study the influence of family, maternal, and perinatal factors on subsequent hospital admission for meningococcal, Haemophilus, and enteroviral meningitis in the children. In this summary, we report key findings that were significant in multivariate analysis. Meningococcal meningitis was significantly associated with maternal smoking [odds ratio (OR) 2·1, 95% confidence interval (CI) 1·2-3·7]. Haemophilus meningitis was associated with having older siblings (e.g. second child compared to first-born, OR 3·3, 95% CI 2·0-5·6). Enteroviral meningitis was associated with low birth weight (OR 2·2, 95% CI 1·3-3·6) and male sex (OR 1·7, 95% CI 1·2-2·3). The mothers of six of the 312 children with enteroviral meningitis had previously had enteroviral meningitis themselves. We concluded that several maternal characteristics influence the risk of these types of meningitis.

Increased risk of tuberculosis disease in people with diabetes mellitus: record-linkage study in a UK population.

BACKGROUND: The authors aimed to determine whether, and by how much, diabetes mellitus (DM) increases the risk of tuberculosis (TB) and conversely whether TB increases the risk of DM. METHODS: Retrospective cohort analyses using data from two Oxford Record Linkage Study (ORLS) datasets, containing information on hospital admissions and day-case care between 1963 and 1998 (ORLS1) and between 1999 and 2005 (ORLS2), were carried out. The rate ratio (RR) for tuberculosis after admission to hospital with diabetes and for diabetes after hospital admission with tuberculosis was calculated. RESULTS: In ORLS1, the RR for TB in people admitted to hospital with DM, comparing the latter with a reference cohort, was 1.83 (95% CI 1.26 to 2.60), and in ORLS2 the RR was 3.11 (1.17 to 7.03). RRs for pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) within ORLS1 were similar at, respectively, 1.80 (1.16 to 2.67) and 1.98 (0.88 to 3.92). In ORLS 2 the RR for PTB was 2.63 (0.91 to 6.30). In ORLS1, there was no indication that TB was a risk factor for DM (RR 1.12, 0.76 to 1.60). The ORLS2 dataset was too small to analyse whether TB led to DM. DISCUSSION: DM was associated with a two- to threefold increased risk of TB within this predominantly white, English population. The authors found no evidence that TB increases the risk of DM. Our findings suggest that the risks of PTB and EPTB were both raised among individuals with DM. As DM prevalence rises, this association will become increasingly important for TB control and treatment.

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

AIMS/HYPOTHESIS: The aim of this study was to determine the risk of cancer in people admitted to hospital for diabetes mellitus when aged 30 or older. METHODS: This 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. RESULTS: The 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/INTERPRETATION: Diabetes 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.

Immune-mediated and chronic inflammatory disease in people with sarcoidosis: disease associations in a large UK database.

BACKGROUND: Sarcoidosis is a multi-system disorder characterised by non-caseating granulomas. Coexistence of sarcoidosis with immune-mediated and chronic inflammatory diseases has been described in case series. However, the coexistence of two different diseases in individuals can occur by chance, even if each of the diseases is rare. AIM: To determine whether sarcoidosis necessitating hospital admission or day-case care coexists with a range of immune-mediated and chronic inflammatory diseases more commonly than expected by chance. DESIGN: Analysis of an epidemiological database of hospital admission and day-case statistics, spanning 30 years. RESULTS: 1510 patients with sarcoidosis were identified (mean age 44 years, median follow-up 19 years) who had been admitted to hospital or day-case care. Significant associations in the sarcoidosis cohort were identified with systemic lupus erythematosus (odds ratio (OR) 8.3; 95% CI 2.7 to 19.4), autoimmune chronic hepatitis (OR 6.7; 95% CI 1.8 to 17.1), multiple sclerosis (OR 3.3; 95% CI 1.7 to 5.6), coeliac disease (OR 3.1; 95% CI 1.01 to 7.3), thyrotoxicosis (OR 2.5; 95% CI 1.4 to 4.0), myxoedema (OR 2.2; 95% CI 1.2 to 3.7) and ulcerative colitis (OR 2.1; 95% CI 1.1 to 3.7). Weaker associations were found for diabetes mellitus with a first admission aged 30-49 years (OR 2.9; 95% CI 2.1 to 4.0) or age >50 (OR 1.7; 95% CI 1.2 to 2.3), but not for people age <30. No significant association with Crohn's disease (OR 1.52; 95% CI 0.61 to 3.14) or primary biliary cirrhosis (OR 3.75; 95% CI 0.77 to 11.0),was found. When all immune-mediated and chronic inflammatory diseases for which associations were sought were combined, the overall rate ratio associated with sarcoidosis was 2.2 (95% CI 1.9 to 2.6). CONCLUSION: This study adds epidemiological evidence to information from clinical reports that there is a connection between sarcoidosis and other immune-mediated and chronic inflammatory diseases.

Associations between infectious mononucleosis and cancer: record-linkage studies.

Infection with Epstein-Barr virus (EBV) followed by infectious mononucleosis (IM) is now considered to be a risk factor for Hodgkin's disease (HD). It is less clear whether EBV infection and IM are associated with an increased risk of cancer generally. We used a longstanding record-linkage dataset in Oxford (years 1963-1998), and a more recent record-linkage dataset covering England (1999-2005), to compare rate ratios for cancer between people admitted to hospital for IM and a reference cohort. In the Oxford cohort, there was an increased risk of subsequent HD [rate ratio (RR) 6.0, 95% confidence interval (CI) 2.4-12.5] but not of other cancers combined (RR 0.85, 95% CI 0.57-1.23). In the England cohort, there were increased risks of HD (RR 3.2, 95% CI 1.2-7.0), non-Hodgkin's lymphoma (RR 5.6, 95% CI 2.9-9.8), and oropharyngeal cancer (RR 5.4, 95% CI 1.1-16.2), but no significant overall risk of cancer when lymphomas were excluded (RR 1.01, 95% CI 0.71-1.41). We confirm an association between IM and lymphoma; but the risk, if any, of cancer more generally is likely to be small.

Cancer and immune-mediated disease in people who have had meningococcal disease: record-linkage studies.

The mechanisms that cause susceptibility to invasive meningococcal disease are largely unknown, but are likely to have important genetic and immunological components. We postulated that susceptibility to meningococcal disease might be associated with altered risks of development of other clinical disease. We studied cancer and immune-mediated disease in people who have been hospitalized with meningococcal disease. In cohorts of people who had invasive meningococcal disease, compared with reference cohorts, the rate ratio for cancer in an Oxford dataset studied from 1963 to 1998 was 0.88 [95% confidence interval (CI) 0.42-1.61] and in an all-England dataset studied from 1999 to 2005 it was 1.02 (95% CI 0.80-1.27). The respective rate ratios for immune-mediated disease were 1.49 (95% CI 0.81-2.50) and 0.69 (95% CI 0.53-0.89). Susceptibility to meningococcal disease was not associated with an altered risk of cancer. Occurrence of immune-mediated disease was, if anything, low in the large all-England cohort of people who had meningococcal disease.

Immune-related disease before and after vasectomy: an epidemiological database study.

BACKGROUND: Vasectomy can be followed by an autoimmune-antibody response. We aimed to determine whether men with immune-related diseases were more or less likely than others to have a vasectomy and then to determine whether vasectomy is associated with the subsequent development of immune-related diseases. METHODS: A database of linked records of hospital statistics was analysed. By comparing a population of men who underwent vasectomy with a reference population, we calculated the rate ratios for selected immune-related diseases before and after vasectomy. RESULTS: Some diseases studied (e.g. asthma and diabetes mellitus) were a little less common, prior to operation, in the vasectomy group than in the reference group. Others were not different. The mean period of follow-up was 13 years. We found no long-term elevation of risk following vasectomy of asthma, diabetes mellitus, ankylosing spondylitis, thyrotoxicosis, multiple sclerosis, myasthenia gravis, inflammatory bowel disease, rheumatoid arthritis or testicular atrophy. There was a short-term elevation of risk of orchitis/epididymitis. CONCLUSIONS: In this large study, with many years of follow-up, we found no evidence that vasectomy increases the subsequent long-term risk of immune-related diseases.

Cancer following hip and knee arthroplasty: record linkage study.

Concerns have been raised that degradation of implants used in hip and knee arthroplasty may lead to an increased risk of some cancers, particularly those of the haematopoietic, lymphatic and urinary systems. We used linked statistical records of hospital admissions and deaths to compare cancer rates in cohorts of people who had undergone hip or knee arthroplasty with a comparison cohort. We did not find an elevated risk for cancer, overall, in either the hip or knee cohort or in both combined (rate ratio for both combined 0.99; 95% confidence intervals 0.95-1.02), or for haematopoietic, lymphatic or urinary system cancers. There was also no elevation in risk of cancer more than 10 years after arthroplasty. Our findings add to the evidence that arthroplasty is safe in respect of cancer risk.

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.