Cancer of the body of the uterus: trends in mortality and incidence in England, 1985-2008.

OBJECTIVE: To report on trends in mortality and incidence for uterine cancer in England, 1985-2008. DESIGN: Database analysis. SETTING: England. POPULATION: Data sets of English national mortality and cancer registration statistics. METHODS: Analysis of data from death certificates with a mention of malignant neoplasm of corpus uteri or malignant neoplasm of uterus without specification of part, and analysis of incidence data from cancer registries in England. MAIN OUTCOME MEASURES: Age-adjusted and age-specific trends in rates. RESULTS: Mortality rates in the UK declined from 41.3 per million women in 1985 until about 1999 (30.0 per million), and then increased to 35.9 per million in 2008. Incidence rates for those aged 55 years and over showed little or no change from 1985 to the early 1990s, but then increased: for example, for women aged 60-64 years, the rates per million women in 1985, 1993, 2001 and 2008 were, respectively, 448, 461, 647 and 728. Rates for younger women showed a decline, followed by an increase: for example, for women aged 50-54 years the corresponding rates were 290, 254, 267 and 294. Over the period 2001-2008, the age-adjusted average annual percentage increase was 2.55% per annum (95% CI 2.13-2.98%). The increase in incidence rates, observed from the 1990s, preceded the increase in mortality by about 10 years. CONCLUSIONS: After many years of declining rates, uterine cancer has become more common in the first decade of this century. One possible contributor to this increase may be an association with the increase in body mass index in women, but other causes are possible and are discussed.

Differences between women and men in surgical treatment and case fatality rates for ruptured aortic abdominal aneurysm in England.

BACKGROUND: Differences between women and men in treatment and outcome after admission with a ruptured abdominal aortic aneurysm (AAA) in England were studied. METHODS: Routinely collected data in Hospital Episode Statistics, linked to death records, for emergency admissions for ruptured AAA in England were analysed. The percentage of patients who underwent surgical repair was calculated, together with 30-day case fatality rates and age-adjusted odds ratios (ORs), comparing women with men. RESULTS: A total of 2463 women and 7615 men were admitted with a primary diagnosis of ruptured AAA (mean age 79.8 and 74.9 years respectively); 39.6 per cent of women and 66.4 per cent of men underwent surgical repair (OR 0.47 (95 per cent confidence interval 0.42 to 0.52)). Overall, 75.6 per cent of women and 61.7 per cent of men died within 30 days of admission (OR 1.36 (1.22 to 1.52)). The death rate for women and men who had surgery was similar (OR 1.01 (0.88 to 1.17)); when no operation was performed the mortality rate was higher in women, but not significantly so (OR 1.14 (0.91 to 1.42)). CONCLUSION: Women with a ruptured AAA were less likely to be treated surgically than men, and their overall mortality rate was higher. Lower rates of surgery in women than in men may contribute to the higher mortality in women, but other explanations are possible.

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.

Changes to the daily pattern of methadone-related deaths in England and Wales, 1993-2003.

Previous studies suggest that fatal poisoning deaths involving methadone occur more frequently on the weekends. We assessed changes in the daily pattern of mortality because of methadone poisoning following a review of drug misuse services in 1996 and publication of revised clinical guidelines in 1999. We also compared this to the daily pattern of deaths involving heroin/morphine. The Office for National Statistics provided data on all deaths in England and Wales between 1993 and 2003 for which methadone and heroin/morphine were mentioned on the coroner's certificate of death registration after inquest, with or without alcohol or other drugs. There were 3098 deaths involving methadone. The death rate increased up to 1997 and then declined. Initially, there was a marked excess of deaths occurring on Saturdays. The rate of decline was greatest for deaths occurring on Saturdays. As a result, the Saturday peak disappeared (P = 0.006). There were 6328 deaths involving heroin/morphine. No change in the daily pattern of heroin/morphine deaths was observed during the study period. Although the marked change in the epidemiology of methadone deaths coincided with recommendations for service redevelopment and clinical management of methadone treatment, the contribution of improved prescribing practice or treatment services is unclear.

Impact of socio-economic deprivation on death rates after surgery for upper gastrointestinal tract cancer.

We hypothesised that socio-economic deprivation in England may be a prognostic factor for death after oesophagectomy or gastrectomy for cancer of the upper gastrointestinal tract. We analysed statistical data from hospital records linked to death records for patients who underwent operations for oesophageal and gastric cancer in England from April 1998 to March 2002. The patients were stratified into quintiles according to the index of multiple deprivation (IMD) (2000) for their place (ward) of residence. Age and sex standardised death rates at 30 and 90 days for each deprivation quintile were calculated. Following oesophagectomy, death rates showed a significant association with IMD. They increased with increasing levels of deprivation: the odds ratio for death, comparing highest with lowest quintile for deprivation, was 1.37 (95% confidence interval 1.03-1.85) at 30 days and 1.30 (1.04-1.64) at 90 days. Following gastrectomy, the death rates showed smaller and nonsignificant associations with IMD with odds ratios of 1.16 (0.84-1.62) and 1.10 (0.86-1.41), respectively. There is a significant association between social deprivation and death after oesophagectomy, but less of an association, if any, after gastrectomy in current UK practice.

Risk of multiple sclerosis after head injury: record linkage study.

BACKGROUND: The possibility that head injury may influence the development of multiple sclerosis (MS) has been studied inconclusively in the past. OBJECTIVE: To determine whether head injury is associated with an increased risk of MS. METHOD: Analysis of database of linked hospital and death records, comparing the occurrence of MS in a cohort of people admitted to hospital with head injury and a reference cohort. RESULTS: The rate ratio for MS after head injury, compared with the reference cohort, was 1.1 (95% confidence interval, 0.88 to 1.36). There was no significant increase in the risk of MS at either short or long time periods after head injury. Using length of hospital stay as a proxy for severity of injury, there was no significant increase in the rate ratio for MS after head injuries with hospital stays of less than two days (rate ratio = 1.1 (0.71 to 1.57)), two or more days (rate ratio = 1.0 (0.68 to 1.45)), or seven or more days (rate ratio = 1.3 (0.64 to 2.34)). CONCLUSIONS: The method used, record linkage, ensures that patients' recollection of injury, or any tendency to attribute MS to injury, cannot have influenced the results. Injuries to the head were not associated with either the aetiological initiation or the clinical precipitation of onset of multiple sclerosis.

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.

Cancer after cholecystectomy: record-linkage cohort study.

We investigated whether cholecystectomy is associated with subsequent cancer and, if so, whether the association is likely to be causal, by undertaking a retrospective cohort study using linked medical statistics, comprising a cholecystectomy group (n=39 254) and a reference cohort admitted for a range of other medical and surgical conditions (n=334 813). We found a short-term significant elevation of rates of cancers of the colon, pancreas, liver, and stomach after cholecystectomy, but no long-term elevation. Excluding colon cancers within 2 years of admission to hospital, the rate ratio for colon cancer after cholecystectomy, compared with the reference cohort, was 1.01 (95% confidence interval 0.90-1.12) and after 10 years or more follow-up it was 0.94 (0.79-1.10). It is highly improbable that the short-term associations between cholecystectomy and gastrointestinal cancers are causal, and we conclude that cholecystectomy does not cause cancer.

Established and emerging coronary risk factors in patients with heterozygous familial hypercholesterolaemia.

OBJECTIVES: To assess the clinical and biochemical factors associated with inter-individual variation in susceptibility to coronary artery disease (CAD) in treated heterozygous familial hypercholesterolaemia. DESIGN: A cross sectional study was conducted of 410 patients recruited from six lipid clinics in the UK. RESULTS: CAD was documented in 104 of the 211 men and in 55 of the 199 women with mean ages of onset of 43.1 and 46.5 years, respectively. CAD was significantly more common in men (49% v 28%, p < 0.001) and in patients who had smoked cigarettes versus patients who had never smoked (51% v 28%, p < 0.001). After adjusting for age, sex, and current smoking status, there were no significant differences between patients with or without CAD in lipoprotein(a), homocysteine, fibrinogen, plasminogen activator inhibitor-1, white blood cell count, body mass index, glucose, triglyceride or total cholesterol. However, high density lipoprotein (HDL) cholesterol concentrations were significantly lower in those with CAD (6%, 95% confidence interval (CI) 1% to 11%, p = 0.03) and this difference was greater in women than men (12% v 2%, p = 0.041). CONCLUSIONS: These results indicate that emerging coronary risk factors appear not to be associated with CAD in adults with treated familial hypercholesterolaemia, but the strong association with smoking suggests that patients should be identified early in childhood and discouraged from ever starting to smoke.

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.

Skin cancer in people with multiple sclerosis: a record linkage study.

OBJECTIVE: The prevalence of multiple sclerosis (MS) varies with latitude: it increases with distance from the equator in both hemispheres. To seek evidence on whether solar radiation is a protective factor for MS, this study investigated whether skin cancer, as an indicator of solar radiation, is less common in people with MS than in others. DESIGN: Analysis of a database of linked hospital records and death certificates. SETTING: The Oxford Region of the National Health Service, England. SUBJECTS: A cohort comprising all people in the database with MS, and comparison cohorts of people with other diseases. RESULTS: Skin cancer was significantly less common in people with MS than in the main comparison cohort (rate ratio 0.49; 95% confidence interval 0.24 to 0.91). There was no general deficit of cancer in the MS cohort, and no deficit of skin cancer in cohorts of people with other autoimmune or neurological diseases. CONCLUSION: The findings support the hypothesis that solar radiation may have a protective influence on the development of MS.

Crohn's disease, ulcerative colitis, and measles vaccine in an English population, 1979-1998.

STUDY OBJECTIVE: s: To study the hospitalised incidence of Crohn's disease (CD) and ulcerative colitis (UC) from 1979 to 1998; and to determine whether the introduction of the measles vaccination programme was associated with an increase in the young. DESIGN: Analysis of linked data on hospital admissions; a cohort analysis of the effect of the measles vaccination programme on the incidence of hospitalised CD and UC; and a comparison of these results with those from previous studies on the association between measles vaccine and CD or UC. SETTINGS: Southern England. SUBJECTS: People admitted to hospital with a main diagnosis of CD (1959 people) or UC (2018 people). MAIN RESULTS: Overall, the incidence of hospitalised CD showed no significant change over the 20 year period: the average change per year was 0.08% (95% confidence interval: -0.7% to 0.9%). The relative risk associated with the measles vaccination programme was not significant (0.91: 0.5 to 1.4). The estimate differed significantly from the relative risk of 3.0 obtained in the original study reporting an association, but agreed with the combined estimate from three subsequent studies (0.95: 0.6 to 1.5). The results for UC were similar. CONCLUSIONS: The incidence of hospitalised CD and UC remained stable over the 20 years, 1979 to 1998. Whatever caused the marked increases in CD and UC in the mid-20th century must itself have stabilised in this region. These results, together with those from other studies, provide strong evidence against measles vaccine causing CD or UC.

Appendicectomy, tonsillectomy, and inflammatory bowel disease: a case-control record linkage study.

STUDY OBJECTIVE: To determine whether appendicectomy and tonsillectomy are associated with ulcerative colitis (UC) or Crohn's disease (CD); and, if so, whether the associations are related to age at operation. DESIGN: Nested case-control studies using a longitudinal database of linked hospital and death record abstracts. SETTING: Southern England. PATIENTS: Statistical records of people diagnosed with UC, CD, or a control condition admitted to hospitals in a defined area. MAIN RESULTS: Appendicectomy under the age of 20 years was associated with a significantly reduced subsequent risk of UC (relative risk =0.48, 95% confidence interval 0.30 to 0.73). The association appeared strongest for appendicectomy between 10 and 14 years of age (relative risk =0.29, 95% CI 0.09 to 0.68). Appendicectomy at the age of 20 years and over was associated with an increased subsequent risk of CD (relative risk =1.92, 95% CI 1.58 to 2.32), largely confined to those people whose CD was diagnosed within a year of appendicectomy. Appendicectomy under 20 years of age, undertaken five years or more before case or control conditions, was suggestively associated with a reduced risk of CD (relative risk =0.71, 95% CI 0.47 to 1.03). Prior tonsillectomy was not associated with any increase or decrease of risk of either UC or CD. CONCLUSIONS: Appendicectomy is associated with a reduced risk of UC; and the association is specific to young age groups when the population risk of appendicitis is itself highest. The increased risk of CD after appendicectomy, at short time intervals between the two, is probably attributable to the misdiagnosis of CD as appendicitis.

Use of large medical databases to study associations between diseases.

We describe the use of a dataset of statistical medical records, the Oxford Record Linkage Study (ORLS), to identify diseases which occur together more commonly (association), or less commonly (dissociation), than their individual frequencies in the population would predict. We investigated some conditions known or suspected to enhance the subsequent risk of cancer, some conditions thought to be linked with schizophrenia, and some associations between conditions with a known autoimmune component. Diseases may occur in combination more often (or less often) than expected by chance because one predisposes to (or protects against) another or because they share environmental and/or genetic mechanisms in common. The investigation of such associations can yield important information for clinicians interested in potential disease sequelae, for epidemiologists trying to understand disease aetiology, and for geneticists attempting to determine the genetic basis of variation in disease course among individuals. We suggest that, through the use of datasets like the ORLS, it will be possible to 'map' comprehensively the phenomic expression of co-occurring diseases.

Olive oil, diet and colorectal cancer: an ecological study and a hypothesis.

STUDY OBJECTIVES: Colorectal cancer (CRC) is a common cancer in many western countries and is probably caused in part by dietary factors. Southern European countries have lower incidence rates of CRC than many other western countries. It was postulated that, because olive oil is thought to influence bile salt secretion patterns in rats, it may influence the occurrence of CRC. The purpose of this study was to compare national levels of dietary factors, with particular reference to olive oil, with national differences in CRC incidence. DESIGN: Ecological study using existing international databases. Incidence rates for CRC, food supply data, and olive oil consumption data were extracted from published sources, combined, and analysed to calculate the correlations between CRC and 10 dietary factors. Associations were then explored using stepwise multiple regression. SETTING: 28 countries from four continents. MAIN RESULTS: 76% of the intercountry variation in CRC incidence rates was explained by three significant dietary factors-meat, fish and olive oil-in combination. Meat and fish were positively associated, and olive oil was negatively associated, with CRC incidence. CONCLUSION: Olive oil may have a protective effect on the development of CRC. The proposed hypothesis is that olive oil may influence secondary bile acid patterns in the colon that, in turn, might influence polyamine metabolism in colonic enterocytes in ways that reduce progression from normal mucosa to adenoma and carcinoma.

Secular trends in proximal femoral fracture, Oxford record linkage study area and England 1968-86.

OBJECTIVE: To study hospital admission rates for fractures of the proximal femur over a period when incidence is reported to have increased, compensating for known lack of precision in coding, excluding nonemergency admissions and transfers, and modelling for age, period, and cohort effects. DESIGN: Validation of coding of a sample of hospital admissions followed by study of two sets of routinely collected statistical abstracts of hospital records; graphical analysis and statistical modelling were used to search for period and cohort effects. SETTING: Oxfordshire and west Berkshire in 1968-86, covered by the Oxford record linkage study (ORLS), and ENGLAND in 1968-85, covered by the hospital inpatient enquiry (HIPE). The ORLS and HIPE datasets are almost independent (ORLS contributed about 1.8% of the HIPE data). SUBJECTS: Records of patients aged 65 and over. OUTCOME MEASURES: Admission rates for fractured neck of femur and fracture of other and unspecified parts of femur (N820 and N821), and evidence of period and cohort effects. RESULTS: The validation study indicated that it was important to combine the codes 820 and 821 in this age group. Admission rates increased over the period studied in both HIPE and ORLS datasets. In HIPE the pattern was of two plateaux separated by a period of rapid rise in the late 1970s. In the ORLS data there was a more steady rise. Statistical analysis showed significant period and cohort effects but much of this was attributable to the component of the model common to both period and cohort effects (termed "drift"). CONCLUSIONS: The finding that admission rates increased in both datasets, combining relevant codings and restricting analysis to emergency admissions, strongly suggests that the rise was real. At least part of the period effect in the HIPE data, however, might be attributable to a sampling artefact. The cohort effect in incidence rates of femoral fracture has not been previously shown and would be compatible with a number of aetiological hypotheses.

Neural tube defects 1974-94--down but not out.

AIMS: To describe accurately the total prevalence of neural tube defects (NTDs) in England and Wales over time, and to provide a benchmark up to 1994. METHODS: National data about NTDs reported as births or terminations are available from 1974-94, but reporting is incomplete. A local register of NTDs covering Oxfordshire/west Berkshire from 1965-94 was used to validate national data for the locality, using the method of capture and recapture, and hence to estimate incompleteness of reporting nationally. RESULTS: National underreporting is consistent at about two thirds of the true number of cases reaching at least the second trimester. The local register is much more complete, but time trends locally and nationally are similar. In England and Wales total prevalence declined from about 34 per 10000 live and stillbirths in 1974 to a plateau of just under 8 per 10000 in the 1990s. CONCLUSIONS: The decline in NTD prevalence is real and seems to have stopped. How this relates to changes in diet or the practice of vitamin supplementation is unknown, and the implications of the plateau are uncertain. OPCS figures of 500 NTDs annually in England and Wales represent about two thirds of the true number of cases.