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Background: The neurofibromatoses (NF) are genetic disorders. Increased risks of some cancers in people with NF are well recognised, but there is no comprehensive enumeration of the risks across the whole range of site-specific cancers. Our aim was to provide this.Methods: A linked data set of hospital admissions and deaths in England was used to compare rates of tumours in an NF cohort with rates in a comparison cohort, with results expressed as rate ratios (RR).Results: The RR for all cancers combined, in people with both types of NF combined, was 4.3 (95% confidence interval (CI): 4.0-4.6), based on 769 cases of cancer in 8003 people with NF. Considering only people with presumed NF1 (as defined in the main article), the RR for all cancers excluding nervous system malignancies remained elevated (2.7, 95% CI: 2.4-2.9); and risks were significantly high for cancer of the oesophagus (3.3), stomach (2.8), colon (2.0), liver (3.8), lung (3.0), bone (19.6), thyroid (4.9), malignant melanoma (3.6), non-Hodgkin's lymphoma (3.3), chronic myeloid leukaemia (6.7), female breast (2.3) and ovary (3.7).Conclusion: Neurofibromatosis was associated with an increased risk of many individual cancers. The relationships between NF and cancers may hold clues to mechanisms of carcinogenesis more generally. [ABSTRACT FROM AUTHOR]

Objective: To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders.Research Design and Methods: Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies.Results: Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little.Conclusions: The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies. [ABSTRACT FROM AUTHOR]

Objective: It is well recognised that variation in the geographical distribution of multiple sclerosis (MS) exists. Early studies in England have shown the disease to have been more common in the North than the South. However, this could be an artefact of inaccurate diagnosis and ascertainment, and recent data on MS prevalence are lacking. In the present study, data were analysed to provide a more contemporary map of the distribution of MS in England and, as infectious mononucleosis (IM) has been shown to be associated with the risk of MS, the geographical distribution of IM with that of MS was compared.Methods: Analysis of linked statistical abstracts of hospital data for England between 1999 and 2005.Results: There were 56,681 MS patients. The admission rate for MS was higher in females (22/10(5); 95% CI 21.8 to 22.3) than males (10.4/10(5); 95% CI 10.2 to 10.5). The highest admission rate for MS was seen for residents of Cumbria and Lancashire (North of England) (20.1/10(5); 95% CI 19.3 to 20.8) and the lowest admission rate was for North West London residents (South of England) (12.4/10(5); 95% CI 11.8 to 13.1). The geographical distributions of IM and MS were significantly correlated (weighted regression coefficient (r (w))=0.70, p<0.0001). Admission rates for MS were lowest in the area quintile with the highest level of deprivation and they were also lowest in the area quintile with the highest percentage of population born outside the UK. A significant association between northernliness and MS remained after adjustment for deprivation and UK birthplace.Conclusions: The results show the continued existence of a latitude gradient for MS in England and show a correlation with the distribution of IM. The data have implications for healthcare provision, because lifetime costs of MS exceed £1 million per case in the UK, as well as for studies of disease causality and prevention. [ABSTRACT FROM AUTHOR]

Objective To report on trends in mortality from appendicitis and from gallstone disease. Design and setting Analysis of data from death certificates including all certified causes of death, termed 'mentions', not just the underlying cause, using data from Oxford ('mentions' available from 1979 to 2006) and all England ('mentions' available from 1995 to 2006). Outcome measures Mortality rates across all years studied, and in periods defined by changes to national rules in selecting the underlying cause of death. Results In the Oxford region, mortality rates for appendicitis based on underlying cause fluctuated between periods defined by coding rule changes. Those based on mentions were more stable: they were 3.3 per million population in 1979-83 and 3.5 in 2001-6. Nationally, mentions-based rates fell from 3.4 per million in 1995-2000 to 3.1 in 2001-2006, a small but statistically significant decline. For gallstone disease in Oxford, rates fell in the early years but then levelled off. Mortality rates for gallstones in England actually rose slightly between 1995-2000 (15.0 deaths per million) and 2001-6 (15.6 per million). The majority of deaths from appendicitis and gallstone disease were in the elderly. Conclusions Appendicitis and gallstones are considered to be avoidable causes of death. Mortality rates for each cause have not shown any substantial falls in the recent periods covered by this study. It is possible that deaths were not, in fact, avoidable, but audits into the circumstances of deaths from these diseases may be warranted. Mortality data based on underlying cause alone substantially underestimate deaths from these two conditions. [ABSTRACT FROM AUTHOR]

Background. Some doctors who initially choose psychiatry do not pursue it as a long-term career. The study seeks to identify reasons for leaving psychiatry.Method. Postal questionnaire survey of UK medical graduates of 1988, 1993, 1996 and 1999 identified as having left psychiatry; for comparison, doctors who left general practice or trauma and orthopaedics.Results. Response rate was 74% (572/778); 488 respondents satisfied study criteria (59 psychiatry, 318 general practice, 111 trauma and orthopaedics). The speciality's poor public image, perceived lack of respect from medical peers, perceived threat of violence from patients, under-resourcing and low morale were problems for psychiatry leavers. Job stress, self-assessed unsuitability, and concerns about the lack of evidence-based treatments also influenced decisions to leave psychiatry.Conclusions. Early exposure to psychiatry may help trainees assess their suitability. Negative perceptions of workforce issues (e.g. low morale) and of clinical issues (e.g. perceived lack of ability to improve prognosis) need addressing to increase retention. [ABSTRACT FROM AUTHOR]

The Alcohol Harm Reduction Strategy for England, recently published, highlights current concerns about alcohol consumption in this country. We used a database to examine trends in mortality for all deaths certified as effects of alcohol from 1979-1999, including mentions as well as underlying cause, in a relatively prosperous population in southern England. Mortality, certified as direct effects of alcohol, tripled during the 21 years of study; and mortality rates based on mentions were about double those based on underlying cause. The increase in recent years in mortality based on mentions was considerably greater than that based on underlying cause. Data on age, sex and occupational social class show that people whose alcohol intake kills them are from a broad cross-section of society. [ABSTRACT FROM AUTHOR]

AIMS: Mortality statistics have customarily been coded and analysed using only one underlying cause of death. Rules for selecting the underlying cause, when more than one cause is certified on a death certificate, have changed twice in England over the past 20 years. We used data from death certificates for 1979-99 to compare mortality rates for diabetes mellitus certified anywhere on death certificates with those certified as the underlying cause. METHODS: Analysis of data from 18,917 death certificates that included diabetes mellitus in the former Oxford health region. RESULTS: Based on the underlying cause of death, mortality rates for diabetes varied substantially between the periods defined by rule changes. Based on mentions of diabetes anywhere on the death record, mortality rates were almost unchanged over time: they showed a non-significant rise of 0.1% per year (95% confidence interval -0.3, 0.6). Circulatory diseases were certified causes of death in 71% of all deaths in people with diabetes. Although mortality rates from circulatory diseases in the general population fell by 2.5% per year, rates for circulatory diseases in combination with diabetes did not fall. CONCLUSIONS: Two explanations are possible for the lack of change in mortality rates for diabetes based on all certified mentions between 1979 and 1999. Increasing prevalence and improved survival may have resulted in no net change; and/or there may have been no improvement in survival for people whose diabetes is associated with life-threatening pathology and in particular with circulatory diseases. Copyright 2004 Diabetes UK [ABSTRACT FROM AUTHOR]

We analysed a mortality database in which all causes of death on each death certificate were coded, as well as underlying cause, to study trends from 1979 to 1998. Multiple-cause-coded death rates for pneumonia and acute bronchitis fell steadily and consistently. There were complementary rises and falls in death rates for individual chronic obstructive pulmonary diseases (COPD)--chronic bronchitis, emphysema, chronic obstructive airways disease--attributable to changes in clinical terminology. Judged by underlying cause, death rates for COPD were lower than those for lung cancer; but, judged by all mentions, death rates for COPD were appreciably higher than for lung cancer. Death rates for COPD, like lung cancer, fell over time in women under 65 years of age and in men; and increased in older women. For all respiratory diseases studied, except lung cancer, the underlying cause of death alone considerably underestimated the extent of their certification on death certificates. [ABSTRACT FROM AUTHOR]

Until recently, national coding and analysis of routine mortality statistics in most countries included only underlying cause of death. There were changes in the rules for selection and coding of underlying cause in England in 1984 and 1993. We report on trends in mortality rates in an English region from 1979 to 1998, comparing multiple-cause and underlying-cause coded rates, for individual diseases that were affected by coding changes. Among many others, these include pneumonia, venous thromboembolism, heart failure, respiratory distress syndrome, tuberculosis, diabetes, dementia, alcohol and drug abuse, epilepsy, multiple sclerosis, stroke, asthma, peptic ulcer, appendicitis, and cancers of the breast, colon and prostate. Comparisons over time of mortality rates based on underlying cause alone will be misleading when the time-period crosses years in which rules changed for selecting underlying cause. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVE: To determine whether depression or anxiety co-occurs with ulcerative colitis (UC) or Crohn's disease (CD) more often than expected by chance, and, if so, whether the mental disorders generally precede or follow the inflammatory bowel diseases (IBD). DESIGN: Nested case-control studies using a database of linked hospital record abstracts. SETTING: Southern England. MAIN RESULTS: Both depression and anxiety preceded UC significantly more often than would be predicted from the control population's experience. The associations were strongest when the mental conditions were diagnosed shortly before UC, although the association between depression and UC was also significant when depression preceded UC by five or more years. Neither depression nor anxiety occurred before CD more often than expected by chance. However, depression and anxiety were significantly more common after CD; the associations were strongest in the year after the initial record of CD. UC was followed by anxiety, but not by depression, more often than expected by chance and, again, the association was strongest within one year of diagnosis with UC. CONCLUSIONS: The concentration of risk of depression or anxiety one year or less before diagnosis with UC suggests that the two psychiatric disorders might be a consequence of early symptoms of the as yet undiagnosed gastrointestinal condition. The data are also, however, compatible with the hypothesis that the psychiatric disorders could be aetiological factors in some patients with UC. Most of the excess anxiety or depression diagnosed subsequent to diagnosis of IBD occurs during the year after IBD is diagnosed and the probable explanation is that the mental disorders are sequelae of IBD. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine whether graduate entry to medical school, taking an intercalated degree during medical school, and age at entry to medical school are related to choice of eventual career. DesignPostal questionnaires. SettingUnited Kingdom (UK). SubjectsAll doctors who qualified in the UK in 1993 or 1996. ResultsWe analysed whether graduate status and age on entry to medical school, and taking an intercalated degree during medical school, were predictors of the choice of eventual career, adjusting for differences by sex, year of qualification and medical school. General practice was the career choice of 27·0% (79/293) of graduate entrants and 21·6% (1095/5073) of non-graduate entrants, a difference of borderline significance (P=0·04). Of the non-graduate entrants, general practice was the career choice of 15·3% (319/2081) of doctors who took an intercalated degree and 25·9% (776/2992) of doctors who did not (P < 0·001). Within the hospital specialties, those who took an intercalated degree were more likely than others to choose the hospital medical specialties or pathology. Age alone was not a predictor for choice of any area of practice. ConclusionsThere was no evidence of an association between age at entry to medical school and choice of eventual career. Graduates at entry to medical school were a little more likely than non-graduates to choose general practice but the relationship was not a strong one. In these respects, changing the entry profile of medical students is unlikely to result in major shifts of career choice towards general practice. [ABSTRACT FROM AUTHOR]

Background: Using data from the Oxford Record Linkage Study (ORLS) we conducted a case-control study to examine pre-natal and early life risk factors for childhood and adolescent onset diabetes mellitus.Methods: We identified 160 boys and 155 girls born 1965-1986 and admitted to hospital with a diagnosis of diabetes during 1965-1987 in the ORLS area. Up to eight controls were matched to each case on sex, year of birth and hospital or place of birth. We linked the hospital records for each child to all of that child's hospital records and to his or her mother's maternity record.Results: There were no significant associations between subsequent diabetes and birthweight, gestational age, birthweight for gestational age, maternal age and parity. There were increased risks with not breastfeeding (relative risk [RR] = 1.33; 95% CI: 0.76-2.34), and with diabetes recorded in the mother during pregnancy (RR = 5.87; 95% CI : 0.90-38.3), but these were not statistically significant. There was a significantly raised risk with pre-eclampsia or eclampsia during pregnancy (RR = 1.48; 95% CI: 1.05-2.10).Conclusions: Pre-eclampsia may be the result of an immunogenetic incompatibility between mother and fetus, and this early immunological disturbance might be related to incidence of diabetes in later life. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning the reduced incidence of cancer in Huntington's disease (HD).