Low risk of some common cancers in women with anorexia nervosa: Evidence from a national record-linkage study.

BACKGROUND: Some studies report that women with anorexia nervosa (AN) have lower risk than others of breast cancer, but increased risk of cancers of other sites. No work has been done to quantify the risk in the English population. METHODS: Retrospective cohort study using a national linked dataset of Hospital Episode Statistics for 1999-2021. We selected individuals with a hospital admission for AN, and compared their relative risk (RR) of developing site-specific cancers, with that in a reference cohort. RESULTS: We identified 75 cancers in 15,029 women hospitalised with AN. There was a low RR of all cancers combined at 0.75 (95%CI 0.59-0.94), and, notably, low RR for breast cancer 0.43 (0.20-0.81), cancers of secondary and ill-defined sites 0.52 (0.26-0.93). The RR for parotid gland cancer was 4.4 (1.4-10.6) within a year of first recorded diagnosis of AN. In men, we found 12 cancers in 1413 individuals hospitalised with AN, but no increased risks beyond the first year of diagnosis of AN. CONCLUSIONS: This is the first report on the association between AN and cancers in the all-England population. The study showed low rates of breast cancer, and of all cancers combined, in women hospitalised with AN. It is possible that some of the metabolic or hormonal changes observed in AN could work as a protective factor for breast cancer. More experimental work is needed to identify and explain these factors. The new finding on the higher risk of salivary gland tumours could inform clinicians caring for patients with AN.

National record-linkage study of hospital admissions for schizophrenia in childhood and adolescence in England.

BACKGROUND: There is a lack of information on changes in hospital admission rates for childhood-onset schizophrenia (COS), or on patient characteristics, to inform clinical research and health service provision. AIMS: To report age- and sex-specific incidence rates of hospital admissions and day patient care for schizophrenia (ICD-10 F20) and non-affective psychosis (ICD-10 F20-29), by year of occurrence and age, in childhood and adolescence. METHODS: Population-based study using person-linked data for England (available 2001-2016); time-periods in single years and 4-year groups. RESULTS: Hospitalised incidence for schizophrenia increased with increasing age, from 0.03 (95% confidence interval (CI) 0.02-0.05) and 0.01 (0-0.01) per 100,000 in, respectively, males and females aged 5-12 years, to 3.67 (3.44-3.91) in males and 1.58 (1.43-1.75) in females aged 13-17 years. There was no gender difference in hospitalised incidence rates in children aged 5-12, but in 13-17 years old, there was a male excess. Rates for schizophrenia were stable over time in 5-12 years old. In ages 13-17, rates for schizophrenia decreased between 2001-2004 and 2013-2016 in males, from 6.65 (6.04-7.31) down to 1.40 (1.13-1.73), and in females from 2.42 (2.05-2.83) to 1.18 (0.92-1.48). The hospitalisation rates for schizophrenia and non-affective psychosis, combined, in 13-17 years old decreased in males from 14.20 (13.30-15.14) in 2001-2004 to 10.77 (9.97-11.60) in 2013-2016, but increased in females from 7.49 (6.83-8.20) to 10.16 (9.38-11.00). CONCLUSIONS: The study confirms that childhood-onset schizophrenia is extremely rare, with only 32 cases identified over a 15-year period in the whole of England. The incidence of schizophrenia and non-affective psychosis increased substantially in adolescence; however, the marked reduction in the proportion of those diagnosed with schizophrenia in this age group suggests a possible change in diagnostic practice.

Clinical associations between gout and multiple sclerosis, Parkinson's disease and motor neuron disease: record-linkage studies.

BACKGROUND: Uric acid has antioxidant effects on neurons. Abnormally high levels of uric acid are, however, associated with gout. Previous studies have suggested that high levels of uric acid (and the presence of gout) may exert a protective effect against the risk of developing some neurological diseases. We aimed to investigate this hypothesis in a large database of hospital admissions in England. METHODS: We analysed a database of linked statistical records of hospital admissions and death registrations in England (1999-2012). A cohort of people with gout was constructed and followed for development of multiple sclerosis (MS), Parkinson's disease (PD) or motor neuron disease (MND). Then, conversely, cohorts of all people in the database with MS, PD or MND were constructed and followed for subsequent gout. Rate ratios (RRs) were determined, comparing these cohorts with people in a reference cohort. RESULTS: In the gout cohort, we observed a modest elevation of the overall risk of subsequent MS, PD and MND (respectively, RR = 1.27 (95% confidence interval 1.03-1.55), 1.11 (1.05-1.17) and 1.28 (1.11-1.48) which was largely attributable to an increased risk observed in the early years after hospitalisation for gout. The increased risk of neurological disease did not remain after 5 years. In the cohorts of people with MS or PD, there was a significantly reduced risk of subsequent gout admission (RR = 0.79 (0.69-0.89) and 0.83 (0.79-0.87), respectively). This inverse association was sustained over time. There was also a reduced risk of MND following gout which only emerged more than five years following initial gout admission (RR at 5+ years 0.35 (0.15-0.68)). CONCLUSIONS: This study investigated the epidemiological evidence for a protective role of high serum concentration of uric acid, for which we used gout as a proxy, in the aetiology of MS, PD or MND. Our observations do not support this hypothesis. However, when the order was reversed, and we retrospectively followed up patients with MS, PD and MND for a number of years, we found a statistically significant deficit of gout. This suggests that there is relationship between some aspects of these neurodegenerative diseases and metabolism of uric acid.

A protocol for a living mapping review of global research funding for infectious diseases with a pandemic potential - Pandemic PACT.

The COVID CIRCLE initiative Research Project Tracker by UKCDR and GloPID-R and associated living mapping review (LMR) showed the importance of sharing and analysing data on research at the point of funding to improve coordination during a pandemic. This approach can also help with research preparedness for outbreaks and hence our new programme the Pandemic Preparedness: Analytical Capacity and Funding Tracking Programme (Pandemic PACT) has been established. The LMR described in this protocol builds on the previous UKCDR and GloPID-R COVID-19 Research Project database with addition of the priority diseases from the WHO Blueprint list plus initial additions of pandemic influenza, mpox and plague. We capture data on new funding commitments directly from funders and map these against a core ontology (aligned to existing research roadmaps). We will analyse regularly collated new research funding commitments to provide an open, accessible, near-real-time overview of the funding landscape for a wide range of infectious disease and pandemic preparedness research and assess gaps. The periodicity of updates will be increased in the event of a major outbreak. We anticipate that this LMR and the associated online tool will be a useful resource for funders, policy makers and researchers. In the future, our work will inform a more coordinated approach to research funding by providing evidence and data, including identification of gaps in funding allocation with a particular focus on low- and middle-income countries.

Risk of pneumonia and pneumococcal disease in people with severe mental illness: English record linkage studies.

BACKGROUND: People with severe mental illness have a higher risk than others of some physical diseases. The risk of pneumococcal disease in people with mental disorders is unknown. This is potentially important because vaccines against the pneumococcus are available. METHODS: We used two datasets of linked hospital admission and death records, the Oxford Record Linkage Study and all-England linked Hospital Episode Statistics, to estimate the risk of lobar pneumonia and other pneumococcal disease (here, all collectively termed pneumococcal disease) in people hospitalised with schizophrenia, bipolar disorder, depression or anxiety. We compared rates of pneumococcal disease in each cohort with rates in a comparison cohort of people without a record of hospitalisation for these psychiatric disorders. FINDINGS: The risk of pneumococcal disease in each psychiatric group was significantly high in both datasets. In the English national dataset (spanning 1999-2011), the risk of pneumococcal disease in people hospitalised with schizophrenia, bipolar disorder, depression or anxiety was, respectively, 2.3 (95% CI 2.2 to 2.4), 2.3 (2.2 to 2.3), 2.1 (2.0 to 2.1) and 2.2 (2.1 to 2.2). The risk remained high for years after discharge, suggesting an association with the psychiatric disorder rather than with the event of hospitalisation. CONCLUSIONS: Severe mental illness is a risk factor for lobar pneumonia, pneumococcal pneumonia, pneumococcal septicaemia and meningitis. Possible explanations for the elevated risk include factors relating to lifestyle and health-risk activities. If our findings are replicated elsewhere, there would be a case for considering routine pneumococcal immunisation for people with severe mental illness.

Gout as a risk factor for myocardial infarction and stroke in England: evidence from record linkage studies.

OBJECTIVE: Some studies suggest that gout is a risk factor for cardiovascular disease. There is more evidence about the association between gout and acute myocardial infarction (MI) than about gout and stroke, and only limited information about risks by age group and sex. We aimed to study MI and stroke following gout, including types of stroke, by age group and comparing men and women. METHODS: We analysed an all-England national linked dataset of hospital admissions and death records from 1999 to 2011, and a similar dataset in the Oxford Record Linkage Study spanning 1963-98. The occurrence of MI and stroke was estimated in cohorts of patients admitted to hospital with gout, compared with MI and stroke in control cohorts, and the comparisons were expressed as rate ratios (RRs). RESULTS: The risk of MI and stroke was elevated, and similar, in both datasets. In the all-England dataset, which included 202 033 hospital patients with gout, the RR for MI following gout was 1.82 (95% CI 1.78, 1.85), for all stroke 1.71 (1.68, 1.75), ischaemic stroke 1.68 (1.64, 1.73), haemorrhagic stroke 1.69 (1.61, 1.77) and stroke of unspecified type 2.00 (1.95, 2.06). Associations were stronger in younger than older age groups, and in the younger were stronger in women than men. CONCLUSION: Gout was associated with increased risk of stroke as well as MI. These findings should be considered by clinicians and may have implications for preventive management of circulatory disease risks in people with gout.

Association between multiple sclerosis and epilepsy: large population-based record-linkage studies.

BACKGROUND: Multiple sclerosis (MS) and epilepsy are both fairly common and it follows that they may sometimes occur together in the same people by chance. We sought to determine whether hospitalisation for MS and hospitalisation for epilepsy occur together more often than expected by chance alone. METHODS: We analysed two datasets of linked statistical hospital admission records covering the Oxford Record Linkage Study area (ORLS, 1963-1998) and all England (1999-2011). In each, we calculated the rate of occurrence of hospital admission for epilepsy in people after admission for MS, compared with equivalent rates in a control cohort, and expressed the results as a relative risk (RR). RESULTS: The RR for hospital admission for epilepsy following an admission for MS was significantly high at 4.1 (95% confidence interval 3.1-5.3) in the ORLS and 3.3 (95% CI 3.1-3.4) in the all-England cohort. The RR for a first recorded admission for epilepsy 10 years and more after first recorded admission for MS was 4.7 (2.8-7.3) in ORLS and 3.9 (3.1-4.9) in the national cohort. The RR for the converse-MS following hospitalisation for epilepsy-was 2.5 (95% CI 1.7-3.5) in the ORLS and 1.9 (95% CI 1.8-2.1) in the English dataset. CONCLUSIONS: MS and epilepsy occur together more commonly than by chance. One possible explanation is that an MS lesion acts as a focus of an epileptic seizure; but other possibilities are discussed. Clinicians should be aware of the risk of epilepsy in people with MS. The findings may also suggest clues for researchers in developing hypotheses about underlying mechanisms for the two conditions.

Risk of subarachnoid haemorrhage in people admitted to hospital with selected immune-mediated diseases: record-linkage studies.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating cause of stroke, occurring in relatively young people. It has been suggested that some immune-mediated diseases may be associated with an increased risk of SAH. METHODS: We analysed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999-2011). Rate ratios for SAH were determined, comparing immune-mediated disease cohorts with comparison cohorts. RESULTS: There were significantly elevated risks of SAH after hospital admission for the following individual immune-mediated diseases: Addison's disease, ankylosing spondylitis, autoimmune haemolytic anaemia, Crohn's disease, diabetes mellitus, idiopathic thrombocytopenia purpura, myxoedema, pernicious anaemia, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, scleroderma, Sjogren's syndrome, SLE and thyrotoxicosis. Elevated risks that were greater than 2-fold were found for Addison's disease (rate ratio (RR) = 2.01, 95% confidence interval 1.3-2.97), idiopathic thrombocytopenia purpura (RR = 2.42, 1.86-3.11), primary biliary cirrhosis (RR = 2.21, 1.43-3.16) and SLE (RR = 3.76, 3.08-4.55). CONCLUSIONS: Our findings strongly support the suggestion that patients with some immune-mediated diseases have an increased risk of SAH. Further studies of the mechanisms behind this association are warranted.

Risk of fractures in patients with multiple sclerosis: record-linkage study.

BACKGROUND: Patients with multiple sclerosis (MS) have been reported to be at higher risk of fracture than other people. We sought to test this hypothesis in a large database of hospital admissions in England. METHODS: We analysed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999-2010). Rate ratios for fractures were determined, comparing fracture rates in a cohort of all people in England admitted with MS and rates in a comparison cohort. RESULTS: Significantly elevated risk for all fractures was found in patients with MS (rate ratio (RR) = 1.99, 95% confidence interval (CI) = 1.93-2.05)). Risks were particularly high for femoral fractures (femoral neck fracture RR = 2.79 (2.65-2.93); femoral shaft fracture RR 6.69 (6.12-7.29)), and fractures of the tibia or ankle RR = 2.81 (2.66-2.96). CONCLUSIONS: Patients with MS have an increased risk of fractures. Caregivers should aim to optimize bone health in MS patients.

Relative contribution of trends in myocardial infarction event rates and case fatality to declines in mortality: an international comparative study of 1·95 million events in 80·4 million people in four countries.

BACKGROUND: Myocardial infarction mortality has declined since the 1970s, but contemporary drivers of this trend remain unexplained. The aim of this study was to compare the contribution of trends in event rates and case fatality to declines in myocardial infarction mortality in four high-income jurisdictions from 2002-15. METHODS: Linked hospitalisation and mortality data were obtained from New South Wales (NSW), Australia; Ontario, Canada; New Zealand; and England, UK. People aged between 30 years and 105 years were included in the study. Age-adjusted trends in myocardial infarction event rates and case fatality were estimated from Poisson and binomial regression models, and their relative contribution to trends in myocardial infarction mortality calculated. FINDINGS: 1 947 895 myocardial infarction events from a population of 80·4 million people were identified in people aged 30 years or older. There were significant declines in myocardial infarction mortality, event rates, and case fatality in all jurisdictions. Age-standardised myocardial infarction event rates were highest in New Zealand (men 893/100 000 person-years in 2002, 536/100 000 person-years in 2015; women 482/100 000 person-years in 2002, 271/100 000 person-years in 2015) and lowest in England (men 513/100 000 person-years in 2002, 382/100 000 person-years in 2015; women 238/100 000 person-years in 2002, 173/100 000 person-years in 2015). Annual age-adjusted reductions in event rates ranged from -2·6% (95% CI -3·0 to -2·3) in men in England to -4·3% (-4·4 to -4·1) in women in Ontario. Age-standardised case fatality was highest in England in 2002 (48%), but declined at a greater rate than in the other jurisdictions (men -4·1%/year, 95% CI -4·2 to -4·0%; women -4·4%/year, -4·5 to -4·3%). Declines in myocardial infarction mortality rates ranged from -6·1%/year to -7·6%/year. Event rate declines were the greater contributor to myocardial infarction mortality reductions in Ontario (69·4% for men and women), New Zealand (men 68·4%; women 67·5%), and NSW women (60·1%), whereas reductions in case fatality were the greater contributor in England (60% in men and women) and for NSW men (54%). There were greater contributions from case fatality than event rate reductions in people younger than 55 years in all jurisdictions, with contributions to mortality declines varying by country in those aged 55-74 years. Event rate declines had a greater impact than changes in case fatality in those aged 75 years and older. INTERPRETATION: While the mortality burden of myocardial infarction has continued to fall across these four populations, the relative contribution of trends in myocardial infarction event rates and case fatality to declining mortality varied between jurisdictions, including by age and sex. Understanding the causes of this variation will enable optimisation of prevention and treatment efforts. FUNDING: National Health and Medical Research Council, Australia; Australian Research Council; Health Research Council of New Zealand; Canadian Institutes of Health Research, Canada; National Institute for Health Research, UK.

Determinants of the decline in mortality from acute stroke in England: linked national database study of 795 869 adults.

OBJECTIVES: To study trends in stroke mortality rates, event rates, and case fatality, and to explain the extent to which the reduction in stroke mortality rates was influenced by changes in stroke event rates or case fatality. DESIGN: Population based study. SETTING: Person linked routine hospital and mortality data, England. PARTICIPANTS: 795 869 adults aged 20 and older who were admitted to hospital with acute stroke or died from stroke. MAIN OUTCOME MEASURES: Stroke mortality rates, stroke event rates (stroke admission or stroke death without admission), and case fatality within 30 days after stroke. RESULTS: Between 2001 and 2010 stroke mortality rates decreased by 55%, stroke event rates by 20%, and case fatality by 40%. The study population included 358 599 (45%) men and 437 270 (55%) women. Average annual change in mortality rate was -6.0% (95% confidence interval -6.2% to -5.8%) in men and -6.1% (-6.3% to -6.0%) in women, in stroke event rate was -1.3% (-1.4% to -1.2%) in men and -2.1% (-2.2 to -2.0) in women, and in case fatality was -4.7% (-4.9% to -4.5%) in men and -4.4% (-4.5% to -4.2%) in women. Mortality and case fatality but not event rate declined in all age groups: the stroke event rate decreased in older people but increased by 2% each year in adults aged 35 to 54 years. Of the total decline in mortality rates, 71% was attributed to the decline in case fatality (78% in men and 66% in women) and the remainder to the reduction in stroke event rates. The contribution of the two factors varied between age groups. Whereas the reduction in mortality rates in people younger than 55 years was due to the reduction in case fatality, in the oldest age group (≥85 years) reductions in case fatality and event rates contributed nearly equally. CONCLUSIONS: Declines in case fatality, probably driven by improvements in stroke care, contributed more than declines in event rates to the overall reduction in stroke mortality. Mortality reduction in men and women younger than 55 was solely a result of a decrease in case fatality, whereas stroke event rates increased in the age group 35 to 54 years. The increase in stroke event rates in young adults is a concern. This suggests that stroke prevention needs to be strengthened to reduce the occurrence of stroke in people younger than 55 years.

Risk of individual malignant neoplasms in patients with sickle cell disease: English national record linkage study.

OBJECTIVE: Case reports suggest that there may be an increased risk of some cancers associated with sickle cell disease. However, population-based studies are scarce and there is no comprehensive enumeration of the risks across the whole range of site-specific cancers. Our aim was to provide this. DESIGN: We used an English national dataset of linked statistical records of hospital admissions and deaths from 1999 to 2011 to undertake a retrospective cohort study. SETTING: England. PARTICIPANTS: Records of all hospital admissions in England with SCD or with conditions included in the control cohort. MAIN OUTCOME MEASURES: Rate ratios were calculated comparing rates of cancer in a sickle cell disease cohort and a control cohort, confining the analyses to people whose ethnicity was recorded as Black. RESULTS: Comparing the sickle cell disease cohort with the cohort without sickle cell disease, the rate ratio for all cancers combined was 2.1 (95% confidence interval 1.7-2.5). There were significantly high rate ratios for haematological malignancies, including Hodgkin's lymphoma (rate ratio 3.7, 1.5-8.4), non-Hodgkin's lymphoma (2.6, 1.3-4.8), multiple myeloma (5.5, 2.8-10.1), lymphoid leukaemia (3.3, 1.3-8.0) and myeloid leukaemia (10.0, 4.6-21.5). Four solid tumours showed elevated rate ratios: colon cancer (2.8, 1.2-5.5), non-melanoma skin cancer (4.4, 1.3-12.2), kidney cancer (5.4, 2.3-11.5) and thyroid cancer (5.1, 1.3-15.4). CONCLUSIONS: The risk of some malignancies may be raised in patients with sickle cell disease. However, this study was based on administrative data without the scope to validate these against patients' full clinical records. Our findings need confirmation or refutation. If confirmed, work to elucidate, at the genetic and molecular level, why people with sickle cell disease have elevated risks of individual cancers might make contributions to the fundamental understanding of carcinogenesis.

Associations between Klinefelter's syndrome and autoimmune diseases: English national record linkage studies.

There are reports suggesting that people with Klinefelter's syndrome (KS) may be at increased risk of some autoimmune diseases, but the evidence is not substantial. We wanted to add to the evidence by systematically assessing the risk of autoimmune diseases in a national cohort of people with KS. We selected records of all people with KS in a record-linked dataset of all hospital day cases and inpatient admissions in England, 1999-2011; and we followed them up by electronic record linkage to identify the occurrence of autoimmune diseases. We compared their occurrence in the KS cohort with a control cohort, studied in the same way, and expressed the results as rate ratios (RR). Of 30 autoimmune diseases studied in people with KS, there were significantly increased risks of seven-Addison's disease (RR 11.7, 95% confidence interval 2.4-34.4), diabetes mellitus type 1 (6.1, 4.4-8.3), multiple sclerosis (4.3, 1.2-11.0), acquired hypothyroidism (2.7, 1.8-4.0), rheumatoid arthritis (3.3, 2.0-5.2), Sjogren's syndrome (19.3, 4.0-57.0) and systemic lupus erythematosus (18.1, 2.2-65.6). We concluded that people with KS have increased risk of some autoimmune diseases, particularly those that are female-predominant. The increased risk of autoimmune diseases associated with the XXY karyotype may hold clues to the pathogenesis of some aspects of autoimmunity.

Turner syndrome and autoimmune diseases: record-linkage study.

BACKGROUND: There is increasing evidence that Turner syndrome is associated with an elevated risk of a range of autoimmune disorders. We aimed to document this in a national study. METHOD: Use of a record-linked dataset of all hospital admissions in England, 1999-2011, to construct a retrospective cohort of people with Turner syndrome and a control cohort of people without it. Statistical follow-up to identify the occurrence of 29 separate autoimmune disorders in each cohort. Calculation of rate ratios, comparing the Turner and control cohorts. RESULTS: In the Turner syndrome cohort (2459 people), rate ratios were elevated for 16 of the 29 conditions. Examples included coeliac disease (rate ratio 14.0, 95% CI 10.2 to 18.8), Crohn's disease (5.3, 3.5 to 7.8), ulcerative colitis (3.9, 2.3 to 6.1), hypothyroidism (8.8, 7.8 to 9.9) and hyperthyroidism (4.9, 3.2 to 7.1). CONCLUSIONS: The increased risk of autoimmune disorders in people with Turner syndrome covers a wide range of conditions.

Risk of self-harm and suicide in people with specific psychiatric and physical disorders: comparisons between disorders using English national record linkage.

Background Psychiatric illnesses are known risk factors for self-harm but associations between self-harm and physical illnesses are less well established. We aimed to stratify selected chronic physical and psychiatric illnesses according to their relative risk of self-harm. Design Retrospective cohort studies using a linked dataset of Hospital Episode Statistics (HES) for 1999-2011. Participants Individuals with selected psychiatric or physical conditions were compared with a reference cohort constructed from patients admitted for a variety of other conditions and procedures. Setting All admissions and day cases in National Health Service (NHS) hospitals in England. Main outcome measures Hospital episodes of self-harm. Rate ratios (RRs) were derived by comparing admission for self-harm between cohorts. Results The psychiatric illnesses studied (depression, bipolar disorder, alcohol abuse, anxiety disorders, eating disorders, schizophrenia and substance abuse) all had very high RRs (> 5) for self-harm. Of the physical illnesses studied, an increased risk of self-harm was associated with epilepsy (RR = 2.9, 95% confidence interval [CI] 2.8-2.9), asthma (1.8, 1.8-1.9), migraine (1.8, 1.7-1.8), psoriasis (1.6, 1.5-1.7), diabetes mellitus (1.6, 1.5-1.6), eczema (1.4, 1.3-1.5) and inflammatory polyarthropathies (1.4, 1.3-1.4). RRs were significantly low for cancers (0.95, 0.93-0.97), congenital heart disease (0.9, 0.8-0.9), ulcerative colitis (0.8, 0.7-0.8), sickle cell anaemia (0.7, 0.6-0.8) and Down's syndrome (0.1, 0.1-0.2). Conclusions Psychiatric illnesses carry a greatly increased risk of self-harm as well as of suicide. Many chronic physical illnesses are also associated with an increased risk of both self-harm and suicide. Identifying those at risk will allow provision of appropriate monitoring and support.