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Analysis by sex: observed numbers of people with NMSC who had a subsequent record of primary malignant cancer, risk ratios (RR) and 95% confidence intervals

Background: Conflicting evidence exists about whether people with a history of nonmelanoma skin cancer (NMSC) are at higher risk of subsequent primary malignant cancers than those without.Methods: An all England record-linked hospital and mortality dataset spanning from 1999 to 2011 was used. We constructed two cohorts: one that comprised people with a history of NMSC (502,490 people), and a control cohort that comprised people without. We “followed up” these two cohorts electronically to determine observed and expected numbers of people with subsequent primary cancers in each, based on person-years at risk, and calculated standardized risk ratios (RR).Results: Comparing the NMSC cohort with the non-NMSC cohort, the RR for all subsequent malignant cancers combined was 1.36 [95% confidence interval (CI), 1.35–1.37]. Significantly increased RRs (P < 0.05) were found for 26 of the 29 cancer types studied, in particular for salivary gland, melanoma, bone, and upper gastrointestinal tract cancers. The RRs were also particularly high when comparing younger people with and without NMSC.Conclusions: NMSC is strongly associated with a broad spectrum of other primary cancers, particularly in younger age groups. The pattern suggests a genetic or early-acquired etiologic association.Impact: These results represent what can be done using very large, linked, routinely collected administrative datasets; but such datasets lack detail. Further work to establish the mechanisms behind these associations is warranted. Cancer Epidemiol Biomarkers Prev; 23(3); 490–8. ©2014 AACR.

OBJECTIVE Occasionally, patients with eating disorders have been subsequently diagnosed with esophageal achalasia. We sought to establish whether eating disorders and achalasia coexisted more often than expected by chance alone. METHOD National record-linkage study of hospital inpatients in England, between 2001 and 2017. Use of Cox proportional hazards to compare the occurrence of achalasia in cohorts of people with or without anorexia nervosa (AN), and with or without bulimia nervosa (BN), with adjustment of the comparisons for such confounders as age, sex, and year of admission. RESULTS There were 18,500 people in the AN cohort, 11,300 in the BN cohort, and 8.7 million in the comparison cohort. The Cox regression hazard ratio, comparing the AN cohort with the reference cohort, was 3.4 (95% confidence interval 1.8-6.3) and that in the BN cohort was 4.2 (2.2-8.2). DISCUSSION AN and achalasia, and BN and achalasia, were diagnosed in the same individuals, more often than expected by chance. Clinicians should be aware of the possible associations with achalasia because the treatment of eating disorders and achalasia is different.

BackgroundAlthough morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described.MethodsAnalyses used national administrative electronic hospital records in England, Scotland and Wales for 2016-2021. Admissions and procedures during the pandemic (2020-2021) related to six major cardiovascular conditions (acute coronary syndrome, heart failure, stroke/transient ischaemic attack, peripheral arterial disease, aortic aneurysm, and venous thromboembolism) were compared to the annual average in the pre-pandemic period (2016-2019). Differences were assessed by time period and urgency of care.ResultsIn 2020, there were 31,064 (−6%) fewer hospital admissions (14,506 [-4%] fewer emergencies, 16,560 [-23%] fewer elective admissions) compared to 2016-2019 for the six major cardiovascular diseases combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries (−10,996 [-15%] fewer admissions). However, these reductions were offset by higher than expected total emergency admissions (+25,878 [+6%] higher admissions), notably for heart failure and stroke in England, and for venous thromboembolism in all three countries. Analyses for procedures showed similar temporal variations to admissions.ConclusionThis study highlights increasing emergency cardiovascular admissions as a result of the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.Key QuestionWhat is the impact in 2020 and 2021 of the COVID-19 pandemic on hospital admissions and procedures for six major cardiovascular diseases in England, Scotland and Wales?Key FindingIn 2020, there were 6% fewer hospital admissions (emergency: -4%, elective: -23%) compared to 2016-2019 for six major cardiovascular diseases, across three UK countries. Overall, admissions returned to pre-pandemic levels in 2021, but elective admissions remained below expected levels.Take-home MessageThere was increasing emergency cardiovascular admissions as a result of the pandemic, with substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.

Background Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described. Methods and results Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016–21. Admissions and procedures during the pandemic (2020–21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016–19). Differences were assessed by time period and urgency of care. In 2020, there were 31 064 (−6%) fewer hospital admissions [14 506 (−4%) fewer emergencies, 16 560 (−23%) fewer elective admissions] compared with 2016–19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [−10 996 (−15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions. Conclusion The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.

Background Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. Methods In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. Findings Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. Interpretation Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. Funding British Heart Foundation Data Science Centre, led by Health Data Research UK.

ObjectiveTo investigate the association between type 2 diabetes mellitus (T2DM) and subsequent Parkinson disease (PD).MethodsLinked English national Hospital Episode Statistics and mortality data (1999–2011) were used to conduct a retrospective cohort study. A cohort of individuals admitted for hospital care with a coded diagnosis of T2DM was constructed, and compared to a reference cohort. Subsequent PD risk was estimated using Cox regression models. Individuals with a coded diagnosis of cerebrovascular disease, vascular parkinsonism, drug-induced parkinsonism, and normal pressure hydrocephalus were excluded from the analysis.ResultsA total of 2,017,115 individuals entered the T2DM cohort and 6,173,208 entered the reference cohort. There were significantly elevated rates of PD following T2DM (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.29–1.35; p < 0.001). The relative increase was greater in those with complicated T2DM (HR 1.49, 95% CI 1.42–1.56) and when comparing younger individuals (HR 3.81, 95% CI 2.84–5.11 in age group 25–44 years).ConclusionsWe report an increased rate of subsequent PD following T2DM in this large cohort study. These findings may reflect shared genetic predisposition and/or disrupted shared pathogenic pathways with potential clinical and therapeutic implications.

BackgroundThe epidemiology of psychiatric comorbidity in multiple sclerosis (MS) remains poorly understood.ObjectiveWe aimed to determine the risk of schizophrenia and bipolar disorder in MS patients.Material and MethodsRetrospective cohort analyses were performed using an all-England national linked Hospital Episode Statistics (HES) dataset (1999-2016) and to determine whether schizophrenia or bipolar disorder are more commonly diagnosed subsequently in people with MS (n=128,194), and whether MS is more commonly diagnosed subsequently in people with schizophrenia (n=384,188) or bipolar disorder (n=203,592), than would be expected when compared with a reference cohort (∼15 million people) after adjusting for age and other factors. Adjusted hazard ratios (aHRs) were calculated using Cox proportional hazards models.ResultsFindings were dependent on whether the index and subsequent diagnoses were selected as the primary reason for hospital admission or were taken from anywhere on the hospital record. When searching for diagnoses anywhere on the hospital record, there was a significantly elevated risk of subsequent schizophrenia (aHR 1.51, 95% confidence interval (CI) 1.40 to 1.60) and of bipolar disorder (aHR 1.14, 95% CI 1.04 to 1.24) in people with prior-recorded MS and of subsequent MS in people with prior-recorded schizophrenia (aHR 1.26, 1.15-1.37) or bipolar disorder (aHR 1.73, 1.57-1.91), but most of these associations were reduced to null when analyses were confined to diagnoses recorded as the primary reason for admission.ConclusionFurther research is needed to investigate the potential association between MS and schizophrenia and/or bipolar disorder as it may shed light on underlying pathophysiology and help identify potential shared risk factors.

Background Population-based coronary heart disease (CHD) studies have historically focused on myocardial infarction (MI) with limited data on trends across the spectrum of CHD. We investigated trends in hospitalisation rates for acute and chronic CHD subgroups in England and Australia from 1996–2013. Methods CHD hospitalisations for 35–84 year olds were identified using the primary diagnosis in electronic hospital records from 1996–2013 for England and Australia and from the Oxford Region and Western Australia (WA). CHD subgroups identified were acute coronary syndromes (MI and unstable angina) and chronic CHD (stable angina and ‘Other CHD’). We calculated age-standardised and age-specific rates, and estimated annual changes (95% CI) from age-adjusted Poisson regression separately for 1996–2003 and 2004–2013 to account for non-linear trends. Regional person-linked data from the Oxford Region and WA were used to account for the effect of transfers and coronary procedure admissions on trends. Results From 1996–2013, there were 4.9 million CHD hospitalisations in England and 2.6 million in Australia (67% men). From 1996–2003, there was between-country variation in the direction of trends in acute coronary syndromes (ACS) and chronic CHD hospitalisation rates (p Conclusion Since 2004, rates of all CHD subgroups have fallen in both countries, with greater declines in acute than chronic presentations. The slower declines and high proportion of chronic CHD admissions involving coronary procedures requires greater focus. Differing MI trends in younger women in both countries warrant further investigation.

BackgroundPopulation-based coronary heart disease (CHD) studies have focused on myocardial infarction (MI) with limited data on trends across the spectrum of CHD. We investigated trends in hospitalisation rates for acute and chronic CHD subgroups in England and Australia from 1996 to 2013.MethodsCHD hospitalisations for individuals aged 35–84 years were identified from electronic hospital data from 1996 to 2013 for England and Australia and from the Oxford Region and Western Australia. CHD subgroups identified were acute coronary syndromes (ACS) (MI and unstable angina) and chronic CHD (stable angina and ‘other CHD’). We calculated age-standardised and age-specific rates and estimated annual changes (95% CI) from age-adjusted Poisson regression.ResultsFrom 1996 to 2013, there were 4.9 million CHD hospitalisations in England and 2.6 million in Australia (67% men). From 1996 to 2003, there was between-country variation in the direction of trends in ACS and chronic CHD hospitalisation rates (pConclusionsSince 2004, rates of all CHD subgroups have fallen, with greater declines in acute than chronic presentations. The slower declines and high proportion of chronic CHD admissions undergoing coronary procedures requires greater focus.

Aims To study trends over time in the incidence of congenital anophthalmia, microphthalmia, and orbital malformations in England, along with changes in hospital admission rates for these conditions. Methods Using English national hospital episode statistics, the annual rate of hospital admissions related to anophthalmia (1990-2011), microphthalmia (1990-2011) and congenital malformations of orbit/ of lacrimal apparatus (1999-2011) were calculated per 100,000 infants. The records were person-linked from 1999 to 2011, which enabled annual person-based ‘first record’ rates to be calculated as proxies for incidence. Results The annual incidence of congenital anophthalmia remained stable in England over the period 1999-2011 at approximately 1.5 (95% CI 1.2-1.8) cases per 100,000 infants. The annual incidence of congenital microphthalmia increased modestly in recent years, for example from 5.9 (95% CI 3.9-7.8) cases per 100,000 infants in 2004 to 11.4 (95% CI 8.9-14.0) in 2010. The annual incidence of hospitalised congenital orbital/lacrimal malformations remained steady over the study period. Counting multiple admissions per person, annual admission rates for anophthalmia fluctuated but generally remained stable. They doubled for microphthalmia from 11.0 (95% CI 8.4-13.5) admissions per 100,000 infants in 1990 to 22.1 (95% CI 17.7-24.6) in 2011. They showed a small non-significant increase for orbital/lacrimal malformations. Conclusion The incidence of congenital anophthalmia has remained stable in England in recent years, as has that of congenital orbital/lacrimal malformations, while the incidence of microphthalmia has increased modestly. Hospital admission rates for this group of conditions increased over time. These data may be useful for planning service provision.

Background Primary open angle glaucoma (POAG) is thought to be associated with obstructive sleep apnoea (OSA) but previous studies are conflicting and have methodological limitations. This potential relationship has implications for investigation and treatment strategies, and may provide insights into disease pathogenesis. The relationship between OSA and age-related macular degeneration (AMD) is unknown. Methods A sleep apnoea cohort of 67 786 people was constructed from linked English hospital episode statistics (1999–2011). We compared this cohort with a reference cohort (2 684 131 people) for rates of subsequent POAG and AMD. A POAG cohort (comprising 87 435 people) and an AMD cohort (248 408 people) were also constructed and compared with the reference cohort for rates of subsequent sleep apnoea. All analyses were restricted to people aged 55 and over and, within this age range, were age standardised using 5-year age groups. Results Risk of POAG following sleep apnoea was not elevated: the rate ratio for POAG was 1.01 (95% CI 0.85 to 1.19). Similarly, the risk of sleep apnoea following POAG was not elevated: the rate ratio was 1.00 (0.86 to 1.17). These findings held true across subgroup analysis according to sex and age group. By contrast, the risk of AMD following sleep apnoea was significantly elevated, with rate ratio 1.44 (1.32 to 1.57). Conclusions Although plausible mechanisms exist to consider a link between OSA and POAG, the two conditions are not positively associated. This holds true in either temporal direction. By contrast, OSA is positively associated with AMD. While potential confounding factors may contribute, obesity does not appear sufficient to explain this association.

The epidemiologic relationship between age-related macular degeneration (AMD) and arthritis is unknown and has implications for understanding disease pathogenesis and treatment strategies.An AMD cohort of 245,912 people was constructed from English linked hospital episode statistics (1999-2011), principally comprising neovascular AMD patients undergoing anti-vascular endothelial growth factor therapy. We compared the AMD cohort with a reference cohort (2,134,771 people) for rates of subsequent osteoarthritis (OA) and rheumatoid arthritis. Osteoarthritis (2,032,472 people) and rheumatoid arthritis (261,232 people) cohorts were also constructed and compared with the reference cohort for rates of subsequent AMD.Risk of arthritis after AMD was not elevated. The rate ratio for OA was 0.96 (95% confidence interval 0.95-0.97) and for rheumatoid arthritis was 0.98 (0.94-1.02). However, risk of AMD after arthritis was modestly raised. For OA, the rate ratio was 1.06 (1.04-1.08), but risk increased with longer OA duration, for example, 1.15 (1.08-1.23) for10 years. For rheumatoid arthritis, the rate ratio was also modestly elevated at 1.15 (1.12-1.19).Age-related macular degeneration and arthritis are degenerative aging conditions that share some disease mechanisms and extracellular matrix involvement. However, considering arthritis after AMD, they are not positively associated. By contrast, people with OA experience modestly increased AMD risk, perhaps owing to medical treatments for OA.

Introduction: The profile of psychiatric disorders associated with multiple sclerosis (MS) may differ in children. We aimed to assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa. Patients and methods: We analyzed linked English Hospital Episode Statistics, and mortality data, 1999–2011. Cohorts were constructed of children admitted with MS and other central nervous system (CNS) demyelinating diseases. We searched for any subsequent episode of care with psychiatric disorders in these cohorts and compared to a reference cohort. Results: Children with CNS demyelinating diseases had an increased rate of psychotic disorders (rate ratio (RR) = 5.77 (95% confidence interval (CI) = 2.48–11.41)); anxiety, stress-related, and somatoform disorders (RR = 2.38 (1.39–3.81)); intellectual disability (RR = 6.56 (3.66–10.84)); and other behavioral disorders (RR = 8.99 (5.13–14.62)). In analysis of the pediatric MS cohort as the exposure, there were elevated rates of psychotic disorders (RR = 10.76 (2.93–27.63)), mood disorders (RR = 2.57 (1.03–5.31)), and intellectual disability (RR = 6.08 (1.25–17.80)). In reverse analyses, there were elevated rates of a recorded hospital episode with CNS demyelinating disease after a previous recorded episode with anxiety, stress-related, and somatoform disorders; attention-deficit hyperactivity disorder (ADHD); autism; intellectual disability; and other behavioral disorders. Conclusion: This analysis of a national diagnostic database provides strong evidence for an association between pediatric CNS demyelinating diseases and psychiatric disorders, and highlights a need for early involvement of mental health professionals.

Importance: Spontaneous pneumothorax is a common disease known to have an unusual epidemiological profile, but there are limited contemporary population-based data. Objective: To estimate the incidence of hospital admissions for spontaneous pneumothorax, its recurrence and trends over time using large, longstanding hospitalization data sets in England. Design, Setting, and Participants: A population-based epidemiological study was conducted using an English national data set and an English regional data set, each spanning 1968 to 2016, and including 170 929 hospital admission records of patients 15 years and older. Final date of the study period was December 31, 2016. Exposures: Calendar year (for incidence) and readmission to hospital for spontaneous pneumothorax (for recurrence). Main Outcomes and Measures: Primary outcomes were rates of hospital admissions for spontaneous pneumothorax and recurrence, defined as a subsequent hospital readmission with spontaneous pneumothorax. Record-linkage was used to identify multiple admissions per person and comorbidity. Risk factors for recurrence over 5 years of follow-up were assessed using cumulative time-to-failure analysis and Cox proportional hazards regression. Results: From 1968 to 2016, there were 170 929 hospital admissions for spontaneous pneumothorax (median age, 44 years [IQR, 26-88]; 73.0% male). In 2016, there were 14.1 spontaneous pneumothorax admissions per 100 000 population 15 years and older (95% CI, 13.7-14.4), a significant increase compared with earlier years, up from 9.1 (95% CI, 8.1-10.1) in 1968. The population-based rate per 100 000 population 15 years and older was higher for males (20.8 [95% CI, 20.2-21.4]) than for females (7.6 [95% CI, 7.2-7.9]). Of patients with spontaneous pneumothorax, 60.8% (95% CI, 59.5%-62.0%) had chronic lung disease. Record-linkage analysis demonstrated that the overall increase in admissions over time could be due in part to an increase in repeat admissions, but there were also significant increases in the annual rate of first-known spontaneous pneumothorax admissions in some population subgroups, for example in women 65 years and older (annual percentage change from 1968 to 2016, 4.08 [95% CI, 3.33-4.82], P Conclusions and Relevance This study provides contemporary information regarding the trends in incidence and recurrence of inpatient-treated spontaneous pneumothorax.

AimsNon-specific abdominal pain (NSAP) is the most common diagnosis on discharge following admission for abdominal pain in childhood. Our aim was to determine the risk of subsequent hospital diagnosis of organic and functional gastroenterological conditions following a diagnosis of NSAP, and to assess the persistence of this risk.MethodsAn NSAP cohort of 268 623 children aged 0–16 years was constructed from linked English Hospital Episode Statistics from 1999 to 2011. The control cohort (1 684 923 children, 0–16 years old) comprised children hospitalised with unrelated conditions. Clinically relevant outcomes were selected and standardised rate ratios were calculated.ResultsFrom the NSAP cohort, 15 515 (5.8%) were later hospitalised with bowel pathology and 13 301 (5%) with a specific functional disorder. Notably, there was a 4.84 (95% CI 4.45 to 5.27) times greater risk of Crohn's disease following NSAP and a 4.23 (4.13 to 4.33) greater risk of acute appendicitis than in the control cohort. The risk of irritable bowel syndrome (IBS) was 7.22 (6.65 to 7.85) times greater following NSAP. The risks of inflammatory bowel disease (IBD), IBS and functional disorder (unspecified) were significantly increased in all age groups except ConclusionsOnly a small proportion of those with NSAP go on to be hospitalised with underlying bowel pathology. However, their risk is increased even at 10 years after the first hospital admission with NSAP. Diagnostic strategies need to be assessed and refined and active surveillance employed for children with NSAP.

Aims To investigate English national trends in ophthalmia neonatorum and dacryocystitis (ON) of the newborn and the completeness of statutory notification of this serious infection. Design Analysis of hospital episode statistics (HES) from 2000 to 2011. Materials and methods Using linked HES, numbers of neonates hospitalised with ON were identified from 2000 to 2011. The numbers of hospitalised cases were compared with numbers of statutory notifications for ON published by the Notifications of Infectious Diseases (NOIDS). Results The national incidence rate of hospitalised cases showed a gradual decline from 464 (95% CI 447 to 482) per 100 000 live births in 2000 to 216 (204 to 228) per 100 000 live births in 2005. It then gradually increased to 471 (455 to 487) per 100 000 live births in 2010, but dropped to 257 (245 to 269) per 100 000 in 2011. From 2000 to 2009, when NOIDS data were available, the NOIDS data showed only 1006 cases compared with 20 505 cases in HES, and thus the notification system captured only about 1 case in 20. Conclusions As shown by hospital statistics, there were marked cyclical fluctuations in ON over the study period. The annual figures for ON reported during the study period, under statutory health protection regulations, underestimated the actual occurrence of this disease by a very substantial amount. Linked hospital data should be used routinely to monitor the national incidence of ON.

Systemic lupus erythematosus (SLE) has a high female predominance with a 9:1 female-to-male sex ratio, but males have poorer clinical outcomes than females. Gonadal hormones may mediate gender differences in SLE, but their role in SLE remains largely uncharacterised. We aimed to investigate a potential association between testicular hypofunction (TH), as a proxy for low testosterone levels, and SLE in males. A retrospective cohort study was conducted by analysing linked English national Hospital Episode Statistics (HES) and mortality data from 1999 to 2011. We calculated rates for SLE following TH, and TH following SLE, stratified and standardised by age, calendar year of first recorded admission, region of residence, and quintile of patients' Index of Deprivation score. The adjusted rate ratio (RR) of SLE following TH was 7.7 (95% confidence interval (95% CI) 2.5-18.1, p

Polycystic liver disease is a well-described manifestation of autosomal dominant polycystic kidney disease (ADPKD). Biliary tract complications are less well-recognised. We report a 50-year single-centre experience of 1,007 patients, which raised a hypothesis that ADPKD is associated with biliary tract disease. This was then tested using all-England Hospital Episode Statistics data (1998-2012) within which 23,454 people recorded as having ADPKD and 6,412,754 hospital controls were identified. Hospitalisation rates for biliary tract disease, serious liver complications and a range of other known ADPKD manifestations were adjusted for potential confounders and then compared. Compared to non-ADPKD hospital controls, the rates of admission for biliary tract disease were 2.2-times higher in those with ADPKD (rate ratio [RR] 2.24, 95% confidence interval 2.16-2.33) and 4.7-times higher for serious liver complications (RR 4.67, 4.35-5.02). When analyses were restricted to those on maintenance dialysis or with a kidney transplant, RRs attenuated substantially, but ADPKD remained positively associated with both biliary tract disease (RR 1.19, 1.08-1.31) and with serious liver complications (RR 1.15, 0.98-1.33). The ADPKD versus non-ADPKD hospital control RRs for biliary tract disease were larger for men than women (heterogeneity p

Objective:To study associations between viral hepatitis and Parkinson disease (PD).Methods:A retrospective cohort study was done by analyzing linked English National Hospital Episode Statistics and mortality data (1999–2011). Cohorts of individuals with hepatitis B, hepatitis C, autoimmune hepatitis, chronic active hepatitis, and HIV were constructed, and compared to a reference cohort for subsequent rates of PD.Results:The standardized rate ratio (RR) of PD following hepatitis B was 1.76 (95% confidence interval [CI] 1.28–2.37) (p < 0.001), based on 44 observed compared with 25 expected cases. The RR of PD following hepatitis C was 1.51 (95% CI, 1.18–1.9) (p < 0.001), based on 48.5 expected and 73 observed cases. There was no significant association between autoimmune hepatitis, chronic active hepatitis or HIV, and subsequent PD. When including only those episodes of care for PD that occurred first at least 1 year following each exposure condition, the RR for hepatitis B and hepatitis C were 1.82 (1.29–2.5) and 1.43 (1.09–1.84), respectively.Conclusions:We report strong evidence in favor of an elevation of rates of subsequent PD in patients with hepatitis B and hepatitis C. These findings may be explained by factors peculiar to viral hepatitis, but whether it reflects consequences of infection, shared disease mechanisms, or the result of antiviral treatment remains to be elucidated. Further work is needed to confirm this association and to investigate pathophysiologic pathways, potentially advancing etiologic understanding of PD more broadly.

BACKGROUND: There is evidence that people with Parkinson's disease (PD) have a decreased risk of developing cancer. PD has also variably been shown to be associated with an increased risk of cancers like melanoma and breast. We investigated this relationship in a very large cohort of PD patients. METHODS: We constructed two cohorts of people from an all-England record-linked hospital and mortality dataset spanning 1999-2011. One cohort comprised people with a record of PD; the other comprised people without a record of PD. We 'followed up' these two cohorts to determine observed and expected numbers of people with subsequent primary cancers in each, based on person-years at risk, and calculated standardised rate ratios (RRs). RESULTS: In 219,194 people with PD, the RR for all subsequent primary malignant cancers combined was 0.92 (95% confidence interval (CI) 0.91-0.93). Increased RRs (p

The influence of gonadal hormones on multiple sclerosis (MS) is not well characterized and has thus far been investigated primarily in animal models or as a proposed therapeutic approach. We investigated a potential association between testicular hypofunction, as a proxy for low testosterone levels, and MS risk through analysis of linked English national Hospital Episode Statistics from 1999 to 2011. We report a strong positive association between testicular hypofunction and subsequent MS (rate ratio = 4.62, 95% confidence interval = 2.3-8.24, p < 0.0001). Future work should aim more directly to elucidate the relationship between testosterone levels and MS in both males and females.

A disease of ‘young women and old men’, myasthenia gravis (MG) exhibits a bimodal distribution in age with a peak in the second and third decades of life with a female predominance, and a later peak in the sixth-to-eighth decades of life with a male predominance [1]. A role for low testosterone in influencing MG risk in males is suggested by the fact that the age-dependent risk of MG in males coincides with an age-related decline in male testosterone levels [2]. Exploration of a role of testosterone has previously been limited to one case report of hypergonadotropic hypogonadism and MG [3]. We aimed to investigate an association between testicular hypofunction (TH), as a proxy for low testosterone levels, and subsequent MG risk in males.

Objectives: Even though multiple sclerosis (MS) and HIV infection are well-documented conditions in clinical medicine, there is only a single case report of a patient with MS and HIV treated with HIV antiretroviral therapies. In this report, the patient' s MS symptoms resolved completely after starting combination antiretroviral therapy and remain subsided for more than 12 years. Authors hypothesised that because the pathogenesis of MS has been linked to human endogenous retroviruses, antiretroviral therapy for HIV may be coincidentally treating or preventing progression of MS. This led researchers from Denmark to conduct an epidemiological study on the incidence of MS in a newly diagnosed HIV population (5018 HIV cases compared with 50 149 controls followed for 31 875 and 393 871 person-years, respectively). The incidence rate ratio for an HIV patient acquiring MS was low at 0.3 (95% CI 0.04 to 2.20) but did not reach statistical significance possibly due to the relatively small numbers in both groups. Our study was designed to further investigate the possible association between HIV and MS. Methods: We conducted a comparative cohort study accessing one of the world's largest linked medical data sets with a cohort of 21 207 HIV-positive patients and 5 298 496 controls stratified by age, sex, year of first hospital admission, region of residence and socioeconomic status and 'followed up' by record linkage. Results: Overall, the rate ratio of developing MS in people with HIV, relative to those without HIV, was 0.38 (95% CI 0.15 to 0.79). Conclusions: HIV infection is associated with a significantly decreased risk of developing MS. Mechanisms of this observed possibly protective association may include immunosuppression induced by chronic HIV infection and antiretroviral medications.

Aims The potential association between primary open angle glaucoma (POAG) and Alzheimer9s disease (AD) is uncertain and has implications for understanding disease pathogenesis, referral and treatments. The aim was to determine whether individuals diagnosed with POAG are at higher risk of subsequently developing AD or vascular dementia. Methods A POAG cohort of 87 658 people was constructed from English National Health Service linked hospital episode statistics from 1999 to 2011. An AD cohort (251 703 people), vascular dementia cohort (217 302 people) and reference cohort (>2.5 million people) were constructed in similar ways. Risk of dementia following POAG was determined: rate ratios were calculated based on standardised rates of dementia in the POAG cohort. Results The risk of AD following a diagnosis of POAG was not elevated: the rate ratio was 1.01 (95% CI 0.96 to 1.06). The risk of vascular dementia after POAG was modestly elevated, with rate ratio 1.10 (1.05 to 1.16). The likelihood of a hospital record of POAG following AD or vascular dementia was very low, with rate ratios 0.28 (0.24 to 0.31) and 0.32 (0.28 to 0.37), respectively. Conclusions POAG and AD are neurodegenerative conditions that share some pathological features. However, considering AD after POAG, their coexistence at the individual level is no different from that expected by chance. By contrast, a diagnosis of POAG is modestly associated with later development of vascular dementia, presumably owing to shared vascular risk factors. People with dementia in England are much less likely to be admitted subsequently with POAG, perhaps through poor access to hospital eye services and diagnostic challenges.

Objective: To study whether the risk of amyotrophic lateral sclerosis (ALS) is increased in people with prior autoimmune disease. Methods: An all-England hospital record-linkage dataset spanning 1999–2011 was used. Cohorts were constructed of people with each of a range of autoimmune diseases; the incidence of ALS in each disease cohort was compared with the incidence of ALS in a cohort of individuals without prior admission for the autoimmune disease. Results: There were significantly more cases than expected of ALS associated with a prior diagnosis of asthma, celiac disease, younger-onset diabetes (younger than 30 years), multiple sclerosis, myasthenia gravis, myxedema, polymyositis, Sjogren syndrome, systemic lupus erythematosus, and ulcerative colitis. Conclusions: Autoimmune disease associations with ALS raise the possibility of shared genetic or environmental risk factors.

The influence of gonadal hormones on multiple sclerosis (MS) is not well characterized and has thus far been investigated primarily in animal models or as a proposed therapeutic approach. We investigated a potential association between testicular hypofunction, as a proxy for low testosterone levels, and MS risk through analysis of linked English national Hospital Episode Statistics from 1999 to 2011. We report a strong positive association between testicular hypofunction and subsequent MS (rate ratio = 4.62, 95% confidence interval = 2.3-8.24, p0.0001). Future work should aim more directly to elucidate the relationship between testosterone levels and MS in both males and females.

To investigate English national trends in ophthalmia neonatorum and dacryocystitis (ON) of the newborn and the completeness of statutory notification of this serious infection.Analysis of hospital episode statistics (HES) from 2000 to 2011.Using linked HES, numbers of neonates hospitalised with ON were identified from 2000 to 2011. The numbers of hospitalised cases were compared with numbers of statutory notifications for ON published by the Notifications of Infectious Diseases (NOIDS).The national incidence rate of hospitalised cases showed a gradual decline from 464 (95% CI 447 to 482) per 100,000 live births in 2000 to 216 (204 to 228) per 100,000 live births in 2005. It then gradually increased to 471 (455 to 487) per 100,000 live births in 2010, but dropped to 257 (245 to 269) per 100,000 in 2011. From 2000 to 2009, when NOIDS data were available, the NOIDS data showed only 1006 cases compared with 20,505 cases in HES, and thus the notification system captured only about 1 case in 20.As shown by hospital statistics, there were marked cyclical fluctuations in ON over the study period. The annual figures for ON reported during the study period, under statutory health protection regulations, underestimated the actual occurrence of this disease by a very substantial amount. Linked hospital data should be used routinely to monitor the national incidence of ON.

Background: Conflicting evidence exists about whether people with a history of nonmelanoma skin cancer (NMSC) are at higher risk of subsequent primary malignant cancers than those without. Methods: An all England record-linked hospital and mortality dataset spanning from 1999 to 2011 was used. We constructed two cohorts: one that comprised people with a history of NMSC (502,490 people), and a control cohort that comprised people without. We “followed up” these two cohorts electronically to determine observed and expected numbers of people with subsequent primary cancers in each, based on person-years at risk, and calculated standardized risk ratios (RR). Results: Comparing the NMSC cohort with the non-NMSC cohort, the RR for all subsequent malignant cancers combined was 1.36 [95% confidence interval (CI), 1.35–1.37]. Significantly increased RRs (P < 0.05) were found for 26 of the 29 cancer types studied, in particular for salivary gland, melanoma, bone, and upper gastrointestinal tract cancers. The RRs were also particularly high when comparing younger people with and without NMSC. Conclusions: NMSC is strongly associated with a broad spectrum of other primary cancers, particularly in younger age groups. The pattern suggests a genetic or early-acquired etiologic association. Impact: These results represent what can be done using very large, linked, routinely collected administrative datasets; but such datasets lack detail. Further work to establish the mechanisms behind these associations is warranted. Cancer Epidemiol Biomarkers Prev; 23(3); 490–8. ©2014 AACR.

IMPORTANCE: The potential association between age-related macular degeneration (AMD) and Alzheimer disease (AD) is uncertain and has implications for understanding disease pathogenesis, referral, and treatments. OBJECTIVES: To determine whether individuals admitted to the hospital with AMD were significantly more or less likely to develop AD or dementia in the following years, as well as to assess whether people with AD or dementia were significantly more or less likely to be admitted to the hospital for AMD treatment in the years following diagnosis of dementia. DESIGN, SETTING, AND PARTICIPANTS: An AMD cohort of 65,894 people was constructed from English National Health Service, linked hospital episode statistics from January 1, 1999, through February 28, 2011, by identifying computerized record abstracts for all people with an admission or day case care for AMD. A dementia cohort (168,092 people) and a reference cohort (>7.7 million people) were constructed in similar ways. MAIN OUTCOMES AND MEASURES: Risk of AD or dementia following AMD and risk of AMD following AD or dementia. Rate ratios were calculated based on standardized rates of AD and dementia in the AMD cohort, as well as standardized rates of AMD in the AD and dementia cohort, relative to those in the reference cohort. RESULTS The risk of AD or dementia following AMD was not elevated. The rate ratio was 0.86 (95% CI, 0.67-1.08) for AD and 0.91 (0.79-1.04) for dementia. The likelihood of being admitted for AMD following AD or dementia was very low: the rate ratio was 0.04 (0.01-0.10) for people with AD and 0.07 (0.04-0.11) for those with dementia. CONCLUSIONS AND RELEVANCE: These neurodegenerative conditions may share environmental risk factors and histopathologic features. However, considering AD and other dementia after AMD, their coexistence at the individual level is no different from that expected by chance. Our data also suggest that patients in England with dementia may be substantially less likely to receive AMD treatment. Further research is required to determine whether people with dementia receive appropriate investigation and treatment for AMD, as well as identify and address potential barriers.

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.

Background Previous studies have suggested that there may be an association between vitamin D deficiency and the risk of developing immune-mediated diseases. Methods We analyzed a database of linked statistical records of hospital admissions and death registrations for the whole of England (from 1999 to 2011). Rate ratios for immune-mediated disease were determined, comparing vitamin D deficient cohorts (individuals admitted for vitamin D deficiency or markers of vitamin D deficiency) with comparison cohorts. Results After hospital admission for either vitamin D deficiency, osteomalacia or rickets, there were significantly elevated rates of Addison’s disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active hepatitis, celiac disease, Crohn’s disease, diabetes mellitus, pemphigoid, pernicious anemia, primary biliary cirrhosis, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, thyrotoxicosis, and significantly reduced risks for asthma and myxoedema. Conclusions This study shows that patients with vitamin D deficiency may have an increased risk of developing some immune-mediated diseases, although we cannot rule out reverse causality or confounding. Further study of these associations is warranted and these data may aid further public health studies.

Background Previous studies have suggested that there may be an association between some immune-mediated diseases and risk of tuberculosis (TB). Methods We analyzed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999 to 2011), and a similar database (the Oxford Record Linkage Study (ORLS)) for a region of southern England in an earlier period. Rate ratios for TB were determined, comparing immune-mediated disease cohorts with comparison cohorts. Results In the all-England dataset, there were significantly elevated risks of TB after hospital admission for the following individual immune-mediated diseases: Addison's disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active hepatitis, coeliac disease, Crohn's disease, dermatomyositis, Goodpasture's syndrome, Hashimoto's thyroiditis, idiopathic thrombocytopenia purpura (ITP), myasthenia gravis, myxedema, pemphigoid, pernicious anemia, polyarteritis nodosa, polymyositis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, scleroderma, Sjögren's syndrome, systemic lupus erythematosus (SLE), thyrotoxicosis and ulcerative colitis. Particularly high levels of risk were found for Addison’s disease (rate ratio (RR) = 11.9 (95% CI 9.5 to 14.7)), Goodpasture’s syndrome (RR = 10.8 (95% CI 4.0 to 23.5)), SLE (RR = 9.4 (95% CI 7.9 to 11.1)), polymyositis (RR = 8.0 (95% CI 4.9 to 12.2)), polyarteritis nodosa (RR = 6.7 (95% CI 3.2 to 12.4)), dermatomyositis (RR = 6.6 (95% CI 3.0 to 12.5)), scleroderma (RR = 6.1 (95% CI 4.4 to 8.2)) and autoimmune hemolytic anemia (RR = 5.1 (95% CI 3.4 to 7.4)). Conclusions These two databases show that patients with some immune-mediated diseases have an increased risk of TB, although we cannot explicitly state the direction of risk or exclude confounding. Further study of these associations is warranted, and these findings may aid TB screening, control and treatment policies.

Background Less than one-third of newly qualified doctors in the UK want a career in general practice. The English Department of Health expects that half of all newly qualified doctors will become GPs. Aim To report on the reasons why doctors choose or reject careers in general practice, comparing intending GPs with doctors who chose hospital careers. Design and setting Questionnaire surveys in all UK medical graduates in selected qualification years. Method Questions about specialty career intentions and motivations, put to the qualifiers of 1993, 1996, 1999, 2000, 2002, 2005, 2008, and 2009, 1 year after qualification, and at longer time intervals thereafter. Results ‘Enthusiasm for and commitment to the specialty’ was a very important determinant of choice for intending doctors, regardless of chosen specialty. ‘Hours and working conditions’ were a strong influence for intending GPs (cited as having had ‘a great deal’ of influence by 75% of intending GPs in the first year after qualification), much more so than for doctors who wanted a hospital career (cited by 30%). Relatively few doctors had actually considered general practice seriously but then rejected it; 78% of the doctors who rejected general practice gave ‘job content’ as their reason, compared with 32% of doctors who rejected other specialties. Conclusion The shortfall of doctors wanting a career in general practice is not accounted for by doctors considering and rejecting it. Many do not consider it at all. There are very distinctive factors that influence choice for, and rejection of, general practice.

BACKGROUND: The Academic Clinical Fellowship (ACF) programme in England was introduced in 2007 to support the training of clinical academics. AIM: To report on career plans and views of ACF trainees. METHOD: Questionnaire survey of trainees appointed in 2008. RESULTS: Of 102 responders, 63% expected to work eventually wholly in clinical academic posts, 34% in clinical service posts with some teaching and research, and none in clinical service posts with no teaching or research. Of factors that had influenced the choice of an academic career 'a great deal', 83% of responders cited having a 'varied and stimulating career', 79% the 'intellectual environment' of academic departments, 78% the 'challenge of research' and 62% the 'stimulation of teaching'. The most important factors that might dissuade them from eventually pursuing an academic career were 'difficulty obtaining research grants' (specified by 42%), followed by 'competing pressures in the three areas of research, clinical work and teaching', lack of 'pay parity with NHS colleagues', and concerns about adequate availability of academic posts at senior levels. CONCLUSIONS: The responders were highly motivated by the challenges of academic work. However, policymakers need to consider what, if anything, might realistically be done about potentially demotivating factors.

Introduction and objectives Spontaneous Pneumothorax (SP) is a common pathology. Incidence rates are quoted as 16–24 and 1.2–6 per 100,000 cases per annum for males and females respectively, based on two studies in single centres (45 years ago, USA; 30 years ago, Sweden) and 4-year periods of national data in UK (1991–4) and France (2008–2011). The aim of this study is to determine the incidence and recurrence of spontaneous pneumothorax in a larger dataset in England. Methods An all-England Hospital Episode Statistics (HES) dataset from 1968–2011 was used to determine the incidence of Spontaneous Pneumothorax using International Classification of Diseases codes as the main diagnosis in a hospital admission. A record-linked HES dataset (only available from 1999–2011) was used to distinguish between Primary and Secondary Spontaneous Pneumothorax (PSP and SSP) and to determine the risk of a second pneumothorax within specified time intervals. SSP was defined as the patient having a diagnosis of a chronic lung disease (e.g. COPD, emphysema, lung malignancy, asthma, bronchiectasis, sarcoidosis) made at any time covered by the linked data. Results and discussion From 1968–2011, in a population of 50 million, there were a total of 246,534 episodes of spontaneous pneumothorax (no data for 1986–89). In 1999–2011, the average annual incidence was 9.1 per 100,000 males and 3.2 per 100,000 females for PSP; 11.9 and 4.7 for SSP; and 21.0 and 7.9 for SP overall. The incidence of SP appears to be increasing (Figure 1): it was 12.5 (95% confidence interval 12.2–12.8) in 1999 and 13.6 (13.3–13.9) in 2011. It is unclear whether this reflects a true rise in new cases, better reporting or increasing recurrence rates. The overall risk of recurrence is 13.5% within 1 year (18.7% within 5 years). Recurrence is more common in SSP than PSP at 1 year (16.1% vs 10.6%) and 5 years (21.2% vs 14.7%). Conclusions This is the largest epidemiological study of pneumothorax to date. These data only cover hospitalised pneumothorax, and therefore may be a conservative estimate of the true burden of disease. Pneumothorax appears to be increasing in incidence.

Background A decline in mortality rates from stroke has been observed in many industrialised countries in recent decades. We were interested in whether any of the observed decline in stroke, and its subtypes, might be artefactual rather than real. In particular, we wanted to determine whether any of the trends over time might be attributable to shifts in death certification practice between underlying cause and contributory cause, and/or shifts over time between certification of specific subtypes (haemorrhagic and ischaemic stroke) and stroke without specification of type. Methods We analysed mortality data from the former Oxford NHS region 1979–2011. This has a longer run of multiple-cause coded mortality data than all-England mortality (though findings from the latter will also be shown). We calculated age-standardised rates, presented as mortality rates per million population, in each year from 1979–2011 and in grouped years for periods defined by national changes to the rules for selection of underlying cause (the rules changed in 1984, 1992 and 2001). Results Mortality rates based on any mention of stroke on the death certificate, and on underlying cause, showed broadly similar trends. Mortality rates for each code for stroke – ischaemic, haemorrhagic and ‘unspecified’ – and for stroke overall fell at a broadly similar rate between 1979–1992. Thereafter, trends diverged. The average annual rate for mortality in men from ischaemic stroke in 2001–2011, at 72.7 per million, was 11% lower than that in 1993–2000 at 84.2. The corresponding rates for haemorrhagic stroke were 93.6 and 92.7, i.e. they did not fall at all. By contrast, the average annual rate for stroke ‘unspecified’ in men was 355.9 in 2001–11 which was 56% lower than the rate of 600.8 in 1993–2000. Stroke mortality, overall, fell from 768.1 to 504.5 between 1993–2000 and 2001–2011. In recent years, when national multiple-cause coding data were available, national trends were similar to those in Oxford in these respects. Rates for women will also be shown (they exhibited the same pattern). Conclusion There have been substantial changes in certification practice with a shift in recent years away from specifying stroke type. Studies of trends in mortality from ischaemic stroke alone, or haemorrhagic stroke alone, without being put into the broader context of all stroke, would be seriously misleading. They would suggest a levelling off of the decline in ischaemic and haemorrhagic stroke mortality in recent years which is, in fact, an artefact of certification and coding practice.