Kate M. Fleming

The rising incidence of idiopathic pulmonary fibrosis in the UK

Background Previous studies have shown that the incidence of idiopathic pulmonary fibrosis (IPF) is rising in the UK and USA. Death registrations and primary care data were used to determine the current trends in IPF incidence in the UK. Because routine clinical data sets were used, the term IPF clinical syndrome (IPF-CS) is used to describe individuals in this study. Methods Age- and stratum-specific death registration rates between 1968 and 2008 were calculated and these were applied to the 2008 population to generate annual standardised expected number of deaths. Annual mortality rate ratios were calculated using Poisson regression. Computerised primary care records were used to determine incidence rates of IPF-CS between 2000 and 2008 stratified by age, sex and geographical region, and survival rates between calendar periods were compared. Results Annual death certificate recording of IPF-CS rose sixfold across the study period from 0.92 per 100 000 in the 1968–1972 calendar periods to 5.10 per 100 000 in the 2006–2008 calendar period, and were higher in men and the older age groups. The incidence of IPF-CS in primary care increased by 35% from 2000 to 2008, with an overall incidence rate of 7.44 per 100 000 person-years (95% CI 7.12 to 7.77). Incidence was higher in men, the older population and in Northwest England. Conclusions The incidence of IPF-CS in primary care and registered deaths from this cause in the UK continues to rise in the 21st century. The current findings suggest that there are >5000 new cases diagnosed each year in the UK.

Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study

Abstract Objective To provide perinatal mortality and congenital anomaly rates for babies born to women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland. Design National population based pregnancy cohort. Setting 231 maternity units in England, Wales, and Northern Ireland. Participants 2359 pregnancies to women with type 1 or type 2 diabetes who delivered between 1 March 2002 and 28 February 2003. Main outcome measures Stillbirth rates; perinatal and neonatal mortality; prevalence of congenital anomalies. Results Of 2359 women with diabetes, 652 had type 2 diabetes and 1707 had type 1 diabetes. Women with type 2 diabetes were more likely to come from a Black, Asian, or other ethnic minority group (type 2, 48.8%; type 1, 9.1%) and from a deprived area (type 2, 46.3% in most deprived fifth; type 1, 22.8%). Perinatal mortality in babies of women with diabetes was 31.8/1000 births. Perinatal mortality was comparable in babies of women with type 1 (31.7/1000 births) and type 2 diabetes (32.3/1000) and was nearly four times higher than that in the general maternity population. 141 major congenital anomalies were confirmed in 109 offspring. The prevalence of major congenital anomaly was 46/1000 births in women with diabetes (48/1000 births for type 1 diabetes; 43/1000 for type 2 diabetes), more than double that expected. This increase was driven by anomalies of the nervous system, notably neural tube defects (4.2-fold), and congenital heart disease (3.4-fold). Anomalies in 71/109 (65%) offspring were diagnosed antenatally. Congenital heart disease was diagnosed antenatally in 23/42 (54.8%) offspring; anomalies other than congenital heart disease were diagnosed antenatally in 48/67 (71.6%) offspring. Conclusion Perinatal mortality and prevalence of congenital anomalies are high in the babies of women with type 1 or type 2 diabetes. The rates do not seem to differ between the two types of diabetes.

Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study

Objective To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom. Design Retrospective historical cohort study. Setting Computerised medical records from the health improvement network, a large population based UK general practice database. Participants Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls. Main outcome measures Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation. Results 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2). Conclusions Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases.

Incidence and Prevalence of Celiac Disease and Dermatitis Herpetiformis in the UK Over Two Decades: Population-Based Study

OBJECTIVES:Few studies have quantified the incidence and prevalence of celiac disease (CD) and dermatitis herpetiformis (DH) nationally and regionally by time and age groups. Understanding this epidemiology is crucial for hypothesizing about causes and quantifying the burden of disease.METHODS:Patients with CD or DH were identified in the Clinical Practice Research Datalink between 1990 and 2011. Incidence rates and prevalence were calculated by age, sex, year, and region of residence. Incidence rate ratios (IRR) adjusted for age, sex, and region were calculated with Poisson regression.RESULTS:A total of 9,087 incident cases of CD and 809 incident cases of DH were identified. Between 1990 and 2011, the incidence rate of CD increased from 5.2 per 100,000 (95% confidence interval (CI), 3.8–6.8) to 19.1 per 100,000 person-years (95% CI, 17.8–20.5; IRR, 3.6; 95% CI, 2.7–4.8). The incidence of DH decreased over the same time period from 1.8 per 100,000 to 0.8 per 100,000 person-years (average annual IRR, 0.96; 95% CI, 0.94–0.97). The absolute incidence of CD per 100,000 person-years ranged from 22.3 in Northern Ireland to 10 in London. There were large regional variations in prevalence for CD but not DH.CONCLUSIONS:We found a fourfold increase in the incidence of CD in the United Kingdom over 22 years, with large regional variations in prevalence. This contrasted with a 4% annual decrease in the incidence of DH, with minimal regional variations in prevalence. These contrasts could reflect differences in diagnosis between CD (serological diagnosis and case finding) and DH (symptomatic presentation) or the possibility that diagnosing and treating CD prevents the development of DH.

Incidence and prevalence of cirrhosis in the United Kingdom, 1992-2001 : A general population-based study

BACKGROUND/AIMS To determine the incidence and prevalence of cirrhosis in the United Kingdom. METHODS We identified patients aged 25 or over with cirrhosis, oesophageal varices or portal hypertension from the UK General Practice Research Database between 1992 and 2001. We measured incidence rates by sex, year and aetiology, incidence rate ratios and estimated prevalence figures. RESULTS Three thousand three hundred and sixty cases of cirrhosis were identified. Crude incidence was 14.55 per 100,000 person years increasing from 12.05 to 16.99 per 100,000 person years from 1992 to 2001. Incidence was over 50% higher in men compared with women (adjusted incidence rate ratio 1.52 (95%CI [1.42-1.63])). A statistically significant increase in incidence of both alcoholic cirrhosis and non-alcohol-related cirrhosis was seen in men and women. Prevalence of cirrhosis was an estimated 76.3 per 100,000 population aged over 25 in mid-2001. CONCLUSIONS There was a 45% increase in the incidence of cirrhosis during the decade 1992-2001 in the UK and a 68% increase in prevalence. Cirrhosis occurred more commonly and at younger ages in men than women. Cirrhosis represents a growing burden of morbidity and mortality in the UK, with an estimated 30,000 people living with cirrhosis and at least 7000 new cases being diagnosed each year.

Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom

Knowledge of the absolute risk (AR) for venous thromboembolism (VTE) in women around pregnancy and how potential risk factors modify this risk is crucial in identifying women who would benefit most from thromboprophylaxis. We examined a large primary care database containing 376 154 pregnancies ending in live birth or stillbirth from women aged 15 to 44 years between 1995 and 2009 and assessed the effect of risk factors on the incidence of antepartum and postpartum VTE in terms of ARs and incidence rate ratios (IRR), using Poisson regression. During antepartum, varicose veins, inflammatory bowel disease (IBD), urinary tract infection, and preexisting diabetes were associated with an increased risk for VTE (ARs, ≥139/100 000 person-years; IRRs, ≥1.8/100 000 person-years). Postpartum, the strongest risk factor was stillbirth (AR, 2444/100 000 person-years; IRR, 6.2/100 000 person-years), followed by medical comorbidities (including varicose veins, IBD, or cardiac disease), a body mass index (BMI) of 30 kg/m(2) or higher, obstetric hemorrhage, preterm delivery, and caesarean section (ARs, ≥637/100 000 person-years; IRRs, ≥1.9/100 000 person-years). Our findings suggest that VTE risk varies modestly by recognized factors during antepartum; however, women with stillbirths, preterm births, obstetric hemorrhage, caesarean section delivery, medical comorbidities, or a BMI of 30 kg/m(2) or higher are at much higher risk for VTE after delivery. These risk factors should receive careful consideration when assessing the potential need for thromboprophylaxis during the postpartum period.

Risk of first venous thromboembolism in and around pregnancy: a population‐based cohort study

Knowledge of the absolute and relative risk of venous thromboembolism (VTE) in and around pregnancy would be crucial in identifying when to commence and cease thromboprophylaxis in women who would benefit from such intervention. We addressed this hypothesis using a large prospective primary care database from the United Kingdom, containing details on 972 683 women aged 15–44 years between 1987 and 2004. Risks of a first VTE during antepartum, postpartum and outside of pregnancy were compared using Poisson regression. The rate of VTE during the third trimester antepartum was six times higher than time outside pregnancy [Incidence Rate Ratio (IRR) = 6·1; 95% confidence interval, 4·7–7·9]. In contrast, both the first (IRR = 1·6) and second (IRR = 2·1) trimesters conferred little increase in risk. The first 6 weeks postpartum was associated with a 22‐fold increase in risk, with the peak occurring in the first 3 weeks. Increased age was found to be associated with VTE during postpartum and outside of pregnancy, but not during antepartum. Our findings of a notably raised risk of VTE persisting for 3 weeks postpartum and of a raised antepartum risk constrained to the third trimester have implications for modifying the current recommendations for VTE prophylaxis in pregnancy and the puerperium.

Concurrent drug use and the risk of perforated colonic diverticular disease: a population-based case–control study

Objective To determine the risk of diverticular perforation associated with current and ever use of corticosteroids, opiate analgesics, non-steroidal anti-inflammatory drugs, aspirin, cyclo-oxygenase-2 inhibitors, statins and calcium antagonists. Design, setting and participants Case–control analysis using conditional logistic regression analysis of data from the UK General Practice Research Database. The study involved 899 cases of incident diverticular perforation and 8980 population controls from 1990 to 2005. Main outcome measures Odds ratios (ORs) are presented for perforation associated with use of corticosteroids, opiate analgesics, non-steroidal anti-inflammatory drugs, aspirin, cyclo-oxygenase-2 inhibitors, statins and calcium antagonists. Data were adjusted for smoking, comorbidity, prior abdominal pain and body mass index. Results A total of 899 patients with an incident diagnosis of perforated diverticular disease were identified. Current use of opiate analgesics (OR=2.16; 95% CI 1.55 to 3.01) and oral corticosteroids (OR=2.74; 95% CI 1.63 to 4.61) was associated with a two- and threefold increase in the risk of diverticular perforation, respectively. Current use of a calcium antagonist and aspirin were not associated with an increased risk of diverticular perforation. Current statin use was associated with a reduction in the risk of perforation (OR=0.44; 95% CI 0.20 to 0.95). Conclusion Perforated diverticular disease is a serious surgical emergency with current opiate analgesics and oral corticosteroids being strongly associated with an increased risk of diverticular perforation.

Risk of first venous thromboembolism in and around pregnancy

Knowledge of the absolute and relative risk of venous thromboembolism (VTE) in and around pregnancy would be crucial in identifying when to commence and cease thromboprophylaxis in women who would benefit from such intervention. We addressed this hypothesis using a large prospective primary care database from the United Kingdom, containing details on 972 683 women aged 15–44 years between 1987 and 2004. Risks of a first VTE during antepartum, postpartum and outside of pregnancy were compared using Poisson regression. The rate of VTE during the third trimester antepartum was six times higher than time outside pregnancy [Incidence Rate Ratio (IRR) = 6·1; 95% confidence interval, 4·7–7·9]. In contrast, both the first (IRR = 1·6) and second (IRR = 2·1) trimesters conferred little increase in risk. The first 6 weeks postpartum was associated with a 22‐fold increase in risk, with the peak occurring in the first 3 weeks. Increased age was found to be associated with VTE during postpartum and outside of pregnancy, but not during antepartum. Our findings of a notably raised risk of VTE persisting for 3 weeks postpartum and of a raised antepartum risk constrained to the third trimester have implications for modifying the current recommendations for VTE prophylaxis in pregnancy and the puerperium.

All‐cause mortality in people with cirrhosis compared with the general population: a population‐based cohort study

Background: Mortality due to cirrhosis has tripled over the last 30 years in the UK. However, we lack adequate, contemporary, population‐based estimates of the excess mortality patients who are at risk compared with the general population.