Colin J Crooks

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 of venous thromboembolism in patients with cancer – A cohort study using linked United Kingdom databases

BACKGROUND Accurate population-based data are needed on the incidence of venous thromboembolism (VTE) in patients with different cancers in order to inform guidelines on which hospitalised and ambulatory cancer patients should receive VTE prophylaxis. METHODS We conducted a cohort study using data from the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data and Office for National Statistics cause of death data. We determined the incidence rates (cases per 1000 person-years) of VTE separately for 24 cancer sites. To determine relative risk, incidence rates were compared to frequency-matched controls (by age) with no record of cancer. FINDINGS We identified 83,203 cancer patients and 577,207 controls. New cases of VTE were diagnosed in 3352 cancer patients, and 6353 controls. The absolute rate of VTE in all cancers was 13.9 per 1000 person-years (95% confidence interval [CI] 13.4-14.4), corresponding to an age, sex and calendar year adjusted hazard-ratio of 4.7 (CI 4.5-4.9) between cancer patients and the general population. Rates varied greatly by cancer site (range; 98 (CI 80-119) in pancreatic cancer to 3.1 (CI 1.5-6.5) in thyroid cancer), age (range; 16.9 for patients over 80 years to 4.9 for those under 30 years) and time from diagnosis (range; 75 in the first three months to 8.4, >1 year after diagnosis). INTERPRETATION VTE is strongly linked to cancer, but the annual rate varies greatly by cancer site, proximity to diagnosis and age. Prophylaxis guidelines should take account of cancer site and such intervention should also be targeted towards the three months following diagnosis.

Reductions in 28-Day Mortality Following Hospital Admission for Upper Gastrointestinal Hemorrhage

Background & Aims It is unclear whether mortality from upper gastrointestinal hemorrhage is changing: any differences observed might result from changes in age or comorbidity of patient populations. We estimated trends in 28-day mortality in England following hospital admission for gastrointestinal hemorrhage. Methods We used a case-control study design to analyze data from all adults administered to a National Health Service hospital, for upper gastrointestinal hemorrhage, from 1999 to 2007 (n = 516,153). Cases were deaths within 28 days of admission (n = 74,992), and controls were survivors to 28 days. The 28-day mortality was derived from the linked national death register. A logistic regression model was used to adjust trends in nonvariceal and variceal hemorrhage mortality for age, sex, and comorbidities and to investigate potential interactions. Results During the study period, the unadjusted, overall, 28-day mortality following nonvariceal hemorrhage was reduced from 14.7% to 13.1% (unadjusted odds ratio, 0.87; 95% confidence interval: 0.84–0.90). The mortality following variceal hemorrhage was reduced from 24.6% to 20.9% (unadjusted odds ratio, 0.8; 95% confidence interval: 0.69–0.95). Adjustments for age and comorbidity partly accounted for the observed trends in mortality. Different mortality trends were identified for different age groups following nonvariceal hemorrhage. Conclusions The 28-day mortality in England following both nonvariceal and variceal upper gastrointestinal hemorrhage decreased from 1999 to 2007, and the reduction had been partly obscured by changes in patient age and comorbidities. Our findings indicate that the overall management of bleeding has improved within the first 4 weeks of admission.

Comorbidities Affect Risk of Nonvariceal Upper Gastrointestinal Bleeding

Background & Aims The incidence of upper gastrointestinal bleeding (GIB) has not been reduced despite the decreasing incidence of peptic ulcers, strategies to eradicate Helicobacter pylori infection, and prophylaxis against ulceration from nonsteroidal anti-inflammatory drugs. Other factors might therefore be involved in the pathogenesis of GIB. Patients with GIB have increasing nongastrointestinal comorbidity, so we investigated whether comorbidity itself increased the risk of GIB. Methods We conducted a matched case-control study using linked primary and secondary care data collected in England from April 1, 1997 through August 31, 2010. Patients older than 15 years with nonvariceal GIB (n = 16,355) were matched to 5 controls by age, sex, year, and practice (n = 81,636). All available risk factors for GIB were extracted and modeled using conditional logistic regression. Adjusted associations with nongastrointestinal comorbidity, defined using the Charlson Index, were then tested and sequential population attributable fractions calculated. Results Comorbidity had a strong graded association with GIB; the adjusted odds ratio for a single comorbidity was 1.43 (95% confidence interval [CI]: 1.35–1.52) and for multiple or severe comorbidity was 2.26 (95% CI: 2.14%–2.38%). The additional population attributable fraction for comorbidity (19.8%; 95% CI: 18.4%–21.2%) was considerably larger than that for any other measured risk factor, including aspirin or nonsteroidal anti-inflammatory drug use (3.0% and 3.1%, respectively). Conclusions Nongastrointestinal comorbidity is an independent risk factor for GIB, and contributes to a greater proportion of patients with bleeding in the population than other recognized risk factors. These findings could help in the assessment of potential causes of GIB, and also explain why the incidence of GIB remains high in an aging population.

1 and 5 year survival estimates for people with cirrhosis of the liver in England, 1998–2009: A large population study

BACKGROUND & AIMS Large, population-based studies that have included the full spectrum of cirrhosis estimating survival, taking into account time-at-risk are lacking. We aimed to report 1- and 5-year average survival rates for people with cirrhosis to be used in a clinical and healthcare policy setting. METHODS We used the Clinical Practice Research Datalink and linked English Hospital Episode Statistics to identify adult cases of cirrhosis from January 1998 to December 2009. We estimated 1- and 5-year survival according to whether time-at-risk was ambulatory or followed an emergency hospital admission related to liver disease, stratified by age, sex, and aetiology to be used in a clinical setting. We used a multivariate Cox-proportional hazards model with a time-varying variable, adjusted for Baveno IV stage of cirrhosis at diagnosis, age, aetiology, and sex. RESULTS We identified 5118 incident cases. Average survival probabilities at 1- and 5-years were 0.84 (95% CI 0.83-0.86) and 0.66 (95% CI 0.63-0.68) for the ambulatory group and 0.55 (95% CI 0.53-0.57) and 0.31 (95% CI 0.29-0.33) following hospitalisation, respectively. A hospital admission at diagnosis or subsequently for liver disease substantially impaired prognosis independent of stage of cirrhosis (HR=2.78, 95% CI 2.53, 3.06). CONCLUSIONS Emergency hospitalisation for liver disease heralds a downturn in a patients outlook independent of their stage of cirrhosis. Our results provide population-based clinically translatable estimates of prognosis for the purposes of healthcare delivery and planning and communication to patients.

Diagnosis of liver cirrhosis in England, a cohort study, 1998-2009: a comparison with cancer.

OBJECTIVES:There is no routine registration of the occurrence of newly diagnosed cases of cirrhosis in the United Kingdom. This study seeks to determine precise estimates and trends of the incidence of cirrhosis in England, and directly compare these figures with those for the 20 most commonly diagnosed cancers in the United Kingdom.METHODS:We used the Clinical Practice Research Datalink and linked English Hospital Episode Statistics to perform a population-based cohort study. Adult incident cases with a diagnosis of cirrhosis between January 1998 and December 2009 were identified. We described trends in incidence by sex and etiology. We performed a direct standardization to estimate the number of people being newly diagnosed with cirrhosis in 2009, and calculated the change in incidence between 1998 and 2009.RESULTS:A total of 5,118 incident cases of cirrhosis were identified, 57.9% were male. Over the 12-year period, crude incidence increased by 50.6%. Incidence increased for both men and women and all etiology types. We estimated approximately 17,000 people were newly diagnosed with cirrhosis in 2009 in the United Kingdom, greater than that of the fifth most common cancer non-Hodgkins lymphoma. The percentage change in incidence of cirrhosis between 1998 and 2009 for both men (52.4%) and women (38.3%) was greater than that seen for the top four most commonly diagnosed cancers in the United Kingdom (breast, lung, bowel, and prostate).CONCLUSIONS:The occurrence of cirrhosis increased more than that of the top four cancers during 1998 to 2009 in England. Strategies to monitor and reduce the incidence of this disease are urgently needed.

Upper gastrointestinal haemorrhage and deprivation: a nationwide cohort study of health inequality in hospital admissions

Objective Inequalities in health are well recognized in cardiovascular disease and cancer, but in comparison, we have minimal understanding for upper gastrointestinal bleeding. Since furthering our understanding of such inequality signposts preventable disease, we investigated in detail the association between upper gastrointestinal bleeding and socioeconomic status. Design Population-based cohort study. Setting All English National Health Service hospitals. Population English adult population, 1 January 2001 to 31 December 2007. Exposure measures Deprivation scores defined according to quintiles of neighbourhood areas ranked by the Indices of Multiple Deprivation for England 2007. Outcome measures Rates of all adult admissions coded with a primary diagnosis of upper gastrointestinal bleed were analysed by deprivation quintile and adjusted for age, sex, region and year using Poisson regression. Results The annual hospitalization rate for non-variceal haemorrhage was 84.6 per 100 000 population (95% CI 83.5 to 84.1; n=237 145), and for variceal haemorrhage, it was 2.83 per 100 000 population (95% CI 2.87 to 2.99; n=8291). There was a twofold increase in the hospitalization rate ratio for non-variceal haemorrhage from the most deprived areas compared to the least deprived (2.00, 95% CI 1.98 to 2.03). The ratio for variceal haemorrhage was even more pronounced (2.49, 95% CI 2.32 to 2.67). Inequality increased over the study period (non-variceal p<0.0001, variceal p=0.0068), and adjusting for age and sex increased the disparity between deprived and affluent areas. Case fatality did not have a similar socioeconomic gradient. Conclusion Both variceal and non-variceal haemorrhage hospitalization rates increased with deprivation, and there was a similar gradient in all areas of the country and in all age bands. The existence of such a steep gradient suggests that there are opportunities to reduce hospitalizations down to the low rates seen in the most affluent, and thus, there is the potential to prevent almost 10 000 admissions and over 1000 deaths a year.

Causes of Death in People with Liver Cirrhosis in England Compared with the General Population: A Population-Based Cohort Study

OBJECTIVES:There is a need for unbiased estimates of cause-specific mortality by etiology in patients with liver cirrhosis. The aim of this study is to use nationwide linked electronic routine healthcare data from primary and secondary care alongside the national death registry data to report such estimates.METHODS:We identified from the linked Clinical Practice Research Datalink (CPRD) and English Hospital Episode Statistics adults with an incident diagnosis of liver cirrhosis linked to the Office for National Statistics between 1998 and 2009. Age-matched controls from the CPRD general population were selected. We calculated the cumulative incidence (adjusting for competing risks) and excess risk of death by 5 years from diagnosis for different causes of death, stratified by etiology and stage of disease.RESULTS:Five thousand one hundred and eighteen patients with cirrhosis were matched to 152,903 controls. Among compensated patients, the 5-year excess risk of liver-related death was higher than that of any other cause of death for all patients, except those of unspecified etiology. For example, those of alcohol etiology had 30.8% excess risk of liver-related death (95% confidence interval (CI): 27.9%, 33.1%) compared with 9.9% excess risk of non-liver-related death. However, patients of unspecified etiology had a higher excess risk of non-liver-related compared with liver-related death (10.7% vs. 6.7%). This was due to a high excess risk of non-liver neoplasm death (7.7%, 95% CI: 5.9%, 9.5%). All decompensated patients had a higher excess of liver-related mortality than any other cause.CONCLUSIONS:In order to reduce associated mortality among people with liver cirrhosis, patients’ care pathways need to be tailored depending on the etiology and stage of the disease.

Causes of death in people with coeliac disease in England compared with the general population: a competing risk analysis

Introduction Quantifying excess cause-specific mortality among people with coeliac disease (CD) compared with the general population accounting for competing risks will allow accurate information to be given on risk of death from specific causes. Method We identified from the Clinical Practice Research Datalink all patients with CD linked to Office for National Statistics between 1998 and 2012. We selected controls by frequency matching from the registered general practice population within 10-year age bands. We calculated the adjusted cumulative incidence (including adjustment for competing risks) and excess cumulative incidence for different causes of death up to 10 years from diagnosis. Results Of the 10 825 patients with CD, 773 died within the study period. The overall mortality rate among patients with CD was 128/10 000 person years compared with 153/10 000 in controls (HR=0.94 95% CI 0.84 to 1.01). We found no overall difference in the cumulative incidence of respiratory disease, digestive disease or cancer related death among cases and controls. The adjusted cumulative incidence of death from cardiovascular deaths was slightly lower compared with those without CD diagnosis (CD 0.32% vs controls 0.41%) with a corresponding excess cumulative incidence of −0.08% (95% CI −0.13 to −0.04). However, patients with CD had 0.15% excess risk (95% CI 0.03 to 0.27) of deaths from non-Hodgkins lymphoma from the general population baseline risk. Conclusions Overall, people with CD have no major excess risk of cancer, digestive disease or respiratory disease related or cardiovascular mortality compared with the general population. These findings should be reassuring to patients with CD and clinicians managing their care.

The epidemiology of haemochromatosis: a population-based study.

Background  The discovery of the HFE genotype has revolutionized the diagnosis of haemochromatosis, changing the associated mortality and morbidity.