Search

Background It is unclear whether an upper gastrointestinal bleed is an isolated gastrointestinal event or an indicator of a deterioration in a patient's overall health status. Therefore, we investigated the excess causes of death in individuals after a non-variceal bleed compared with deaths in a matched sample of the general population. Methods and Findings Linked longitudinal data from the English Hospital Episodes Statistics (HES) data, General Practice Research Database (GPRD), and Office of National Statistics death register were used to define a cohort of non-variceal bleeds between 1997 and 2010. Controls were matched at the start of the study by age, sex, practice, and year. The excess risk of each cause of death in the 5 years subsequent to a bleed was then calculated whilst adjusting for competing risks using cumulative incidence functions. 16,355 patients with a non-variceal upper gastrointestinal bleed were matched to 81,523 controls. The total 5-year risk of death due to gastrointestinal causes (malignant or non-malignant) ranged from 3.6% (≤50 years, 95% CI 3.0%–4.3%) to 15.2% (≥80 years, 14.2%–16.3%), representing an excess over controls of between 3.6% (3.0%–4.2%) and 13.4% (12.4%–14.5%), respectively. In contrast the total 5-year risk of death due to non-gastrointestinal causes ranged from 4.1% (≤50 years, 3.4%–4.8%) to 46.6% (≥80 years, 45.2%–48.1%), representing an excess over controls of between 3.8% (3.1%–4.5%) and 19.0% (17.5%–20.6%), respectively. The main limitation of this study was potential misclassification of the exposure and outcome; however, we sought to minimise this by using information derived across multiple linked datasets. Conclusions Deaths from all causes were increased following an upper gastrointestinal bleed compared to matched controls, and over half the excess risk of death was due to seemingly unrelated co-morbidity. A non-variceal bleed may therefore warrant a careful assessment of co-morbid illness seemingly unrelated t

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.

Background: Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism. Aim: To determine when patients are at high risk of thromboembolic events, including after major surgery, and to guide timing of thromboprophylaxis. Methods: Each inflammatory bowel disease patient from Clinical Practice Research Datalink, linked with Hospital Episode Statistics, was matched to up to five non-IBD patients in this cohort study. We examined their risk of thromboembolism in hospital and within six weeks after leaving hospital, with or without undergoing major surgery, and while ambulant. Hazard ratios were estimated using Cox regression, with adjustment for age, sex, body mass index, smoking and history of malignancy or thromboembolism. Results: Overall 23,046 inflammatory bowel disease patients had a thromboembolic risk 1.74 times (95% CI = 1.55–1.96) higher than 106,795 non-IBD patients. Among ambulant patients, the thromboembolic risk was raised during acute (hazard ratio = 3.94, 2.79–5.57) or chronic disease activity (3.97, 2.90–5.45) but their absolute risk remained below 5/1000 person-years. The hazard ratio for thromboembolism among in-patients not undergoing major surgery was 1.13 (0.63–2.02), compared to 2.43 (1.20–4.92) among surgical patients, with a near doubling of absolute risk associated with surgery (59.5/1000 person-years, compared with 31.1 without surgery). The absolute risk remained elevated within six weeks after leaving hospital (18.6/1000 person-years in inflammatory bowel disease patients after surgery). Conclusions: Inflammatory bowel disease patients are at an increased risk of venous thromboembolism. Absolute risks are raised during active disease, when in hospital, and after leaving hospital following major surgery.

Background & aims: Cirrhosis is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. Methods: We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients versus controls, adjusted for age, sex and comorbidity. Results: The 5-year hip fracture risk was raised both in England (2.9% vs 0.8% for controls) and Denmark (4.6% vs 0.9% for controls). With confounder adjustment, patients with cirrhosis had 5-fold (adjusted HR 5.5 (95% CI 4.3-6.9)), and 10-fold (adjusted HR 9.9 (95% CI 8.9-11.0)) increased rates. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p<0.001), being stronger in younger age groups (under 45 years HR: 17.9 and 16.6 respectively for English, Danish) than in patients over 75 years (HR 2.1 and 2.9 respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. Conclusions: Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population.

Background Although alcohol use disorders (AUD) are known to increase the relative risk of all-cause and some cause-specific mortalities, the absolute mortality rates of the AUD population are unknown. Such knowledge would benefit planners of the provision of services for this population, including in prioritising the identification and/or treatment of diseases likely to cause their death. Methods We conducted a systematic review of studies in English, reporting the cause-specific mortality rates among people treated for AUD. Number of deaths by cause, and total person-years of follow-up were extracted. All-cause and cause-specific mortality rates per 1000 person-years were meta-analysed assuming random effects. Results 31 studies were included. Participants were mainly middle-aged males. The quality of studies was generally good. 6,768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients) were recorded and the pooled all-cause mortality rate was 27.67/1000 person years (py) (95% confidence interval (CI) 23.9, 32.04). The commonest cause of death in the AUD population was cardiovascular disease (CVD) (6.9/1000py (95%CI 5.61, 8.49)), followed by gastrointestinal deaths (5.63/1000py (95%CI 4.1, 7.74)), unnatural deaths (4.95/1000py (95%CI 4.01, 6.09)), neoplasms, respiratory diseases and substance use disorders. Conclusions Patients with AUD have increased rates of all-cause and cause-specific mortality compared to the general population. Like the general population, they are most likely to die of CVD. In contrast to the general population, gastrointestinal and unnatural deaths are the next most common causes of death. We believe these facts should be considered when planning healthcare services for patients with AUD.

Background: Gastrointestinal infection is an important risk factor for developing IBS. Our aim was to characterise postinfectious IBS (PI-IBS) compared to other IBS patients. Methods: An internet survey of IBS patients using Rome III diagnostic questionnaire, Hospital Anxiety & Depression Scale (HADS) and Patient Health Questionnaire-12 somatic symptom score (PHQ12-SS) documenting the mode of onset. Results: 7811 participants, 63.2% female of whom 1004 (13.3%) met criteria for PI-IBS. 70% of PI-IBS described sudden onset, 35% onset while travelling, 49.6% vomiting, 49.9 fever and 20.3% bloody diarrhoea. Compared to other IBS, PI-IBS was significantly associated with living in Northern Europe and North America, having a hysterectomy, not having an appendectomy, higher PHQ12-SS score and having more than one toilet in the family home. PI-IBS patients had more frequent stools. At 1 year recovery rate in PI-IBS and non-PI-IBS group was 19.7% and 22.2%, p=0.15. Recovery rates were lower for females (20.7%) versus males (38.8%), those with somatisation ( 23.0%) versus those without (33.2%) and living in North America or Northern Europe (21.1%) versus living elsewhere (33.9%) p=<0.001. Conclusion: PI-IBS accounts for around 13% of all IBS in this internet sample, with some distinctive features but a similar prognosis to the remainder.

Laboratory studies have suggested that adrenergic blockers may inhibit the proliferation and migration of cancer cells, but epidemiological evidence of their effect on cancer incidence has proven inconsistent. We therefore conducted a case-control study using the Clinical Practice Research Datalink to assess the effect of adrenergic blockers on the incidence of prostate, lung, bowel and breast cancers. From among patients aged 18 years or older who contributed at least 2 years of prospectively gathered data between 1 January 1987 and 31 December 2012, we selected incident cases of relevant cancers and controls, frequency matched 10 : 1 by age. Logistic regression was used to adjust effect estimates for age, sex, smoking, alcohol use, and a number of potentially confounding comorbidities and coprescriptions. A total of 18 968 colorectal, 19 082 lung, 21 608 prostate and 29 109 breast cancers were identified. We found no evidence of a protective effect of adrenergic blockade in lung and prostate cancers and found a slightly increased risk for colorectal and breast cancers in users. This was largely explained by the effects of confounding in multivariate analyses, with final odds ratio estimates for lung, colorectal, breast and prostate cancers of 0.99 [95% confidence interval (0.96-1.04)], 1.14 (1.09-1.18), 1.10 (1.06-1.14), and 1.01 (0.98-1.05), respectively, for beta-blocker exposure, and final odds ratio estimates for lung, colorectal and breast cancer of 1.03 (0.97-1.09), 1.13 (1.07-1.20), and 1.08 (1.00-1.17), respectively, for alpha-blocker exposure. We found no evidence to suggest that adrenergic blocker use prevents common cancers. Indeed, we found a slightly increased risk for colorectal and breast cancers, which may reflect

Background: Rising cirrhosis incidence and mortality in the United Kingdom has been attributed predominantly to excess alcohol consumption. However, metabolic risk factors such as type 2 diabetes and obesity may also be important. Aim: To screen at-risk individuals in general practice for undetected cirrhosis using transient elastography and study the risk factors underlying these cases. Methods: The study was undertaken in 4 general practices (adult patient population 20,868) between February 2012 and September 2014. Patients with defined risk factors for chronic liver disease (hazardous alcohol use and/or type 2 diabetes) were identified from the General Practice electronic records and invited for transient elastography. Elevated liver stiffness was defined as ≥8 kilopascals. Cirrhosis was confirmed by established histological, radiological and biochemical methods. Results: 2,368 patients were invited for transient elastography and 899/919 who attended (97.8%) had valid measurements. Of these 230 patients had elevated liver stiffness (25.6%) and 27 had cirrhosis (2.9%). Risk factors for new cirrhosis diagnoses were obesity and/or type 2 diabetes in 16 patients (59.3%), alcohol alone in 3 (11.1%) and both alcohol and obesity and/or diabetes in 8 (29.6%). Presence of cirrhosis was significantly increased in obese patients with type 2 diabetes or hazardous alcohol use compared to non-obese (odds ratio 9.4 (95% CI 2.2-40.9) and 5.6 (95% CI 1.6-19.7) respectively). Conclusions: The number of new cases of cirrhosis diagnosed clearly demonstrates that existing estimates of prevalence are likely to be gross underestimates. Obesity was an important risk factor for cirrhosis within both alcohol users and diabetics.

At present, there is no evidence based pathway to stratify risk of chronic liver disease in a general population setting. Non-invasive tests of liver fibrosis may provide a mechanism for earlier diagnosis. These tests have been extensively validated in the hospital setting but their performance in a general population setting is unclear. We performed a systematic review of non-invasive tests used to stratify patients at risk of clinically significant liver disease in a general population setting and report the prevalence of chronic liver disease as defined by these tests. We systematically searched EMBASE, MEDLINE, Web of Science, reference lists from the original studies and recent conference proceedings. All study designs were considered. Nineteen studies were identified, utilising eleven non-invasive tests. Only transient elastography and Fibrotest were compared against histological end-points. The prevalence of liver fibrosis varied between 0.7% and 25.7%. More focussed stratification for advanced liver fibrosis (0.9%-2%) or cirrhosis (0.1%-1.7%) narrowed estimates of prevalence. Studies targeting patients with liver disease risk factors such as hazardous alcohol use or type 2 diabetes reported higher prevalence of advanced liver fibrosis (0%-27.9%) and cirrhosis (2.4%-4%). Validated non-invasive tests of liver fibrosis consistently detected otherwise unrecognised liver disease in the general population. Studies targeting risk factors found cirrhosis in 2.4 to 4 % of their target populations. Reliance on abnormal liver function tests will miss the majority of patients with significant liver injury. New pathways to stratify chronic liver, using non-invasive markers of liver fibrosis, are needed in the general population setting.

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-Hodgkin's 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.

Background Autoimmune Hepatitis is a chronic liver disease which affects young people and can result in liver failure leading to death or transplantation yet there is a lack of information on the incidence and prevalence of this disease and its natural history in the UK. A means of obtaining this information is via the use of clinical databases formed of electronic primary care records. How reliably the diagnosis is coded in such records is however unknown. The aim of this study therefore was to assess the proportion of consultant hepatologist diagnoses of Autoimmune Hepatitis which were accurately recorded in General Practice computerised records. Methods Our study population were patients with Autoimmune Hepatitis diagnosed by consultant hepatologists in the Queens Medical Centre, Nottingham University Hospitals (UK) between 2004 and 2009. We wrote to the general practitioners of these patients to obtain the percentage of patients who had a valid READ code specific for Autoimmune Hepatitis. Results We examined the electronic records of 51 patients who had biopsy evidence and a possible diagnosis of Autoimmune Hepatitis. Forty two of these patients had a confirmed clinical diagnosis of Autoimmune Hepatitis by a consultant hepatologist: we contacted the General Practitioners of these patients obtaining a response rate of 90.5% (39/42 GPs). 37/39 of these GPs responded with coding information and 89% of these patients (33/37) used Read code J638.00 (Autoimmune Hepatitis) to record a diagnosis. Conclusions The diagnosis of Autoimmune Hepatitis made by a Consultant Hepatologist is accurately communicated to and electronically recorded by primary care in the UK. As a large proportion of cases of Autoimmune Hepatitis are recorded in primary care, this minimises the risk of introducing selection bias and therefore selecting cases using these data will be a valid method of conducting population based studies on Autoimmune Hepatitis.

Background: Studies have found an association between proton pump inhibitor (PPI) use and Clostridium difficile infection. The purpose of this study was to determine whether the mechanism by which PPIs induce an increased risk of C. difficile infection is supported by the same mechanism acting in another cause of achlorhydria, pernicious anaemia. Methods: Using a database of anonymised primary care records between 1990 and 2013, we selected exposed patients with a diagnosis of pernicious anaemia treated with vitamin B12 therapy. Each exposed patient was matched by age, gender and general practice to up to 10 controls. Cox regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for C. difficile infection with pernicious anaemia, adjusted for potential confounders. Results: We identified 45,467 exposed patients matched to 449,635 controls. The crude incidence rate of C. difficile infection was 1.85/1000 person-years for the exposed cohort and 1.09/1000 person-years for controls. Patients with pernicious anaemia had a greater risk of C. difficile infection than the controls (adjusted HR 1.57, 95% CI 1.40–1.76). Conclusions: Pernicious anaemia patients have an increased risk of C. difficile infection. This supports the theory that severe achlorhydria is the mechanism that increases the risk of C. difficile infection in long-term PPI users.

Background: Among patients with cirrhosis, only those determined to be at risk for hepatocellular carcinoma (HCC) should undergo surveillance. However, little is known about how different aetiologies of cirrhosis affect risk for HCC. Aim: To quantify the cumulative incidence of HCC among a representative population of people with cirrhosis of the liver of varying aetiology. Methods: We identified subjects with hepatic cirrhosis from the UK's General Practice Research Database (1987-2006). Diagnoses of HCC were obtained from linked national cancer registries (1971-2006). Cox proportional hazards regression was used to estimate hazard ratios. The predicted 10-year cumulative incidence of HCC for each aetiology of cirrhosis was estimated while accounting for competing risks of death from any cause and liver transplant. Results: Among 3107 people with cirrhosis the adjusted relative risk of HCC was increased 2- to 3-fold among people with viral and autoimmune/metabolic aetiologies, compared to those with alcohol-associated cirrhosis. The 10-year predicted cumulative incidence estimates of HCC for each aetiology were: alcohol, 1.2%; chronic viral hepatitis 4.0%; autoimmune or metabolic disease 3.2%; and cryptogenic 1.1%. Conclusions: In a population-based study in the UK, people with cirrhosis have an estimated cumulative 10-year incidence of HCC of 4% or lower. Cumulative incidence varies with aetiology such that individuals with alcohol or cryptogenic cirrhosis have the lowest risk for Risk of HCC in cirrhosis HCC. These findings provide important information for cost-effectiveness analyses of HCC surveillance.

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.

Background: Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal system affecting a large number of people worldwide. Whilst it has no attributable mortality, it has substantial impact on patients' quality of life (QoL) and is associated with considerable healthcare resource use. Aim: To review the economic impact of IBS, firstly on the individual, secondly on healthcare systems internationally and thirdly to society. Methods: Appropriate databases were searched for relevant papers using the terms: Irritable Bowel Syndrome; IBS; irritable colon; functional bowel/colonic disease; economics; health care/service costs; health expenditure/resources; health care/service utilisation; productivity. Results: Irritable bowel syndrome impacts most substantially on patients' work and social life. Reduction in QoL is such that on average patients would sacrifice between 10 and 15 years of their remaining life expectancy for an immediate cure. Between 15% and 43% of patients pay for remedies. No studies quantify loss of earnings related to IBS. Direct care costs are substantial; 48% of patients incur some costs in any year with annual international estimates per patient of: USA $742–$7547, UK £90–£316, France €567–€862, Canada $259, Germany €791, Norway NOK 2098 (€262) and Iran $92. Minimising extensive diagnostic investigations could generate savings and has been shown as not detrimental to patients. Cost to industry internationally through absenteeism and presenteeism related to IBS is estimated between £400 and £900 per patient annually. Conclusions: costs to patients, healthcare systems and society. Considerable benefit could be obtained from effective interventions.

Purpose: To determine the prevalence and pattern of proton pump inhibitor (PPI) prescription and the practices employed to reduce PPI use in the UK general population. Methods: The UK's Clinical Practice Research Database was used to identify individuals who were issued with ≥1 PPI prescription during the period 1990–2014. Point and period prevalence of PPI use were estimated annually. Additionally, new users of PPI therapy who had 5 years of follow-up data were included in a cohort analysis to describe patterns of cessation and duration of PPI use. Results: Both the period and point prevalence of PPI use increased between 1990 and 2014 (period prevalence increased from 0.2 to 15.0% and point from 0.03 to 7.7%). A total of 596 334 new users of PPI therapy in the cohort study received 8 784 272 prescriptions. Of these, 26.7% used PPI therapy long term (≥1 year continuously), while 3.9% remained on PPI therapy for 5 years. Clear attempts to step down dose were identified in 39.9% of long-term users, while this was 47% in patients whose initial indication did not mandate long-term use. Conclusion: A considerable increase in PPI use was observed in UK general practice. Of long-term PPI users, 60% did not have an attempt to discontinue or step down. Considerable opportunities may therefore exist to reduce the cost and side effects of PPI use through improving adherence to recommended withdrawal strategies.

Background: We have assessed whether the linkage between routine primary and secondary care records provided an opportunity to develop an improved population based co-morbidity score with the combined information on co-morbidities from both health care settings. Methods: We extracted all people older than 20 years at the start of 2005 within the linkage between the Hospital Episodes Statistics, Clinical Practice Research Datalink, and Office for National Statistics death register in England. A random 50% sample was used to identify relevant diagnostic codes using a Bayesian hierarchy to share information between similar Read and ICD 10 code groupings. Internal validation of the score was performed in the remaining 50% and discrimination was assessed using Harrell’s C statistic. Comparisons were made over time, age, and consultation rate with the Charlson and Elixhauser indexes. Results: 657,264 people were followed up from the 1st January 2005. 98 groupings of codes were derived from the Bayesian hierarchy, and 37 had an adjusted weighting of greater than zero in the Cox proportional hazards model. 11 of these groupings had a different weighting dependent on whether they were coded from hospital or primary care. The C statistic reduced from 0.88 (95% confidence interval 0.88–0.88) in the first year of follow up, to 0.85 (0.85–0.85) including all 5 years. When we stratified the linked score by consultation rate the association with mortality remained consistent, but there was a significant interaction with age, with improved discrimination and fit in those under 50 years old (C=0.85, 0.83–0.87) compared to the Charlson (C=0.79, 0.77–0.82) or Elixhauser index (C=0.81, 0.79–0.83). Conclusions: The use of linked population based primary and secondary care data developed a co-morbidity score that had improved discrimination, particularly in younger age groups, and had a greater effect when adjusting for co-morbidity than existing scores.

Background and Aims: Numerous studies have established that mortality risk in IBD patients is higher than the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD. Methods: A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records. We described the distribution of causes of death among IBD patients by age at death and time since IBD diagnosis. We estimated age-specific mortality rates and hazard ratios of death in multivariable Cox proportional hazards models. Results: 20,293 IBD patients were matched to 83,261 non-IBD patients. The mortality rate was 40% higher in IBD patients (2005 deaths) than in non-IBD patients (6024 deaths) (adjusted overall hazard ratio = 1.4, 95% CI = 1.4—1.5), with greater risk of death in Crohn’s disease (hazard ratio = 1.6, 1.5—1.7) than in ulcerative colitis (1.3, 1.3—1.4). Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis and 8.3% in Crohn’s disease. Among IBD patients, death was less likely to be due to circulatory, respiratory or neoplastic diseases than non-IBD patients. In both IBD and non-IBD patients all these causes became more clinically important with advancing age, with the commonest neoplastic cause of death being lung cancer, rather than gastrointestinal cancers. Conclusion: IBD patients have an additional risk of death. Most IBD patients die of circulatory or respiratory causes, and the contribution to mortality from long-term complications of IBD are clinically less important.

Objective To examine the risk of community acquired pneumonia before and after prescription of proton pump inhibitor (PPI) and assess whether unmeasured confounding explains this association. Design Cohort study and self controlled case series. Setting Clinical Practice Research Datalink (1990 to 2013) in UK. Participants Adult patients with a new prescription for a PPI individually matched with controls. Main outcome measures Association of community acquired pneumonia with PPI prescription estimated by three methods: a multivariable Cox model comparing risk in PPI exposed patients with controls, corrected for potential confounders; a self controlled case series; and a prior event rate ratio (PERR) analysis over the 12 month periods before and after the first PPI prescription. Results 160 000 new PPI users were examined. The adjusted Cox regression showed a risk of community acquired pneumonia 1.67 (95% confidence interval 1.55 to 1.79) times higher for patients exposed to PPI than for controls. In the self controlled case series, among 48 451 PPI exposed patients with a record of community acquired pneumonia, the incidence rate ratio was 1.19 (95% confidence interval 1.14 to 1.25) in the 30 days after PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 1.84 to 2.00). The Cox regressions for prior event rate ratio similarly showed a greater increase in community acquired pneumonia in the year before than the year after PPI prescription, such that the analysis showed a reduced relative risk of pneumonia associated with PPI use (prior event rate ratio 0.91, 95% confidence interval 0.83 to 0.99). Conclusion The association between the use of PPIs and risk of community acquired pneumonia is likely to be due entirely to confounding factors.

BACKGROUND: Celiac disease has been linked to decreased quality of life and certain mood disorders. The effect of the gluten free diet on these psychological aspects of the disease is still unclear. OBJECTIVES: The objective of this article is to review the literature on psychological morbidity of celiac disease. METHODS: We performed a PubMed search for the time period from 1900 until June 1, 2014, to identify papers on psychological aspects of celiac disease looking specifically at quality of life, anxiety, depression and fatigue. RESULTS: Anxiety, depression and fatigue are common complaints in patients with untreated celiac disease and contribute to lower quality of life. While aspects of these conditions may improve within a few months after starting a gluten-free diet, some patients continue to suffer from significant psychological morbidity. Psychological symptoms may affect the quality of life and the dietary adherence. CONCLUSION: Health care professionals need to be aware of the ongoing psychological burden of celiac disease in order to support patients with this disease.

Background: Venous thromboembolism is a potentially preventable cause of death in people with lung cancer. Identification of those most at risk and high risk periods may provide the opportunity for better targeted intervention. Methods: We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics and Cancer Registry data. Our cohort comprised 10,598 people with lung cancer diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, tumour and treatment-related factors (time-varying effects of chemotherapy and surgery) independently affected VTE risk. We also determined the effect of a VTE diagnosis on the survival of people with lung cancer. Results: People with lung cancer had an overall VTE incidence of 39.2 per 1000 person years (95% confidence Interval (CI), 35.4-43.5), though rates varied depending on the patient group and treatment course. Independent factors associated with increased VTE risk were: metastatic disease (hazard ratio (HR)=1.9, CI 1.2, 3.0 vs. local disease); adenocarcinoma sub-type (HR =2.0, CI 1.5, 2.7, vs. squamous cell; chemotherapy administration, (HR=2.1, CI 1.4, 3.0 vs. outside chemotherapy courses); and diagnosis via emergency hospital admission (HR=1.7, CI 1.2-2.3 vs. other routes to diagnosis). Patients with VTE had an approximately 50% higher risk of mortality than those without VTE. Conclusions: People with lung cancer have especially high risk of VTE if they have advanced disease, adenocarcinoma, or are undergoing chemotherapy. Presence of VTE is an independent risk factor for death.

INTRODUCTION: Health economic models are increasingly important in funding decisions but most are based on data, which may therefore not represent the general population. We sought to establish the potential of real-world data available within the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) to determine comprehensive healthcare utilisation and costs as input variables for economic modelling. METHODS: A cohort of patients with irritable bowel syndrome (IBS) who first saw a gastroenterologist in 2008 or 2009, and with 3 years of data before and after their appointment, was created in the CPRD. Primary care, outpatient, inpatient, prescription and colonoscopy data were extracted from the linked CPRD and HES. The appropriate cost to the NHS was attached to each event. Total and stratified annual healthcare utilisation rates and costs were calculated before and after the gastroenterology appointment with distribution parameters. Absolute differences were calculated with 95 % confidence intervals. RESULTS: Total annual healthcare costs over 3 years increase by £935 (95 % CI £928–941) following a gastroenterology appointment for IBS. We derived utilisation and cost data with parameter distributions stratified by demographics and time. Women, older patients, smokers and patients with greater comorbidity utilised more healthcare resources, which generated higher costs. CONCLUSIONS: These linked datasets provide comprehensive primary and secondary care data for large numbers of patients, which allows stratification of outcomes. It is possible to derive input parameters appropriate for economic models and their distributions directly from the population of interest.

BACKGROUND: Patients with colorectal cancer are at high risk of developing venous thromboembolism (VTE), and recent international guidelines have advised extended prophylaxis for some of these patients following surgery or during chemotherapy. However, our understanding of which patients are at increased risk, and to what extent, is limited. OBJECTIVES: To determine absolute and relative rates of VTE among patients with colorectal cancer according to Dukes stage, surgical intervention, and chemotherapy. METHODS: We analyzed data from four linked databases from 1997 to 2006: the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data, and Office for National Statistics cause of death data, all from England. Rates were compared by the use of Cox regression. RESULTS: There were 10 309 patients with colorectal cancer, and 555 developed VTE (5.4%). The incidence varied by Dukes stage, being three-fold higher among Dukes D patients than among Dukes A patients (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.95–4.84), and 40% higher for those receiving chemotherapy than for those not receiving chemotherapy (HR 1.39, 95% CI 1.14–1.69). The risk following surgery varied by stage of disease and chemotherapy, with Dukes A patients having a low incidence of VTE (0.74%; 95% CI 0.28–1.95) at 6 months, with all events occurring within 28 days of surgery, as compared with Dukes B and Dukes C patients, whose risk at 6 months was ∼ 2%. CONCLUSION: Twenty-eight days of prophylaxis following surgery for colorectal cancer is appropriate for Dukes A patients. However, Dukes B and Dukes C patients receiving postoperative chemotherapy have a longer duration of risk.

Background: Inflammatory bowel disease (IBD) patients are sometimes first diagnosed with irritable bowel syndrome (IBS), which may be construed as a misdiagnosis. Objective: The objective of this article is to determine if this occurs more than expected by chance. Methods: We conducted a case-control study nested in the General Practice Research Database. We selected incident cases of IBD and up to 10 matched controls for each. We assessed the proportions with IBS recorded prior to the IBD diagnosis and variation by age, sex, and calendar time. We compared proportions affected in fixed time periods and conducted conditional logistic regression to derive odds ratios. Results: The 20, 193 cases were three times as likely as controls to have a prior record of IBS. Fifteen per cent of IBD cases and 5% of controls had IBS coded before diagnosis with 11% having a code for IBS over one year before IBD (cf. 5% of controls) and 6% over five years earlier (cf. 3%). These figures roughly doubled if typical antispasmodic therapies were assumed to represent IBS diagnoses. Conclusion: If excess IBS diagnoses represent misdiagnoses of IBD, our results suggest that about 10% of IBD patients are misdiagnosed and in 3% of cases this may persist for five or more years.

Background: More than 20% of colorectal cancers are diagnosed following an emergency presentation. We aimed to examine pre-diagnostic primary care consultations and related symptoms comparing patients diagnosed as emergencies with those diagnosed through nonemergency routes. Methods: Cohort study of colorectal cancers diagnosed in England 2005-06 using cancer registration data individually linked to primary care data (CPRD/GPRD), allowing a detailed analysis of clinical information referring to the 5-year pre-diagnostic period. Results: Emergency diagnosis occurred in 35% and 15% of the 1029 colon and 577 rectal cancers. ‘Background’ primary care consultations (2-5 years before diagnosis) were similar for either group. In the year before diagnosis, more than 95% of emergency and non-emergency presenters had consulted their doctor, but emergency presenters had less frequently relevant symptoms (colon cancer: 48% versus 71% (p<0.001); rectal cancer: 49% versus 61% (p=0.043)). ‘Alarm’ symptoms were recorded less frequently in emergency presenters (e.g. rectal bleeding: 9% versus 24% (p=0.002)). However, about 1/5 of emergency presenters (18% and 23% for colon and rectal cancers) had 'alarm' symptoms the year before diagnosis. Conclusions: Emergency presenters have similar ‘background’ consultation history as nonemergency presenters. Their tumours seem associated with less typical symptoms, however opportunities for earlier diagnosis might be present in a fifth of them.