The epidemiology of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional condition of the bowel that is diagnosed using clinical criteria. This paper discusses the nature of the diagnostic process for IBS and how this impacts epidemiological measurements. Depending on the diagnostic criteria employed, IBS affects around 11% of the population globally. Around 30% of people who experience the symptoms of IBS will consult physicians for their IBS symptoms. These people do not have significantly different abdominal symptoms to those who do not consult, but they do have greater levels of anxiety and lower quality of life. Internationally, there is a female predominance in the prevalence of IBS. There is 25% less IBS diagnosed in those over 50 years and there is no association with socioeconomic status. IBS aggregates within families and the genetic and sociological factors potentially underlying this are reviewed. Patients diagnosed with IBS are highly likely to have other functional disease and have more surgery than the general population. There is no evidence that IBS is associated with an increased mortality risk. The epidemiological evidence surrounding these aspects of the natural history is discussed

A contribution to knowledge of the aetiology and indirect impact of inflammatory bowel diseases: (based upon analysis of routinely and semi-routinely available data)

The incidence of the idiopathic inflammatory bowel diseases ulcerative colitis and Crohn’s disease appears to have risen markedly during the 20th century. These diseases now account for a considerable proportion of the workload of gastroenterologists in the developed world, and may affect as much as 1% of the population at some point in their lives. The aetiology of these diseases has been subject of much research over a number of decades and it is clear that both genetic and environmental factors are involved. The certain knowledge of environmental risk factors however remains scant. Similarly although inflammatory bowel diseases cause considerable morbidity and a small amount of mortality for their sufferers directly there is little agreement as to their overall impact once indirect effects are accounted for. This thesis contains studies contributing to the knowledge of both these areas using routinely or semi-routinely collected data. It examines two hypotheses relating to the aetiology of IBD (that risk is related to the season of birth, and that it is related to antibiotic use), and two areas of the impact of the diseases (overall mortality and fracture risk). With regard to aetiology the studies described show no variation in the risk of IBD with season of birth. They do show an increase in risk associated with the use of antibiotics, but since this is not specific (it is seen to occur with other groups of drugs also) it is far from clear that the association is causal. With regard to the indirect impact of the diseases a significant excess in overall mortality is demonstrated which is greater in Crohn’s disease than in ulcerative colitis, and is greatest in relative terms in the young but in absolute terms in the elderly. An excess is also shown for hip fractures in those with inflammatory bowel diseases, which is only partially explained by the use of corticosteroids

Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study

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

A comparison of the recording of comorbidity in primary and secondary care by using the Charlson Index to predict short-term and long-term survival in a routine linked data cohort

OBJECTIVE: Hospital admission records provide snapshots of clinical histories for a subset of the population admitted to hospital. In contrast, primary care records provide continuous clinical histories for complete populations, but might lack detail about inpatient stays. Therefore, combining primary and secondary care records should improve the ability of comorbidity scores to predict survival in population-based studies, and provide better adjustment for case-mix differences when assessing mortality outcomes. DESIGN: Cohort study. SETTING: English primary and secondary care 1 January 2005 to 1 January 2010. PARTICIPANTS: All patients 20 years and older registered to a primary care practice contributing to the linked Clinical Practice Research Datalink from England. OUTCOME: The performance of the Charlson index with mortality was compared when derived from either primary or secondary care data or both. This was assessed in relation to short-term and long-term survival, age, consultation rate, and specific acute and chronic diseases. RESULTS: 657,264 people were followed up from 1 January 2005. Although primary care recorded more comorbidity than secondary care, the resulting C statistics for the Charlson index remained similar: 0.86 and 0.87, respectively. Higher consultation rates and restricted age bands reduced the performance of the Charlson index, but the index's excellent performance persisted over longer follow-up; the C statistic was 0.87 over 1 year, and 0.85 over all 5 years of follow-up. The Charlson index derived from secondary care comorbidity had a greater effect than primary care comorbidity in reducing the association of upper gastrointestinal bleeding with mortality. However, they had a similar effect in reducing the association of diabetes with mortality. CONCLUSIONS: These findings support the use of the Charlson index from linked data and show that secondary care comorbidity coding performed at least as well as that derived from primary care in predicting survival

The risk of Clostridium difficile infection in patients with pernicious anaemia: a retrospective cohort study using primary care database.

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

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

A contribution to knowledge of the aetiology and indirect impact of inflammatory bowel diseases: (based upon analysis of routinely and semi-routinely available data)

The incidence of the idiopathic inflammatory bowel diseases ulcerative colitis and Crohn’s disease appears to have risen markedly during the 20th century. These diseases now account for a considerable proportion of the workload of gastroenterologists in the developed world, and may affect as much as 1% of the population at some point in their lives. The aetiology of these diseases has been subject of much research over a number of decades and it is clear that both genetic and environmental factors are involved. The certain knowledge of environmental risk factors however remains scant. Similarly although inflammatory bowel diseases cause considerable morbidity and a small amount of mortality for their sufferers directly there is little agreement as to their overall impact once indirect effects are accounted for. This thesis contains studies contributing to the knowledge of both these areas using routinely or semi-routinely collected data. It examines two hypotheses relating to the aetiology of IBD (that risk is related to the season of birth, and that it is related to antibiotic use), and two areas of the impact of the diseases (overall mortality and fracture risk). With regard to aetiology the studies described show no variation in the risk of IBD with season of birth. They do show an increase in risk associated with the use of antibiotics, but since this is not specific (it is seen to occur with other groups of drugs also) it is far from clear that the association is causal. With regard to the indirect impact of the diseases a significant excess in overall mortality is demonstrated which is greater in Crohn’s disease than in ulcerative colitis, and is greatest in relative terms in the young but in absolute terms in the elderly. An excess is also shown for hip fractures in those with inflammatory bowel diseases, which is only partially explained by the use of corticosteroids

The pattern of underlying cause of death in patients with inflammatory bowel disease in England: a record linkage study

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

Change in quality of life for patients with irritable bowel syndrome following referral to a gastroenterologist: a cohort study

BACKGROUND: Irritable bowel syndrome (IBS), a chronic functional condition, considerably reduces quality of life (QoL) and referral to gastroenterology is common. Until now, however, the impact of seeing a gastroenterologist for IBS on patients’ QoL and utility has not been assessed.METHODS: Patients referred with “probable IBS” to the Nottingham Treatment Centre between October 2012 and March 2014 were invited to complete a QoL questionnaire (EuroQol–5 Dimension) before their first appointment. Patients with confirmed IBS who completed this baseline assessment were sent follow-up questionnaires three and twelve months later. Global QoL and utility were measured at each time point and change from baseline calculated. Paired t-tests analysed the significance of any change. RESULTS: Of 205 invited patients, 69 were eligible and recruited. Response at three and twelve months was 45% and 17% respectively. Median global QoL at baseline was 67.5 (Interquartile range [IQR] 50.0 to 80.0), with a mean increase of 3.25 (95% confidence interval [CI] -5.38 to 11.88) three months later and a mean decrease of -1.82 (95% CI -16.01 to 12.38) after one year. The median utility at baseline was 0.76 (IQR 0.69 to 0.80), with a mean increase of 0.06 (95%CI -0.01 to 0.14) at three months and no change, 0.00 (-0.16 to 0.16), after one year. CONCLUSION: Patients experienced a small but not statistically significant increase in QoL and utility three months after seeing a gastroenterologist for IBS, which was not maintained. Gastroenterology referral does not appear to appreciably improve Qol for most people with IBS

Obesity is the most common risk factor for chronic liver disease: Results from risk stratification pathway using transient elastography

IntroductionObesity has been associated with liver fibrosis yet guidelines do not emphasise it as an independent risk factor in which to have a high index of suspicion of advanced disease. We aimed to elucidate the effect of a raised body mass index on the risk of liver disease using data from a community risk stratification pathway. MethodsWe prospectively recruited patients from a primary care practice with hazardous alcohol use and/or type 2 diabetes and/or obesity. Subjects were invited for a transient elastography reading. A threshold of ≥8.0kPa defined an elevated reading consistent with clinically significant liver disease. ResultsFive hundred and seventy six patients participated in the pathway of which, 533 patients had a reliable reading and 66 (12.4%) had an elevated reading. Thirty one percent of patients with an elevated reading had obesity as their only risk factor. The proportion of patients with an elevated reading was similar among those with obesity (8.9%) to patients with more recognised solitary risk factors (Type 2 diabetes 10.8%; Hazardous alcohol use 4.8%). Obesity in combination with other risk factors further increased the proportion of patients with an elevated reading. In multivariate logistic regression, increasing BMI and type 2 diabetes were significantly associated with an elevated reading. ConclusionObesity as a single or additive risk factor for chronic liver disease is significant. Future case finding strategies using a risk factor approach should incorporate obesity within proposed algorithms