Utilization and safety of proton-pump inhibitors and histamine-2 receptor antagonists in children and adolescents: an observational cohort study.

BACKGROUND: Little is known about the use of acid-suppressing treatments and related safety events in children. OBJECTIVE: This study compared patient characteristics and safety outcomes among children prescribed acid-suppressing drugs for the first time. METHODS: The Health Improvement Network was used to determine the characteristics of children prescribed a proton pump inhibitor (PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H2RA) by UK primary care physicians between October 2009 and September 2012. Pre-defined safety outcomes were compared among the treatment groups in up to 18 months of follow-up. RESULTS: The cohorts comprised 8,172 patients on PPIs (including 24 patients on esomeprazole) and 7,905 on H2RAs. The baseline characteristics were similar between cohorts, although the children in the PPI cohorts tended to be older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n = 36; 39.1%). In the H2RAs cohort, 193 safety outcomes occurred, most commonly gastroenteritis (n = 62; 32.1%). The incidence of most safety outcomes was higher in the H2RAs cohort than in the other-PPIs cohort, including failure to thrive (3.11 [95% confidence interval (CI) = 2.25-4.28] vs 0.49 per 1,000 person-years [95% CI = 0.22-1.07]) and gastroenteritis (5.27 [95% CI = 4.11-6.75] vs 3.04 per 1,000 person-years [95% CI = 2.20-4.20]). CONCLUSION: Esomeprazole is rarely prescribed to children when they first require acid-suppressing medication, compared with other PPIs/H2RAs. Overall, more safety outcomes occurred in the H2RAs cohort than in the PPI cohorts.

Incidence of intracranial bleeds in new users of low-dose aspirin: a cohort study using The Health Improvement Network.

Essentials Intracranial bleeds (ICB) are serious clinical events that have been associated with aspirin use. Incidence rates of ICB were calculated among new-users of low-dose aspirin in the UK (2000-2012). Over a median follow-up of 5.58 years, the incidence of ICB was 0.08 per 100 person-years. Our estimates are valuable for inclusion in risk-benefit assessments of low-dose aspirin use. SUMMARY: Background Low-dose aspirin protects against both ischemic cardiovascular (CV) events and colorectal cancer (CRC). However, low-dose aspirin may be associated with a slightly increased risk of intracranial bleeds (ICBs). Objectives To obtain the incidence rates of ICBs overall and by patient subgroups among new users of low-dose aspirin. Patients/Methods Using The Health Improvement Network (THIN) UK primary-care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N = 199 079; mean age at start of follow-up, 63.9 years) and followed them for up to 14 years (median 5.58 years). Incident ICB cases were identified and validated through linkage to hospitalization data and/or review of THIN records with free-text comments. Incidence rates with 95% confidence intervals (CIs) were calculated. Results Eight hundred and eighty-one incident ICBs cases were identified: 407 cases of intracerebral hemorrhage (ICH), 283 cases of subdural hematoma (SDH), and 191 cases of subarachnoid hemorrhage (SAH). Incidence rates per 100 person-years were 0.08 (95% CI 0.07-0.08) for all ICBs, 0.04 (95% CI 0.03-0.04) for ICH, 0.03 (95% CI 0.02-0.03) for SDH, and 0.02 (95% CI 0.01-0.02) for SAH. The ICB incidence rates per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (95% CI 0.06-0.07) and 0.09 (95% CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. Conclusions Our results provide valuable estimates of the absolute ICB risk for incorporation into risk-benefit assessments of low-dose aspirin use.

Risk factors for diabetic macular oedema in type 2 diabetes: A case-control study in a United Kingdom primary care setting.

AIM: To identify risk factors associated with the development of DMO among patients diagnosed with type 2 diabetes managed in a primary care setting in the UK. METHODS: A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000-2007. Cases were people with DMO (N=211) and controls were a DMO-free sample (N=2194). No age restrictions were applied. Adjusted odds ratios and 95%CIs were estimated (OR; 95%CI). RESULTS: DMO increased with high alcohol use (2.88; 1.49-5.55), cataracts (4.10; 2.73-6.15), HbA1c ≥7% (1.58; 1.08-2.32), systolic blood pressure ≥160mm Hg (2.03; 1.17-3.53), total cholesterol ≥5mmol/L (1.66; 1.15-2.39), LDL ≥3mmol/L (1.73; 1.14-2.61), and microalbuminuria (1.78; 1.16-2.73). Diuretic drugs were associated with a reduced risk of DMO (0.68; 0.47-0.99), as did smoking (0.47; 0.28-0.77), overweight (0.53; 0.30-0.96) or obesity (0.52; 0.30-0.91) at diabetes diagnosis, and high triglyceride levels (0.51; 0.35-0.74). Patients treated with anti-diabetic drugs showed higher risk of DMO than non-treated patients, particularly those with sulphonylureas (3.40; 2.42-4.78), insulin (3.21; 1.92-5.36) or glitazones (1.88; 1.17-3.04). CONCLUSION: In patients with type 2 diabetes managed in primary care, multiple factors associated with DMO were identified, such as cataracts, microalbuminuria and high levels of HbA1c, systolic BP, total cholesterol, and LDL. Diuretic drugs were associated with a reduced risk of DMO. Treated diabetes, particularly with sulphonylureas, insulin or glitazones showed highest risk of DMO. The inverse association between smoking, obesity, and triglycerides and DMO deserves further research.

Exposure to acid-suppressing drugs during pregnancy and the risk of asthma in childhood: an observational cohort study.

BACKGROUND: Some research has suggested a potential link between prenatal exposure to proton pump inhibitors (PPIs) or H2 -receptor antagonists (H2 RAs) and the development of childhood asthma. AIM: To quantify the relative risk of asthma in children who experienced pre-natal exposure to PPIs and/or H2 RAs, adjusting for potential confounders. METHODS: In this observational cohort study (NCT01787435), women aged 18-45 years with completed pregnancies between January 1996 and December 2010 were identified from The Health Improvement Network in the United Kingdom, and were linked to infants. Hazard ratios (HRs) were estimated using Cox proportional hazard models. RESULTS: Our analysis identified 2371 prenatally exposed and 7745 unexposed infants. The incidence of asthma (per 1000 person-years) was 19.52 in the unexposed cohort, 23.88 in the PPI cohort and 32.16 in the H2 RA cohort. After adjusting for maternal healthcare utilisation during the year before pregnancy, the HR for asthma in infants whose mothers received prescriptions at any time during pregnancy was 1.12 (95% confidence interval: 0.88-1.44) for PPIs and 1.43 (1.20-1.70) for H2 RAs, when compared with unexposed infants. With further adjustment for maternal comorbidities and other medications, the HR for asthma was 1.03 (0.76-1.40) for PPIs and 1.32 (1.05-1.64) for H2 RAs. CONCLUSIONS: Our analysis showed no association between prenatal exposure to PPIs and asthma in childhood after adjusting for confounders. The association found for H2 RAs may be explained largely by underlying environmental or genetic factors, as suggested by reductions in hazard ratio estimates following adjustment for maternal comorbidities.

Peptic Ulcer Bleeding Risk. The Role of Helicobacter Pylori Infection in NSAID/Low-Dose Aspirin Users.

OBJECTIVES: Helicobacter pylori (H. pylori) infection and NSAID/low-dose aspirin (ASA) use are associated with peptic ulcer disease. The risk of peptic ulcer bleeding (PUB) associated with the interaction of these factors remains unclear. The objective of this study was to determine the risk of PUB associated with the interaction between H. pylori infection and current nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose ASA use. METHODS: This was a case-control study of consecutive patients hospitalized because of PUB. Controls were matched by age, sex, and month of admission. H. pylori infection status was determined in all cases and controls by serology. Drug use was determined by structured questionnaire. Adjusted relative risk (RR) associated with different factors, and the interaction between NSAID/ASA and H. pylori infection was estimated by logistic regression analysis. RESULTS: The study included 666 cases of PUB and 666 controls; 74.3% cases and 54.8% controls (RR: 2.6; 95% confidence interval (CI): 2.0-3.3) tested positive for H. pylori infection; 34.5% of cases had current NSAID use compared with 13.4% of controls (RR: 4.0; 95% CI: 3.0-5.4). Respective proportions for low-dose ASA use were 15.8 and 12%, respectively (RR: 1.9; 95% CI: 1.3-2.7). The RR of PUB for concomitant NSAID use and H. pylori infection suggested an additive effect (RR: 8.0; 95% CI: 5.0-12.8), whereas no interaction was observed with ASA use (RR: 3.5; 95% CI: 2.0-6.1). CONCLUSIONS: NSAID, low-dose ASA use, and H. pylori infection are three independent risk factors for the development of PUB, but there were differences in the interaction effect between low-dose ASA (no interaction) or NSAID (addition) use and H. pylori infection, which may have implications for clinical practice in prevention strategies.

Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study.

OBJECTIVE: To assess the risk of non-fatal ischemic stroke associated with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied. METHODS: We performed a population-based case-control study. Patients were considered exposed if they were on treatment within a 30-day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. RESULTS: Two thousand eight hundred and eighty-eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90-1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19-1.97), in particular when used at high doses (OR = 1.62; 1.06-2.46), over long-term periods (> 365 days; OR = 2.39; 1.52-3.76) and in patients with a high background CV risk (OR = 1.78; 1.23-2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05-2.67), in long-term treatments (OR = 2.00; 1.14-3.53) and in patients with CV risk factors (OR = 2.33; 1.40-3.87). No association was found with ibuprofen (OR = 0.94; 0.76-1.17) or naproxen (OR = 0.68; 0.36-1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85-1.10) or in patients at high CV risk (OR = 0.94; 0.78-1.14). CONCLUSIONS: Diclofenac and aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in patients with a high background CV risk.

Incidence rates and trends of hip/femur fractures in five European countries: comparison using e-healthcare records databases.

Hip fractures represent a major public health challenge worldwide. Multinational studies using a common methodology are scarce. We aimed to estimate the incidence rates (IRs) and trends of hip/femur fractures over the period 2003-2009 in five European countries. The study was performed using seven electronic health-care records databases (DBs) from Denmark, The Netherlands, Germany, Spain, and the United Kingdom, based on the same protocol. Yearly IRs of hip/femur fractures were calculated for the general population and for those aged ≥50 years. Trends over time were evaluated using linear regression analysis for both crude and standardized IRs. Sex- and age-standardized IRs for the UK, Netherlands, and Spanish DBs varied from 9 to 11 per 10,000 person-years for the general population and from 22 to 26 for those ≥50 years old; the German DB showed slightly higher IRs (about 13 and 30, respectively), whereas the Danish DB yielded IRs twofold higher (19 and 52, respectively). IRs increased exponentially with age in both sexes. The ratio of females to males was ≥2 for patients aged ≥70-79 years in most DBs. Statistically significant trends over time were only shown for the UK DB (CPRD) (+0.7% per year, P < 0.01) and the Danish DB (-1.4% per year, P < 0.01). IRs of hip/femur fractures varied greatly across European countries. With the exception of Denmark, no decreasing trend was observed over the study period.

Use of prescription contraceptive methods in the UK general population: a primary care study.

OBJECTIVE: To determine prescription contraceptive use in the UK. DESIGN: Observational study using a primary care database. SETTING: The Health Improvement Network (THIN). POPULATION: Women in THIN aged 12-49 years in 2008, registered with their primary care doctor for at least 5 years, and with a prescription history of at least 1 year were included. METHODS: THIN was searched using the Read and MULTILEX codes for the following methods: combined oral contraceptives (COCs), progestogen-only pills (POPs), copper intrauterine devices (Cu-IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS), progestogen-only implants, progestogen-only injections, and contraceptive patches. MAIN OUTCOME MEASURES: Prevalence, switching, and duration of prescriptions. RESULTS: A cohort of 194 054 women was identified. The prevalence of contraceptive use was: COCs, 16.2% (95% confidence interval, 95% CI 16.1-16.3%); POPs, 5.6% (95% CI 5.5-5.6%); Cu-IUD, 4.5% (95% CI 4.4-4.5%); LNG-IUS, 4.2% (95% CI 4.1-4.2%); progestogen-only implants, 1.5% (95% CI 1.5-1.6%); progestogen-only injections, 2.4% (95% CI 2.3-2.4%); and contraceptive patches, 0.1% (95% CI 0.1-0.2%). Within 1 year, 9.8% of new COC users switched to alternative COCs, and 9.0% changed to a different method. Among new COC users who did not switch method, 34.8% did not continue use beyond 3 months, and were no longer using a prescription contraceptive. CONCLUSIONS: Among users of oral contraceptives who did not switch method, over one-third did not continue use beyond 3 months. This supports current UK guidelines recommending a follow-up consultation with a healthcare professional 3 months after the first prescription of COCs.

Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study.

AIMS/HYPOTHESIS: The aim of this study was to determine the contemporary rate ratio of mortality and changes over time in individuals with vs without diabetes. METHODS: Annual age- and sex-adjusted mortality rates were compared for adults (>20 years) with and without diabetes in Ontario, Canada, and the UK from January 1996 to December 2009 using The Health Improvement Network (THIN) and Ontario databases. The total number of individuals evaluated increased from 8,757,772 in 1996 to 12,696,305 in 2009. RESULTS: The excess risk of mortality for individuals with diabetes in both cohorts was significantly lower during later vs earlier years of the follow-up period (1996-2009). In Ontario the diabetes mortality rate ratio decreased from 1.90 (95% CI 1.86, 1.94) in 1996 to 1.51 (1.48, 1.54) in 2009, and in THIN from 2.14 (1.97, 2.32) to 1.65 (1.57, 1.72), respectively. In Ontario and THIN, the mortality rate ratios among diabetic patients in 2009 were 1.67 (1.61, 1.72) and 1.81 (1.68, 1.94) for those aged 65-74 years and 1.11 (1.10, 1.13) and 1.19 (1.14, 1.24) for those aged over 74 years, respectively. Corresponding rate ratios in Ontario and THIN were 2.45 (2.36, 2.54) and 2.64 (2.39, 2.89) for individuals aged 45-64 years, and 4.89 (4.35, 5.45) and 5.18 (3.73, 6.69) for those aged 20-44 years. CONCLUSIONS/INTERPRETATION: The excess risk of mortality in individuals with vs without diabetes has decreased over time in both Canada and the UK. This may be in part due to earlier detection and higher prevalence of early diabetes, as well as to improvements in diabetes care.

Use of clopidogrel and proton pump inhibitors after a serious acute coronary event: risk of coronary events and peptic ulcer bleeding.

Some pharmacokinetic studies have reported that proton pump inhibitors (PPIs) reduce the activity of clopidogrel, but the results of studies assessing clinical outcomes in patients receiving both drugs are inconsistent. We have therefore carried out a population-based cohort study with nested case-control analysis, in order to evaluate changes in the risk of cardiovascular and peptic ulcer bleeding (PUB) events associated with PPI use in patients receiving clopidogrel. A total of 42,542 patients aged 50-84 years in 2000-2007 who survived an acute coronary event were identified in two UK-based primary care databases (The Health Improvement Network and the General Practice Research Database). Individuals were followed up to identify incident cases of non-fatal myocardial infarction/coronary death (n = 2,546) and PUB (n = 194). Controls were frequency matched to cases by age, sex and calendar year. Compared with PPI non-use, current continuous PPI use was not associated with a significant change in risk of non-fatal myocardial infarction/coronary death among current continuous users of clopidogrel monotherapy (relative risk [RR], 1.06; 95% confidence interval [95% CI], 0.47 to 2.36) or dual antiplatelet therapy (DAT; RR, 0.80; 95% CI, 0.47 to 1.37) who initiated their antiplatelet therapy shortly after their coronary event. Among patients prescribed DAT at the start date, the RR of PUB events associated with current PPI use initiated at the start date was 0.66 (95% CI, 0.27 to 1.60).

Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma: a case-control study.

BACKGROUND: Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting. METHODS: We used national registries in Denmark to identify all patients aged 20-85 years with a first diagnosis of histologically verified glioma during 2000-2009. Each case was matched on birth year and sex to eight population controls using risk-set sampling. We used prescription data to assess NSAID use and classified exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential confounders. RESULTS: A total of 2688 glioma cases and 18,848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin or of NA-NSAIDs was associated with ORs of 0.80 (95% CI: 0.53-1.21) and 1.11 (0.57-2.17), respectively. We observed no clear patterns of risk in stratified analysis according to estimated doses of low-dose aspirin (≤ 100 mg, 150 mg). CONCLUSION: We did not find any apparent association between aspirin or NA-NSAID use and risk of glioma, although our results may be consistent with a slight reduction in glioma risk with long-term use of low-dose aspirin.

Risk factors for intestinal ischaemia among patients registered in a UK primary care database: a nested case-control study.

BACKGROUND: Intestinal ischaemia, including ischaemic colitis and acute mesenteric ischaemia, causes significant morbidity and mortality. Few population-based studies have estimated incidence and potential risk factors for this disease. AIMS: To estimate the incidence of intestinal ischaemia and identify the associated risk factors in cohorts: (i) patients with irritable bowel syndrome and/or chronic constipation (IBS/CC/both), (ii) individuals free of these conditions. METHODS: Population-based case-control analysis nested in a cohort of patients with first ever recorded diagnosis of IBS/CC/both and a cohort free of these conditions from general population using the General Practice Research Database. RESULTS: Of 78 cases of intestinal ischaemia, 71 were from general population, seven from the IBS/CC/both cohort. Incidence rate of intestinal ischaemia in IBS/CC/both patients vs. general population was 4.49:1.09 per 100,000 person-years; age- and gender-adjusted incidence rate ratio (95% CI) was 2.7 (1.2-5.9). Inflammatory bowel disease and heart failure showed an association with ischaemic colitis [OR (95% CI): 4.2 (0.5-38.4) and 5.6 (2.2-14.1)], but none with acute mesenteric ischaemia. Diabetes and prior cardiovascular surgery were associated with higher risk of acute mesenteric ischaemia, but showed no association with ischaemic colitis. CONCLUSIONS: Results suggest that different risk factors are associated with acute mesenteric ischaemia and ischaemic colitis. However, due to small number of patients, associations should be carefully interpreted.

The changing face of hospitalisation due to gastrointestinal bleeding and perforation.

BACKGROUND: Temporal changes in the incidence of cause-specific gastrointestinal (GI) complications may be one of the factors underlying changing medical practice patterns. AIM: To report temporal changes in the incidence of five major causes of specific gastrointestinal (GI) complication events. METHODOLOGY: Population-based study of patients hospitalised due to GI bleeding and perforation from 1996 to 2005 in Spain. We report crude rates, and estimate regression coefficients of temporal trends, severity and recorded drug use for five frequent GI events. GI hospitalisation charts were validated by independent review of large random samples. RESULTS: The incidence per 100 000 person-years of hospitalisations due to upper GI ulcer bleeding and perforation decreased over time [from 54.6 and 3.9 in 1996 (R² = 0.944) to 25.8 and 2.9 in 2005 (R² = 0.410) respectively]. On the contrary, the incidence per 100 000 person-years of colonic diverticular and angiodysplasia bleeding increased over time [3.3 and 0.9 in 1996 (R² = 0.443) and 8.0 and 2.6 in 2005 (R² = 0.715) respectively]. A small increasing trend was observed for the incidence per 100 000 person-years of intestinal perforations (from 1.5 to 2.3 events). Based on data extracted from the validation process, recent recorded drug intake showed an increased frequency of anticoagulants with colonic diverticular and angiodysplasia bleeding, whereas NSAID and low-dose aspirin use were more prevalent in peptic ulcer bleeding and colonic diverticular bleeding respectively. CONCLUSIONS: From 1996 to 2005, hospitalisations due to peptic ulcer bleeding and perforation have decreased significantly, whereas the number of cases of colonic diverticular and angiodysplasia bleeding have increased.

Depression and treatment with antidepressants are associated with the development of gastro-oesophageal reflux disease.

BACKGROUND: The roles of depression and antidepressants in triggering reflux symptoms remain unclear. AIM: To compare the incidence of gastro-oesophageal reflux disease (GERD) in individuals with and without a depression diagnosis and to evaluate risk factors for a GERD diagnosis. The relationship between antidepressant treatment and GERD was also assessed. METHODS: The Health Improvement Network UK primary care database was used to identify patients with incident depression and an age- and sex-matched control cohort with no depression diagnosis. Incident GERD diagnoses were identified during a mean follow-up of 3.3 years. Furthermore, we performed nested case-control analyses where odds ratios (OR) with 95% confidence intervals (CI) were estimated by unconditional logistic regression in multivariable models. RESULTS: The incidence of GERD was 14.2 per 1000 person-years in the depression cohort and 8.3 per 1000 person-years in the control cohort. The hazard ratio of GERD in patients with depression compared with controls was 1.72 (95% CI: 1.60-1.85). Among patients with depression, tricyclic antidepressant use was associated with an increased risk of GERD (OR: 1.71; 95% CI: 1.34-2.20), while selective serotonin reuptake inhibitors were not associated with GERD. CONCLUSIONS: A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants.

Uncomplicated peptic ulcer in the UK: trends from 1997 to 2005.

BACKGROUND: Few studies have examined the incidence of uncomplicated peptic ulcer or the trends in factors affecting its incidence. AIM: To estimate the incidence rate of uncomplicated peptic ulcer in the UK from 1997 to 2005 and report temporal changes in the main known preventive and risk factors. METHODS: Population-based cohort study of 1 049 689 patients enrolled in The Health Improvement Network in the UK. We estimated the incidence rate of uncomplicated peptic ulcer and evaluated temporal trends in demographic characteristics and prescription patterns for various anti-inflammatory and gastroprotective agents. RESULTS: Overall uncomplicated peptic ulcer incidence was 0.75 cases per 1000 persons-years, declining from 1.1 to 0.52 cases per 1000 person-years between 1997 and 2005. Distributions of age, gender and alcohol habits were similar in 1997 and 2005. The proportion of documented Helicobacter pylori-negative cases increased from 5% to 12%. Monthly prevalence of subjects with prescriptions for traditional non-aspirin NSAIDs changed from 7.7% to 6.8%, Coxibs from 0% to 0.7%, and proton pump inhibitors (PPIs) from 2.4% to 7.4%. The proportion of subjects on prescription NSAIDs on PPIs increased continuously over time. CONCLUSION: A reduction in H. pylori-related peptic ulcers, changing patterns in NSAID use and increasing PPI use may have contributed to a decline in uncomplicated peptic ulcer incidence in the UK.

Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study.

BACKGROUND: Between 3% and 40% of patients surviving an episode of upper gastrointestinal bleeding (UGIB) experience a recurrence within 1 year. Aim To characterize further the recurrence rate of UGIB and to investigate the role of long-term acid suppressive therapy in its secondary prevention. METHODS: Recurrent cases of UGIB were identified among patients registered in The Health Improvement Network in the UK. A nested case-control analysis provided relative risk (RR) estimates of factors associated with recurrence. RESULTS: Of 1287 patients included, 67 (5.2%) were identified with a recurrent UGIB episode, corresponding to a recurrence rate of 17.5 per 1000 person-years during a mean follow-up of 3 years. The greatest risk of recurrence was in patients prescribed the oral anticoagulant warfarin (RR: 5.38; 95% confidence interval: 2.02-14.36). Use of a single proton pump inhibitor (PPIs) was associated with a reduced risk of recurrence (RR: 0.51; 95% confidence interval: 0.26-0.99), even in patients taking warfarin, while current use of H(2)-receptor antagonists was not. After the first episode of UGIB, use of nonsteroidal anti-inflammatory drugs and aspirin was greatly reduced, preventing estimation of the risk associated with these drugs. CONCLUSION: Long-term PPI therapy reduces the risk of UGIB recurrence.

Unspecified abdominal pain in primary care: the role of gastrointestinal morbidity.

BACKGROUND: Many patients with abdominal pain have no obvious cause for their symptoms and receive a diagnosis of unspecified abdominal pain. AIM: The objective of this study was to ascertain risk factors and consequences of a diagnosis of unspecified abdominal pain in primary care. METHODS: A population-based, case-control study was conducted using the UK General Practice Research Database. We identified 29,299 patients with a new diagnosis of abdominal pain, and 30,000 age- and sex-matched controls. Only diagnostic codes that did not specify the type or location of abdominal pain were included. RESULTS AND DISCUSSION: The incidence of newly diagnosed unspecified abdominal pain was 22.3 per 1000 person-years. The incidence was higher in females than in males, and 29% of patients were below 20 years of age. Prior gastrointestinal morbidity was associated with abdominal pain, but high body mass index, smoking and alcohol intake were not. Patients newly diagnosed with abdominal pain were 16 to 27 times more likely than controls to receive a subsequent new diagnosis of gallbladder disease, diverticular disease, pancreatitis or appendicitis in the year after the diagnosis of abdominal pain. The likelihood of receiving other gastrointestinal diagnoses such as peptic ulcer disease, hiatus hernia, gastro-oesophageal reflux disease (GERD), irritable bowel syndrome (IBS) or dyspepsia was increased three- to 14-fold among patients consulting for abdominal pain. CONCLUSION: When managing abdominal pain in primary care, morbidities such as GERD and IBS should be considered as diagnoses once potentially life-threatening problems have been excluded.

Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK.

BACKGROUND: Gastric acid suppressing drugs (that is, histamine(2) receptor antagonists and proton pump inhibitors) could affect the risk of oesophageal or gastric adenocarcinoma but few studies are available. AIMS: To study the association between long term treatment with acid suppressing drugs and the risk of oesophageal or gastric adenocarcinoma. PATIENTS: Persons registered in the general practitioners research database in the UK and aged 40-84 years during the period 1994-2001. METHODS: Population based nested case control study. Multivariable unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: In 4 340 207 person years of follow up, 287 patients with oesophageal adenocarcinoma, 195 with gastric cardia adenocarcinoma, and 327 with gastric non-cardia adenocarcinoma were identified, and 10 000 control persons were randomly sampled. "Oesophageal" indication for long term acid suppression (that is, reflux symptoms, oesophagitis, Barrett's oesophagus, or hiatal hernia) rendered a fivefold increased risk of oesophageal adenocarcinoma (odds ratio (OR) 5.42 (95% confidence interval (CI) 3.13-9.39)) while no association was observed among users with a group of other indications, including peptic ulcer and "gastroduodenal symptoms" (that is, gastritis, dyspepsia, indigestion, and epigastric pain) (OR 1.74 (95% CI 0.90-3.34)). "Peptic ulcer" indication (that is, gastric ulcer, duodenal ulcer, or unspecified peptic ulcer) was associated with a greater than fourfold increased risk of gastric non-cardia adenocarcinoma among long term users (OR 4.66 (95% CI 2.42-8.97)) but no such association was found in those treated for a group of other indications (that is, "oesophageal" or "gastroduodenal symptoms") (OR 1.18 (95% CI 0.60-2.32)). CONCLUSIONS: Long term pharmacological gastric acid suppression is a marker of increased risk of oesophageal and gastric adenocarcinoma. However, these associations are most likely explained by the underlying treatment indication being a risk factor for the cancer rather than an independent harmful effect of these agents per se.