Non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding,a post-marketing surveillance case-control study

A post-marketing surveillance case-control study was set up and applied in an Italian hospital network to quantify the risk of upper gastrointestinal bleeding (UGB) and exposure to non-steroidal anti-inflammatory drugs (NSAIDs). During the period of study 441 cases of UGB and 1323 controls were recruited. The odds ratios associated with NSAIDs use were estimated for intake occurring over two different periods of time prior to hospital admission (i.e. during the preceding week and month). A strong association emerged for aspirin intake, both in the week (OR_MLR = 11.2; 95% CI 7.8–16.9) and in the month (OR_MLR = 6.9; 95% CI 4.6–10.2) preceding hospital admission. A significant increase in the risk of UGB and use of diclofenac, naproxen and ibuprofen, and indomethacin was also found in the two exposure periods considered, while for piroxicam a significant association was only apparent in the analysis of 1-month exposure. As expected, paracetamol and pyrazolone derivatives were not associated with UGB. This pilot experience has shown the feasibility of setting up a multicentre post-marketing surveillance programme and of establishing a network for drug monitoring within the Italian National Health Service, capable of providing a thorough evaluation of the benefit/risk profile of drugs.     

Risk of digoxin intoxication in heart failure patients exposed to digoxin�Cdiuretic interactions: a population-based study

AIMS

To quantify the digoxin intoxication risk associated with exposure to digoxin–diuretic interactions, and evaluate whether the risk varies by diuretic type, individually or in combination.

METHODS

This was a population-based nested case–control study in which data from the National Health Insurance Research Database (NHIRD) in Taiwan were analysed.

RESULTS

The study cohort comprised 154 058 heart failure (HF) patients taking digoxin between 2001 and 2004, in whom digoxin intoxication requiring a hospitalization (ICD-9 code 972.1) occurred in 595 cases. A total of 28 243 matched controls were also selected for analysis. Cases were 3.08 times (adjusted OR 3.08, 95% CI 2.50, 3.79) more likely to have been prescribed diuretic medication in the previous month than controls. Regarding the class of diuretics, loop diuretics carried the greatest risk (adjusted OR 2.97, 95% CI 2.35, 3.75), followed by thiazides (OR 2.36, 95% CI 1.70, 3.29) and potassium-sparing diuretics (OR 1.72, 95% CI 0.83, 3.56). The risk was also observed to vary with different combinations of diuretics, and the loops/thiazides/potassium-sparing diuretics combination carried the greatest risk (adjusted OR 6.85, 95% CI 4.93, 9.53). Among the individual diuretics examined, hydrochlorothiazide carried the greatest risk (adjusted OR 4.63, 95% CI 2.50, 8.57).

CONCLUSIONS

This study provided empirical evidence that digoxin–diuretic interactions increased the risk of hospitalization for digoxin intoxication in HF patients. The risk was particularly high for concomitant use of digoxin with a combination of loop diuretics, thiazide and potassium-sparing diuretics. The combined use of digoxin and diuretics should be avoided if possible.     

The development of new-onset type 2 diabetes associated with choosing a calcium channel blocker compared to a diuretic or beta-blocker

ABSTRACT

Objective: It has been acknowledged that patients who receive a beta-blocker or diuretic based regimen are at increased risk of developing new-onset diabetes. Recently, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to decrease patients’ odds of developing new-onset type 2 diabetes. A number of large placebo-controlled multi-center trials in post-myocardial infarction and heart failure patients have shown the ability of renin-angiotensin-aldosterone system medications to reduce the onset of type 2 diabetes. Pharmacologic data has shown improved insulin sensitivity with ACEIs and ARBs. Controversy persists regarding the influence of calcium channel blockers on the development of new-onset diabetes.

Research design and methods: Two reviewers conducted a systematic literature search of Medline, EMBASE, CINAHL, and the Cochrane Library (1966 to December 2006) to extract a consensus of trial data involving calcium channel blockers versus diuretics or beta-blockers with an endpoint of new-onset type 2 diabetes. Studies were included if they were randomized controlled trials versus routine treatment, not observational studies of clinical practice. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted.

Results: Out of 1721 trials, six meeting inclusion criteria were identified, including 99?006 patients. Calcium channel blockers were associated with a reduced incidence of new-onset type 2 diabetes (odds ratio 0.81; 95% confidence interval [CI] 0.73–0.90; p = 0.0001) compared with diuretic or beta-blocker therapy. The reduction in new-onset type 2 diabetes was maintained when a calcium channel blocker was compared to only thiazide diuretics (OR 0.86; 95% CI 0.75–0.99; p = 0.0346). The meta-analysis was limited by the varying definition of new-onset type 2 diabetes mellitus, as well as the potential for publication bias, which is a limit of any meta-analysis.

Conclusions: Calcium channel blockers may be associated with reduced odds of developing new-onset type 2 diabetes compared to diuretics and beta-blockers.     

Cough due to ace inhibitors: a case-control study using automated general practice data

Objectives: To determine the risk of coughing as an adverse reaction to ACE inhibitors under everyday circumstances in a large population, and to study whether this adverse effect was duration or dose dependent. Design: A population-based case-control study. Setting: Ten general practices of 14 Dutch general practitioners (GP), in which all consultations, morbidity and medical interventions, including drugs prescribed, were registered over the 18 month period from 1st September, 1992 to 1st March, 1994. Subjects: 1458 patients with incident coughing and up to four controls per case were obtained (total 4182 controls), matched for GP. All cases and controls were 20 years or older and had no record of respiratory infection, influenza, tuberculosis, asthma, chronic bronchitis, emphysema, congestive heart failure, sinusitis, laryngitis, haemoptysis or respiratory neoplasms during the study period. Results: Cases were 2.1-times more likely than controls to have been exposed to ACE inhibitors (95% CI 1.5–3.1), but after adjustment the odds ratio was 1.4 (95% CI 0.9–2.1). The crude odds ratio for captopril was 1.3 (95% CI 0.7–2.5), for enalapril 2.6 (95% CI 1.6–4.2) and for lisinopril 2.0 (95% CI 0.5–9.3). The adjusted odds ratio for captopril was 0.9 (95% CI 0.4–1.7), for enalapril 1.7 (95% CI 1.03–2.8) and for lisinopril 1.7 (95% CI 0.4–7.9). For patients who had been on ACE inhibitor treatment for no longer than 2 months the odds ratio was 4.8 (95% CI 1.7–13.3). The odds ratio declined to 2.0 (95% CI 1.1–3.8) for those who had taken an ACE inhibitor for 2–6 months, and to 1.6 (95% CI 0.9–2.7) for those on ACE-inhibitors for more than 6 months. Conclusion: The risk of coughing was increased twofold among ACE inhibitor users, but the odds ratios were no longer significant after controlling for several confounding factors. The risk of developing cough due to ACE-inhibitors declines with the duration of treatment, possibly due to depletion of susceptible persons.     

Risk of upper gastrointestinal bleeding with oral bisphosphonates and non steroidal anti-inflammatory drugs: a case-control study

Background Gastrointestinal injuries including gastric ulcers have been reported with oral bisphosphonate therapy. However, the risk of the more serious upper gastrointestinal bleeding (UGB) especially in the community setting with these drugs remains unknown. Similarly, the risk of UGB among users of both bisphosphonates and non steroidal anti‐inflammatory drugs (NSAIDs) in the community is also unknown. Aim To explore the risk of more serious UGB among users of bisphosphonates and the risk of UGB among users of both bisphosphonates and NSAIDs in the community. Methods We conducted a case‐control study within a cohort of Quebec residents who had received a revascularization procedure from 1995 to 2004. Cohort members were followed up from the date of their first procedure until the earliest of: (1) study outcome, (2) date of death or (3) end of health care coverage. Cases were defined as those with the first diagnosis of a UGB. For each case, 20 controls were selected and matched to the cases by index date, age and cohort entry. Adjusted odds ratios for current use of bisphosphonates, NSAIDs and co‐therapy of both drugs were computed. Results Within the initial cohort, 3253 incident cases of UGBs and corresponding 65 060 matched controls were identified. The adjusted odds ratio (OR) for UGB by current users of bisphosphonates was 1.01 (95% CI, 0.72–1.43). Current NSAID use was associated with an increased risk of UGB OR = 1.75; 95% CI, 1.53–1.99. The OR for use of bisphosphonates and NSAIDs was elevated OR = 2.00; 95% CI, 1.12–3.57. This risk was still elevated for users of bisphosphonates and COX‐2 inhibitors [OR = 2.38 (95% CI, 1.26–4.50)]. Conclusion We found no evidence of an increase in the risk of UGB among current users of bisphosphonates. The risk of combined NSAID and bisphosphonate therapy was increased, but this risk was not higher than the risk for NSAID users alone.     

Antihypertensive drugs and the risk of idiopathic aplastic anaemia

AIMS: A recent report has raised concern that nifedipine may be associated with an increased risk of aplastic anaemia. This large population-based study evaluated the risk of idiopathic aplastic anaemia in users of calcium channel blockers compared with that of other antihypertensive drugs. METHODS: The study was based on information derived from the General Practice Research Database. We conducted a follow-up study with a nested case-control analysis of 322 448 subjects who received antihypertensive drugs. Cases were people who had a first-time diagnosis of aplastic anaemia during January 1, 1988 through September 30, 1997. The risk estimate of aplastic anaemia was calculated for all antihypertensive drugs. For the nested case-control analysis, six controls were matched to each case on age, sex and general practice attended. Odds ratios compared the risk of idiopathic aplastic anaemia for all antihypertensive drugs relative to nonusers. RESULTS: There were 13 cases of newly diagnosed idiopathic aplastic anaemia. The estimated risk of aplastic anaemia per 100 000 users was 0.8 (95% CI 0.1, 4.7) for calcium channel blockers, 1.4 (95% CI 0.5, 4.1) for beta-adrenoceptor blockers, 2.3 (95% CI 0.6, 8.6) for angiotension-converting enzyme (ACE) inhibitors and 5.9 (95% CI 1.6, 21.5) for users of other antihypertensive drugs. In the case-control analysis of 13 cases and 77 controls, the odds ratio was 0.3 (95% CI 0.02, 3.3) for calcium channel blockers, 0.5 (95% CI 0.1, 2.5) for beta-adrenoceptor blockers, 0.7 (95% CI 0.1, 5.6) for ACE inhibitors, 1.2 (95% CI 0.1, 11.8) for users of other antihypertensive drugs and 0.7 (95% CI 0.1, 7.2) for users of multiple drugs with a calcium channel blocker compared with nonusers. CONCLUSIONS: The present study suggests that the use of calcium channel blockers is not associated with an increased risk of aplastic anaemia.     

Sudden death in patients receiving drugs tending to prolong the QT interval

AIMS

To examine risks of sudden death in the community associated with drugs grouped by their risk of causing torsades de pointes (TdP) and to explore the risks for individual drugs.

METHODS

Case–control study comparing prior drug intakes and morbidities, using the Arizona classification of drugs causing TdP. Participants included 1010 patients dying suddenly where post-mortem examination did not identify a clear cause of death, and 3030 matched living controls from primary care.

RESULTS

Noncardiac drug risk was posed by antipsychotics and antidepressants. Significantly raised odds ratios (ORs) were found for takers of typical and atypical antipsychotics, ORs [95% confidence interval] 3.94 (2.05, 7.55) and 4.36 (2.54, 7.51), and of selective serotonin reuptake inhibitors [SSRIs] rather than tricyclic antidepressants, ORs 2.21 (1.61, 3.05) and 1.44 (0.96, 2.13). No significant risk was associated with other, noncardiac or psychiatric drugs, OR 1.09 (0.85, 1.41). Arizona classified drugs considered to raise risk of TdP were associated with raised risk of sudden death, as were those only weakly associated with TdP and not considered to pose a risk in normal use, ORs 2.08 (1.45, 3.00) and 1.74 (1.33, 2.28), respectively.

CONCLUSIONS

Atypical and typical antipsychotic drug use were both strongly associated with raised risks, as were SSRIs. Tricyclic antidepressants were not associated with raised risks. The Arizona classification of risk of TdP was a poor predictor of likelihood of noncardiac drug-associated sudden death.     

Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p?p?p?p?=?0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p?=?0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p?=?0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p?=?0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.     

Association of death from renal failure with calcium levels in drinking water

The possible association between the risk of death from renal failure (RF) and the levels of calcium in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Characteristics for all eligible RF-related deaths (2469 cases) among Taiwan residents from 1991 through 2000 were compared with those of people who died from other causes (2469 controls). The levels of calcium in the drinking water of these residents were determined from data obtained from the Taiwan Water Supply Corporation (TWSC). The controls were pair-matched to the RF-related cases by year of birth and death. The adjusted odds ratios (ORs) (95% confidence interval, CI) for RF-related deaths were 1.21 (1.03-1.43) for the group with water calcium levels between 25.1 and 43.0 mg/L and 1.34 (1.12-1.60) for the group with calcium levels of 43.3 mg/L or more. There was a significant trend for increased risk of death from RF with higher calcium levels in drinking water.     

End-stage renal disease and non-narcotic analgesics: a case-control study

1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case-control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesics taken at least every other day for 30 days or longer before the first symptom of renal disease was 2.89 (95% CI, 1.78 to 4.68). 3. The risk increased in relation to the use duration. 4. The previous regular consumption of combinations containing phenacetin was strongly associated with ESRD (odds ratio, 19.05; 95% CI, 2.31 to 157.4). The odds ratio for previous regular consumption of salicylates was 2.54 (95% CI, 1.24 to 5.20) and for pyrazolones 2.16 (95% CI, 0.87 to 5.32). 5. An analysis for possible confounding by a history of repeated headaches, arthritis, kidney stones, hypertension, and diabetes did not alter the results. 6. The odds ratio estimates for different pathological subgroups of ESRD patients in relation to previous use of any non-narcotic analgesic were glomerulonephritis. 10.57 (95% CI, 1.25 to 89.0), interstitial nephritis, 3.33 (95% CI, 1.21 to 9.17), cystic kidney disease, 0.71 (95% CI, 0.25 to 1.97), and unknown, 5.15 (95% CI, 2.29-11.57). 7. The results of this study suggest that the regular consumption of analgesics should be routinely considered as a risk factor for any non-congenital cause of chronic renal failure. They also suggest that the risk of ESRD associated with the regular consumption of phenacetin is much higher than the risk associated with other non-narcotic analgesics.     

Association of Death from Renal Failure with Calcium Levels in Drinking Water

The possible association between the risk of death from renal failure (RF) and the levels of calcium in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Characteristics for all eligible RF-related deaths (2469 cases) among Taiwan residents from 1991 through 2000 were compared with those of people who died from other causes (2469 controls). The levels of calcium in the drinking water of these residents were determined from data obtained from the Taiwan Water Supply Corporation (TWSC). The controls were pair-matched to the RF-related cases by year of birth and death. The adjusted odds ratios (ORs) (95% confidence interval, CI) for RF-related deaths were 1.21 (1.03-1.43) for the group with water calcium levels between 25.1 and 43.0 mg/L and 1.34 (1.12-1.60) for the group with calcium levels of 43.3 mg/L or more. There was a significant trend for increased risk of death from RF with higher calcium levels in drinking water.     

Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding

AIM: To investigate the role of Helicobacter pylori, expressing the virulence marker CAGA (cytotoxin associated gene product A) in ulcer complications and its interaction with nonsteroidal anti-inflammatory drugs (NSAIDs) and other risk factors. DESIGN: Case control study using conditional logistic regression analysis. SETTING: University and City Hospitals, Nottingham. SUBJECTS: 203 consecutive patients with ulcer bleeding and 203 age- and sex-matched controls. RESULTS: Ulcer bleeding was more likely with positive H. pylori serology (odds ratio = 3.3, 95% CI: 1.7--6.6 for CagA positive, but only OR = 1.6, 95% CI: 0.7-3.7 for CagA negative serology), current smoking (OR 2.2, 95% CI: 1.04-4.7), aspirin < or = 300 mg daily (OR 7.7, 95% CI: 2.8-20.6), all other nonsteroidal anti-inflammatory drugs (NSAIDs: OR 10.6, 95% CI: 3.1-35.7 for < or = 1 defined daily dose lower and OR 22.6, 95% CI: 6.2-82.0 for higher doses) and past ulcer history (OR 5.6, 95% CI: 2.3-14.1). Aspirin < or = 300 mg daily was used by 25.1% of patients vs. 7.4% of controls. Smoking only enhanced risk in the presence of H. pylori, with a synergistic interaction (interaction odds ratio = 4.9, 2.4-9.9, P=0.002). Conversely, risks with non-aspirin NSAIDs were reduced in the presence of H. pylori, particularly if CagA-positive (interaction odds ratio=0.21, 0.05-0.9, P=0.03). CONCLUSIONS: CagA positive H. pylori infection is associated with an increased risk of ulcer bleeding. The risk from non-aspirin NSAIDs is even higher, but is less in H. pylori infected people. Low-dose aspirin is now commonly associated with ulcer bleeding.     

Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study.

OBJECTIVE: To investigate the association between the use of fluoroquinolone agents and the risk of tendinitis in a large population-based case-control study. METHODS: The study was performed by linking automated health databases from the Region of Lombardia, Italy. Cases were patients aged > or =18 years who had a hospital discharge diagnosis of non-traumatic tendinitis in 2002-3. For each case, up to five controls were randomly selected among those eligible for inclusion in the study. A conditional logistic regression model was used to estimate the odds ratio of tendinitis associated with the current, recent and past use of fluoroquinolones. Odds ratios were adjusted for exposure to other antibacterials and other drugs. RESULTS: 22,194 cases and 104,906 controls met the inclusion criteria. Current use of fluoroquinolones significantly increased the risk of tendon disorders as a whole (odds ratio [OR] = 1.7; 95% CI 1.4, 2.0), tendon rupture (OR = 1.3; 95% CI 1.0, 1.8) and rupture of the Achilles' tendon (OR = 4.1; 95% CI 1.8, 9.6). Concomitant use of corticosteroids and fluoroquinolones increased the risk of both tendon rupture (OR = 3.1; 95% CI 1.5, 6.3) and rupture of the Achilles' tendon (OR = 43.2; 95% CI 5.5, 341.1). DISCUSSION: Evidence that exposure to fluoroquinolones is associated with the sudden occurrence of tendinitis is supported by this large population-based study. We can estimate that a single case of rupture of the Achilles' tendon would occur for every 5958 persons treated with fluoroquinolones (95% CI 2148, 23,085). The corresponding number needed to harm is 979 (95% CI 122, 9172) for patients who concomitantly use corticosteroids and 1638 (95% CI 351, 8843) for those aged >60 years. CONCLUSION: Clinicians should be aware of this adverse effect, and the increased risk for fluoroquinolone-associated tendinitis in elderly patients with corticosteroid use must be considered when these agents are prescribed.     

A comparison of the effects of parental risk markers on pre- and perinatal variables in multiple patient cohorts with fetal alcohol syndrome, autism, Tourette syndrome, and sudden infant death syndrome: an enviromic analysis

The prevalence and magnitude of effect of individual risk markers for specific developmental disorders vary widely across diagnostic category. The four study cohorts for this project were patients from four diagnostic registries in North Dakota for fetal alcohol syndrome (FAS), autism, sudden infant death syndrome (SIDS), and Tourette syndrome. These four cohorts were used to estimate prevalence and magnitude of effect of parental risk markers in patients with developmental disabilities. Cases with North Dakota birth certificates were matched with controls. Using birth certificate data, we then examined five parental risk markers for each cohort and estimated direct and indirect effects for each risk marker by cohort. The authors found two significant paternal risk markers (age in SIDS and education in FAS). Significant maternal markers were age in SIDS, education in FAS, autism, and SIDS. Marital status was a significant risk marker in FAS. Effect sizes were estimated using paired t tests, odds ratios, and population attributable risk (PAR) for both direct and indirect effects for each marker. We estimated both direct and indirect effects to allow for direct comparisons of the differential effect estimates of each of these markers. The direct effect of parental markers differs across diagnostic cohorts of patients. Use of cohorts from similar denominator populations obtained from prevalence studies is a useful methodological tool for estimating the prevalence and magnitude of effect of risk markers.     

Drugs with anticholinergic effects and cognitive impairment,falls and all-cause mortality in older adults: A systematic review and meta-analysis

AimThe aim was to investigate associations between drugs with anticholinergic effects (DACEs) and cognitive impairment, falls and all-cause mortality in older adults.MethodsA literature search using CINAHL, Cochrane Library, Embase and PubMed databases was conducted for randomized controlled trials, prospective and retrospective cohort and case-control studies examining the use of DACEs in subjects ≥65 years with outcomes on falls, cognitive impairment and all-cause mortality. Retrieved articles were published on or before June 2013. Anticholinergic exposure was investigated using drug class, DACE scoring systems (anticholinergic cognitive burden scale, ACB; anticholinergic drug scale, ADS; anticholinergic risk scale, ARS; anticholinergic component of the drug burden index, DBI_AC) or assessment of individual DACEs. Meta-analyses were performed to pool the results from individual studies.ResultsEighteen studies fulfilled the inclusion criteria (total 124 286 participants). Exposure to DACEs as a class was associated with increased odds of cognitive impairment (OR 1.45, 95% CI 1.16, 1.73). Olanzapine and trazodone were associated with increased odds and risk of falls (OR 2.16, 95% CI 1.05, 4.44; RR 1.79, 95% CI 1.60, 1.97, respectively), but amitriptyline, paroxetine and risperidone were not (RR 1.73, 95% CI 0.81, 2.65; RR 1.80, 95% CI 0.81, 2.79; RR 1.39, 95% CI 0.59, 3.26, respectively). A unit increase in the ACB scale was associated with a doubling in odds of all-cause mortality (OR 2.06, 95% CI 1.82, 2.33) but there were no associations with the DBI_AC (OR 0.88, 95% CI 0.55, 1.42) or the ARS (OR 3.56, 95% CI 0.29, 43.27).ConclusionsCertain individual DACEs or increased overall DACE exposure may increase the risks of cognitive impairment, falls and all-cause mortality in older adults.     

Risk of schizophrenia in people with coeliac disease, ulcerative colitis and Crohn's disease: a general population-based study

BACKGROUND: Recently, interest has been revived in whether people with coeliac disease, in contrast to other inflammatory gastrointestinal diseases, have an increased risk of schizophrenia. AIM: To compare the risk of schizophrenia in people diagnosed with coeliac disease, ulcerative colitis and Crohn's disease with the general population. METHODS: We used data from the UK General Practice Research Database. People with coeliac disease, Crohn's disease and ulcerative colitis were matched individually with five age-, sex- and general practice-matched controls. The prevalence of schizophrenia was calculated and compared between disease groups and their respective controls. We calculated odds ratios for schizophrenia using conditional logistic regression adjusting for smoking status. RESULTS: In people with coeliac disease, Crohn's disease and ulcerative colitis the prevalence of schizophrenia was 0.25%, 0.27% and 0.24%, respectively, compared with a general population prevalence of 0.37%. The adjusted odds ratios showed no association between schizophrenia and gastrointestinal disease (coeliac disease vs. controls 0.76, 95% CI: 0.41-1.4; Crohn's disease vs. controls 0.74, 95% CI: 0.44-1.3; ulcerative colitis 0.71, 95% CI: 0.44-1.1). CONCLUSIONS: Contrary to recent findings we found no evidence of an increased risk of schizophrenia in people with coeliac disease compared with the general population.