Linkage of national soil quality measurements to primary care medical records in England and Wales: a new resource for investigating environmental impacts on human health.

BACKGROUND: Long-term, low-level exposure to toxic elements in soil may be harmful to human health but large longitudinal cohort studies with sufficient follow-up time to study these effects are cost-prohibitive and impractical. Linkage of routinely collected medical outcome data to systematic surveys of soil quality may offer a viable alternative. METHODS: We used the Geochemical Baseline Survey of the Environment (G-BASE), a systematic X-ray fluorescence survey of soil inorganic chemistry throughout England and Wales to obtain estimates of the concentrations of 15 elements in the soil contained within each English and Welsh postcode area. We linked these data to the residential postcodes of individuals enrolled in The Health Improvement Network (THIN), a large database of UK primary care medical records, to provide estimates of exposure. Observed exposure levels among the THIN population were compared with expectations based on UK population estimates to assess representativeness. RESULTS: Three hundred seventy-seven of three hundred ninety-five English and Welsh THIN practices agreed to participate in the linkage, providing complete residential soil metal estimates for 6,243,363 individuals (92% of all current and former patients) with a mean period of prospective computerised medical data collection (follow-up) of 6.75 years. Overall agreement between the THIN population and expectations was excellent; however, the number of participating practices in the Yorkshire & Humber strategic health authority was low, leading to restricted ranges of measurements for some elements relative to the known variations in geochemical concentrations in this area. CONCLUSIONS: The linked database provides unprecedented population size and statistical power to study the effects of elements in soil on human health. With appropriate adjustment, results should be generalizable to and representative of the wider English and Welsh population.

Risk of fall in patients with COPD.

A matched cohort study was conducted to determine the incidence of falls in patients following a diagnosis of COPD using a UK primary care database. 44 400 patients with COPD and 175 545 non-COPD subjects were identified. The incidence rate of fall per 1000 person-years in patients with COPD was higher (44.9; 95% CI 44.1 to 45.8) compared with non-COPD subjects (24.1; 95% CI 23.8 to 24.5) (P<0.0001). Patients with COPD were 55% more likely to have an incident record of fall than non-COPD subjects (adjusted HR, 1.55; 95% CI 1.50 to 1.59). The greater falls risk in patients with COPD needs consideration and modifiable factors addressed.

The recording and characteristics of pulmonary rehabilitation in patients with COPD using The Health Information Network (THIN) primary care database.

Pulmonary rehabilitation is recommended for patients with COPD to improve physical function, breathlessness and quality of life. Using The Health Information Network (THIN) primary care database in UK, we compared the demographic and clinical parameters of patients with COPD in relation to coding of pulmonary rehabilitation, and to investigate whether there is a survival benefit from pulmonary rehabilitation. We identified patients with COPD, diagnosed from 2004 and extracted information on demographics, pulmonary rehabilitation and clinical parameters using the relevant Read codes. Thirty six thousand one hundred and eighty nine patients diagnosed with COPD were included with a mean (SD) age of 67 (11) years, 53% were male and only 9.8% had a code related to either being assessed, referred, or completing pulmonary rehabilitation ever. Younger age at diagnosis, better socioeconomic status, worse dyspnoea score, current smoking, and higher comorbidities level are more likely to have a record of pulmonary rehabilitation. Of those with a recorded MRC of 3 or worse, only 2057 (21%) had a code of pulmonary rehabilitation. Survival analysis revealed that patients with coding for pulmonary rehabilitation were 22% (95% CI 0.69-0.88) less likely to die than those who had no coding. In UK THIN records, a substantial proportion of eligible patients with COPD have not had a coded pulmonary rehabilitation record. Survival was improved in those with PR record but coding for other COPD treatments were also better in this group. GP practices need to improve the coding for PR to highlight any unmet need locally. CHRONIC LUNG DISEASE: ROLLING OUT THE REHAB: Analysis of recent UK data suggests that more patients with chronic lung disease could benefit from lung rehabilitation programmes. During pulmonary rehabilitation (PR), patients with chronic obstructive pulmonary disease (COPD) work with specialists to learn exercises and optimise breathing techniques. The programmes are recommended under current guidelines, particularly for patients with a high breathlessness score. Despite this, when Charlotte Bolton and co-workers at the University of Nottingham analysed 36,189 patient primary care records gathered since 2004, they found only 9.8% of COPD patients had ever had a coded record of being assessed, referred for, or undertaken PR. Those patients who completed PR were 22% less likely to die that those who didn't, although appeared they had also received better overall COPD care. Current smokers, those suffering from co-morbidities and younger patients were more likely to receive PR than other patient groups.

Timing of onset of symptoms in people with idiopathic pulmonary fibrosis.

Little is known about when symptoms of idiopathic pulmonary fibrosis first develop. We identified incident cases of idiopathic pulmonary fibrosis-clinical syndrome (IPF-CS) from a UK primary care database and assessed the frequency of consultations for common symptoms in the 5 years prior to diagnosis. 1671 cases were identified with 5 years of data prior to diagnosis. Breathlessness was the most common symptom, followed by cough. Cases were significantly more likely than controls to experience these symptoms (p<0.001), even 4-5 years before diagnosis (OR for breathlessness for this period 2.79, 95% CI 2.13 to 3.65). This suggests that some patients with IPF may be symptomatic for more than 5 years before diagnosis.

A supervised adverse drug reaction signalling framework imitating Bradford Hill's causality considerations.

Big longitudinal observational medical data potentially hold a wealth of information and have been recognised as potential sources for gaining new drug safety knowledge. Unfortunately there are many complexities and underlying issues when analysing longitudinal observational data. Due to these complexities, existing methods for large-scale detection of negative side effects using observational data all tend to have issues distinguishing between association and causality. New methods that can better discriminate causal and non-causal relationships need to be developed to fully utilise the data. In this paper we propose using a set of causality considerations developed by the epidemiologist Bradford Hill as a basis for engineering features that enable the application of supervised learning for the problem of detecting negative side effects. The Bradford Hill considerations look at various perspectives of a drug and outcome relationship to determine whether it shows causal traits. We taught a classifier to find patterns within these perspectives and it learned to discriminate between association and causality. The novelty of this research is the combination of supervised learning and Bradford Hill's causality considerations to automate the Bradford Hill's causality assessment. We evaluated the framework on a drug safety gold standard known as the observational medical outcomes partnership's non-specified association reference set. The methodology obtained excellent discrimination ability with area under the curves ranging between 0.792 and 0.940 (existing method optimal: 0.73) and a mean average precision of 0.640 (existing method optimal: 0.141). The proposed features can be calculated efficiently and be readily updated, making the framework suitable for big observational data.

What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK?

BACKGROUND: The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis. METHODS: All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice. RESULTS: Of 20,142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65-69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths. CONCLUSIONS: Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment.

First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.

BACKGROUND: Despite their widespread use the effects of taking benzodiazepines and non-benzodiazepine hypnotics during pregnancy on the risk of major congenital anomaly (MCA) are uncertain. The objectives were to estimate absolute and relative risks of MCAs in children exposed to specific anxiolytic and hypnotic drugs taken in the first trimester of pregnancy, compared with children of mothers with depression and/or anxiety but not treated with medication and children of mothers without diagnosed mental illness during pregnancy. METHODS: We identified singleton children born to women aged 15-45 years between 1990 and 2010 from a large United Kingdom primary care database. We calculated absolute risks of MCAs for children with first trimester exposures of different anxiolytic and hypnotic drugs and used logistic regression with a generalised estimating equation to compare risks adjusted for year of childbirth, maternal age, smoking, body mass index, and socioeconomic status. RESULTS: Overall MCA prevalence was 2.7% in 1,159 children of mothers prescribed diazepam, 2.9% in 379 children with temazepam, 2.5% in 406 children with zopiclone, and 2.7% in 19,193 children whose mothers had diagnosed depression and/or anxiety but no first trimester drug exposures. When compared with 2.7% in 351,785 children with no diagnosed depression/anxiety nor medication use, the adjusted odds ratios were 1.02 (99% confidence interval 0.63-1.64) for diazepam, 1.07 (0.49-2.37) for temazepam, 0.96 (0.42-2.20) for zopiclone and 1.27 (0.43-3.75) for other anxiolytic/hypnotic drugs and 1.01 (0.90-1.14) for un-medicated depression/anxiety. Risks of system-specific MCAs were generally similar in children exposed and not exposed to such medications. CONCLUSIONS: We found no evidence for an increase in MCAs in children exposed to benzodiazepines and non-benzodiazepine hypnotics in the first trimester of pregnancy. These findings suggest that prescription of these drugs during early pregnancy may be safe in terms of MCA risk, but findings from other studies are required before safety can be confirmed.

Signalling paediatric side effects using an ensemble of simple study designs.

BACKGROUND: Children are frequently prescribed medication 'off-label', meaning there has not been sufficient testing of the medication to determine its safety or effectiveness. The main reason this safety knowledge is lacking is due to ethical restrictions that prevent children from being included in the majority of clinical trials. OBJECTIVE: The objective of this paper is to investigate whether an ensemble of simple study designs can be implemented to signal acutely occurring side effects effectively within the paediatric population by using historical longitudinal data. The majority of pharmacovigilance techniques are unsupervised, but this research presents a supervised framework. METHODS: Multiple measures of association are calculated for each drug and medical event pair and these are used as features that are fed into a classifier to determine the likelihood of the drug and medical event pair corresponding to an adverse drug reaction. The classifier is trained using known adverse drug reactions or known non-adverse drug reaction relationships. RESULTS: The novel ensemble framework obtained a false positive rate of 0.149, a sensitivity of 0.547 and a specificity of 0.851 when implemented on a reference set of drug and medical event pairs. The novel framework consistently outperformed each individual simple study design. CONCLUSION: This research shows that it is possible to exploit the mechanism of causality and presents a framework for signalling adverse drug reactions effectively.

A novel semisupervised algorithm for rare prescription side effect discovery.

Drugs are frequently prescribed to patients with the aim of improving each patient's medical state, but an unfortunate consequence of most prescription drugs is the occurrence of undesirable side effects. Side effects that occur in more than one in a thousand patients are likely to be signaled efficiently by current drug surveillance methods, however, these same methods may take decades before generating signals for rarer side effects, risking medical morbidity or mortality in patients prescribed the drug while the rare side effect is undiscovered. In this paper, we propose a novel computational metaanalysis framework for signaling rare side effects that integrates existing methods, knowledge from the web,metric learning, and semisupervised clustering. The novel framework was able to signal many known rare and serious side effects for the selection of drugs investigated, such as tendon rupture when prescribed Ciprofloxacin or Levofloxacin, renal failure with Naproxen and depression associated with Rimonabant. Furthermore, for the majority of the drugs investigated it generated signals for rare side effects at a more stringent signaling threshold than existing methods and shows the potential to become a fundamental part of post marketing surveillance to detect rare side effects.

Impact of socioeconomic deprivation on maternal perinatal mental illnesses presenting to UK general practice.

BACKGROUND: Although maternal perinatal mental illnesses commonly present to and are primarily treated in general practice, few population-based estimates of this burden exist, and the most affected socioeconomic groups of pregnant women remain unclear. AIM: To provide estimates of maternal depression, anxiety and serious mental illness (SMI) in UK general practice and quantify impacts of socioeconomic deprivation. DESIGN AND SETTING: Cross-sectional analysis of prospectively recorded general practice records from a UK-wide database. METHOD: A pregnancy ending in live birth was randomly selected for every woman of childbearing age, 1994-2009. Prevalence and diagnostic overlap of mental illnesses were calculated using a combination of medical diagnoses and psychotropic drug prescriptions. Socioeconomic deprivation was assessed using multivariate logistic regression, adjusting for calendar period and pregnancy history. RESULTS: Among 116 457 women, 5.1% presented with antenatal depression and 13.3% with postnatal depression. Equivalent figures for anxiety were 2.6% and 3.7% and for SMI 1/1000 and 2/1000 women. Socioeconomic deprivation increased the risk of all mental illnesses, although this was more marked in older women. Those age 35-45 years in the most deprived group had 2.63 times the odds of antenatal depression (95% confidence interval [CI] = 2.22 to 3.13) compared with the least deprived; in women aged 15-25 years the increased odds associated with deprivation was more modest (odds ratio = 1.35, 95% CI = 1.07 to 1.70). Similar patterns were found for anxiety and SMI. CONCLUSION: Strong socioeconomic inequalities in perinatal mental illness persist with increasing maternal age. Targeting detection and effective interventions to high-risk women may reduce inequity and avoid substantial psychiatric morbidity.

Live and non-live pregnancy outcomes among women with depression and anxiety: a population-based study.

BACKGROUND: Women taking antidepressant or anti-anxiety medications during early pregnancy have high risks of non-live pregnancy outcomes, although the contribution of the underlying illnesses to these risks remains unclear. We examined the impacts of antenatal depression and anxiety and of commonly prescribed treatments on the risks of non-live pregnancy outcomes. METHODS: We identified all pregnancies and their outcome (live birth, perinatal death, miscarriage or termination) among women aged 15-45 years between 1990 and 2009 from a large primary care database in the United Kingdom. Women were grouped according to whether they had no history of depression and anxiety, a diagnosis of such illness prior to pregnancy, illness during pregnancy and illness during pregnancy with use of medication (stratified by medication type). Multinomial logistic regression models were used to compare risks of non-live outcomes among these groups, adjusting for major socio-demographic and lifestyle characteristics. RESULTS: Among 512,574 pregnancies in 331,414 women, those with antenatal drug exposure showed the greatest increased risks for all non-live pregnancy outcomes, relative to those with no history of depression or anxiety, although women with prior (but not currently medicated) illness also showed modest increased risks. Compared with un-medicated antenatal morbidity, there was weak evidence of an excess risk in women taking tricyclic antidepressants, and stronger evidence for other medications. CONCLUSIONS: Women with depression or anxiety have higher risks of miscarriage, perinatal death and decisions to terminate a pregnancy if prescribed psychotropic medication during early pregnancy than if not. Although underlying disease severity could also play a role, avoiding or reducing use of these drugs during early pregnancy may be advisable.

The impact of the United Kingdom's national smoking cessation strategy on quit attempts and use of cessation services: findings from the International Tobacco Control Four Country Survey.

INTRODUCTION: The World Health Organization Framework Convention on Tobacco Control recommends that provision of cessation support should be included in national tobacco control strategies. This study examines the impact of the United Kingdom's national smoking cessation strategy on quit attempts, use of treatment and short-term abstinence, relative to the United States, Canada, and Australia where less support is provided. METHODS: Data on quitting behavior and use of support were obtained for all smokers enrolled in the International Tobacco Control 4 Country Survey between 2002 and 2005. Generalized estimating equations were used to calculate the relative odds (adjusted by age, sex, and Heaviness of Smoking Index) that smokers in each country made quit attempts, used behavioral or pharmacological support, and to compare rates of short-term (28 days) abstinence between countries and users of different forms of support. RESULTS: U.K. smokers were less likely to have attempted to quit smoking than those in Australia (odds ratio [OR] = 1.25, 95% CI: 1.12-1.40), Canada (OR = 1.50, 95% CI: 1.34-1.67), and the United States (OR = 1.25, 95% CI: 1.11-1.40) but were more likely to use pharmacotherapy and/or support from a clinic, helpline, or health professional when attempting to quit than smokers in the other countries. U.K. smokers making quit attempts were significantly more likely to achieve 28-day abstinence than those in Australia (OR = 0.59, 95% CI: 0.49-0.71), Canada (OR = 0.72, 95% CI: 0.61-0.87), and the United States (OR = 0.51, 95% CI: 0.42-0.62). CONCLUSIONS: U.K. smokers report fewer quit attempts but are more likely to use support when quitting and to achieve short-term abstinence.

Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care.

BACKGROUND: Comorbidities associated with systemic inflammation including cardiovascular disease (CVD), stroke and diabetes mellitus (DM) are common among individuals with chronic obstructive pulmonary disease (COPD). A study was undertaken to quantify the burden of comorbidity and to determine the risk of first acute arteriovascular events among individuals with COPD. METHODS: The computerised primary care records of 1,204,100 members of the general population aged ≥ 35 years on 25 February 2005 were searched for recordings of each disease. Data were analysed using multivariate logistic regression. Cox regression was used to determine whether individuals with COPD were at increased risk of acute myocardial infarction (MI) and stroke. RESULTS: Cross-sectional analyses showed that physician-diagnosed COPD was associated with increased risks of CVD (OR 4.98, 95% CI 4.85 to 5.81; p<0.001), stroke (OR 3.34, 95% CI 3.21 to 3.48; p<0.001) and DM (OR 2.04, 95% CI 1.97 to 2.12; p<0.001). In the follow-up analyses, after adjusting for confounding by sex and smoking status and stratifying for age, the greatest increase in the rate of acute arteriovascular events was found in the youngest age groups; the HR for acute MI was 10.34 (95% CI 3.28 to 32.60; p<0.001) and for stroke the HR was 3.44 (95% CI 0.85 to 13.84; p<0.001) compared with the oldest age group. CONCLUSION: Individuals with COPD are substantially more likely to have pre-existing CVD, DM or a previous stroke and are at high risk of acute arteriovascular events. National COPD guidelines and models of care need to adapt to provide an integrated approach to addressing these comorbidities.

Association between perinatal depression in mothers and the risk of childhood infections in offspring: a population-based cohort study.

BACKGROUND: Previous studies have suggested that children of mothers who experience depression during the perinatal period may have more infections, but such studies are few in number and none have been carried out in the United Kingdom (UK) population. The aim of this study was to investigate the association between perinatal depression in mothers and the risk of childhood infections in offspring in the UK general population. METHODS: We used data from The Health Improvement Network (THIN), a large database of electronic primary care medical records to conduct a cohort study among all first-born singleton children born and enrolled in THIN between 1988 and 2004. We used Poisson regression to compare the incidence of gastrointestinal infections and lower respiratory tract infections reported between birth and age 4 years among children of mothers with a record of perinatal depression with those born to mothers with no such history. RESULTS: Children of mothers with perinatal depression had a 40% increased risk of gastrointestinal infections and a 27% increased risk of lower respiratory tract infections compared with children of mothers without perinatal depression (incidence rate ratios = 1.40 and 1.27; 95% confidence intervals 1.37-1.42 and 1.22-1.32, respectively). On restricting to antibiotic-treated infections there was a slight increase in the magnitude of association with gastrointestinal infections but a decrease in that with lower respiratory tract infections (incidence rate ratios = 1.47 and 1.19; 95% confidence intervals 1.34-1.61 and 1.11-1.27, respectively). CONCLUSIONS: Maternal perinatal depression is associated with increased rates of childhood gastrointestinal infections, particularly more severe infections, and lower respiratory tract infections in the UK. Preventing maternal perinatal depression may avoid substantial morbidity among offspring, although further work is also needed to investigate the detailed reasons for these findings.

Pneumonia mortality in a UK general practice population cohort.

BACKGROUND: Pneumonia is a common diagnosis in general practice in the United Kingdom and yet there is little known about the short- and long-term prognosis of people with a diagnosis of pneumonia in general practice. We investigated the short- and long-term survival of people with pneumonia diagnosed in general practice as compared to the general population for all ages. METHODS: This was a general population-based cohort study. Data was obtained from a comprehensive general practice database called The Health Improvement Network (THIN) database which has computerized medical records from 300 general practice surgeries in the United Kingdom. We used Cox regression for our analyses. RESULTS: For pneumonia cases the 30-day mortality was 18.5% and the 3-year mortality was 30.8%. The equivalent figures for the general population controls were 0.4% and 10.3% respectively. The adjusted hazard ratio (HR) for all-cause mortality (for total follow-up time) in pneumonia cases vs. general population was 4.64 (95% CI 4.35-4.95). For the first 30 days the risk of mortality in cases was 46 times more (adj. HR 45.90, 95% CI 36.80-55.20). Even in the period of follow-up 91 days after diagnosis cases were almost 20% more likely to die compared to general population (adj. HR 1.19, 95% CI 1.08-1.31). CONCLUSION: People in general practice who have a diagnosis of pneumonia have a markedly increased mortality in the short-term but some increase in mortality persists during longer-term follow-up.

The impact of statins, ACE inhibitors and gastric acid suppressants on pneumonia mortality in a UK general practice population cohort.

BACKGROUND: Pneumonia is a common diagnosis in general practice in the United Kingdom. Previous studies suggest that commonly prescribed drugs in general practice may influence pneumonia mortality. AIM: We investigated whether statins, angiotensin converting enzyme inhibitors (ACEIs), proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H(2)RAs) have an impact on short-term and long-term mortality in pneumonia cases. DESIGN OF STUDY: Population-based cohort study SETTTING: United Kingdom METHODS: Data on 3681 pneumonia cases above the age of 40 years were obtained from a comprehensive database called the health improvement network (THIN) which has computerised medical records from 300 general practice surgeries in the United Kingdom. We used Cox regression for our analyses. RESULTS: Current statin use was associated with a 67% decrease in 30-day mortality (adj. HR: 0.33, 95% CI: 0.19-0.58) and a 55% decrease in long-term mortality (adj. HR: 0.45, 95% CI: 0.32-0.62) over a median follow-up of 2.8 years as compared to no-use. Current ACEI use decreased the 30-day mortality risk by nearly 38% as compared to no-use (adj. HR: 0.62, 95% CI: 0.47-0.82) but was not associated with long-term mortality. No significant impact on mortality was observed for either gastric acid suppressant. CONCLUSION: The use of statins is associated with a lower risk of short- and long-term mortality following pneumonia whereas the use of ACEIs is associated with a decreased mortality risk only in the short-term.

Use of self-controlled analytical techniques to assess the association between use of prescription medications and the risk of motor vehicle crashes.

Case-crossover and case-series analyses are 2 epidemiologic approaches that can be used to evaluate the association of exposures with acute events. Using a primary care database from the United Kingdom and these 2 statistical approaches, the authors investigated the impact of using benzodiazepines, nonbenzodiazepine hypnotics, beta-blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, opioids, and antihistamines on the risk of motor vehicle crashes in 1986-2004. For 49,821 individuals aged 18-74 years, involvement in a motor vehicle crash was documented. The outcome of the case-crossover analyses varied according to the choice of control period, so the case-series approach was preferred. The first 4 weeks of treatment with a combined acetaminophen and opioid preparation was associated with an increased risk of motor vehicle crash (incidence rate ratio = 2.06, 99% confidence interval: 1.84, 2.32), as was use of an opioid alone (incidence rate ratio = 1.70, 99% confidence interval: 1.39, 2.08) and benzodiazepines (incidence rate ratio = 1.94, 99% confidence interval: 1.62, 2.32). Use of selective serotonin reuptake inhibitors, nonbenzodiazepine hypnotics, and antihistamines for more than 4 weeks was associated with motor vehicle crash, but shorter term use was not. The results obtained are broadly consistent with those from well-designed case-control studies and demonstrate how case-only techniques optimize the use of routinely collected data for epidemiologic studies.

Risk of community-acquired pneumonia and the use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study.

PURPOSE: Previous studies have shown that treatment with gastric acid suppressants may be associated with an increased risk of pneumonia whilst the use of statins and ACE inhibitors (ACEI) may decrease the risk of acquiring pneumonia. The evidence is conflicting however. Our aim was to investigate the effect of these drugs on pneumonia using population-based data from the UK. METHODS: We conducted a general population-based case-control study using the health improvement network (THIN), a comprehensive UK general practice database. Conditional multiple logistic regression was used to assess the association between the exposures and pneumonia. RESULTS: After adjusting for potential confounders, a current prescription for statins was associated with a significant reduction in the risk of pneumonia (adjusted OR 0.78, 95% CI 0.65-0.94). Similarly, a current prescription for ACEI was associated with a reduction in the risk of pneumonia (adjusted OR 0.75, 95% CI 0.65-0.86). Contrary to previous study results we did not find a significant association between current prescription for histamine 2 receptor antagonist (H(2)RA) and pneumonia risk (adjusted OR 1.14, 95% CI 0.92-1.40) but current prescriptions for proton pump inhibitors (PPI) were associated with an increased risk of pneumonia (adjusted OR 1.55, 95% CI 1.38-1.77). CONCLUSIONS: Statins and ACE inhibitors were associated with a lower risk of pneumonia but these effects were smaller than those observed in previous studies. People prescribed a PPI, but not an H(2)RA at an increased risk of acquiring pneumonia.