[show abstract][hide abstract] ABSTRACT: BACKGROUND: Few studies have evaluated the prevention of upper gastrointestinal complications (UGIC; bleeding or perforation) in patients with uncomplicated peptic ulcer (PU). We assessed the effect of proton pump inhibitors (PPI) in a non-randomized setting. To maximize exchangeability of exposed and unexposed groups we restricted the study to patients with a new diagnosis of PU, i.e., a clear indication. To minimize selection bias we mimicked an intention to treat approach by assessing the effect of PPI prescription after PU diagnosis. METHODS: Within a population of subjects aged 40-84 years from The Health Improvement Network database, 1997-2006, we identified 3,850 patients with incident PU. Among them, we confirmed 74 first UGIC episodes during a mean follow-up of 4 years. Exposure was prescription coverage during the month following PU diagnosis. We performed a nested case-control analysis and compared UGIC cases with 400 controls matched for age, sex, year and duration of follow-up. Relative risks (RR) and 95 % confidence intervals (CI) were estimated. RESULTS: The overall incidence of UGIC was 4.6 cases/1,000 person-years; it was highest during the months after PU diagnosis, increased with age, and it was higher in men and subjects with Helicobacter pylori infection, anemia, and alcohol use at PU diagnosis. The RR for UGIC associated with PPI prescriptions during the month after PU diagnosis was 0.56 (95 % CI 0.31-1.0). The RR for NSAIDs with and without a PPI was 1.72 (0.68-4.45) and 3.27 (0.85-12.67), respectively. CONCLUSIONS: Findings suggest that prescription of PPIs after a PU diagnosis is associated with a reduced risk of UGIC.
Digestive Diseases and Sciences 01/2013; · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: To describe the validity of recorded diabetic retinopathy (DR) and diabetic maculopathy (DMP) diagnoses, including edema (DMO) in The Health Improvement Network (THIN) database.
In two independent computer searches, we detected 20,838 patients with diabetes aged 1-84 years with a first DR computer Read entry in 2000-2008 and 4,064 with a first DMP entry. A two-step strategy was used to validate both outcomes as follows: 1) review of patient profiles including free-text comments from primary care practitioners (PCPs) (containing referral information and test results) of a random sample of 500 DR and all DMP computer-detected patients. We classified them in probable, possible, and noncase according to the diagnosis plausibility based on the manual review of the computerized information; and 2) review of questionnaires sent by PCPs and medical records in a random sample (N = 200 for each outcome including 36 diabetic macular edema [DMO]). Gold standard was PCPs' confirmation.
After profiles review, we categorized 418 as probable/possible DR. In addition, 3,676 DMP were categorized as probable/possible (including 711 DMO). After review of information sent by PCPs, confirmation rates were 87.3 and 87.2%, respectively (90.3% for DMO). When we applied them to the whole sample of computer-detected patients, the weighted confirmation rate was 78.0% for DR and 78.8% for DMP (86.2% for DMO).
Read codes for DR, DM, and DMO are moderately accurate in identifying incident case subjects of these ophthalmologic complications. The validity improved when incorporating PCPs' text comments to the patient's profile. THIN database proved to be a valuable resource to study ophthalmological diabetes complications.
Diabetes care 02/2012; 35(4):762-7. · 8.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Androgen deprivation therapy (ADT) is used to delay tumour development and improve survival in patients with prostate cancer. However, several randomized controlled trials and observational studies have suggested that ADT may increase the risk of cardiovascular events.
The aim of the study was to evaluate the risk of coronary heart disease (CHD) and heart failure (HF) in patients with prostate cancer receiving ADT in UK primary care, and to evaluate the risks associated with individual ADT and combination ADT.
The UK General Practice Research Database was used to identify a cohort of patients with a first prostate cancer diagnosis during 1999-2005. These patients were followed up to assess the occurrence of acute myocardial infarction (AMI), death from CHD, incident HF and hospitalization due to acute decompensated HF. Nested case-control analyses were performed to assess the risk of these outcomes associated with anti-androgen therapy, as well as different types of ADT and combinations of ADT.
Current anti-androgen use was associated with a significant increase in the risk of hospitalization due to HF (odds ratio [OR] 2.15; 95% CI 1.08, 4.29), but not of incident HF, CHD or AMI. When assessed individually, there was no significant association of bicalutamide or cyproterone use with the risk of AMI or CHD. Current use of bicalutamide 50 mg/day was associated with a significant increase in the risk of HF (OR 3.28; 95% CI 1.31, 8.18); however, this increased risk of HF was only found in patients taking bicalutamide 50 mg/day in combination with luteinizing hormone-releasing hormone (LHRH) receptor agonists. There were no cases of hospitalized HF in patients taking bicalutamide 50 mg/day as monotherapy and there was no significant association between current use of bicalutamide 150 mg/day and the risk of hospitalized HF. Combination therapy with LHRH agonists and anti-androgens was associated with a significant increase in the risk of CHD (OR 4.35; 95% CI 1.94, 9.75), AMI (OR 3.57; 95% CI 1.44, 8.86), incident HF (OR 3.19; 95% CI 1.10, 9.27) and hospitalized HF (OR 3.39; 95% CI 1.07, 10.70) compared with non-use of these drugs.
In men with prostate cancer, combination therapy with LHRH agonists and anti-androgens is associated with significant increases in the risk of CHD, AMI, incident HF and hospitalized HF. Individual therapies do not appear to increase the risk of these outcomes.
Drug Safety 11/2011; 34(11):1061-77. · 3.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ischaemic cerebrovascular accident (ICVA) is a common cause of morbidity and mortality. Identification of risk factors can reduce its incidence. We aim to estimate the incidence rate (IR) of hospitalised ICVA in the general population by sex and quantify its risk associated with several factors.
We followed up 907, 001 individuals aged 40-84 years during a mean of 3.63 years to ascertain the first episode of hospitalised ICVA between 2000 and 2004 using a UK primary care database. We evaluated the risk factors for ICVA through unconditional logistic regression (OR) with a nested case-control analysis, using 2953 incident cases and 10, 000 random controls frequency-matched by age, sex and year.
The IR of hospitalised ICVA was 1.94 (95%CI: 1.87-2.01) per 1000 person-years in men and 1.59 (95%CI: 1.53-1.65) in women. The IR ratio adjusted by age was 1.35 (95%CI: 1.28-1.43). Major risk factors for the first ICVA were atrial fibrillation (AF) (OR of 1.96 (95%CI: 1.59-2.42) for men and 3.54 (95%CI: 2.85-4.39) for women), smoking, epilepsy and hypertension. AF patients on anticoagulant therapy presented a reduced risk of ICVA (OR: 0.39; 95%CI: 0.27-0.56) in both sexes. Hypertensive women that discontinued the treatment had an increased risk (OR: 2.53; 95%CI: 1.63-3.91).
Men had higher incidence of hospitalised ICVA than women. AF was the major risk factor for ICVA (more in women than men), followed by smoking. Among AF patients, those under anticoagulant therapy showed a significant reduced risk of first ICVA. Antihypertensive drug discontinuation increased the risk of ICVA among women.
Pharmacoepidemiology and Drug Safety 08/2011; 20(10):1050-6. · 2.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the risk of myocardial infarction and death from coronary heart disease after discontinuation of low dose aspirin in primary care patients with a history of cardiovascular events.
Nested case-control study.
The Health Improvement Network (THIN) database in the United Kingdom.
Individuals aged 50-84 with a first prescription for aspirin (75-300 mg/day) for secondary prevention of cardiovascular outcomes in 2000-7 (n=39,513).
Individuals were followed up for a mean of 3.2 years to identify cases of non-fatal myocardial infarction or death from coronary heart disease. A nested case-control analysis assessed the risk of these events in those who had stopped taking low dose aspirin compared with those who had continued treatment.
There were 876 non-fatal myocardial infarctions and 346 deaths from coronary heart disease. Compared with current users, people who had recently stopped taking aspirin had a significantly increased risk of non-fatal myocardial infarction or death from coronary heart disease combined (rate ratio 1.43, 95% confidence interval 1.12 to 1.84) and non-fatal myocardial infarction alone (1.63, 1.23 to 2.14). There was no significant association between recently stopping low dose aspirin and the risk of death from coronary heart disease (1.07, 0.67 to 1.69). For every 1000 patients, over a period of one year there were about four more cases of non-fatal myocardial infarction among patients who discontinued treatment with low dose aspirin (recent discontinuers) compared with patients who continued treatment.
Individuals with a history of cardiovascular events who stop taking low dose aspirin are at increased risk of non-fatal myocardial infarction compared with those who continue treatment.
[show abstract][hide abstract] ABSTRACT: The leading comorbidities and causes of death in patients with chronic obstructive pulmonary disease (COPD) are lung cancer and cardiovascular disease. The aim of this study was to establish the incidence of lung cancer, myocardial infarction and heart failure in patients with COPD in UK primary care.
The General Practice Research Database (GPRD) was used to identify a cohort of 1927 patients with a first recorded diagnosis of COPD. This cohort was followed for up to 5 years to identify new diagnoses of lung cancer, myocardial infarction and heart failure. Mortality was also assessed. The relative risk (RR) of each outcome in the COPD cohort was compared with that in a control cohort with no diagnosis of COPD.
The risk of lung cancer was significantly increased in individuals with a diagnosis of COPD compared with those with no COPD diagnosis (RR: 3.33; 95% confidence interval [CI]: 2.33-4.75; adjusted for age, sex and smoking status). A diagnosis of COPD was also associated with a significant increase in the risk of heart failure (age- and sex-adjusted RR: 2.94; 95% CI: 2.46-3.51) and death (age- and sex-adjusted RR: 2.76; 95% CI: 2.45-3.12), but not myocardial infarction (age- and sex-adjusted RR: 1.18; 95% CI: 0.81-1.71).
Patients with a diagnosis of COPD are at significantly increased risk of lung cancer, heart failure and death compared with the general population. They do not appear to be at increased risk of myocardial infarction.
Respiratory medicine 11/2010; 104(11):1691-9. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the validity of recorded diagnoses of ischemic cerebrovascular events requiring hospitalization within The Health Improvement Network (THIN) UK primary care database.
We identified 15 397 individuals aged 40-84 years with a first recorded ischemic event in 2000-2004. Of these, 4239 had a code suggestive of a hospitalization within 2 weeks of the event. A three-step strategy was used to validate the records of these patients: manual review of computerized medical records excluding free-text comments; manual review including free-text comments (which include information gained from specialists, hospital discharge letters and results of diagnostic tests) of a random sample of possible cases (n = 300) and non-cases (n = 100); and review of full medical records of this random sample and a questionnaire completed by their primary care physician. The positive predictive value (PPV) of each step was calculated. The confirmation rate was used to estimate incidence in the general population.
After step 1, 3447 individuals were classified as possible cases and 792 were excluded as non-cases. After step 2, 82% of possible cases were still classified as such. Step 3 showed that inclusion of free-text comments increased the PPV of a diagnosis from 76 to 86%. The weighted incidence of hospitalized ischemic cerebrovascular events was 1.73 per 1000 person-years (95% CI:1.68-1.77).
THIN demonstrates a high validity for the study of ischemic cerebrovascular events when reviewing computer records with additional free-text comments. Accuracy of hospitalization status was not as well recorded.
Pharmacoepidemiology and Drug Safety 06/2010; 19(6):579-85. · 2.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: The exact mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may increase coronary risk is not completely understood. The aim of this study was to quantify the risk for each type of acute coronary syndrome (ACS) associated using NSAIDs and the role played by dose, duration, and patient characteristics. A prospective case-control study was performed, interviewing 2,954 patients hospitalized for ACS at 32 Spanish hospitals and a similar number of age-matched controls using a structured questionnaire collecting information on the use of NSAIDs, risk factors, and cardiovascular history. Odds ratios (ORs) for any type and each ACS type were calculated adjusted for gender, body mass index, other risk factors, and concomitant medications by conditional logistic regression. The adjusted OR of ACS associated with the current use of NSAIDs was 1.16 (95% confidence interval [CI] 0.95 to 1.42). The risk was increased in patients consuming high doses (OR 1.64, 95% CI 1.06 to 2.53) and those with previous ischemic heart disease (OR 1.84, 95% CI 1.13 to 3.00). The hazard was driven mostly by the increase in the risk for non-ST-segment elevation ACS (OR 1.20, 95% CI 0.99 to 1.47), whereas NSAIDs did not increase the risk for ST-segment elevation myocardial infarction (OR 1.00, 95% CI 0.80 to 1.26). In conclusion, the use of NSAIDs was associated with a small, nonsignificant overall coronary risk that was more apparent for non-ST-segment elevation ACS. This risk was stronger when NSAIDs were used at high doses or in patients with previous ischemic heart disease.
The American journal of cardiology 04/2010; 105(8):1102-6. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The roles of depression and antidepressants in triggering reflux symptoms remain unclear.
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.
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.
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.
A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants.
[show abstract][hide abstract] ABSTRACT: To estimate the prevalence and incidence of depression; investigate its association with risk factors including comorbidities and drug and health care use; and describe treatment patterns of depression in primary care using The Health Improvement Network database.
In this cohort study, subjects with a first recorded diagnosis of depression (Read code) between January 1, 2002, and December 31, 2004 (n=47,170) were identified from a source population of 1,287,829 subjects aged 10-79 years. A comparison group was sampled from the same population and frequency matched to the depression cohort by age, sex, and calendar year (n=50,000). Depression diagnoses were validated using physician-completed questionnaires. Odds ratios and 95% CIs for the relationship of depression with a range of factors were estimated using unconditional logistic regression in a nested case-control analysis.
The prevalence of depression was 11.23% (95% CI, 11.18-11.28). This prevalence decreased with increasing age and was higher in women than in men. The incidence was 13.89 per 1,000 person-years (95% CI, 13.82-14.08). Depression was associated with frequent use of health services, smoking, pregnancy in the previous year, anxiety, stress, sleep disorders, digestive and respiratory disorders, and pain. In the trimester following diagnosis, 82% of cases were treated-98% with antidepressants and 81.5% with selective serotonin reuptake inhibitors (SSRIs).
We found a high prevalence and incidence of depression diagnoses in primary care in the United Kingdom. Following diagnosis, the majority of individuals were prescribed SSRIs. A diagnosis of depression is associated with a number of prior comorbidities, which could mask the depression. This fact should be taken into account when screening individuals in primary care.
The Primary Care Companion to The Journal of Clinical Psychiatry 01/2010; 12(1):PCC.08m00764.
[show abstract][hide abstract] ABSTRACT: Anxiety disorders are common and can cause substantial quality of life impairment.
The aim of this study was to investigate the frequency of anxiety in UK primary care. Treatment patterns and factors associated with an anxiety diagnosis were also assessed.
The Health Improvement Network was used to identify all patients aged 10-79 years with a new diagnosis of anxiety in 2002-04 (n = 40 873) and age-, sex- and calendar-year-matched controls (n = 50 000). A nested case-control analysis was used to quantify potential risk factors for anxiety by multivariate logistic regression.
The prevalence of anxiety was 7.2% and the incidence was 9.7 per 1000 person-years. Incidence and prevalence were highest in women and young adults (20-29 years). Anxiety was associated with heavy alcohol use, smoking and addiction problems as well as stress, sleep and depression disorders. Anxiety patients used health care services more frequently than controls. Among patients diagnosed with anxiety, 63% were treated pharmacologically. Antidepressants accounted for almost 80% of prescriptions.
The prevalence and incidence of anxiety are high in UK primary care and are almost twice as high in women than in men. Anxiety is associated with other psychiatric morbidity as well as frequent health care use. Antidepressants are the most commonly used pharmacological treatment.
Family Practice 11/2009; 27(1):9-16. · 1.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: We determined whether men treated with oral antimuscarinics are at increased risk for acute urinary retention.
In this population based, retrospective cohort study using a nested case-control design we analyzed data from a large primary care database containing patient information entered by general practitioners in the United Kingdom. Our study cohort comprised men 20 to 84 years old. Cases of acute urinary retention were identified by reviewing diagnostic codes and were confirmed in a random sample through questionnaires sent to the treating physician.
The overall incidence of acute urinary retention in the study cohort (1,844) was 1.0 per 1,000 person-years, with the incidence rate increasing with age. The first 30 days (early treatment) of antimuscarinic use was associated with a relative risk of acute urinary retention of 8.3 (95% CI 4.8-14.2) and with longer term use (more than 30 days) the relative risk was 2.0 (95% CI 1.2-3.1). The relative risk of acute urinary retention was similar for low/medium and high antimuscarinic doses (relative risk 2.8 vs 3.0, 95% CI 2.1-3.8 and 1.3-6.8, respectively). The relative risk of acute urinary retention was highest during early treatment for a urogenital indication (relative risk 14.2, 95% CI 6.8-29.6). The risk of acute urinary retention was not increased when antimuscarinics were used as antispasmodics or for drug induced parkinsonism.
Men prescribed antimuscarinics, particularly for a urogenital condition, should be closely monitored during the first 30 days of treatment for signs or symptoms of urinary retention.
The Journal of urology 09/2009; 182(4):1442-8. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastroesophageal reflux symptoms may be more common in patients with COPD than in control subjects. The aim of this study was to investigate the relationship between diagnoses of COPD and gastroesophageal reflux disease (GERD) in primary care.
We used the UK General Practice Research Database to identify a cohort of patients with a first diagnosis of GERD (n = 4,391) and another cohort of patients with a first diagnosis of COPD (n = 1,628) during 1996, which we compared with age-matched and sex-matched comparison cohorts without either diagnosis. We calculated the incidence of a GERD diagnosis among the patients with COPD and control subjects, and of a COPD diagnosis among the patients with GERD and control subjects. We also calculated the relative risk (RR) estimates of these diagnoses using the Mantel-Haenszel test. Risks associated with medication use, comorbidities, and demographic and lifestyle factors were examined using a nested case-control analysis.
During the 5-year follow-up, the RR of an incident COPD diagnosis in patients with a diagnosis of GERD was 1.17 (95% confidence interval [CI], 0.91 to 1.49), while the RR of an incident GERD diagnosis among patients with a diagnosis of COPD was 1.46 (95% CI, 1.19 to 1.78). A COPD diagnosis was associated with current or former smoking, prior diagnosis of asthma, or the use of asthma medication. A GERD diagnosis was associated with a prior diagnosis of ischemic heart disease.
Patients with a diagnosis of COPD are at a significantly increased risk of a diagnosis of GERD compared with individuals with no COPD diagnosis.