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Biomedical subjects

Luis A García Rodríguez

Publications and source records attributed to Luis A García Rodríguez.

At least 19 recordsLinked to original sources
PubMed2007

Nonsteroidal anti-inflammatory drugs and risk of lung cancer.

Regular aspirin and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use is associated with a reduced risk of colorectal cancer. The effect of NSAIDs on the risk of other cancers remains unclear. To evaluate whether use of aspirin or other specific NSAIDs protects against lung cancer, we conducted a case-control study nested in a cohort of subjects 40-84 years old in 1995-2004, without a diagnosis of cancer before the study start date, and with at least 2 years of enrollment with a general practitioner providing data to the The Health Improvement Network (THIN) database in the UK. Patients who had a first diagnosis of primary lung cancer during the study period were considered cases. A random sample of 10,000 controls was frequency-matched to the cases for age, sex and calendar year. The index date for exposure definition was 1 year before the date of diagnosis for cases and 1 year before a random date within the study period for controls. Relative risks and 95% confidence intervals were estimated using conditional logistic regression stratified for matching factors. Factors such as smoking, chronic obstructive pulmonary disease, cardiovascular diseases and body mass index were introduced in the model. We identified 4,336 cases with primary incident lung cancer (incidence rate 7.6 per 10,000 person-years). Compared with subjects with no prescription of non-aspirin NSAID prior to the index date, the risk of lung cancer was 0.76 (0.61-0.94) among those who received a prescription the previous year and had a treatment duration of at least 1 year. The corresponding relative risk was 1.15 (0.99-1.34) for aspirin. In conclusion, prescription of non-aspirin NSAIDs for at least 1 year might be associated with a slightly reduced risk of lung cancer. Aspirin was not associated with a risk reduction, perhaps due to residual confounding.

Adult↗
PubMed2007

Gallbladder disease in the general population: association with cardiovascular morbidity and therapy.

PURPOSE: Both gallbladder (GB) and cardiovascular disease are very common diagnoses that carry substantial economic costs. Prior studies suggest that personal history of ischaemic heart disease (IHD) could determine the occurrence of GB disease. Additionally the use of thiazide diuretics may also be a risk factor for this condition. We aimed to evaluate different cardiovascular conditions and related drugs that could be associated with GB disease. METHODS: We identified all incident cases of gallbladder disease occurring during 1996 among patients aged 20-79 years old registered in the General Practitioner Research Database. We performed a nested case control analysis using 2353 cases and 10,000 controls frequency matched to the cases by age and sex. RESULTS: After adjusting for potential confounders IHD was associated with a small increased risk of GB disease (1.29, 95%CI:1.08-1.55). When only cases requiring cholecystectomy were considered in the analysis, the resulting estimate was 1.06 (95%CI:0.83-1.35). Users of thiazide diuretics presented an OR of 1.36 (95%CI:1.08-1.71). Other antihypertensive drugs were not associated with GB disease. CONCLUSIONS: Our results confirm the small increased risk of GB disease associated with thiazide diuretics. On the other hand, our data do not support a major association between IHD and GB disease.

Adult↗
PubMed2006

Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications.

BACKGROUND: To balance the cardiovascular benefits from low-dose aspirin against the gastrointestinal harm caused, studies have considered the coronary heart disease risk for each individual but not their gastrointestinal risk profile. We characterized the gastrointestinal risk profile of low-dose aspirin users in real clinical practice, and estimated the excess risk of upper gastrointestinal complications attributable to aspirin among patients with different gastrointestinal risk profiles. METHODS: To characterize aspirin users in terms of major gastrointestinal risk factors (i.e., advanced age, male sex, prior ulcer history and use of non-steroidal anti-inflammatory drugs), we used The General Practice Research Database in the United Kingdom and the Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria in Spain. To estimate the baseline risk of upper gastrointestinal complications according to major gastrointestinal risk factors and the excess risk attributable to aspirin within levels of these factors, we used previously published meta-analyses on both absolute and relative risks of upper gastrointestinal complications. RESULTS: Over 60% of aspirin users are above 60 years of age, 4 to 6% have a recent history of peptic ulcers and over 13% use other non-steroidal anti-inflammatory drugs. The estimated average excess risk of upper gastrointestinal complications attributable to aspirin is around 5 extra cases per 1,000 aspirin users per year. However, the excess risk varies in parallel to the underlying gastrointestinal risk and might be above 10 extra cases per 1,000 person-years in over 10% of aspirin users. CONCLUSION: In addition to the cardiovascular risk, the underlying gastrointestinal risk factors have to be considered when balancing harms and benefits of aspirin use for an individual patient. The gastrointestinal harms may offset the cardiovascular benefits in certain groups of patients where the gastrointestinal risk is high and the cardiovascular risk is low.

Adult↗
PubMed2006

Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease.

Animal and epidemiologic studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of Parkinson disease (PD). The authors studied 1,258 PD cases and 6,638 controls from the General Practice Research Database. The odds ratios (95% CI) for ever vs never use were 0.93 (0.80 to 1.08) for nonaspirin NSAIDs, 1.29 (1.05 to 1.58) for aspirin, and 1.16 (1.00 to 1.35) for acetaminophen. Nonaspirin NSAID use was associated with a higher risk in women and a lower risk in men.

Acetaminophen↗
PubMed2006

Cancer incidence in a general population of asthma patients.

PURPOSE: Several studies have assessed the association between asthma and cancer but none of them revealed a clear pattern of association. We aimed to examine the association between asthma, chronic obstructive pulmonary disease (COPD), and cancer. METHODS: We performed a cohort study with a nested case-control analysis using the General Practitioner Research Database in the UK. We defined three cohorts: patients with asthma, patients with COPD, and general population. During the follow-up, we identified a total of 5263 incident cases of cancer. We conducted a nested case-control analysis that included all cancer cases as well as 20 000 controls free of cancer frequency-matched on age, sex, and calendar year. RESULTS: Patients with asthma did not have an overall greater risk of cancer compared with the general population (odds ratio = 0.93, 95% confidence interval (CI): 0.86-1.00). However, they presented an elevated risk of experiencing lung cancer (odds ratio = 1.84, 95%CI: 1.58-2.15). Controlling for smoking and other potential confounding factors yielded a lower estimate (odds ratio = 1.35, 95%CI: 1.15-1.59). This estimate contrasted with that observed for non-smoking related cancer (0.87, 95%CI: 0.80-0.94). Overall, respiratory drugs did not seem to be associated with cancer among asthmatic patients. Patients with COPD had an Odds ratio of cancer of 1.26 (95%CI: 1.12-1.43) compared with the general population. CONCLUSIONS: Asthma was not associated with an increased risk of cancer. In fact, the risk of non-smoking related cancer was slightly reduced. However, we observed a small-elevated risk of lung cancer among asthmatic patients. Whether this result is a due to residual confounding and/or protopathic bias remains unclear. Further investigation is warranted to confirm or discard these associations.

Adult↗
PubMed2006

Rosuvastatin safety: a comprehensive, international pharmacoepidemiology programme.

Results from clinical trials and clinical practice have shown statins to be generally well tolerated with a low frequency of clinically relevant side effects. Nevertheless, there are rare occasions when adverse events (AEs), sometimes serious, may occur. Rosuvastatin is the newest statin to be approved in the USA and many other countries. As part of the continued assessment of the benefit-risk profile of rosuvastatin, AstraZeneca has developed a progressive, comprehensive pharmacoepidemiology programme to complement safety data obtained from randomised clinical trials and spontaneous reporting systems, which have demonstrated that rosuvastatin has a safety profile in line with comparator statins. This programme comprises nine studies conducted in recognised centres of excellence assessing over 50,000 patients treated with rosuvastatin. It consists of three components: patient characteristics studies (four studies), safety evaluation studies (four studies); and review of data generated from the Prescription-Event Monitoring (PEM) study, designed and run by an independent third party. Patient characteristics studies are designed to describe the characteristics and drug utilisation patterns of new users of rosuvastatin compared with new users of other statins in automated databases. Safety evaluation studies will examine the rates of specific AEs in different cohorts of statin users and determine risk factors for these events using data recorded prospectively in automated databases with case adjudication via medical record review. The independent PEM study will monitor any significant events recorded by general practitioners since starting rosuvastatin treatment. This article is an overview of the rationale and methodology of the rosuvastatin pharmacoepidemiology programme.

Canada↗
PubMed2006

Upper gastrointestinal complications among users of paracetamol.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with upper gastrointestinal complications such as bleeding or perforation. Paracetamol has been traditionally considered a safer alternative to NSAIDs. In a previous case-control study we found that paracetamol at high doses increased the risk of upper gastrointestinal complications. We proposed to review all studies addressing the association between paracetamol and upper gastrointestinal complications and placed our results in the context of existing literature. We conducted a nested case-control study using the United Kingdom General Practice Research Database during the period between April 1993 and October 1998. Then we performed a systematic review of the literature indexed in MEDLINE published between 1980 and 2004. We identified a total of twelve studies that assessed the association between paracetamol and upper gastrointestinal complications. We used a fixed effects model to calculate a summary estimate of these studies. In the nested case control study, use of paracetamol was associated with a small elevated risk of upper gastrointestinal complications (relative risk (RR), 1.3; 95% confidence interval (CI), 1.1-1.5). The RR was 3.6 (95% CI, 2.6-5.1) among paracetamol users of more than 2 g daily, whereas smaller doses did not increase the risk. Among the twelve studies identified in the systematic review, estimates ranged from 0.2 through 2.0 with a summary estimate of 1.3 (95% CI, 1.2-1.5). Our findings indicate that use of paracetamol at the doses most commonly used confer little or no increased risk of upper gastrointestinal complications. More data are needed to confirm or refute the suggestion that high-dose paracetamol is associated with an increased risk of upper gastrointestinal complications of the same magnitude as the one observed with traditional NSAIDs.

Acetaminophen↗
PubMed2006

Non-steroidal antiinflammatory drugs and the risk of acute myocardial infarction.

Whether non-aspirin non-steroidal antiinflammatory drugs (NSAIDs) affect the risk of myocardial infarction is unclear. Also, it is unknown whether the effect varies by individual NSAIDs. To summarize the evidence from published observational studies on the risk of myocardial infarction associated with both traditional NSAIDs (tNSAIDs) and selective inhibitors of cyclooxygenase-2 (Coxibs), the authors conducted a systematic review of cohort and case-control studies on NSAIDs and myocardial infarction published between 2000 and 2005. Sixteen original studies were selected according to predefined criteria. Two researchers independently extracted the data on individual study characteristics and results. The authors calculated pooled relative risk (RR) estimates of myocardial infarction for specific NSAIDs compared with no NSAID use, tested the heterogeneity of effects, and evaluated potential reasons for heterogeneity. The pooled RR of myocardial infarction was 0.98 (95% confidence interval (CI): 0.92-1.05) for naproxen, 1.07 (95% CI: 1.02-1.12) for ibuprofen, 1.44 (95% CI: 1.32-1.56) for diclofenac, 0.96 (95% CI: 0.90-1.02) for celecoxib, and 1.26 (95% CI: 1.17-1.36) for rofecoxib (all doses). The pooled RR for rofecoxib at doses >25 mg/day was 1.78 (95% CI: 1.36-2.34), and 1.18 (95% CI: 1.07-1.31) for doses < or =25 mg/day. The RR associated with naproxen was 0.83 (95% CI: 0.72-0.90) among non-users of low-dose aspirin. The RR associated with rofecoxib (all doses) was 1.39 (95% CI: 1.25-1.54) among subjects without a history of myocardial infarction. The risk of myocardial infarction varies with individual NSAIDs. An increased risk was observed for diclofenac and rofecoxib, the latter one with a clear dose-response trend. There was a suggestion of a small increased risk with ibuprofen. Also, data suggest a small reduced risk for naproxen present only in non-users of aspirin, mainly people free of clinically apparent vascular disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Antidepressants and risk of upper gastrointestinal bleeding.

Selective serotonin reuptake inhibitors (SSRIs) are nowadays the most widely used antidepressants in the world, mainly because they have a better adverse reaction profile and a higher safety margin in overdoses, when compared to other antidepressants. These drugs recently have been the target of important debates concerning safety issues, among them the possibility that they may increase the risk of bleeding. Over the 1990s, an increasing number of individual cases of bleeding disorders were reported in the literature and to the pharmacovigilance programmes which prompted several epidemiological and pharmacological studies. In this review we have examined all available data. The whole evidence supports the hypothesis that antidepressants with a relevant blockade action on serotonin reuptake mechanism increase the risk of bleeding. Such disorders may have different degrees of severity and may be located anywhere in the body. The epidemiological evidence is, however, more robust for upper gastrointestinal bleeding. It has been estimated that upper gastrointestinal bleeding may occur at a frequency ranging from 1 in 100 to 1 in 1,000 patient-years of exposure to high-affinity drugs (the SSRIs), with the very old patients being in the highest part of the range. The increased risk may be of particular relevance when the SSRIs are associated with NSAIDs as well as low-dose aspirin.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population.

BACKGROUND: Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients. METHODS: We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year. RESULTS: Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95-1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00-1.48). The corresponding RR was 1.34 (95% CI, 1.06-1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01-1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47-1.62) with naproxen to 1.38 (95% CI, 1.00-1.90) with diclofenac. CONCLUSION: This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs.

Aged↗
PubMed2005

Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case-control study.

OBJECTIVES: To prospectively assess the influence of body mass index (BMI), tobacco, and alcohol on the occurrence of esophageal, gastric cardia, and non-cardia gastric adenocarcinoma, and to detect any sex differences that could explain the male predominance of these tumors. METHODS: A case-control study nested in the General Practitioner Research Database in the United Kingdom, 1994--2001. Odds ratios (ORs) were calculated with 95% confidence intervals (CI), including multivariate analysis. RESULTS: During follow-up of 4,340,207 person-years, we identified 287 esophageal adenocarcinomas, 195 gastric cardia adenocarcinomas, 327 gastric non-cardia adenocarcinomas, and 10,000 controls. A positive association was found between overweight (BMI > 25 kg/m(2)) and esophageal adenocarcinoma (OR 1.67, 95% CI 1.22--2.30), and gastric cardia adenocarcinoma (OR 1.46, 95% CI 0.98--2.18), but not non-cardia gastric adenocarcinoma. The association between BMI and esophageal and gastric cardia adenocarcinoma were dose-dependent and seemingly independent of reflux. No strong sex differences were identified. Smokers, particularly females, were at increased risk of all studied adenocarcinomas, while no association with alcohol was found. CONCLUSIONS: Overweight increases risk of esophageal and gastric cardia adenocarcinoma, while tobacco smoking increases risk of esophageal, gastric cardia, and non-cardia gastric adenocarcinoma. The male predominance is not explained by sex differences in risk factor profiles of the studied exposures.

Adenocarcinoma↗
PubMed2005

Breast cancer risk among users of antidepressant medications.

BACKGROUND: Breast cancer is the most common cancer in women. Laboratory studies suggest that antidepressants may promote breast cancer tumor growth. Several epidemiologic studies have evaluated this association with conflicting results. METHODS: We conducted a cohort study with a secondary nested case-control analysis based on the General Practice Research Database. Our goal was to assess the association between the risk of breast cancer and use of serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other antidepressants. We calculated adjusted estimates controlling for breast cancer risk factors using unconditional logistic regression. RESULTS: A total of 3708 cases of breast cancer were ascertained. Overall, antidepressant use was not associated with an increased risk of breast cancer. Current users of SSRIs had an odds ratio (OR) of 0.98 (95% confidence interval=0.81-1.19), whereas current users of TCAs had an OR of 0.86 (0.73-1.00). When only use for longer than 1 year was considered, the corresponding estimates for SSRIs and TCAs were 0.76 (0.53-1.09) and 0.87 (0.70-1.09), respectively. None of the individual drugs was associated with breast cancer risk. CONCLUSIONS: Use of antidepressants was not associated with an increased risk of breast cancer regardless of duration of use, daily dose, or specific drug being used. These results, together with evidence from prior studies, support the lack of a clinically meaningful association between breast cancer risk and antidepressants.

Antidepressive Agents↗
PubMed2005

Respiratory medications and the risk of cardiac arrhythmias.

BACKGROUND: Medications used to treat respiratory diseases include beta-adrenoceptors, antimuscarinics, inhaled and oral corticosteroids, and theophyllines. Most of these drugs have been associated indirectly with cardiac rhythm disorders, but epidemiologic evidence is limited. METHODS: To evaluate the association between respiratory drugs and the occurrence of rhythm disorders among patients with asthma and those with chronic obstructive pulmonary disease, we conducted a case-control study nested in a population-based cohort of individuals 10-79 years of age and registered in the U.K. General Practice Research Database after 1 January 1994. The analysis included 710 confirmed cases and 5000 controls frequency-matched to cases by age (interval of 1 year) and sex. RESULTS: No increased risk of arrhythmias overall was found among users of inhaled steroids (relative risk = 1.0; 95% confidence interval = 0.8-1.3). Short-term use of theophylline was weakly associated with arrhythmia (1.8; 1.0-3.3). An increased risk was found among users of oral steroids, and the relative risk was greater at the beginning of therapy (2.6; 2.0-3.5). The risk of atrial fibrillation was increased, especially for short-term use of oral steroids (2.7; 1.9-3.8), and a weak association was seen for theophyllines, especially short-term use (1.8; 0.9-3.7). Supraventricular tachycardia was associated with long-term use of oral steroids (2.1; 0.8-5.7), long-term use of antimuscarinics (1.7; 0.7-4.1), and short-term use of theophylline (4.0; 0.9-18.1). Ventricular arrhythmias were associated with oral steroids (3.2; 0.8-13.3) and beta-adrenoceptors (7.1; 0.8-65.9). CONCLUSIONS: Oral steroids and theophylline were the therapeutic groups associated with risk of developing atrial fibrillation, especially with new courses of therapy. Results from this study also are consistent with certain suspected dysrhythmic effects of theophyllines, with supraventricular tachycardia associated with antimuscarinics, and with ventricular arrhythmias associated with beta-adrenoceptors.

Adolescent↗
PubMed2005

Nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAID) might reduce risks of esophageal and gastric cancer, but previous studies are limited and provide somewhat conflicting results. METHODS: We tested these associations in a prospective, nested case-control study based on the General Practitioners Research Database, including over 2 million persons in the United Kingdom between 1994 and 2001. In multivariate analyses we calculated odds ratios (OR) with 95% confidence intervals (95% CI). Data were stratified by history of upper gastrointestinal (UGI) disorders and recalculated using 2 years lag time on data (i.e., excluding all information 2 years before index date). RESULTS: Among 4,340,207 person-years of follow-up, we identified 909 patients with esophageal cancer and 1,023 patients with gastric cancer. We randomly selected 10,000 control subjects. Overall analysis suggested that long-term users of nonaspirin NSAIDs were at reduced risks of esophageal (OR, 0.82; 95% CI, 0.57-1.18) and gastric cancer (OR, 0.65; 95% CI, 0.44-0.94), whereas long-term aspirin users might be at decreased risk of esophageal cancer (OR, 0.76; 95% CI, 0.53-1.08), but not of gastric cancer (OR, 1.09; 95% CI, 0.82-1.45). All estimates of reduced risk were weakened in the 2 years lag time analysis except the association between nonaspirin NSAIDs long-term users and gastric cancer. Potentially protective effects were suggestive of being more marked among subjects with a history of UGI disorders. CONCLUSIONS: Nonaspirin NSAIDs long-term use was associated with a reduced risk of gastric cancer, whereas no other studied associations could be firmly established. Our results suggest that UGI disorders could distort the associations, although we could not show this with statistical significance. If such bias was to be true, the previously reported inverse associations might, at least partly, be explained by lack of appropriate adjustment for such disorders.

Adult↗
PubMed2004

Nonsteroidal antiinflammatory drugs and the risk of myocardial infarction in the general population.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) are reversible inhibitors of cyclooxygenase (COX)-1 and COX-2. Whether transient and incomplete COX-1 inhibition with NSAIDs other than aspirin will translate into clinical cardioprotection is unclear. Some reports suggest that concurrent aspirin and ibuprofen might be associated with lower cardioprotection than aspirin alone because of a pharmacodynamic interaction. METHODS AND RESULTS: We conducted a cohort study with a nested case-control analysis. Overall, 4975 cases of acute myocardial infarction (MI) and death from coronary heart disease (CHD) were identified (January 1997 to December 2000) in the UK. A total of 20,000 controls were randomly sampled, and frequency was matched to cases by age, sex, and calendar year. The incidence rate was 5.0 per 1000 person-years. The multivariate-adjusted OR for current NSAID use compared with nonuse was 1.07 (95% CI, 0.95 to 1.20). Treatment duration or daily dose did not change the results. The effect was similar among patients free of CHD history (1.04; 95% CI, 0.90 to 1.20) and patients with previous history (1.12; 95% CI, 0.91 to 1.38). Estimates for individual NSAIDs were all comparable, with no major effect on the risk of acute MI. Naproxen was associated with an OR of 0.89 (95% CI, 0.64 to 1.24). The OR of aspirin and concurrent NSAIDs use was 1.10 (95% CI, 0.89 to 1.37) compared with aspirin alone. We observed the same result when analyzing ibuprofen and aspirin taken concomitantly. CONCLUSIONS: This study could not demonstrate any detectable risk reduction of NSAIDs on the occurrence of MI. Our results do not support the existence of a clinically meaningful interaction between aspirin and NSAIDs, including ibuprofen.

Aged↗
PubMed2004

A prospective study of alcoholism and the risk of Parkinson's disease.

The lower incidence of Parkinson's disease (PD) among smokers may be explained by a protective effect of cigarette smoke, or by a tendency to avoid addictive behaviors among future PD cases. We conducted an indirect test of the latter hypothesis by comparing the incidence of PD between alcoholics and nonalcoholics in the General Practice Research Database of the United Kingdom. Our case-control study included 1,019 cases and 10,123 matched controls. Overall, we did not find a lower incidence of PD among alcoholics compared with nonalcoholics (odds ratio: 1.09; 95 % CI: 0.67, 1.78).

Adult↗