http://repub.eur.nl/res/aut/26022/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/40074/ 2013-06-01T00:00:00Z What is known and Objective Diuretics can cause changes in calcium levels due to renal effects. Moreover, calcium levels can also vary as a result of changes in intestinal absorption and in the activity of osteoclastic cells. A marker of osteoclastic bone-resorption activity is the level of urinary free deoxypyridinoline (FDP). Deoxypyridinoline (DP) acts as a cross-link between adjacent collagen chains to provide structural rigidity. Our aim was to investigate the association between use of thiazides and loop diuretics and urinary levels FDP. Methods In this follow-up study, data were obtained from the Rotterdam Study, a large population-based prospective cohort study. For a subset of 658 participants, urinary levels of FDP were measured at baseline. Linear regression analysis was performed to assess the association between the use of thiazides and loop diuretics and the urinary levels of FDP. Results In women, current use of loop diuretics for less than 42 days was associated with an increased level of urinary FDP (+3·43 nmol deoxypyridinoline per mmol urinary creatinine; 95% CI 1·85; 5·02) compared with no use. However, use for a period of more than 42 days was not associated with an increased level of FDP, nor was past use of loop diuretics. For thiazide diuretics, no statistically significant associations were found. What is new and Conclusion In women, short-term use of loop diuretics is associated with an increased level of FDP, reflecting increased bone resorption by osteoclasts. As the difference disappears with longer term use, the clinical significance is unclear and the value of FDP as a biomarker in this setting is not established. The molecular mechanism for the observed differences in bone fracture rates with use of diuretics remains unclear. http://repub.eur.nl/res/pub/32890/ 2012-01-01T00:00:00Z Aims/hypothesis Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. Methods Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes. Results Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified. Conclusion/interpretation Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin. http://repub.eur.nl/res/pub/34313/ 2011-04-01T00:00:00Z Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of heart failure. NSAIDs inhibit the synthesis of renal prostaglandin, which results in a higher total blood volume, cardiac output and preload. The association between recent start of NSAIDs in elderly people and echocardiographic parameters was investigated. Methods: In the Rotterdam Study, a population-based cohort study, the effect of NSAIDs on left ventricular end-systolic dimension, left ventricular end-diastolic dimension, fractional shortening and left ventricular systolic function was studied in all participants for whom an echocardiogram was available (n=5307). NSAID use was categorised as current NSAID use on the date of echocardiography, past use and never used before echocardiography during the study period. Current use was divided into short-term NSAID use (≤14 days) and long-term NSAID use (>14 days). Associations between drug exposure and echocardiographic measurements were assessed using linear and logistic regression analyses. Results: Current NSAID use for <14 days was associated with a significantly higher left ventricular endsystolic dimension (+1.74 mm, 95% CI 0.20 to 3.28), left ventricular end-diastolic dimension (+3.69 mm, 95% CI 1.08 to 6.31) and significantly lower fractional shortening (-6.03%, 95% CI -9.81% to -2.26%) compared with non-users. Current NSAID use for >14 days was associated with a higher left end-diastolic dimension (+1.96 mm, 95% CI 0.82 to 3.11) but there was no change in the other echocardiographic parameters. Conclusion: This study is the first to investigate the association between NSAIDs and echocardiographic parameters and suggests that there is a transient effect of short-term use of NSAIDs on the left ventricular dimension and function of the heart. http://repub.eur.nl/res/pub/22062/ 2010-10-01T00:00:00Z Abstract AIMS: Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are associated with an increased breast cancer mortality rate in patients using tamoxifen. MATERIALS & METHODS: In the prospective population based Rotterdam study, the association between CYP2C19*2 carriers and breast cancer mortality was studied among 80 incident users of tamoxifen. Survival was analyzed with life tables and Cox regression analysis, with drug exposure as a time-dependent variable. Adjustments were made for calendar time, average tamoxifen dose, age, the indication for tamoxifen, CYP2D6 genotype and concomitant use of CYP2C19 inhibitors or inducers. RESULTS: In patients on tamoxifen, CYP2C19*2 carriers were associated with a significantly longer breast cancer survival rate than patients with the wild-type (hazard ratio 0.26, 95%CI: 0.08-0.87). CONCLUSION: This study suggests that CYP2C19 genotype may possibly be a predictive factor for survival in breast cancer patients using tamoxifen. http://repub.eur.nl/res/pub/21171/ 2010-09-01T00:00:00Z Introduction: In Caucasians, basal cell carcinoma (BCC) is among the most frequently diagnosed cancers and its incidence is increasing. Known risk factors for the development of BCC are age, sun exposure, and certain skin characteristics. Despite photosensitizing abilities of diuretic agents, little is known about a possible association with BCC. Methods: Data were obtained from the Rotterdam Study; a large prospective population-based follow-up study with coverage of prescription-only drugs from pharmacies. The diagnoses of BCC were obtained through general practitioners, and by linkage with a registry of histo- and cytopathology. Cumulative use of diuretics at the date of diagnosis was categorized into quartiles for users of high-ceiling diuretics, potassium sparing agents and thiazides. The association between these drugs and BCC was assessed by Cox proportional hazard modeling with adjustment for age, gender and potential confounders. Effect modification was tested with interaction terms. Results: Use of high-ceiling diuretics in the highest quartile (>3.7 years cumulative exposure) was associated with an increased hazard of BCC of 62% compared to no use (HR 1.6; 95% CI 1.1-2.4). Patients who used high-ceiling diuretics and had a high tendency of getting sunburned had a higher risk of diagnosis than non-users who do not easily get sunburned. Neither the use of potassium sparing agents, nor the use of thiazides was associated with BCC. Conclusion: In our study, cumulative use of high-ceiling diuretics was associated with an increased risk of diagnosis of BCC. This effect is stronger in patients who easily get sunburned.