Publications

Sort by:

date

author

title

(2010) "New opportunities for drug outcomes research in cancer patients: The linkage of the Eindhoven Cancer Registry and the PHARMO Record Linkage System." van Herk-Sukel, M.P. , L.V. van de Poll-Franse, et.al. Eur J Cancer 46(): 395-404

(2010) "New opportunities for drug outcomes research in cancer patients: The linkage of the Eindhoven Cancer Registry and the PHARMO Record Linkage System." van Herk-Sukel, M.P. , L.V. van de Poll-Franse, et.al. Eur J Cancer 46(): 395-404 BACKGROUND: Insight into co-morbidity and treatment effects is pivotal to improve quality of care for cancer patients. OBJECTIVES: To determine whether linkage of the Eindhoven Cancer Registry (ECR) and the PHARMO Record Linkage System (RLS) was technically feasible and to assess which patient-centric data would result from this linkage. METHODS: The ECR records data on tumour stage and primary treatment of all newly diagnosed cancer patients in the southeastern Netherlands including co-morbidity at diagnosis, whereas the PHARMO RLS includes data from multiple linked observational databases such as data on drug utilisation (for both in- and out-patients, including chemotherapy), hospitalisations and clinical laboratory measurements. All patients who lived or had been living in the overlapping area served by the ECR and the PHARMO RLS during 1998-2006 were selected for linkage which was performed with probabilistic medical record linkage. RESULTS: The linkage resulted in an ECR-PHARMO cohort of 40,004 cancer patients with a total of 42,767 primary tumours. The cancer patients in the linked ECR-PHARMO cohort were representatives for the cancer patients included in the total ECR during 1998-2006. Cancer patients included in the cohorts had a mean history of 5 years and a mean follow-up ranging from 2 to more than 4 years (dependent on the survival rate of the specific cancer type). CONCLUSIONS: Linkage of ECR and the PHARMO RLS creates the possibility to study patient-centric drug utilisation, health resources utilisation and their costs, in addition to the effectiveness and safety of pharmaceuticals in routine daily practice in cancer patients.

(2010) "New opportunities for drug outcomes research in cancer patients: The linkage of the Eindhoven Cancer Registry and the PHARMO Record Linkage System." van Herk-Sukel, M.P. , L.V. van de Poll-Franse, et.al. Eur J Cancer 46(): 395-404   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2010) "Relation between body mass index, physical inactivity and use of prescription drugs: the Doetinchem Cohort Study." Milder, I.E. , O.H. Klungel, et.al. Int J Obes (Lond)

(2010) "Relation between body mass index, physical inactivity and use of prescription drugs: the Doetinchem Cohort Study." Milder, I.E. , O.H. Klungel, et.al. Int J Obes (Lond) Background:Obesity and physical inactivity are associated with several diseases such as diabetes, cardiovascular diseases, musculoskeletal complaints, osteoporosis, certain types of cancer and depression. However, few data are available on the specific types of medication associated with obesity and physical inactivity.Objective:The aim of this study was to determine the independent association of body mass index (BMI) and physical inactivity with use of specific classes of prescription drugs, andthe interaction between BMI and physical inactivity.Methods:The Doetinchem Cohort Study is a population-based longitudinal study. We analyzed cross-sectional data of 1703 men and 1841 women, examined between 1998 and 2002, for whom drug-dispending data were available from the PHARMO database. Drugs were coded according to the WHO Anatomical Therapeutic Chemical (ATC) classification system. Body weight was measured during the physical examination. Physical activity was assessed using an extensive questionnaire. Persons were defined as a user of a certain drug class if they filed at least one prescription in the year around (+/-6 months) the examination.Results:Compared with normal weight persons (BMI 18.5-25 kg m(-2)), obese persons (BMI>30 kg m(-2)) had a higher use of prescription drugs of several drug classes, especially cardiovascular drugs (OR (95% CI): 3.83 (2.61-5.64) in men and 2.80 (2.03-3.86) in women) and diabetes drugs (OR (95% CI): 5.72 (2.32-14.14) in men and 3.92 (1.80-8.54) in women). In women, physical inactivity was also associated with higher use of certain drug classes, such as drugs for blood and blood-forming organs (OR (95% CI): 2.11 (1.22-3.65)) and musculoskeletal drugs (OR (95% CI): 2.07 (1.45-2.97)), whereas in men this wasnot the case. We found no interaction between BMI and physical inactivity with respect to use of prescription drugs.Conclusion:In both men and women, obesity was associated with a higher use of several types of prescription drugs, whereas physical inactivity was only associated with a higher use of certain drug classes in women.International Journal of Obesity advance online publication, 2 February 2010; doi:10.1038/ijo.2010.2.

(2010) "Relation between body mass index, physical inactivity and use of prescription drugs: the Doetinchem Cohort Study." Milder, I.E. , O.H. Klungel, et.al. Int J Obes (Lond)   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2010) "Quality of life in relation to constipation among opioid users." Penning-van Beest, F.J. , P. van den Haak, et.al. J Med Econ

(2010) "Quality of life in relation to constipation among opioid users." Penning-van Beest, F.J. , P. van den Haak, et.al. J Med Econ Abstract Objective: Opioid users often experience constipation. In this study the impact of constipation on QoL was assessed in patients using opioids either for non-advanced illness or advanced illness. Methods: Patients using opioids, recruited via public pharmacies, were asked to complete questionnaires on opioid use, constipation and the EuroQol five-dimension questionnaire (EQ-5D). Patients with a severe non-curable disease and relatively short life-expectancy were classified as having an advanced illness; a disabling yet not directly life-threatening condition was defined as non-advanced illness. Constipation was assessed based on questions on opioid side-effects and laxative use. EQ-5D index scores were compared between patients with and without constipation using Wilcoxon two-samples test. Results: Questionnaires were returned by 588 patients with non-advanced illness, of whom 326 (55%) were classified as having constipation and by 113 patients with advanced illness, of whom 76 (67%) wereclassified as having constipation. The median EQ-5D index, a weighted health state index score with 1 = full health, was lower in patients with constipation than in patients without constipation (0.31 vs. 0.65, p< 0.01 for non-advanced illness and 0.41vs. 0.61, p=0.12 for advanced illness). Conclusion: The results of this study suggest that, in patients using opioids either for non-advanced illness or advanced illness, constipation negatively influences QoL. By separately analysing patients with advanced illness and patients with non-advanced illness, possible selective non-response and confounding was accounted for, but not completely solved.

(2010) "Quality of life in relation to constipation among opioid users." Penning-van Beest, F.J. , P. van den Haak, et.al. J Med Econ   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2010) "Use of Organic Nitrates and the Risk of Hip Fracture: A Population-Based Case-Control Study." Pouwels, S. , A. Lalmohamed, et.al. J Clin Endocrinol Metab

(2010) "Use of Organic Nitrates and the Risk of Hip Fracture: A Population-Based Case-Control Study." Pouwels, S. , A. Lalmohamed, et.al. J Clin Endocrinol Metab Context: Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Objective: Our objective was to evaluate the association between organic nitrates and hip fracture risk. Methods: A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991-2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescriptionwithin 90 d before the index date. The analyses were adjusted for disease and drug history. Results: Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83-1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63-1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97-1.40). No association was found between duration of nitrate use and fracture risk. Conclusions: Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects.

(2010) "Use of Organic Nitrates and the Risk of Hip Fracture: A Population-Based Case-Control Study." Pouwels, S. , A. Lalmohamed, et.al. J Clin Endocrinol Metab   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2010) "Determination of non-treatment with statins of high risk patients in The Netherlands." van den Haak, P. , E. Heintjes, et.al. Curr Med Res Opin 26(2): 271-8

(2010) "Determination of non-treatment with statins of high risk patients in The Netherlands." van den Haak, P. , E. Heintjes, et.al. Curr Med Res Opin 26(2): 271-8 OBJECTIVE: To determine in the Netherlands what proportions of high risk patients with established cardiovascular disease (CVD) or diabetes mellitus type 2 (DM2) who were not treated with statins on 1 January 2007 and which characteristics were associated with non-treatment. METHODS: From the IPCI GP database patients were selected who were registered with a GP on 1 January 2007 who had a history of either CVD (CVD patients), DM2 (diabetics) or both (diabetics with CVD). The proportion of patientsusing statins around 1 January 2007 was determined. Associations of patient characteristics with non-treatment were quantified (CVD patients and diabetics only). RESULTS: In all, 19 628 CVD patients, 5006 diabetics and 3767 diabetics with CVD were identified. Of these patients 71%, 54% and 45%, respectively did not use statins. These proportions were similar in the subgroups of patients with recent LDL-C measurements. Among these subgroups the vast majority of non-treated patients was eligible for statin treatment (LDL-C >2.5 mmol/l). The proportion of statin-treated patients was larger among diabetics than among CVD patients. Among CVD patients, female gender, age below 40 years, living in a deprived area, a history of CVD of less than 1 year and arrhythmia were significantly associated with non-treatment. Among diabetics, significant associations were: living in a deprived area and specialist visits in the previous year. In 2003, treatment rates among diabetics were lower, but among CVD patients they were similar. This suggests that the higher treatment rates among diabetics compared to CVD patients in 2007 may be the result of disease-management programmes introduced for diabetics in 2004. CONCLUSION: The majority of patients with established CVDor DM2 were not treated with statins on 1 January 2007. Eligibility for statin treatment may have been overestimated due to unavailability of cholesterol levels among many non-treated patients. Implementation of care programmes for CVD patients may increase treatment rates among eligible CVD patients.

(2010) "Determination of non-treatment with statins of high risk patients in The Netherlands." van den Haak, P. , E. Heintjes, et.al. Curr Med Res Opin 26(2): 271-8   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2010) "Half of breast cancer patients discontinue tamoxifen and any endocrine treatment before the end of the recommended treatment period of 5 years: a population-based analysis." van Herk-Sukel, M.P. , L.V. van de Poll-Franse, et.al. Breast Cancer Res Treat

(2010) "Half of breast cancer patients discontinue tamoxifen and any endocrine treatment before the end of the recommended treatment period of 5 years: a population-based analysis." van Herk-Sukel, M.P. , L.V. van de Poll-Franse, et.al. Breast Cancer Res Treat Observational studies on long-term endocrine treatment among breast cancer patients have presented discontinuation rates on tamoxifen, but lack information on the continuance of any endocrine treatment [both tamoxifen and aromatase inhibitors (AIs)]within the same cohort. In this study we determined switching rates from tamoxifen to AIs, discontinuation rates of tamoxifen only, discontinuation rates of any endocrine treatment and determinants of first treatment switch and treatment discontinuation. Patients with early stage breast cancer (stage I-IIIa) starting on tamoxifen were selected from the linked Eindhoven Cancer Registry-PHARMO RLS cohort in the period 1998-2006. Continuous use (allowing a 60 days gap between refills) of tamoxifen only and any endocrine treatment were determined after various follow-up periods: 1, 2, 3, 4, and 5 years. Time to first switch from tamoxifen to an AI was assessed. Cox regression was used to identify determinants of first treatment switch, discontinuation oftamoxifen, and discontinuation of any endocrine treatment. A total of 1,451 new early stage breast cancer patients started on tamoxifen. Of those, 380 had a treatment switch to an AI during follow-up. Of the patients followed for 5 years, 40% continuously used tamoxifen, which was 49% for any endocrine treatment. Older age (older than 70 versus 50-69 years) was independently associated with increased discontinuation of tamoxifen and any endocrine therapy. Patients with two or more concomitant diseases (versus no comorbidity) showed an increased likelihood to stop any endocrine treatment or switch treatment from tamoxifen to an AI. In conclusion, up to half of the breast cancer patients starting tamoxifen continued 5 years of endocrine treatment. Identification of patients at risk of discontinuation will assist in the development of interventions to improve treatment continuation comparable to that of patients included in clinical trials.

(2010) "Half of breast cancer patients discontinue tamoxifen and any endocrine treatment before the end of the recommended treatment period of 5 years: a population-based analysis." van Herk-Sukel, M.P. , L.V. van de Poll-Franse, et.al. Breast Cancer Res Treat   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2010) "Medication Changes Prior to Hospitalization for Obstructive Lung Disease: A Case-Crossover Study (February)." Velthove, K.J. , H.G. Leufkens, et.al. Ann Pharmacother

(2010) "Medication Changes Prior to Hospitalization for Obstructive Lung Disease: A Case-Crossover Study (February)." Velthove, K.J. , H.G. Leufkens, et.al. Ann Pharmacother BACKGROUND: Hospitalizations have always been seen as a solid outcome parameter in pharmacoepidemiology. However, the period leading to hospitalization and prehospital management of the patient are equally important. OBJECTIVE: To evaluate medication changes in the period prior to hospitalization for obstructive lung disease and to quantify the association between medication use and the risk of hospitalization. METHODS: We conducted a case-crossover study using the PHARMO record linkage system, which contains drug dispensing data from community pharmacies and hospital admission data. Patients included in the study were adults hospitalized for obstructive lung disease between 2005 and 2007. The index date of the case period was the date of hospitalization, and control moments were set at 3, 6, 9, and 12 months before admission. For each patient, all prescriptions prior to the date of hospitalization were identified. Medication use was ascertained in a 90-day time window prior to each case or control moment. RESULTS: We identified 1481 patients who were hospitalized for obstructive lung disease. It appeared that respiratory medication use increased in the 90 days prior to hospitalization. Hospitalization was associated with the use of 3 or more respiratory drugs (OR 2.2; 95% CI 1.8 to 2.8), systemic glucocorticoids (OR 4.5; 95% CI 3.8 to 5.4), and antibiotics (OR 3.1; 95% CI 2.7 to 3.6). CONCLUSIONS: The use of systemic glucocorticoids, antibiotics, and other respiratory drugs increased prior tohospitalization for obstructive lung disease. These results could be indicative of the development and/or treatment of an exacerbation. There is a need for markers to detect exacerbations in an early phase in order to start treatment as early as possibleand possibly prevent hospitalizations for obstructive lung disease.

(2010) "Medication Changes Prior to Hospitalization for Obstructive Lung Disease: A Case-Crossover Study (February)." Velthove, K.J. , H.G. Leufkens, et.al. Ann Pharmacother   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "The risk for breast cancer is not evidently increased in women with hyperprolactinemia." Dekkers, O.M. , J.A. Romijn, et.al. Pituitary

(2009) "The risk for breast cancer is not evidently increased in women with hyperprolactinemia." Dekkers, O.M. , J.A. Romijn, et.al. Pituitary The question has been raised whether hyperprolactinemia in humans is associated with an excess risk for breast cancer. We aimed to assess the risk of breast cancer in a previously defined large cohort of patients treated for idiopathic hyperprolactinemia or prolactinomas. Based on the pattern of drug prescriptions we identified 11,314 subjects in the PHARMO network with at least one dispensing of dopamine agonists between 1996 and 2006. Of these, 1,607 subjects were considered to have dopamine agonist-treated hyperprolactinemia based on the prescribing pattern. For the present analysis, we included only women (n = 1,342). Patients with breast cancer were identified by hospital discharge codes. Data on breast cancer incidence in the Netherlands were derived from the Dutch cancer registry. Standardized mortality ratio (SMR) was the measure of outcome to assess the association between hyperprolactinemia and breast cancer. The 1,342 patients accounted for a total of 6,576 person years. Eight patientswith breast cancer during follow-up were identified. Indirect standardization with incidence proportions from the general Dutch population revealed a 7.47 expected cases. The calculated SMR for breast cancer risk in patients treated hyperprolactinemia was 1.07 (95% confidence interval 0.50-2.03). In conclusion, there is no clear evidence for increased breast cancer risk in female patients treated for either idiopathic hyperprolactinemia or prolactinomas. The uncertainty about the exact risk that is dueto the relatively low number of breast cancer cases, should be overcome by pooling results in a future meta-analysis.

(2009) "The risk for breast cancer is not evidently increased in women with hyperprolactinemia." Dekkers, O.M. , J.A. Romijn, et.al. Pituitary   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Change of initial oral antidiabetic therapy in type 2 diabetic patients." Plat, A. , F. Penning-van Beest, et.al. Pharm World Sci 31(6): 622-6

(2009) "Change of initial oral antidiabetic therapy in type 2 diabetic patients." Plat, A. , F. Penning-van Beest, et.al. Pharm World Sci 31(6): 622-6 Objective To explore the 'real-life' therapy of type 2 diabetes mellitus with oral antidiabetic drugs (OADs). Methods From the PHARMO Record Linkage System comprising linked drug dispensing and clinical laboratory data from approximately 2.5 millionindividuals in the Netherlands, among others, new users of OADs were identified in the period 1999-2004. New users, aged 30 years and older, without insulin use before cohort entry date and with at least one year follow-up were included. We determined per initial therapy patient characteristics and first therapy change. Results Overall 35,514 patients were included. Metformin and sulfonylureas (SU) were the most frequent initial therapy. Patients on thiazolidinedione (TZD) monotherapy had lower percentages baseline HbA1c >/= 7% compared to patients on metformin and SU. The proportion of patients still on initial therapy after one year ranged from 46% (TZDs) to around 60% (SU). Among patients starting on monotherapy, add-on (15-20%) and discontinuation(16-25%) of therapy occurred most frequently. In patients starting on combination therapy, a switch occurred in 30% of the patients. Conclusion In more than 40% of the patients a change in initial OAD-therapy is already observed in the first year of therapy. Maintaining patients on initial therapy remains a challenge.

(2009) "Change of initial oral antidiabetic therapy in type 2 diabetic patients." Plat, A. , F. Penning-van Beest, et.al. Pharm World Sci 31(6): 622-6   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Measuring exacerbations in obstructive lung disease." Velthove, K.J. , P.C. Souverein, et.al. Pharmacoepidemiol Drug Saf

(2009) "Measuring exacerbations in obstructive lung disease." Velthove, K.J. , P.C. Souverein, et.al. Pharmacoepidemiol Drug Saf PURPOSE: Using hospitalization always has been seen as a solid measurement for exacerbation in pharmacoepidemiology, but might lead to an underestimation of disease exacerbation because of a trend towards outpatient care. The aim of this study was to quantify the incidence of different exacerbation markers in obstructive lung disease and to identify predictors for these exacerbation markers. METHODS: We conducted a cohort study using the PHARMO record linkage system, including demographic details and complete medication histories of more than two million community-dwelling residents in the Netherlands from 1985 onwards. Eligible patients were adult users of inhaled corticosteroids (ICS). Outcome parameters were hospitalization and short courses ofsystemic corticosteroids. Patients were allowed to have multiple exacerbations during follow-up. RESULTS: We identified 5327 patients. During follow-up, 8635 exacerbations occurred in 2332 patients with a trend in time towards treating exacerbations outof the hospital (p-value 0.003). Of all patients with exacerbations, 73% was not hospitalized during follow-up. Exacerbations were associated with high-dose ICS use (adjusted RR 1.4; 95% CI 1.2-1.7) and chronic systemic corticosteroid use (adjusted RR 1.9; 95%CI 1.6-2.2). CONCLUSIONS: Using hospitalization only as exacerbation marker leads to underestimating the exacerbation rate, because of exacerbation treatment out of the hospital. Patients with obstructive lung disease using chronic systemic corticosteroids or high-dose ICS use are more prone to exacerbations. This implies that these patients should be monitored carefully to prevent recurrent exacerbations which are detrimental for their prognosis and quality of life. Copyright (c) 2009 John Wiley& Sons, Ltd.

(2009) "Measuring exacerbations in obstructive lung disease." Velthove, K.J. , P.C. Souverein, et.al. Pharmacoepidemiol Drug Saf   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Comparison of incidences of cardiovascular events among new users of different statins: a retrospective observational cohort study." Heintjes, E.M. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 25(11): 2621-9

(2009) "Comparison of incidences of cardiovascular events among new users of different statins: a retrospective observational cohort study." Heintjes, E.M. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 25(11): 2621-9 OBJECTIVE: To compare incidences of cardiovascular disease (CVD) in general and myocardial infarction (MI) specifically between new users of different statins in daily practice. DESIGN AND METHODOLOGY: Retrospective observational cohort study. Datawere obtained from the PHARMO Record Linkage System; the PHARMO database contains pharmacy dispensing records of 3 million patients in the Netherlands registered with community pharmacies, linked to hospitalisation records. The participants were new statin users in the period 2000-2005, excluding patients hospitalised for CVD events in the year prior to start of statin use. MAIN OUTCOME MEASURES: Adjusted hazard ratios of hospitalisations for CVD (including any type of ischemic heart disease, stroke, orrevascularisation procedure) in general, or MI in particular, occurring during use of the initial statin within two years of start of therapy, comparing users of different statins. RESULTS: The mean follow-up duration of 76,147 new statin users (14,530pravastatin, 27,752 simvastatin, 25,777 atorvastatin, 8088 rosuvastatin) was 55 weeks. Incidence rates of CVD and MI per 100 person years ranged from 0.75 and 0.15 for rosuvastatin to 1.72 and 0.29 for pravastatin. Rosuvastatin users had a lower incidence rate of CVD compared to other statin users in general (28% lower), and simvastatin (29% lower) and pravastatin users (40% lower) in particular. The difference with atorvastatin was not statistically significant. Since this was not a prospective randomised study, there is the potential for unobserved risk factors to be responsible for some of the differences observed. CONCLUSION: Compared to other statin users without recent prior cardiovascular events, the incidence of fatal and non-fatal CVD in thisretrospective observational cohort study was 28% lower among rosuvastatin users.

(2009) "Comparison of incidences of cardiovascular events among new users of different statins: a retrospective observational cohort study." Heintjes, E.M. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 25(11): 2621-9   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Non-steroidal anti-inflammatory drugs and melanoma risk: large Dutch population-based case-control study." Joosse, A. , E.R. Koomen, et.al. J Invest Dermatol 129(11): 2620-7

(2009) "Non-steroidal anti-inflammatory drugs and melanoma risk: large Dutch population-based case-control study." Joosse, A. , E.R. Koomen, et.al. J Invest Dermatol 129(11): 2620-7 This case-control study investigates the potential chemoprophylactic properties of non-steroidal anti-inflammatory drugs (NSAIDs) on the incidence of cutaneous melanoma (CM). Data were extracted from the Dutch PHARMO pharmacy database and the PALGApathology database. Cases had a primary CM between 1991 and 2004, were >or=18 years, and were observed for 3 years in PHARMO before diagnosis. Controls were matched for date of birth, gender, and geographical region. NSAIDs and acetylsalicylic acids (ASAs) were analyzed separately. Adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariable logistic regression, and the results were stratified across gender. A total of 1,318 CM cases and 6,786 controls were eligible to enter the study. CM incidence was not significantly associated with ever ASA use (adjusted OR: 0.92, 95% CI: 0.76-1.12) or ever non-ASA NSAID use (adjusted OR: 1.10, 95% CI: 0.97-1.24). However, continuous use of low-dose ASAs was associated with a significant reduction of CM risk in women (adjusted OR: 0.54, 95% CI: 0.30-0.99) but not in men (OR: 1.01, 95% CI: 0.69-1.47). A significant trend (P=0.04) from no use, non-continuous use to continuous use was observed in women. Continuous use of low-dose ASAsmay be associated with a reduced incidence of CM in women, but not in men.

(2009) "Non-steroidal anti-inflammatory drugs and melanoma risk: large Dutch population-based case-control study." Joosse, A. , E.R. Koomen, et.al. J Invest Dermatol 129(11): 2620-7   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Melanoma incidence and exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers." Koomen, E.R. , R.M. Herings, et.al. Cancer Epidemiol 33(5): 391-5

(2009) "Melanoma incidence and exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers." Koomen, E.R. , R.M. Herings, et.al. Cancer Epidemiol 33(5): 391-5 A reduced incidence of nonmelanoma skin cancer among users of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARb) has been reported. A similar effect is suggested for cutaneous melanoma. We aimed to investigate the possible association between use of ACEi and ARb and the risk of cutaneous melanoma. A general population-based case control study with the PHARMO database, containing drug-dispensing records from community pharmacies and the national pathology database (PALGA) was conducted. Cases were patients with a primary cutaneous melanoma between January 1st 1991 and December 14th 2004, aged > or =18 years and having > or =3 years of follow-up prior to diagnosis. Finally, 1272 cases and 6520 matched controls were included. Multivariable conditional logistic regression showed no statistically significant associations between the incidence of melanoma and the use of ACEi (adjusted OR=1.0, 95%CI: 0.8-1.3) or ARb (adjusted OR=1.0, 95%CI: 0.7-1.5). Thus, in this study, the use of ACEi or ARb does not seem to protect against the development of cutaneous melanoma. However, we cannot exclude an association between ACEi and ARb exposure and an increased or decreased incidence of cutaneous melanoma.

(2009) "Melanoma incidence and exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers." Koomen, E.R. , R.M. Herings, et.al. Cancer Epidemiol 33(5): 391-5   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Does use of estrogens decrease the Breslow thickness of melanoma of the skin? Oral contraceptives and hormonal replacement therapy." Koomen, E.R. , A. Joosse, et.al. Melanoma Res 19(5): 327-32

(2009) "Does use of estrogens decrease the Breslow thickness of melanoma of the skin? Oral contraceptives and hormonal replacement therapy." Koomen, E.R. , A. Joosse, et.al. Melanoma Res 19(5): 327-32 Recently, we showed there was a cumulative dose-dependent association between the use of estrogens and the incidence of cutaneous melanoma (CM). This association was shown for both oral contraceptives (OC) and hormonal replacement therapy (HRT). Some in-vitro studies, however, have suggested a direct inhibitory effect on melanoma tumor growth. Therefore, the use of different types of estrogens, OC and HRT, may be associated with a decreased Breslow thickness. Consequently, the clinical impact of our earlier findings may be limited. In this study, we investigated whether estrogen use (0.5 year), OC or HRT, is associated with a decreased Breslow thickness. For this study, we linked the national Dutch pathology database (PALGA) to a pharmacy database(PHARMO). Cases were women with a primary CM between 1 January 1991 and 14 December 2004, aged > or =18 years and having > or =3 years of follow-up before diagnosis of CM. In total, 687 women with melanoma were included. Univariable linear regression analysis suggested a decreased Breslow thickness with the use of OC and HRT. Statistically significant interaction was observed between age and estrogen use (P<0.01) suggesting effect modification by age. However, in stratified multivariable analyses for different age groups (<45, 45-55, > or =55 years), no statistically significant associations between the use of OC or HRT and Breslow thickness were observed. In conclusion, an association between use of OC and HRT and Breslow thickness could not be confirmed.

(2009) "Does use of estrogens decrease the Breslow thickness of melanoma of the skin? Oral contraceptives and hormonal replacement therapy." Koomen, E.R. , A. Joosse, et.al. Melanoma Res 19(5): 327-32   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Current issues around the pharmacotherapy of ADHD in children and adults." Meijer, W.M. , A. Faber, et.al. Pharm World Sci 31(5): 509-16

(2009) "Current issues around the pharmacotherapy of ADHD in children and adults." Meijer, W.M. , A. Faber, et.al. Pharm World Sci 31(5): 509-16 BACKGROUND: New drugs and new formulations enter the growing market for ADHD medication. The growing awareness of possible persistence of ADHD impairment beyond childhood and adolescence resulting in increased pharmacotherapy of ADHD in adults, is also a good reason for making an inventory of the what is generally known about pharmacotherapy in ADHD. AIM: To discuss current issues in the possible pharmacotherapy treatment of ADHD in children, adolescents and adults with respect to the position of pharmacotherapy in ADHD treatment guidelines, the pharmacoepidemiological trends, and current concerns about the drugs used. METHODS: A search of the literature with an emphasis on the position of pharmacotherapy in ADHD treatment guidelines, the pharmacoepidemiological trends, and current concerns about the drugs used in pharmacotherapy. RESULTS: According to the guidelines, the treatment of ADHD in children consists of psychosocial interventions in combination with pharmacotherapy when needed. Stimulants are the first-choice drugs in the pharmacological treatment of ADHD in children despite a number of well known and frequently reported side effects like sleep disorders and loss of appetite. With regard to the treatment of adults, stimulant treatmentwas recommended as the first-choice pharmacotherapy in the single guideline available. Both in children and adults, there appears to be an additional though limited role for the nonadrenergic drug atomoxetine. The increase of ADHD medication use, in children, adolescents and in adults, can not only be interpreted as a sign of overdiagnosis of ADHD. Despite the frequent use of stimulants, there is still a lack of clarity on the effects of long-term use on growth and nutritional status of children. Cardiovascular effects of both stimulants and atomoxetine are rare but can be severe. The literature suggests that atomoxetine may be associated with suicidal ideation in children. CONCLUSION: Although pharmacotherapy is increasing common in the treatment of ADHD in both children and adults, there are still a lot of questions about side effects and how best to counter them. This suggests an important role for close monitoring of children and adults treated with stimulants or atomoxetine.

(2009) "Current issues around the pharmacotherapy of ADHD in children and adults." Meijer, W.M. , A. Faber, et.al. Pharm World Sci 31(5): 509-16   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Risk of hip/femur fracture after stroke: a population-based case-control study." Pouwels, S. , A. Lalmohamed, et.al. Stroke 40(10): 3281-5

(2009) "Risk of hip/femur fracture after stroke: a population-based case-control study." Pouwels, S. , A. Lalmohamed, et.al. Stroke 40(10): 3281-5 BACKGROUND AND PURPOSE: Stroke increases the risk of hip/femur fracture, as seen in several studies, although the time course of this increased risk remains unclear. Therefore, our purpose is to evaluate this risk and investigate the time course ofany elevated risk. METHODS: We conducted a case-control study using the Dutch PHARMO Record Linkage System database. Cases (n=6763) were patients with a first hip/femur fracture; controls were matched by age, sex, and region. Odds ratio (OR) for the riskof hip/femur fracture was derived using conditional logistic regression analysis, adjusted for disease and drug history. RESULTS: An increased risk of hip/femur fracture was observed in patients who experienced a stroke at any time before the index date(adjusted OR, 1.96; 95% CI, 1.65-2.33). The fracture risk was highest among patients who sustained a stroke within 3 months before the index date (adjusted OR, 3.35; 95% CI, 1.87-5.97) and among female patients (adjusted OR, 2.12; 95% CI, 1.73-2.59). The risk further increased among patients younger than 71 years (adjusted OR, 5.12; 95% CI, 3.00-8.75). Patients who had experienced a hemorrhagic stroke tended to be at a higher hip/femur fracture risk compared with those who had experienced an ischemic stroke. CONCLUSIONS: Stroke is associated with a 2.0-fold increase in the risk of hip/femur fracture. The risk was highest among patients younger than 71 years, females, and those whose stroke was more recent. Fall prevention programs, bone mineral density measurements, and use of bisphosphonates may be necessary to reduce the occurrence of hip/femur fractures during and after stroke rehabilitation.

(2009) "Risk of hip/femur fracture after stroke: a population-based case-control study." Pouwels, S. , A. Lalmohamed, et.al. Stroke 40(10): 3281-5   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Use of anti-depressants and the risk of fracture of the hip or femur." van den Brand, M.W. , M.M. Samson, et.al. Osteoporos Int 20(10): 1705-13

(2009) "Use of anti-depressants and the risk of fracture of the hip or femur." van den Brand, M.W. , M.M. Samson, et.al. Osteoporos Int 20(10): 1705-13 SUMMARY: Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. INTRODUCTION: Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. METHODS: A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. RESULTS: The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. CONCLUSION: Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

(2009) "Use of anti-depressants and the risk of fracture of the hip or femur." van den Brand, M.W. , M.M. Samson, et.al. Osteoporos Int 20(10): 1705-13   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors." van der Linden, M.W. , S. Gaugris, et.al. Pharmacoepidemiol Drug Saf 18(10): 880-90

(2009) "COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors." van der Linden, M.W. , S. Gaugris, et.al. Pharmacoepidemiol Drug Saf 18(10): 880-90 PURPOSE: To compare hospitalization rates for serious upper and lower gastrointestinal (GI) events between chronic and acute users of a traditional non-steroidal anti-inflammatory drugs (tNSAID) + proton pump inhibitor (PPI) and users of a COX-2 selective inhibitor (Coxib). METHODS: The PHARMO Record Linkage System, including linked drug-dispensing and hospital records of approximately 3 million individuals in the Netherlands was used. We selected new Coxib or tNSAID users (01/01/2000-31/12/2004) with > or =1 year history before the first NSAID dispensing and > or =1 year follow-up ending at the first hospitalization for GI event (the outcome), last dispensing, or end of the study period. Chronic users were patients who used any NSAIDs for > or =60 days during the first year (n = 58 770); others were acute users (n = 538 420). Multivariate analysis was performed by Poisson regression adjusted for gender, age, and duration of follow-up, tNSAID and Coxib dose, NSAID/PPI adherence, use of other gastroprotective agents, anticoagulants, acetaminophen, corticosteroids, and cardiovascular disease. RESULTS: The cohort included 23 999 new tNSAIDs + PPI users and 25 977 new Coxib users, with main characteristics: mean +/- SD age 58.1 +/- 15.5 vs. 56.7 +/-17.5; female 55.3% vs. 62.2%; duration of treatment (days): 137 +/- 217 vs. 138 +/- 179, respectively. Among acute users, adjusted hazard ratios (95% Confidence Interval) were 0.21 (0.14-0.32) for upper and 0.26 (0.16-0.42) for lower GI events, for Coxib versus tNSAIDs + PPI users. Among chronic users, these were 0.35 (0.22-0.55) for upper GI and 0.43 (0.25-0.75) for lower GI events. CONCLUSIONS: Coxib users had significantly lower rates of GI events. Further research should elucidate the possible impact of selection bias.

(2009) "COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors." van der Linden, M.W. , S. Gaugris, et.al. Pharmacoepidemiol Drug Saf 18(10): 880-90   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Psoriasis May Not be an Independent Risk Factor for Acute Ischemic Heart Disease Hospitalizations: Results of a Large Population-Based Dutch Cohort." Wakkee, M. , R.M. Herings, et.al. J Invest Dermatol

(2009) "Psoriasis May Not be an Independent Risk Factor for Acute Ischemic Heart Disease Hospitalizations: Results of a Large Population-Based Dutch Cohort." Wakkee, M. , R.M. Herings, et.al. J Invest Dermatol Although psoriasis has been associated with components of the metabolic syndrome, its association with myocardial infarction is less clear. A cohort study was conducted using hospital and pharmacy records of 2.5 million Dutch residents between 1997and 2008. The risk of ischemic heart disease (IHD) hospitalizations was compared between psoriasis patients and a matched reference cohort. Additional adjustments were made for healthcare consumption and use of cardiovascular drugs. A total of 15,820 psoriasis patients and 27,577 reference subjects were included, showing an incidence rate of 611 and 559 IHD per 100,000 person-years, respectively (P=0.066). The age- and gender-adjusted risk of IHD was comparable between both cohorts (hazard ratio (HR)=1.10, 95% confidence interval 0.99-1.23). Before cohort entry, psoriasis patients used more antihypertensive, antidiabetic, and lipid-lowering drugs and were more often hospitalized. Adjusting for these confounders decreased the HR for IHD, but it remainedcomparable between both populations. There was no different risk of IHD between the subgroup of patients who only used topicals versus those who received systemic therapies or inpatient care for their psoriasis. This study, therefore, suggests that psoriasis is not a clinically relevant risk factor for IHD hospitalizations on the population level.Journal of Investigative Dermatology advance online publication, 8 October 2009; doi:10.1038/jid.2009.321.

(2009) "Psoriasis May Not be an Independent Risk Factor for Acute Ischemic Heart Disease Hospitalizations: Results of a Large Population-Based Dutch Cohort." Wakkee, M. , R.M. Herings, et.al. J Invest Dermatol   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "New approaches to drug safety: a pharmacovigilance tool kit." Wise, L. , J. Parkinson, et.al. Nat Rev Drug Discov 8(10): 779-82

(2009) "New approaches to drug safety: a pharmacovigilance tool kit." Wise, L. , J. Parkinson, et.al. Nat Rev Drug Discov 8(10): 779-82 The importance of pharmacovigilance - the ongoing assessment of the safety of a marketed medicine - has been increasingly appreciated in recent years, owing in part to high-profile safety issues with widely used drugs. In response, strategies to improve the collection, integration and analysis of data related to post-marketing drug safety are being initiated or enhanced. In this article, we summarize the key tools that are available for pharmacovigilance, discuss which might be the most appropriateto use in different situations and consider the future directions of the field.

(2009) "New approaches to drug safety: a pharmacovigilance tool kit." Wise, L. , J. Parkinson, et.al. Nat Rev Drug Discov 8(10): 779-82   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Antipsychotic use and the risk of hip/femur fracture: a population-based case-control study." Pouwels, S. , T.P. van Staa, et.al. Osteoporos Int 20(9): 1499-506

(2009) "Antipsychotic use and the risk of hip/femur fracture: a population-based case-control study." Pouwels, S. , T.P. van Staa, et.al. Osteoporos Int 20(9): 1499-506 This case-control study showed that current use of conventional antipsychotics, but not atypical antipsychotics, seems to be associated with an increased risk of a hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. Furthermore, no evidence for a dose effect was found. INTRODUCTION: The aim of this study was to assess the risk of hip/femur fracture associated with antipsychotic use, with particular reference to any difference in risk with conventional versus atypical antipsychotics, dose, and pharmacological properties. METHODS: A case-control study was conducted using data from the PHARMO Record Linkage System among individuals aged 18 years and older between 1991 and 2002. Cases had a record ofa hip or femur fracture, while controls had no evidence of ever having sustained any fracture. RESULTS: Most cases were elderly (77.6% aged > or = 70 years). We found an increased risk for hip/femur fracture associated with the use of antipsychotic drugs. The risk for current users (OR(adj) 1.68 [1.43, 1.99]) was significantly greater than with past use (OR(adj) 1.33 [1.14, 1.56]; p = 0.036). Current use of conventional antipsychotics (OR(adj) 1.76 [1.48, 2.08]) but not atypical antipsychotics (OR(adj)0.83 [0.42, 1.65]) was associated with an increased risk. We did not find evidence for a dose effect. CONCLUSION: The use of conventional, but not atypical antipsychotics, seems to be associated with an increased risk of hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. However, the numbers of atypical antipsychotic users were small, and therefore this observation needs further attention in other study populations.

(2009) "Antipsychotic use and the risk of hip/femur fracture: a population-based case-control study." Pouwels, S. , T.P. van Staa, et.al. Osteoporos Int 20(9): 1499-506   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Effects of corticosteroid use on readmission in obstructive lung disease." Velthove, K.J. , P.C. Souverein, et.al. Respir Med

(2009) "Effects of corticosteroid use on readmission in obstructive lung disease." Velthove, K.J. , P.C. Souverein, et.al. Respir Med OBJECTIVE: Obstructive lung disease is a leading cause of morbidity and mortality worldwide. Some patients are readmitted, but currently predicting parameters for identifying these patients are lacking. The aim of this study was to quantify the incidence of readmission in chronic obstructive lung disease and to identify determinants for hospital readmission. METHODS: We conducted a cohort study using the PHARMO record linkage system, including demographic details and complete medication histories of more than two million community-dwelling residents in the Netherlands from 1985 onwards. Eligible patients were adult users of inhaled corticosteroids (ICS) with an admission for obstructive lung disease. The outcome parameter was readmission within afollow-up period of one year. RESULTS: We identified 605 ICS users with an admission for chronic obstructive lung disease, 132 of these patients were readmitted. Readmission was associated with a high Chronic Disease Score (adjusted HR 2.4; 95% CI 1.1-5.3). Patients using short courses of systemic corticosteroids only (adjusted HR 0.5; 95% CI 0.4-0.8) or combined with antibiotics (adjusted HR 0.4; 95% CI 0.2-0.6) were at decreased risk of readmission. The effect of high-dose ICS use varied over time. CONCLUSIONS: Treatment of exacerbations out of the hospital was associated with a decreased risk of readmission, while patients with multiple chronic diseases are at increased risk of readmission for obstructive lung disease. These patients should be educated and should be invited to consultation more often to be able to detect exacerbation in an early phase and start treatment as early as possible.

(2009) "Effects of corticosteroid use on readmission in obstructive lung disease." Velthove, K.J. , P.C. Souverein, et.al. Respir Med   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Estimated age- and sex-specific incidence and prevalence of dopamine agonist-treated hyperprolactinemia." Kars, M. , P.C. Souverein, et.al. J Clin Endocrinol Metab 94(8): 2729-34

(2009) "Estimated age- and sex-specific incidence and prevalence of dopamine agonist-treated hyperprolactinemia." Kars, M. , P.C. Souverein, et.al. J Clin Endocrinol Metab 94(8): 2729-34 CONTEXT: Few data exist on sex- and age-specific incidence and prevalence of idiopathic hyperprolactinemia and prolactinomas. OBJECTIVES: Our objective was to assess incidence and prevalence of dopamine agonist-treated hyperprolactinemia by age andsex. DESIGN: From the PHARMO network, we identified an open cohort of patients who were ever dispensed dopamine agonists for hyperprolactinemia. The network includes complete medication histories for more than 2 million community-dwelling residents. Prolonged use of low-dose dopamine agonist is a reliable marker for hyperprolactinemia, provided that use for Parkinson's disease and lactation withdrawal is excluded. Diagnoses were verified by prolactin values in a random subsample using the same network.RESULTS: We identified 11,314 subjects with at least one dispensing of dopamine agonist in the period 1996-2006, of whom 1607 subjects were considered to have dopamine agonist-treated hyperprolactinemia based on the prescribing pattern. The majority of patients were women (n = 1342, 84%). The diagnosis proved to be incorrect in only 1.5% of a random subsample. The estimated incidence rate of dopamine agonist-treated hyperprolactinemia for women was 8.7/100,000 person-years and for men 1.4/100,000 person-years. The highest incidence rate was found in women 25-34 yr of age: 23.9/100,000 person-years. The mean prevalence of ever treated female patients was almost five times higher (93.9/100,000) compared with male patients (19.6/100,000). CONCLUSION: Theincidence rates and the prevalence of dopamine agonist-treated hyperprolactinemia showed an overall preponderance in women, with a strong peak for women aged 25-34 yr. In men, no peak was found.

(2009) "Estimated age- and sex-specific incidence and prevalence of dopamine agonist-treated hyperprolactinemia." Kars, M. , P.C. Souverein, et.al. J Clin Endocrinol Metab 94(8): 2729-34   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Withdrawal of statins and risk of subarachnoid hemorrhage." Risselada, R. , H. Straatman, et.al. Stroke 40(8): 2887-92

(2009) "Withdrawal of statins and risk of subarachnoid hemorrhage." Risselada, R. , H. Straatman, et.al. Stroke 40(8): 2887-92 BACKGROUND AND PURPOSE: Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the riskof SAH. METHODS: We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls werematched to each case on age, gender, and calendar date. RESULTS: During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio forrecent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). CONCLUSIONS: Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawalincreased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.

(2009) "Withdrawal of statins and risk of subarachnoid hemorrhage." Risselada, R. , H. Straatman, et.al. Stroke 40(8): 2887-92   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Reasons for non-response in observational pharmacogenetic research." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. Pharmacoepidemiol Drug Saf 18(8): 665-71

(2009) "Reasons for non-response in observational pharmacogenetic research." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. Pharmacoepidemiol Drug Saf 18(8): 665-71 PURPOSE: In epidemiological studies, non-response may introduce bias and limit generalizability. In genetic pharmacoepidemiological research, collection of DNA might be a major reason for non-response. We determined reasons for non-response and compared characteristics of non-responders and responders in a pharmacogenetic case-control study. METHODS: Myocardial infarction (MI) cases and controls, who were antihypertensive drug users, were recruited through community pharmacies that participate in the Pharmaco-Morbidity-Record-Linkage-System (PHARMO). The PHARMO database comprises drug dispensing histories of about 2 000 000 subjects from a representative sample of Dutch community pharmacies linked to the national registry of hospital discharges. Independent samples t-test and ANOVA-statistics were used to analyse the differences in continuous variables between responders and non-responders. chi2 statistics and logistic regression were used to compare categorical variables. RESULTS: We approached1871 cases and 14 102 controls of whom 794 MI cases (42.4%) and 4997 controls (35.4%) responded. We could not approach 2194 patients of whom 63.1% had died and 31.2% moved to another pharmacy. Main reasons for non-response were health problems or hospital stays (16.2%, OR 1.47; 95%CI: 1.00-2.16). Other reasons were old age or dementia (16.9%, OR 1.82; 95%CI: 1.24-2.65). Only a small percentage (1.1%, OR 1.43; 95%CI: 0.41-5.03) mentioned DNA sampling as a reason. About 30% of the non-responders did not give a reason. Women were statistically significantly (p < 0.0005) less willing to participate than men (38.8% versus 31.3%). An association with age was also found (mean age 64.6 versus 66.5 yrs) (p < 0.0005). CONCLUSION: In a pharmacogenetic case-control study fear for genetic screening was not a major reported reason for non-response. Females were less willing to participate than males.

(2009) "Reasons for non-response in observational pharmacogenetic research." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. Pharmacoepidemiol Drug Saf 18(8): 665-71   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "The balance between severe cardiovascular and gastrointestinal events among users of selective and non-selective non-steroidal anti-inflammatory drugs." van der Linden, M.W. , S. van der Bij, et.al. Ann Rheum Dis 68(5): 668-73

(2009) "The balance between severe cardiovascular and gastrointestinal events among users of selective and non-selective non-steroidal anti-inflammatory drugs." van der Linden, M.W. , S. van der Bij, et.al. Ann Rheum Dis 68(5): 668-73 OBJECTIVE: To simultaneously assess cardiovascular (CV) and gastrointestinal (GI) risk with traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and cyclo-oxygenase 2 (COX-2) inhibitors. METHODS: Using the PHARMO Record Linkage System, including drug-dispensing and hospitalisation data of >2 million residents of The Netherlands, subjects with first hospitalisation for acute myocardial infarction (AMI), CV and GI events were identified. Use of COX-2 inhibitors and traditional non-selective NSAIDs was classified into remote, recent and current. Cases were matched to controls in a 1:4 ratio on age and event date. Multivariate analyses adjusted for gender, history of hospitalisations and medications. RESULTS: Compared to remote use, AMI risk was increased among current users of COX-2 inhibitors combined (adjusted odds ratio (OR) 1.73, 95% CI 1.37 to 2.19) and tNSAIDs combined (OR 1.41, 95% CI 1.23 to 1.61). AMI risk with celecoxib (OR 2.53, 95% CI 1.53 to 4.18), rofecoxib (OR 1.60, 95% CI 1.22to 2.10), ibuprofen (OR 1.56, 95% CI 1.19 to 2.05) and diclofenac (OR 1.51, 95% CI 1.22 to 1.87) was significantly increased. CV risk with current use of individual COX-2 inhibitors and tNSAIDs was significantly increased (OR from 1.17 to 1.64), as wasGI risk with current use of rofecoxib (OR 1.99, 95% CI 1.51 to 2.63), naproxen (OR 4.44, 95% CI 3.36 to 5.86), ibuprofen (OR 1.90, 95% CI 1.40 to 2.58), diclofenac (OR 4.77, 95% CI 3.94 to 5.76), other tNSAIDs (OR 2.59, 95% CI 2.08 to 3.21), but not celecoxib (OR 1.36, 95% CI 0.70 to 2.66). Compared to current use of celecoxib and AMI risk was significantly decreased with current use of naproxen (OR 0.48, 95% CI 0.26 to 0.87) only. GI risk was increased with current naproxen (OR 3.26, 95% CI 1.59 to 6.70) and diclofenac (OR 3.50, 95% CI 1.76 to 6.98). CONCLUSIONS: AMI and CV risk increased similarly with individual COX-2 inhibitors and tNSAIDs, whereas GI risk was found to be greater with naproxen and diclofenac. Residual confounding and "channelling"cannot be excluded.

(2009) "The balance between severe cardiovascular and gastrointestinal events among users of selective and non-selective non-steroidal anti-inflammatory drugs." van der Linden, M.W. , S. van der Bij, et.al. Ann Rheum Dis 68(5): 668-73   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Recruitment of participants through community pharmacies for a pharmacogenetic study of antihypertensive drug treatment." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. Pharm World Sci 31(2): 158-64

(2009) "Recruitment of participants through community pharmacies for a pharmacogenetic study of antihypertensive drug treatment." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. Pharm World Sci 31(2): 158-64 OBJECTIVE: To describe the design, recruitment and baseline characteristics of participants in a community pharmacy based pharmacogenetic study of antihypertensive drug treatment. SETTING: Participants enrolled from the population-based Pharmaco-Morbidity Record Linkage System. METHOD: We designed a nested case-control study in which we will assess whether specific genetic polymorphisms modify the effect of antihypertensive drugs on the risk of myocardial infarction. In this study, cases (myocardial infarction) and controls were recruited through community pharmacies that participate in PHARMO. The PHARMO database comprises drug dispensing histories of about 2,000,000 subjects from a representative sample of Dutch community pharmacies linked to the national registrations of hospital discharges. RESULTS: In total we selected 31010 patients (2777 cases and 28233 controls) from the PHARMO database, of whom 15973 (1871 cases, 14102 controls) were approached through their community pharmacy. Overall response rate was 36.3% (n = 5791, 794 cases, 4997 controls), whereas 32.1% (n = 5126, 701 cases, 4425 controls) gave informed consent to genotype their DNA. As expected, several cardiovascular risk factors such as smoking, body mass index, hypercholesterolemia, and diabetes mellitus were more common in cases than in controls. CONCLUSION: Furthermore, cases more often used beta-blockers and calcium-antagonists, whereas controls more often used thiazide diuretics, ACE-inhibitors, and angiotensin-II receptor blockers. We have demonstrated that it is feasible to select patients from a coded database for a pharmacogenetic study and to approach them through community pharmacies, achieving reasonable response rates and without violating privacy rules.

(2009) "Recruitment of participants through community pharmacies for a pharmacogenetic study of antihypertensive drug treatment." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. Pharm World Sci 31(2): 158-64   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Does the length of the first antidepressant treatment episode influence risk and time to a second episode?." Gardarsdottir, H. , E.C. van Geffen, et.al. J Clin Psychopharmacol 29(1): 69-72

(2009) "Does the length of the first antidepressant treatment episode influence risk and time to a second episode?." Gardarsdottir, H. , E.C. van Geffen, et.al. J Clin Psychopharmacol 29(1): 69-72 Antidepressant treatment in primary care is inconsistent with treatment recommendations, and many patients discontinue treatment within 6 months. How this affects treatment outcomes is unknown. The aim of this study was to assess how length of the first antidepressant episode influences risk and time to a second treatment episode within 5 years.The study population included 9423 adults (67% women; mean age, 47.3 years) who initiated selective serotonin reuptake inhibitor use in 1998 or 1999. Basedon the length of the first antidepressant treatment episode, patients were divided into early discontinuers (<6 months), continuing users (6-12 months), and persistent users (>12 months). The Cox proportional hazards model was used to estimate risk ratios (RRs) for the association between the length of the first antidepressant treatment episode and time to reinitiating antidepressant treatment.Time to a second treatment episode did not differ significantly between continuing users and early discontinuers (RR, 0.99; 95% confidence interval, 0.92-1.07). Persistent users showed a higher risk of experiencing a second treatment episode than early discontinuers (RR, 1.23; 95% confidence interval, 1.15-1.32).In conclusion, the risk of experiencing a second antidepressant treatment episode did not differ for those who used antidepressants for 6 to 12 months and those who discontinued early. In general, there is limited information on how length of an antidepressant treatment episode influences the risk of reinitiating treatment of patients in primary care. More research is needed to investigate the effectiveness of antidepressant drug treatment patterns in preventing relapse or recurrence in primary care populations.

(2009) "Does the length of the first antidepressant treatment episode influence risk and time to a second episode?." Gardarsdottir, H. , E.C. van Geffen, et.al. J Clin Psychopharmacol 29(1): 69-72   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study." Koomen, E.R. , A. Joosse, et.al. Ann Oncol 20(2): 358-64

(2009) "Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study." Koomen, E.R. , A. Joosse, et.al. Ann Oncol 20(2): 358-64 BACKGROUND: Multiple studies showed conflicting results on the association between oral contraceptive (OC) use and the development of cutaneous melanoma (CM). We investigated the association between estrogen use and CM incidence. PATIENTS AND METHODS: Data from PHARMO Pharmacy database and PALGA, the pathology database in The Netherlands, were linked. Women, >or=18 years, with a pathology report of a primary CM from 1 January 1991 to 14 December 2004 and >or=3 years of follow-up before CM diagnosiswere eligible cases. Controls were matched for age and geographic region. Multivariate logistic regression was used to calculate adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between CM incidence and estrogen use, OCs andhormonal replacement therapy (HRT), separately. RESULTS: In total, 778 cases and 4072 controls were included. CM risk was significantly associated with estrogen use (>or=0.5 year; adjusted OR = 1.42, 95% CI 1.19-1.69). This effect was cumulative dose dependent (P trend < 0.001). CM risk was also significantly associated with the use of HRT (>or=0.5 year: OR = 2.08; 95% CI 1.37-3.14) and OC (>or=0.5 year: OR = 1.28; 95% CI 1.06-1.54). CONCLUSION: Our study suggests a cumulative dose-dependent increasedrisk of CM with the use of estrogens.

(2009) "Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study." Koomen, E.R. , A. Joosse, et.al. Ann Oncol 20(2): 358-64   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Impact of osteoporosis treatment adherence on fracture rates in North America and Europe." Siris, E.S. , P.L. Selby, et.al. Am J Med 122(2 Suppl): S3-13

(2009) "Impact of osteoporosis treatment adherence on fracture rates in North America and Europe." Siris, E.S. , P.L. Selby, et.al. Am J Med 122(2 Suppl): S3-13 Fragility fractures associated with osteoporosis constitute a significant public health concern. Clinical trials have shown that a variety of agents--bisphosphonates, raloxifene, calcitonin, hormone replacement therapy, teriparatide, and strontium ranelate--can reduce the risk of osteoporosis-related fragility fractures. However, low levels of compliance and persistence in the real-life setting mean that efficacy benefits observed in clinical trials with these agents may not translate into equivalent effectiveness in daily practice. The aim of this review is to provide a comprehensive evaluation of compliance and persistence data from retrospective/observational studies, with particular reference to studies that consider the effects on fracture rates. PubMed of the National Center for Biotechnology Information (NCBI) and Web of Science databases were searched for publications detailing observational or retrospective analyses of adherence, compliance, and persistence with osteoporosis therapies. In addition, authors provided relevant studies that were not retrieved using the search criteria. In total, 17 unique publications were identified. Analysis of the publications indicated that low compliance and persistence rates for osteoporosis therapiesin the real-life setting result in increased rates of fragility fractures. The results emphasize the importance of good treatment compliance and persistence with osteoporosis therapies in order to achieve a significant therapeutic benefit and thereby reduce the burden that osteoporosis and associated fractures place on individuals and healthcare systems.

(2009) "Impact of osteoporosis treatment adherence on fracture rates in North America and Europe." Siris, E.S. , P.L. Selby, et.al. Am J Med 122(2 Suppl): S3-13   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Gastroprotection among new chronic users of non-steroidal anti-inflammatory drugs: a study of utilization and adherence in The Netherlands." Van der Linden, M.W. , S. Gaugris, et.al. Curr Med Res Opin 25(1): 195-204

(2009) "Gastroprotection among new chronic users of non-steroidal anti-inflammatory drugs: a study of utilization and adherence in The Netherlands." Van der Linden, M.W. , S. Gaugris, et.al. Curr Med Res Opin 25(1): 195-204 OBJECTIVE: To describe the use of gastroprotection (GP) among new chronic users of NSAIDs in the Netherlands by gastrointestinal (GI) risk factor (RF) score. METHODS: Data for this retrospective follow-up study were extracted from the PHARMO database. We selected new chronic users of COX-2 inhibitors (coxibs) or traditional NSAIDs (tNSAIDs) between 1st January 2000 and 31st December 2004. GP strategies were defined as: use of proton pump inhibitors (PPI), coxibs or both. GI RF score at index date was based on: history of GI drug use, high dose of NSAIDs, age > 60 years, use of corticosteroids/anticoagulants/SSRIs, rheumatoid arthritis, heart failure or diabetes, with each condition accounting for one factor. Switching was assessed among those with> or = 1 GI RF during the first year of follow-up. RESULTS: Among 58,770 new chronic NSAID users at index date, 80% used tNSAIDs alone, 8% used tNSAID + PPI, 10% used a coxib alone and 2% used coxib + PPI. Mean (SD) number of GI RF among these groups was 1.6 (2.1), 3.1 (1.3), 1.5 (1.5) and 2.8 (1.3), respectively. Among 48 390 patients (82.3%) with a GI RF score of > or = 1, 20.9% used a GP strategy, this increased with number of GI RFs. Within the first year, 5.3% (n = 2067) and 4.8%(n = 1 843) of tNSAID users with > or = 1 GI RF switched to tNSAID+PPI and coxib alone, respectively. CONCLUSIONS: Gastroprotection in users of tNSAIDs was inadequate. Over 80% of NSAID users with > or = 1 GI RF did not receive any gastroprotection, and even when prescribed, a PPI is used only half the time. More research should show if gastroprotection was used for prevention.

(2009) "Gastroprotection among new chronic users of non-steroidal anti-inflammatory drugs: a study of utilization and adherence in The Netherlands." Van der Linden, M.W. , S. Gaugris, et.al. Curr Med Res Opin 25(1): 195-204   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Interaction between the Gly460Trp alpha-adducin gene variant and diuretics on the risk of myocardial infarction." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. J Hypertens 27(1): 61-8

(2009) "Interaction between the Gly460Trp alpha-adducin gene variant and diuretics on the risk of myocardial infarction." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. J Hypertens 27(1): 61-8 INTRODUCTION: The Gly460Trp variant of the alpha-adducin gene has been associated with the salt-sensitive and diuretic responsive form of hypertension. OBJECTIVE: The aim of the study was to determine whether the alpha-adducin 460Trp variant allelemodifies the risk-lowering effect of diuretics on myocardial infarction (MI). DESIGN, SETTING AND PARTICIPANTS: In a population-based registry of pharmacy records linked to hospital discharge records (PHARMO), we used a nested case-control design. We selected patients hospitalized for MI as cases if they had at least one prescription for antihypertensive drugs in the 3 months prior to their first MI and were registered in PHARMO for at least 1 year. Controls that were matched on age, sex, region and calendar date, met the same eligibility criteria as the patients, but were not hospitalized for MI. Only current users of antihypertensive drugs in whom the Gly460Trp polymorphism was genotyped were included for this study. Logistic regression analysis wasused to calculate odds ratio (OR), synergy indices, 95% confidence intervals (CIs) and to adjust for the potential confounding factors high cholesterol, smoking, BMI, diabetes, physical activity, alcohol use, use of loop diuretics, coumarins, antiplatelet drugs, ischemic heart disease and number of antihypertensive drugs. RESULTS: The study included 613 patients and 3627 controls. Compared with users of other antihypertensives, the risk of MI was significantly lower among users of thiazide diuretics (OR0.71, 95% CI 0.55-0.92). Among patients with the adducin variant the risk of MI was similar among thiazide users as compared with users of other antihypertensives (OR 0.88, 95% CI 0.58-1.33), whereas among wild-type carriers this risk was significantlylower (OR 0.62, 95% CI 0.44-0.87). The interaction between current use of diuretics and the alpha-adducin polymorphism was not statistically significantly increased on the multiplicative scale (synergy index 1.41, 95% CI 0.91-2.17). In sensitivity analyses, we found a nonsignificant trend towards a difference between patients who used potassium-sparing diuretics (synergy index 0.98, 95% CI 0.45-2.12) and patients who did not use potassium-sparing diuretics (synergy index 1.60, 95% CI 0.98-2.60) and a statistically significant difference between patients on monotherapy (synergy index 0.69, 95% CI 0.30-1.59) and those on combination therapy (synergy index 1.90, 95% CI 1.04-3.47). CONCLUSION: This study suggests that the alpha-adducin gene does not play an important role in modifying the risk of nonfatal MI associated with the use of thiazide diuretics.

(2009) "Interaction between the Gly460Trp alpha-adducin gene variant and diuretics on the risk of myocardial infarction." van Wieren-de Wijer, D.B. , A.H. Maitland-van der Zee, et.al. J Hypertens 27(1): 61-8   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "A Semantic Approach for the Homogeneous Identification of Events in Eight Patient Databases: A Contribution to the European eu-ADR Project." Avillach, P. , F. Mougin, et.al. Stud Health Technol Inform 150(): 190-4

(2009) "A Semantic Approach for the Homogeneous Identification of Events in Eight Patient Databases: A Contribution to the European eu-ADR Project." Avillach, P. , F. Mougin, et.al. Stud Health Technol Inform 150(): 190-4 The overall objective of the eu-ADR project is the design, development, and validation of a computerised system that exploits data from electronic health records and biomedical databases for the early detection of adverse drug reactions. Eight different databases, containing health records of more than 30 million European citizens, are involved in the project. Unique queries cannot be performed across different databases because of their heterogeneity: Medical record and Claims databases, four different terminologies for coding diagnoses, and two languages for the information described in free text. The aim of our study was to provide database owners with a common basis for the construction of their queries. Using the UMLS, we provided a list of medical concepts, with their corresponding terms and codes in the four terminologies, which should be considered to retrieve the relevant information for the events of interest from the databases.

(2009) "A Semantic Approach for the Homogeneous Identification of Events in Eight Patient Databases: A Contribution to the European eu-ADR Project." Avillach, P. , F. Mougin, et.al. Stud Health Technol Inform 150(): 190-4   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Topical corticosteroids and the risk of diabetes mellitus: a nested case-control study in the Netherlands." van der Linden, M.W. , F.J. Penning-van Beest, et.al. Drug Saf 32(6): 527-37

(2009) "Topical corticosteroids and the risk of diabetes mellitus: a nested case-control study in the Netherlands." van der Linden, M.W. , F.J. Penning-van Beest, et.al. Drug Saf 32(6): 527-37 The relationship between topical corticosteroid use, potency, treatment duration, concomitant exposure to systemic corticosteroids, and risk of diabetes has been incompletely studied. To investigate an association between intense, longstanding topical corticosteroid use and diabetes mellitus. Data for this nested case-control study were obtained from the PHARMO Record Linkage System, including linked drug dispensing and hospital records of >2.5 million individuals in defined areas of the Netherlands. Users of topical corticosteroids during 1992-2004, without diabetes, with >/=2 topical corticosteroid dispensings and >/=4 years of follow-up were selected. Diabetes onset was defined as first occurrence (index date) of an antidiabetic drug dispensingor hospitalization for diabetes. Cases were matched 1 :::: 4 by age and sex to controls, with >/=2 topical corticosteroid dispensings and similar follow-up duration. Use of topical corticosteroids and systemic corticosteroids and/or inhaled corticosteroids as co-medication was classified as current, recent and past/never (4 years ago, respectively). Multivariate regression analyses were adjusted for co-medication and co-morbidity. Among 192 893 incident topical corticosteroidusers, 2212 developed diabetes and could be matched to 8582 controls. Current topical corticosteroid use was associated with an (unadjusted) 1.24-fold increased risk of diabetes (unadjusted OR 1.24; 95% CI 1.11, 1.40). The odds ratio increased to 1.32 with >180 days of topical corticosteroid use (95% CI 1.14, 1.54) and to 1.44 with a cumulative topical corticosteroid load (combined potency and amount) of 731-1460 mg (95% CI 1.21, 1.72). Among past/never users of systemic corticosteroids and/or inhaledcorticosteroids, current use of topical corticosteroids remained associated with a 1.27-fold increased diabetes risk (unadjusted OR 1.27; 95% CI 1.10, 1.47) compared with past users of topical corticosteroids. An increased risk of new-onset diabetes maybe an important consideration in the treatment of patients with topical corticosteroids, especially when intense skin treatment is needed. Future studies are needed to endorse these findings in other populations.

(2009) "Topical corticosteroids and the risk of diabetes mellitus: a nested case-control study in the Netherlands." van der Linden, M.W. , F.J. Penning-van Beest, et.al. Drug Saf 32(6): 527-37   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Large Impact of Antidiabetic Drug Treatment and Hospitalizations on Economic Burden of Diabetes Mellitus in The Netherlands during 2000 to 2004." van der Linden, M.W. , A.W. Plat, et.al. Value Health

(2009) "Large Impact of Antidiabetic Drug Treatment and Hospitalizations on Economic Burden of Diabetes Mellitus in The Netherlands during 2000 to 2004." van der Linden, M.W. , A.W. Plat, et.al. Value Health ABSTRACT Objective: To estimate the burden of diabetes mellitus (DM) and its complications in The Netherlands. Methods: The PHARMO Record Linkage System comprised among others linked drug dispensing, hospital and clinical laboratory data from approximately 2.5 million individuals in The Netherlands. Patients with DM (type 1 and type 2) were included in the study cohort from 2000 to 2004 if they used antidiabetic drugs or had HbA1c >/= 6.5 mmol/L or had a hospitalization for DM or a diabetic complication in the measurement year or in the preceding year. Controls, defined as subjects without a diagnosis of DM and/or subjects not prescribed glucose-lowering medication, were 1:1 matched to patients with diabetes, on birth year, zip code, and gender. Complications (hospitalizations and dispensings for cardiovascular disease/eye problems/amputations) were classified into stages. Complications attributed to DM were estimated as complication stages 1 and 2 among patients minus those among controls. Drugcosts were extrapolated to The Netherlands by direct standardization. Results: Among the total population in The Netherlands, the prevalence of DM increased from 2.8% in 2000 to 4.0% in 2004. Severe cardiovascular complications attributed to DM increasedfrom 18,000 to 39,000 patients. Per DM patient the cost of direct treatment attributed to DM increased from Euro 974 in 2000 to Euro 1283 in 2004. Per 100 members of the total population, this increase was from Euro 2764 in 2000 to Euro 5140 in 2004. Most of these costs (65% in 2004) were because of hospitalizations. Conclusion: Drug treatment, hospitalizations, and cost attributed to diabetes mellitus have almost doubled between 2000 and 2004, but so did the "background" costs in the general population, perhaps because of preventive efforts.

(2009) "Large Impact of Antidiabetic Drug Treatment and Hospitalizations on Economic Burden of Diabetes Mellitus in The Netherlands during 2000 to 2004." van der Linden, M.W. , A.W. Plat, et.al. Value Health   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2009) "Psoriasis may not be an independent predictor for the use of cardiovascular and anti-diabetic drugs: a 5-year prevalence study." Wakkee, M. , W. Meijer, et.al. Acta Derm Venereol 89(5): 476-83

(2009) "Psoriasis may not be an independent predictor for the use of cardiovascular and anti-diabetic drugs: a 5-year prevalence study." Wakkee, M. , W. Meijer, et.al. Acta Derm Venereol 89(5): 476-83 Most studies investigating the association between psoriasis and cardiovascular disease have shown a significant relationship. This comparison study investigated the association between psoriasis and prevalent use of cardiovascular drugs. Drug exposure data for 1998 to 2006 were extracted from the Dutch PHARMO-Record Linkage System database. Psoriasis patients were selected using an algorithm of hospitalization and drug dispensing records specific for psoriasis and matched with controls for gender,age and time-period. From the records of 2.5 million Dutch residents, 9,804 (0.4%) psoriasis patients and 15,288 (0.6%) controls were selected. Psoriasis patients used significantly more anti-hypertensives, anti-coagulant and anti-platelet agents, digoxin, nitrates, lipid-lowering and anti-diabetic drugs than the reference population during a 5-year period observation. In a multiple linear regression model adjusting for the number of unique drugs used, psoriasis was no longer significantly associated with any of these drug classes. Psoriasis patients used more cardiovascular-related drugs, but surveillance bias appears to affect this association considerably.

(2009) "Psoriasis may not be an independent predictor for the use of cardiovascular and anti-diabetic drugs: a 5-year prevalence study." Wakkee, M. , W. Meijer, et.al. Acta Derm Venereol 89(5): 476-83   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study." Roede, B.M. , P. Bresser, et.al. Thorax 63(11): 968-73

(2008) "Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study." Roede, B.M. , P. Bresser, et.al. Thorax 63(11): 968-73 OBJECTIVES: The risk of a subsequent exacerbation after treatment of an exacerbation with oral corticosteroids without (OS) or with (OSA) antibiotics was evaluated in a historical population based cohort study comprising patients using maintenance medication for obstructive lung disease. METHODS: The Pharmo database includes drug dispensing records of more than 2 million subjects in The Netherlands. Eligible were patients >or=50 years who in 2003 were dispensed >or=2 prescriptions of daily used inhaled beta(2) agonists, anticholinergics and/or corticosteroids, and experienced at least one exacerbation before 1 January 2006. Exacerbation was defined as a prescription of OS or OSA. The times to the second and third exacerbations were compared usingKaplan-Meier survival analysis. Independent determinants of new exacerbations were identified using multivariable Cox recurrent event survival analysis. RESULTS: Of 49,599 patients using maintenance medication, 18 928 had at least one exacerbation; in 52%, antibiotics had been added. The OS and OSA groups were comparable for potential confounding factors. Median time to the second exacerbation was 321 days in the OS group and 418 days in the OSA group (p<0.001); and between the second and third exacerbation 127 vs 240 days (p<0.001). The protective effect of OSA was most pronounced during the first 3 months following treatment (hazard ratio (HR) 0.62; 99% CI 0.60 to 0.65). In the OSA group, mortality during follow-up was lower (HR 0.82; 99% CI 0.66 to0.98). CONCLUSION: Treatment with antibiotics in addition to oral corticosteroids was associated with a longer time to the next exacerbation, and a decreased risk of developing a new exacerbation.

(2008) "Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study." Roede, B.M. , P. Bresser, et.al. Thorax 63(11): 968-73   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Antibiotics at COPD exacerbations: the debate continues." Wedzicha, J.A. Thorax 63(11): 940-2

(2008) "Antibiotics at COPD exacerbations: the debate continues." Wedzicha, J.A. Thorax 63(11): 940-2 No abstract available

(2008) "Antibiotics at COPD exacerbations: the debate continues." Wedzicha, J.A. Thorax 63(11): 940-2   Ask PHARMO for copy   Sent reference to friend

(2008) "Effect on non-persistent use of oral glucose-lowering drugs on HbA1c goal attainment." Penning-van Beest, F.J.A. , S. van der Bij, et.al. Curr Med Res Opin 24(9): 2523-2529

(2008) "Effect on non-persistent use of oral glucose-lowering drugs on HbA1c goal attainment." Penning-van Beest, F.J.A. , S. van der Bij, et.al. Curr Med Res Opin 24(9): 2523-2529 Objectives: The aim of this study was to quantify the effect of non-persistence with oral glucose-lowering drugs (OGLD) on HbA1c goal attainment (< 7%) in daily practice.

(2008) "Effect on non-persistent use of oral glucose-lowering drugs on HbA1c goal attainment." Penning-van Beest, F.J.A. , S. van der Bij, et.al. Curr Med Res Opin 24(9): 2523-2529   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Effectiveness of statins in the reduction of the risk of myocardial infarction is modified by the GNB3 C825T variant." Peters, B.J. , A.H. Maitland-van der Zee, et.al. Pharmacogenet Genomics 18(7): 631-6

(2008) "Effectiveness of statins in the reduction of the risk of myocardial infarction is modified by the GNB3 C825T variant." Peters, B.J. , A.H. Maitland-van der Zee, et.al. Pharmacogenet Genomics 18(7): 631-6 INTRODUCTION: The GNB3 C825T polymorphism has been shown to affect lipid parameters, atherosclerosis progression, and incidence of myocardial infarction (MI). Therefore, we assessed whether the effectiveness of statins in reducing the risk of MI wasmodified by the GNB3 C825T polymorphism. METHODS: In a population-based registry of pharmacy records linked to hospital discharge records (PHARMO), we used a nested case-control design. We selected patients hospitalized for MI as cases if they used antihypertensive drugs and had a diagnosis of hypercholesterolemia before their first MI. Controls met the same eligibility criteria, but were not hospitalized for MI. Logistic regression analysis was used to calculate odds ratios (OR) and synergy index withcorresponding 95% confidence intervals (CI), and to adjust for potential confounding factors. RESULTS: We included 459 cases and 1805 controls. The risk of MI was significantly lower among participants exposed to statins compared with participants not exposed to statins (adjusted OR: 0.37, 95% CI: 0.29-0.47). The GNB3T allele was associated with a reduced risk of MI (adjusted OR: 0.74, 95% CI: 0.60-0.92). Among homozygous wild-type (CC) individuals (n=1119), exposure to statins was associated with a lower risk of MI (OR: 0.48, 95% CI: 0.34-0.67). However, T allele carriers (CT and TT) who used statins had an even stronger reduced risk of MI (OR: 0.27, 95% CI: 0.19-0.39). Overall, the interaction between exposure to statins and the GNB3 C825T polymorphism was significantly increased on the multiplicative scale (synergy index: 1.67, 95% CI: 1.06-2.65). CONCLUSION: Our findings show that T allele carriers of the GNB3 C825T polymorphism have less risk of MI and are more likely to benefit from statin therapy in a hypercholesterolemic population of antihypertensive drug users.

(2008) "Effectiveness of statins in the reduction of the risk of myocardial infarction is modified by the GNB3 C825T variant." Peters, B.J. , A.H. Maitland-van der Zee, et.al. Pharmacogenet Genomics 18(7): 631-6   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Differences in the pattern of antibiotic prescription profile and recurrence rate for possible urinary tract infections in women with and without diabetes." Schneeberger, C. , R.P. Stolk, et.al. Diabetes Care 31(7): 1380-5

(2008) "Differences in the pattern of antibiotic prescription profile and recurrence rate for possible urinary tract infections in women with and without diabetes." Schneeberger, C. , R.P. Stolk, et.al. Diabetes Care 31(7): 1380-5 OBJECTIVE: Women with diabetes have a high incidence and complication rate of urinary tract infections (UTIs). Our aims were to compare current treatment strategies with respect to recurrence rates in women with diabetes with those without diabetes.RESEARCH DESIGN AND METHODS: We used a Dutch registration database containing pharmacy dispensing data. A total of 10,366 women with diabetes (17.5% premenopausal) (aged < or =55 years) and 200,258 women without diabetes (68% premenopausal) who receiveda first course of trimethoprim, nitrofurantoin, fosfomycin, or norfloxacin between January 1999 and January 2006 were included. We compared short (< or or =5 days) with long (>5 days) prescriptions and norfloxacin with trimethoprim, nitrofurantoin, andfosfomycin. A recurrence was defined as a second prescription for one of the above-mentioned agents or a first with amoxicillin (clavulanic acid), fluoroquinolones, or trimethoprim/sulfamethoxazole between 6 and 30 days after inclusion. RESULTS: Premenopausal women with diabetes more often received a long (26.5 vs. 19.2%; P < 0.001) treatment with norfloxacin (10.7 vs. 6.2%; P < 0.001) but still had a higher recurrence rate (16.1 vs. 12.2%; P = 0.003) compared with those without diabetes. Similarly, postmenopausal women with diabetes more often received a longer (32.8 vs. 28.8%; P < 0.001) treatment with norfloxacin (15.2 vs. 12.7%; P < 0.001) but had a higher recurrence rate (19.1 vs. 16.4%; P < 0.001) compared with those without diabetes. CONCLUSIONS: Despite the fact that patients with diabetes more often received longer and more potent initial treatment than patients without diabetes, pre- and postmenopausal women with diabetes more often had recurrences of their UTIs.

(2008) "Differences in the pattern of antibiotic prescription profile and recurrence rate for possible urinary tract infections in women with and without diabetes." Schneeberger, C. , R.P. Stolk, et.al. Diabetes Care 31(7): 1380-5   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Substantial increase in the use of adjuvant systemic treatment for early stage breast cancer reflects changes in guidelines in the period 1990-2006 in the southeastern Netherlands." Sukel, M.P. , L.V. van de Poll-Franse, et.al. Eur J Cancer

(2008) "Substantial increase in the use of adjuvant systemic treatment for early stage breast cancer reflects changes in guidelines in the period 1990-2006 in the southeastern Netherlands." Sukel, M.P. , L.V. van de Poll-Franse, et.al. Eur J Cancer BACKGROUND: This study evaluated trends in adjuvant systemic treatment among breast cancer patients and analyzed the factors on which treatment choice was based. PATIENTS AND METHODS: Patients diagnosed with early stage breast cancer in 1990-2006 were selected from the registry of the Comprehensive Cancer Centre South (n= 8261). The probability of receiving therapy was determined per characteristic for the periods 1990-1997, 1998-2001 and 2002-2006, separately. RESULTS: The use of any adjuvant systemic treatment increased from 37% in 1990-1997 to 51% in 1998-2001 and 53% in 2002-2006 (p for trend < 0.0001). In the period 1990-1997, lymph node status (positive vs. negative: probability ratio (PR) =25.8; 95% CI, 16.5-40.4) and age ( 60 vs. 35 years:PR=0.01; 95% CI, 0.00-0.02) were the main determinants of the likelihood of receiving chemotherapy. From 1998 onwards, age remained the most important factor in decreasing the likelihood of receiving chemotherapy. During 1990-1997 the use of hormonal therapy was mainly determined by positive lymph node status (PR=35; 95% CI, 25-49) and age ( 70 vs. 35 years: PR=9.3; 95% CI, 4.4-20), whereas positive hormone receptor status mainly affected hormonal therapy use (PR=17; 95% CI, 10-28) in the period 2002-2006. Marked differences were observed between hospitals in the adoption of adjuvant systemic treatment for node-negative patients. CONCLUSIONS: The impact of patient and tumour characteristics on treatment choice varied over time, reflecting major changes in the Dutch treatment guidelines. Patients older than 70 years received almost no chemotherapy.

(2008) "Substantial increase in the use of adjuvant systemic treatment for early stage breast cancer reflects changes in guidelines in the period 1990-2006 in the southeastern Netherlands." Sukel, M.P. , L.V. van de Poll-Franse, et.al. Eur J Cancer   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "LDL-C reductions and goal attainment among naive statin users in the Netherlands: real life results." Heintjes, E.M. , M.W. Hirsch, et.al. Curr Med Res Opin 24(8): 2241-2250

(2008) "LDL-C reductions and goal attainment among naive statin users in the Netherlands: real life results." Heintjes, E.M. , M.W. Hirsch, et.al. Curr Med Res Opin 24(8): 2241-2250 OBJECTIVE: The effectiveness of statin therapy in a real life setting may differ from that in clinical trials, as physicians make non-randomised treatment decisions for patients with less uniform and possibly different characteristics. We thereforeperformed a study to compare the effectiveness of different statins and doses in routine clinical practice with respect to total serum cholesterol and LDL-cholesterol (LDL-C) reduction and goal attainment according to European guidelines on the prevention of cardiovascular disease (CVD).RESEARCH DESIGN AND METHODS: Naive statin users starting treatment in 2003 and 2004 with LDL-C measurements at baseline and between 30 and 365 days after start of treatment were extracted from the PHARMO database. Duringtreatment with their initial statin dose LDL-C reduction and attainment of cholesterol goals were compared between different statins and doses. RESULTS: Of 2303 identified naive patients, approximately 30% were allocated to the high CVD-risk group. Average LDL-C reductions were 48%, 42%, 39%, and 32% at mean doses of 11 mg rosuvastatin, 17 mg atorvastatin, 22 mg simvastatin and 35 mg pravastatin, respectively. The proportion of patients attaining cholesterol goals was 75% for rosuvastatin, 68% for atorvastatin, 56% for simvastatin, and 42% for pravastatin. Dose comparisons showed greater LDL-C reduction and increased goal attainment for rosuvastatin 10 mg compared to other statins at most doses (adjusted p < 0.05).CONCLUSIONS: In a real life setting,both LDL-C reduction and the proportion of patients attaining cholesterol goals appear to be significantly increased among users of rosuvastatin compared to other statins. These results confirm and extend reported clinical trial results to a real world setting.

(2008) "LDL-C reductions and goal attainment among naive statin users in the Netherlands: real life results." Heintjes, E.M. , M.W. Hirsch, et.al. Curr Med Res Opin 24(8): 2241-2250   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Influence of antidepressants on glycaemic control in patients with diabetes mellitus." Knol, M.J. , H.J. Derijks, et.al. Pharmacoepidemiol Drug Saf 17(6): 577-86

(2008) "Influence of antidepressants on glycaemic control in patients with diabetes mellitus." Knol, M.J. , H.J. Derijks, et.al. Pharmacoepidemiol Drug Saf 17(6): 577-86 PURPOSE: Anecdotal evidence suggests that antidepressants (ADs) may complicate glycaemic control. The objective of this longitudinal study was to investigate the influence of ADs on glycaemic control within diabetes patients. METHODS: From the pharmacy registry database PHARMO, we selected insulin users who did not use oral antidiabetics. The study population comprised: 133 patients with at least 12 months insulin use before and 6 months during an AD episode, including 56 patients with an additional 6 months of insulin use after the AD episode; 180 patients with 24 months insulin use without an AD episode. Glycaemic control was measured as the amount of insulin used, which was calculated intra-individually in 3-month periods. We stratified for selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). RESULTS: Mean age (s.d.) of the subjects was 53.9 (19) years; 46.9% were men. Overall, the amount of insulin used did not change during or after AD use. No-AD users showedan increase of 16% in amount of insulin used over a period of 2 years (p < 0.001). SSRI users showed a decrease of 13% in amount of insulin used during the AD episode (p = 0.029), while no change was seen in TCA users. Notable was the large intra- and interindividual variation in amount of insulin used across all groups. CONCLUSIONS: Overall, AD use did not influence glycaemic control in diabetes patients. The tendency for a difference between SSRIs and TCAs is suggestive for a pharmacologic effect ofADs rather than a general effect of depression on glycaemic control.

(2008) "Influence of antidepressants on glycaemic control in patients with diabetes mellitus." Knol, M.J. , H.J. Derijks, et.al. Pharmacoepidemiol Drug Saf 17(6): 577-86   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Association Between Hospitalization and Discontinuity of Medication Therapy Used in the Community Setting in the Netherlands (July/August)." Stuffken, R. , E.R. Heerdink, et.al. Ann Pharmacother 42(July/Augus): 933-939

(2008) "Association Between Hospitalization and Discontinuity of Medication Therapy Used in the Community Setting in the Netherlands (July/August)." Stuffken, R. , E.R. Heerdink, et.al. Ann Pharmacother 42(July/Augus): 933-939 BACKGROUND: Transitions from one healthcare setting to another often parallel transitions in health status and can be associated with intentional as well as unintentional changes in patient care. Hospitalization may put patients at increased risk ofdiscontinuity of medication use. OBJECTIVE: To assess the association between hospitalization and medication therapy discontinuities. METHODS: A retrospective follow-up study was conducted using data obtained from the PHARMO Record Linkage System. We randomly selected patients who had been hospitalized (index date) between July 1, 1998, and June 30, 2000. For each hospitalized patient, one nonhospitalized patient was matched for age, sex, and geographic area, and was assigned the same index date as thecorresponding hospitalized patient. The primary study outcome was the incidence of one or more medication therapy discontinuities at the index date and at several control moments during a period of 18 months before and 18 months after hospital admission. We defined 4 mutually exclusive types of discontinuities: generic-brand substitution, product substitution, therapeutic switch, and stop. RESULTS: The study population comprised 8681 hospitalized patients and an equal number of age/sex-matched nonhospitalized patients. Of all hospitalized patients on drug therapy at the index date (n = 5265) 3322 (63.1%) had one or more medication therapy discontinuities at the index date, compared with 1390 (33.5%) of the nonhospitalized patients taking medication atthe index date (n = 4147; RR 1.82; 95% CI 1.71 to 1.94). The highest risk estimate was found for therapeutic switch (RR 5.34; 95% CI 3.93 to 7.26), followed by product substitution (RR 2.32; 95% CI 1.88 to 2.86) and stop (RR 1.98; 95% CI 1.85 to 2.13).There was no significantly increased risk for generic-brand name substitution (RR 0.87; 95% CI 0.72 to 1.06). CONCLUSIONS: Hospitalization is associated with discontinuity of drugs used in the community setting. Medication stops were observed most frequently. Hospital safety programs should focus attention on medication therapy discontinuities at times of transition to ensure continuity of care in relation to drug therapy.

(2008) "Association Between Hospitalization and Discontinuity of Medication Therapy Used in the Community Setting in the Netherlands (July/August)." Stuffken, R. , E.R. Heerdink, et.al. Ann Pharmacother 42(July/Augus): 933-939   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis." Penning-van Beest, F.J. , J.A. Erkens, et.al. Curr Med Res Opin 24(5): 1337-1344

(2008) "Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis." Penning-van Beest, F.J. , J.A. Erkens, et.al. Curr Med Res Opin 24(5): 1337-1344 OBJECTIVE: To identify determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis. By considering the year of the introduction of weekly bisphosphonates important additional information is obtained. METHODS: New female users of daily or weekly alendronate or risedronate between 1999 and 2004, aged >or= 45 years were identified from PHARMO RLS, including drug-dispensing and hospitalisation data of > 2 million residents of the Netherlands. One-year compliance with bisphosphonates was measured using the Medication Possession Ratio (MPR). To identify determinants of non-compliance, non-compliant women (MPR < 50%) were compared to compliant women (MPR >or= 80%). The effect of patient age, prescriber, initial dosing regimen, gastrointestinal adverse events, co-medication and fractures on non-compliance was investigated. RESULTS: The study cohort included 8822 new users of bisphosphonates, of whom 5079 (58%) were compliant and 2720 (31%) were non-compliant after 1 year. Only 1023 women (11%) had a MPR between >or= 50% and < 80%. Daily dosing at start, increased number of co-medications and new use of intestinal agents in the year after starting bisphosphonates were independently associated with an increased odds of non-compliance. In contrast, higher age, first prescription from a specialist, osteoporosis related hospitalisation and use of NSAIDs in the year preceding bisphosphonate therapy decreased the odds of non-compliance. CONCLUSION: This study revealed severaldeterminants of non-compliance with bisphosphonates, the best controllable being the type of initial bisphosphonate, with daily dosing leading to more non-compliance than weekly dosing. However, compliance for both regimens is suboptimal, pointing to anunmet medical need.

(2008) "Determinants of non-compliance with bisphosphonates in women with postmenopausal osteoporosis." Penning-van Beest, F.J. , J.A. Erkens, et.al. Curr Med Res Opin 24(5): 1337-1344   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Extent of uncontrolled disease and associated medical costs in severe asthma--a PHARMO study." Breekveldt-Postma, N.S. , J.A. Erkens, et.al. Curr Med Res Opin 24(4): 975-983

(2008) "Extent of uncontrolled disease and associated medical costs in severe asthma--a PHARMO study." Breekveldt-Postma, N.S. , J.A. Erkens, et.al. Curr Med Res Opin 24(4): 975-983 OBJECTIVE: Asthma is a major public health problem with considerable economic impact. The highest costs being observed in patients with severe asthma. Furthermore, despite the use of recommended therapies, asthma control can still be poor. Therefore, the objective of this study was to assess the extent of uncontrolled disease and associated medical costs in severe asthma. METHODS: The PHARMO Record Linkage System includes among others drug dispensing and hospitalizations for > or = 2 million subjects in The Netherlands. Severe asthma patients used long-acting beta-agonists and inhaled corticosteroids for over 200 days and short-acting beta-agonists for at least 100 days in 2004. Severe uncontrolled asthma was defined as a hospitalization for asthma or use of multiple short courses of oral corticosteroids assessed in 2004. Reimbursed costs of asthma drugs and hospitalizations were calculated during this year. A matched nested-case control study was performed to identify treatment-related risk factors for uncontrolled disease. Information on clinical diagnosis of (severity of) asthma was not available. RESULTS: About 17% of patients with severe asthma aged 12-49 years (N = 1158) showed lack of control. Excess drug costs for severe uncontrolled asthma with hospitalization mounted up to 700 Euro per patient per year and 300 Euro per patient per year for patients without hospitalization. Including hospital admission costs, excess costs mounted up to over 10,000 Euro per patient per year. Lack of control did not seem to be caused by under-treatment. CONCLUSION: Poor control of severe asthma leads to disproportionately increased direct costs compared to severe controlled asthma, especially when hospital admission is required.

(2008) "Extent of uncontrolled disease and associated medical costs in severe asthma--a PHARMO study." Breekveldt-Postma, N.S. , J.A. Erkens, et.al. Curr Med Res Opin 24(4): 975-983   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Treatment with inhaled corticosteroids in asthma is too often discontinued." Breekveldt-Postma, N.S. , J. Koerselman, et.al. Pharmacoepidemiol Drug Saf 17(4): 411-422

(2008) "Treatment with inhaled corticosteroids in asthma is too often discontinued." Breekveldt-Postma, N.S. , J. Koerselman, et.al. Pharmacoepidemiol Drug Saf 17(4): 411-422 PURPOSE: To study persistence with inhaled corticosteroids (ICS) and its determinants in asthma-patients. METHODS: From the PHARMO database, asthma-patients (age < 35 years) with a first dispensing for ICS in 1999-2002 and >/= 2 dispensings in the first year were included. Persistence during the first year was defined as the number of days from start to time of first failure to continue renewal of the initial ICS. Potential determinants of persistence were assessed at ICS-start and 1 year before. RESULTS: The study-cohort included 5563 new users of single ICS and 297 of fixed-combined ICS. Less than 10% of patients using single ICS and 15% of patients using fixed-combined ICS were persistent at 1 year. Similar persistence-rates were observed whenstratified for age (children/adolescents: 0-18 years and adults: 19-34 years). Increased persistence with single ICS was observed with the type of ICS (budesonide), prescriber (specialist), prior use of long-acting beta-agonists, previous hospitalizationfor asthma, metered-dose inhaler, low starting-dose and once-daily dosing regimen at start. Persistence with fixed combined ICS-treatment increased with younger age and was decreased in patients having high starting-dose of ICS and prior use of antibiotics. CONCLUSION: New users of both single and fixed combined ICS have alarming low persistence rates with ICS-treatment in the first year of follow-up. Persistence was mainly related to patient factors, such as severity of disease, and to treatment-related factors, such as once-daily dosing frequency. Copyright (c) 2008 John Wiley & Sons, Ltd.

(2008) "Treatment with inhaled corticosteroids in asthma is too often discontinued." Breekveldt-Postma, N.S. , J. Koerselman, et.al. Pharmacoepidemiol Drug Saf 17(4): 411-422   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Effect of persistent use of antihypertensives on blood pressure goal attainment." Breekveldt-Postma, N.S. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 24(4): 1025-1031

(2008) "Effect of persistent use of antihypertensives on blood pressure goal attainment." Breekveldt-Postma, N.S. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 24(4): 1025-1031 OBJECTIVE: Discontinuation rates with antihypertensive drugs in real life are high. The present study investigates the relationship between persistence with antihypertensive drugs (AHT) and blood pressure (BP) goal attainment in daily clinical practice. METHODS: In the PHARMO Record Linkage System, which includes drug dispensing and hospital records for > 2 million inhabitants in the Netherlands, new users of AHT > or = 18 years were identified for the period 1999-2004. Patients with elevated bloodpressure (systolic BP > or = 140 and/or diastolic BP > or = 90 mmHg) within 6 months prior to onset of AHT treatment and a BP measurement within 6-12 months of treatment onset were included in the study cohort. Persistent AHT use was determined by summing the number of days of continuous treatment (gap between dispensings < 30 days) from start of treatment onwards. Patients with a BP below 140/90 mmHg at the first BP measurement within 6-12 months of treatment onset were defined as having attained goal. RESULTS: The study included 1271 patients with a mean systolic BP of 174 +/- 22 mmHg and a mean diastolic BP of 100 +/- 12 mmHg. Persistent AHT use was associated with a 40% increased chance of BP goal attainment (RR(adj) = 1.41; 95% CI: 1.08-1.85) after adjustment for gender, age, systolic blood pressure at start, and time to the BP measurement. CONCLUSION: Persistent use of AHT leads to increased blood pressure goal attainment in daily clinical practice.

(2008) "Effect of persistent use of antihypertensives on blood pressure goal attainment." Breekveldt-Postma, N.S. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 24(4): 1025-1031   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Use of beta2 agonists and risk of acute myocardial infarction in patients with hypertension." de Vries, F. , S. Pouwels, et.al. Br J Clin Pharmacol 65(4): 580-6

(2008) "Use of beta2 agonists and risk of acute myocardial infarction in patients with hypertension." de Vries, F. , S. Pouwels, et.al. Br J Clin Pharmacol 65(4): 580-6 WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Use of beta(2) agonists has been associated with tachycardia, an abnormal ECG and atrial fibrillation. * Previous observational studies of the association between use of beta(2) agonists and the risk of acute myocardial infarction (MI) have demonstrated conflicting results. * Instead of a causal effect, the positive association between beta(2) agonist use and MI may be explained by latent ischaemic heart disease, which has symptoms that appear similar torespiratory complaints in chronic obstructive pulmonary disease. WHAT THIS STUDY ADDS: * The majority of beta(2) agonist users in our study population did not have an increased risk of nonfatal acute MI. * Only patients with ischaemic heart disease and who had recently started beta(2) agonists had an increased risk of acute MI. * It is likely that this increased risk was related to latent cardiovascular disease rather than direct effects of beta(2) agonists. AIM: Observational retrospective studies of the association between use of beta(2) agonists and the risk of acute myocardial infarction (MI) have demonstrated conflicting results, particularly among first-time users. The aim of this study was to examine the association between beta(2) agonist use and first nonfatal acute MI. METHODS: We conducted a case-control study (2476 cases) nested in a cohort of antihypertensive drug users in the Dutch PHARMO RLS database. PHARMO RLS consists of drug dispensing linked to the national hospitalizations register. Each case of nonfatal acute MI was matched with up to 12 control patients by gender, age and region. Drug and disease history and the severity of the underlying respiratory disease were adjusted for. RESULTS: Risk of acute MI was increased in currentbeta(2) agonist users [crude odds ratio (OR) 1.36, 95% confidence interval (CI) 1.15, 1.61]. However, this excess risk was reduced after adjustment for severity of asthma and chronic obstructive pulmonary disease (adjusted OR 1.18, 95% CI 0.93, 1.49). The risk was highest in patients with ischaemic heart disease and low cumulative dose of beta(2) agonists (adjusted OR 2.47, 95% CI 1.60, 3.82). CONCLUSION: Most users of beta(2) agonists did not have an increased risk of acute MI. Only patients with ischaemic heart disease with low cumulative exposure to beta(2) agonists had an increased risk of acute MI. It is likely that this increased risk was related to latent cardiovascular disease rather than to the direct effects of beta(2) agonists.

(2008) "Use of beta2 agonists and risk of acute myocardial infarction in patients with hypertension." de Vries, F. , S. Pouwels, et.al. Br J Clin Pharmacol 65(4): 580-6   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case-control study." Derijks, H.J. , E.R. Heerdink, et.al. Pharmacoepidemiol Drug Saf 17(4): 336-44

(2008) "The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case-control study." Derijks, H.J. , E.R. Heerdink, et.al. Pharmacoepidemiol Drug Saf 17(4): 336-44 PURPOSE: Hypoglycaemia is a limiting factor for glycaemic management of diabetes with intensive insulin and/or oral antidiabetic drug (OAD) regimen. Case reports suggest that antidepressants may interfere with blood glucose metabolism in patients with diabetes mellitus potentially increasing the risk of clinically relevant hypoglycaemia. Comorbid depression treated with antidepressants could therefore further complicate glycaemic control. We have carried out a nested case-control study among diabetic patients to assess the risk of hypoglycaemia requiring hospitalisation associated with the use of antidepressants. METHODS: Diabetic patients treated with insulin and/or OADs were selected from the Dutch Pharmo system. Exposure to antidepressants wasthe primary determinant investigated. Use of antidepressants was further subclassified based on the receptor binding profile to investigate whether specific pharmacological properties could explain a potential influence on glucose homeostasis. Conditional logistic regression was used to estimate odds ratios and to adjust for confounding factors. RESULTS: From the base cohort (40 600 patients), 549 (1.35%) cases were identified and 1897 controls were selected. Current use of any antidepressant was not associated with a significantly higher risk of hypoglycaemia requiring hospitalisation (OR: 1.36 (95%CI: 0.84-2.20)). A trend for a higher risk on hypoglycaemia was identified for antidepressants with high affinity for the serotonin reuptake transporter. The risk on severe hypoglycaemia was increased after 3 years of use (OR: 2.75 (95%CI: 1.31-5.77)). CONCLUSIONS: It is important for diabetic patients using antidepressants for more than 3 years to pay attention for symptoms of hypoglycaemia and strict blood glucose self-monitoring. Copyright (c) 2008 John Wiley & Sons, Ltd.

(2008) "The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case-control study." Derijks, H.J. , E.R. Heerdink, et.al. Pharmacoepidemiol Drug Saf 17(4): 336-44   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Antipsychotic drug use and risk of pneumonia in elderly people." Knol, W. , R.J. van Marum, et.al. J Am Geriatr Soc 56(4): 661-6

(2008) "Antipsychotic drug use and risk of pneumonia in elderly people." Knol, W. , R.J. van Marum, et.al. J Am Geriatr Soc 56(4): 661-6 OBJECTIVES: To investigate the association between antipsychotic drug use and risk of pneumonia in elderly people. DESIGN: A nested case-control analysis. SETTING: Data were used from the PHARMO database, which collates information from community pharmacies and hospital discharge records. PARTICIPANTS: A cohort of 22,944 elderly people with at least one antipsychotic prescription; 543 cases of hospital admission for pneumonia were identified. Cases were compared with four randomly selected controlsmatched on index date. MEASUREMENTS: Antipsychotic drug use in the year before the index date was classified as current, recent, or past use. No prescription for an antipsychotic in the year before the index date was classified as no use. The strength of the association between use of antipsychotics and the development of pneumonia was estimated using multivariate logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Current use of antipsychoticswas associated with an almost 60% increase in the risk of pneumonia (adjusted OR=1.6, 95% CI=1.3-2.1). The risk was highest during the first week after initiation of an antipsychotic (adjusted OR=4.5, 95% CI=2.8-7.3). Similar associations were found after exclusion of elderly people with a diagnosis of delirium. Current users of atypical agents showed a higher risk of pneumonia (adjusted OR=3.1, 95% CI=1.9-5.1) than users of conventional agents (adjusted OR=1.5, 95% CI=1.2-1.9). There was no clear dose-response relationship. CONCLUSION: Use of antipsychotics in elderly people is associated with greater risk of pneumonia. This risk is highest shortly after the initiation of treatment, with the greatest increase in risk found for atypical antipsychotics.

(2008) "Antipsychotic drug use and risk of pneumonia in elderly people." Knol, W. , R.J. van Marum, et.al. J Am Geriatr Soc 56(4): 661-6   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Loss of treatment benefit due to low compliance with bisphosphonate therapy." Penning-van Beest, F.J. , J.A. Erkens, et.al. Osteoporos Int 19(4): 511-7

(2008) "Loss of treatment benefit due to low compliance with bisphosphonate therapy." Penning-van Beest, F.J. , J.A. Erkens, et.al. Osteoporos Int 19(4): 511-7 SUMMARY: Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR >or=80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit. INTRODUCTION: Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit. METHODS: New female users of alendronate or risedronate between 1999-2004, aged >or=45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of >or= 2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression. RESULTS: The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR >or= 80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR >or= 90%. CONCLUSIONS: These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit.

(2008) "Loss of treatment benefit due to low compliance with bisphosphonate therapy." Penning-van Beest, F.J. , J.A. Erkens, et.al. Osteoporos Int 19(4): 511-7   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Risk of major bleeding during concomitant use of antibiotic drugs and coumarin anticoagulants." Penning-van Beest, F.J. , J. Koerselman, et.al. J Thromb Haemost 6(2): 284-90

(2008) "Risk of major bleeding during concomitant use of antibiotic drugs and coumarin anticoagulants." Penning-van Beest, F.J. , J. Koerselman, et.al. J Thromb Haemost 6(2): 284-90 Background: Coumarin anticoagulants are prone to drug-drug interactions. For example, antibiotic drugs may enhance the anticoagulant effect of coumarins. However, whether such interactions are associated with an increased risk of bleeding, and if so, how frequently this occurs remains unknown. Objective: To assess the risk of major bleeding associated with the concomitant use of antibiotic drugs and coumarin anticoagulant therapy. Methods: We analyzed a retrospective cohort study including all users of acenocoumarol or phenprocoumon in the PHARMO Record Linkage System (age range: 40-80 years). All patients were followed up until end of last coumarin treatment, hospitalization for bleeding, death, or end of study period. For each patient, the number of days on either coumarins alone, or on coumarins in combination with antibiotic drugs was determined. From these data, the relative risks of major bleeding were calculated. Results: A total of 52 102 users of acenocoumarol and 7885 users of phenprocoumon met the inclusion criteria of our study cohort and contributed 139 159 person-years of follow-up. During follow-up, 838 patients (1.4%) were hospitalized for a bleeding while taking coumarins. Of the 62 different antibiotics taken by study members,19 were associated with a bleeding episode. Of these, 10 were associated with a statistically significant increased bleeding risk. The relative risk of bleeding was three to five for doxycycline, amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, cotrimoxazole, azithromycin and pheneticillin, nine for tetracycline and 43 for cefradine and neomycin. Conclusion: Based on relative risks and incidence of use, amoxicillin (alone or with clavulanic acid) and doxycycline are the main antibiotic drugs associated with major bleeding when used in combination with coumarin.

(2008) "Risk of major bleeding during concomitant use of antibiotic drugs and coumarin anticoagulants." Penning-van Beest, F.J. , J. Koerselman, et.al. J Thromb Haemost 6(2): 284-90   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "The effect of discontinuation of antihypertensives on the risk of acute myocardial infarction and stroke." Breekveldt-Postma, N.S. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 24(1): 121-7

(2008) "The effect of discontinuation of antihypertensives on the risk of acute myocardial infarction and stroke." Breekveldt-Postma, N.S. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 24(1): 121-7 OBJECTIVE: Adherence to antihypertensive drug treatment is suboptimal. The present study investigates the effect of early treatment discontinuation with antihypertensive drugs on the risk of acute myocardial infarction (AMI) or stroke in daily clinical practice. METHODS: In the PHARMO Record Linkage System, which includes all records of drug dispensings and hospitalisations for > or = 2 million subjects in the Netherlands, new users of antihypertensive (AHT) drugs > or = 18 years of age were studied during the period 1 January 1993 - 1 October 2002 to determine the risk of AMI or stroke related to persistence with AHT. Patients were initially followed for 2 years to determine persistence with AHT, and then for a further 2 years or until the firsthospital admission for AMI or stroke, death, or end of the study period. Patients using AHT for secondary prevention of cardiovascular disease were excluded from the study cohort. RESULTS: The study cohort included 77 193 AHT users. The percentage of non-persistent patients was 55% at 2 years, with the lowest non-persistence rates for angiotensin-receptor blockers (ARBs) and ACE-inhibitors (40%) and the highest rates for beta-blockers, calcium-channel blockers (CCBs) and diuretics (54-61%). Non-persistent AHT use was associated with a 15% increased risk of AMI (RR 1.15; 95% CI 1.00-1.33) and a 28% increased risk of stroke (RR 1.28; 95% CI 1.15-1.45). CONCLUSIONS: The results of this study show that in daily clinical practice early discontinuation of antihypertensive drug treatment in primary prevention increases the risk of subsequent AMI or stroke.

(2008) "The effect of discontinuation of antihypertensives on the risk of acute myocardial infarction and stroke." Breekveldt-Postma, N.S. , F.J. Penning-van Beest, et.al. Curr Med Res Opin 24(1): 121-7   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Use of inhaled corticosteroids and the risk of non-fatal acute myocardial infarction." de Vries, F. , S. Pouwels, et.al. J Hypertens 26(1): 124-129

(2008) "Use of inhaled corticosteroids and the risk of non-fatal acute myocardial infarction." de Vries, F. , S. Pouwels, et.al. J Hypertens 26(1): 124-129 BACKGROUND: Use of inhaled corticosteroids may reduce the risk of acute myocardial infarction (MI) through reductions in systemic inflammation and C-reactive protein. OBJECTIVES: To examine the association between the use of inhaled corticosteroidsand the risk of non-fatal acute MI. METHODS: In the Dutch PHARMO record linkage system database, we conducted a case-control study (2476 MI cases), nested in a cohort of antihypertensive drug users. The use of inhaled corticosteroids 100 days before theindex date was compared with never use. We adjusted the analyses for the severity of the underlying respiratory disease and general drug and disease history. RESULTS: We found that the use of inhaled corticosteroids was not associated with a decreased risk of non-fatal MI in antihypertensive drug users after adjustment for the underlying respiratory disease severity, adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 0.97-1.57. A higher daily dose (adjusted OR 1.82, 95% CI 0.80-4.13) and longerduration of use (adjusted OR 1.28, 95% CI 0.90-1.81) were not associated with a decreased risk of non-fatal MI. An inhaled corticosteroid dispensing in the 30 days before the index date was not protective but resulted in a 1.7-fold increased risk of non-fatal MI. CONCLUSION: Our results do not support the hypothesis that inhaled corticosteroids protect against the risk of non-fatal MI by a reduction of systemic inflammation.

(2008) "Use of inhaled corticosteroids and the risk of non-fatal acute myocardial infarction." de Vries, F. , S. Pouwels, et.al. J Hypertens 26(1): 124-129   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Incidence of cardiovascular events in breast cancer patients receiving chemotherapy in clinical practice." Sukel, M.P. , N.S. Breekveldt-Postma, et.al. Pharmacoepidemiol Drug Saf 17(2): 125-134

(2008) "Incidence of cardiovascular events in breast cancer patients receiving chemotherapy in clinical practice." Sukel, M.P. , N.S. Breekveldt-Postma, et.al. Pharmacoepidemiol Drug Saf 17(2): 125-134 PURPOSE: To assess the incidence of cardiovascular events among breast cancer patients after chemotherapy. METHODS: Women >/=18 years with a breast tumour who received chemotherapy in 1992-2003 were selected from the PHARMO RLS. Chemotherapy with anthracyclines, a combination of anthracyclines and taxanes or second line treatment with trastuzumab was classified as cardiotoxic. Cardiovascular events were determined based on drug use and hospital admissions. Incidence rates of cardiovascular events and hazard ratios (HR) for the cardiotoxic versus non-cardiotoxic chemotherapy group were assessed during the first year and total follow-up. RESULTS: Of 648 patients with breast cancer included in the study cohort, 353 (54%) received cardiotoxic chemotherapy. At baseline, patients who received cardiotoxic chemotherapy compared with patients receiving non-cardiotoxic chemotherapy, received less anticoagulants/haemostatics (5 vs. 11%; p = 0.012) and had been less often hospitalised for cardiovascular disease (1 vs. 5%; p = 0.007) 2 years before the cohort entry date. After 1-year follow-up, the incidence rate of cardiovascular events was 69/1000 person years (py) for patients with cardiotoxic chemotherapy and 98/1000 py for patients with non-cardiotoxicchemotherapy, which did not differ significantly (HR 0.74 95% confidence interval (CI): 0.39, 1.41). After total follow-up, this was 81/1000 py for patients with cardiotoxic and 92/1000 py for patients with non-cardiotoxic chemotherapy (HR 0.81, 95%CI: 0.54, 1.20). CONCLUSIONS: This study showed similar cardiovascular incidence rates during follow-up for breast cancer patients treated with cardiotoxic and non-cardiotoxic chemotherapy. Specialists seemed to take pre-existing cardiovascular diseases intoaccount when treating the breast cancer patient. Copyright (c) 2007 John Wiley & Sons, Ltd.

(2008) "Incidence of cardiovascular events in breast cancer patients receiving chemotherapy in clinical practice." Sukel, M.P. , N.S. Breekveldt-Postma, et.al. Pharmacoepidemiol Drug Saf 17(2): 125-134   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Large-scale stopping and switching treatment with COX-2 inhibitors after the rofecoxib withdrawal." Sukel, M.P. , M.W. van der Linden, et.al. Pharmacoepidemiol Drug Saf 17(1): 9-19

(2008) "Large-scale stopping and switching treatment with COX-2 inhibitors after the rofecoxib withdrawal." Sukel, M.P. , M.W. van der Linden, et.al. Pharmacoepidemiol Drug Saf 17(1): 9-19 PURPOSE: To compare treatment changes after the rofecoxib withdrawal with changes occurring normally and to re-assess 12 months afterwards. METHODS: The PHARMO database comprised medication and hospital discharge records of over 3 million inhabitants in the Netherlands. The Study cohort included chronic coxib users with a coxib prescription on 30th September 2004; the Reference cohort others with a coxib prescription on 1st June 2004. Initial treatment changes were based on first new prescription since cohort entry. Twelve-month changes were studied within the Study cohort only. RESULTS: The Study cohort (n = 6974) and Reference cohort (n = 5393) had similar demographics, stratified on type of coxib. In the Study cohort, 3341 (48%) initially stopped coxibs, of whom 1121 (16%) stopped all analgesic, versus 13 and 5% in the Reference cohort (p < 0.001). Among 'other coxib' users 32% stopped coxibs, and 15% stopped all analgesics, versus 14% and 4%, p < 0.001 in the Reference cohort. Among those whostopped coxibs, 34% switched to non-selective non-steroidal anti-inflammatory drug (nsNSAID) without PPI, 21% to nsNSAID with PPI, and 45% stopped NSAID treatment (Reference cohort: 35, 20, and 44%, respectively). These rates for 'other coxib users' were: switching to nsNSAID without PPI 23% (Study Cohort) versus 35% (Reference Cohort), 13 versus 28%, and 64 versus 37% respectively (p < 0.001). Twelve months later, stopping NSAID increased to 43%, stopping all analgesics to 32%. Rheumatologists continued coxibs more frequently than other caregivers (87, 65, 54%, respectively). CONCLUSIONS: The rofecoxib withdrawal resulted in a large proportion of patients who discontinued analgesic treatment altogether regardless of original coxib therapy. Copyright(c) 2007 John Wiley & Sons, Ltd.

(2008) "Large-scale stopping and switching treatment with COX-2 inhibitors after the rofecoxib withdrawal." Sukel, M.P. , M.W. van der Linden, et.al. Pharmacoepidemiol Drug Saf 17(1): 9-19   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "A cross-national study of the persistence of antihypertensive medication use in the elderly." van Wijk, B.L. , W.H. Shrank, et.al. J Hypertens 26(1): 145-153

(2008) "A cross-national study of the persistence of antihypertensive medication use in the elderly." van Wijk, B.L. , W.H. Shrank, et.al. J Hypertens 26(1): 145-153 INTRODUCTION: Little is known about cross-national comparisons of the persistence of antihypertensive medication treatment, trends in persistence, and factors associated with persistence. The aim of this study was to describe and compare patterns ofuse of antihypertensive drugs in a population of elderly patients in the United States (Pennsylvania), Canada (British Columbia) and the Netherlands. METHODS: A retrospective cohort study of Medicare enrollees in a state pharmacy assistance programme inPennsylvania (USA), residents from British Columbia (Canada) and residents from the Netherlands registered in the PHARMO database was conducted. Each population included patients 65 years and older who were initiated on blood pressure-lowering treatmentbetween 1 January 1998 and 31 December 2003 and who had continuous follow-up for at least 365 days. In these populations, the proportion of patients with at least 180 consecutive days without medication available (non-persistence) were identified as were predictors of non-persistence using Cox proportional hazards. RESULTS: A total of 9664 Medicare enrollees (USA), 25 377 residents from British Columbia and 24 603 residents from the Netherlands were evaluated. During the first year after the initiationof treatment, the percentage of patients with at least 180 days without medication was 23.3% in Pennsylvania, 23.4% in British Columbia and 24.0% in the Netherlands. After 6 years, these percentages increased to 41.1, 36.3 and 38.2%, respectively. Factors associated with non-persistence were different between the three countries. CONCLUSION: Despite differences in factors associated with persistence, non-persistence patterns are strikingly similar in all three populations. This suggests that the problem of non-persistence transcends international boundaries.

(2008) "A cross-national study of the persistence of antihypertensive medication use in the elderly." van Wijk, B.L. , W.H. Shrank, et.al. J Hypertens 26(1): 145-153   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Relationship between duration of compliant bisphosphonate use and the risk of osteoporotic fractures." Meijer, W.M. , F.J. Beest, et.al. Curr Med Res Opin 24(11): 3217-3222

(2008) "Relationship between duration of compliant bisphosphonate use and the risk of osteoporotic fractures." Meijer, W.M. , F.J. Beest, et.al. Curr Med Res Opin 24(11): 3217-3222 OBJECTIVES: To investigate the relationship between duration of compliant bisphosphonate use and the risk of osteoporotic fractures.METHODS: The PHARMO database was used to identify new female bisphosphonate users, aged >/= 45 years or with diagnosed post-menopausal osteoporosis in the period of January 1996 - June 2004. Within this cohort a matched case-control study was performed. Cases were defined as patients who were hospitalized for an osteoporotic fracture and were matched to ten controls without a fracture by duration of follow-up. The duration of compliant bisphosphonate use (i.e., medication possession ratio >/= 80%) preceding the outcome date was determined.RESULTS: Of 14 760 new female bisphosphonate users, 387 fracture patients fulfilled the inclusion criteria. These cases were matched to 3950 controls. Increasing duration of compliant bisphosphonate use was associated with a decreased risk of fracture (trend p < 0.01). Adjusted for several cofactors, 1-2 years of compliant bisphosphonate use and 3-4 years of compliant bisphosphonate use decreased fracture risk by 12% and 46%, respectively, compared to < 1 year of compliant bisphosphonate use (OR 0.88; 95% CI 0.66-1.18 and OR 0.54; 95% CI 0.35-0.84, respectively). Unexpectedly, 5-6years of compliant bisphosphonate use was no longer associated with a decreased risk of fractures compared to < 1 year of compliant bisphosphonate use (OR 1.12, 95% CI 0.66-1.88).CONCLUSIONS: These results show a direct link between duration of compliantbisphosphonate use and fracture risk, and confirm the importance of continuing the use of bisphosphonates to maintain optimal bone protection. However, this link is inconclusive for bisphosphonate use for more than 4 years.

(2008) "Relationship between duration of compliant bisphosphonate use and the risk of osteoporotic fractures." Meijer, W.M. , F.J. Beest, et.al. Curr Med Res Opin 24(11): 3217-3222   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2008) "Haemoglobin A(1)(c) Goal Attainment in Relation to Dose in Patients with Diabetes Mellitus Taking Metformin : A Nested, Case-Control Study." Penning-van Beest, F.J. , B.H. Wolffenbuttel, et.al. Clin Drug Investig 28(8): 487-493

(2008) "Haemoglobin A(1)(c) Goal Attainment in Relation to Dose in Patients with Diabetes Mellitus Taking Metformin : A Nested, Case-Control Study." Penning-van Beest, F.J. , B.H. Wolffenbuttel, et.al. Clin Drug Investig 28(8): 487-493 BACKGROUND and objective: Conclusions from clinical trials suggest possible therapeutic advantages for once-daily agents over twice-daily agents in the treatment of type 2 diabetes mellitus. This study set out to investigate the relationship betweenmetformin dosing frequency and glycosylated haemoglobin (HbA(1c))-goal attainment in daily practice. METHODS: This was a nested case-control study. Data were obtained from the PHARMO Record Linkage System, which includes linked drug-dispensing and clinical-laboratory records for approximately three million individuals in defined areas of the Netherlands. The study cohort included new users of oral antihyperglycaemic drugs between 1999 and 2005 with a baseline HbA(1c)>/=7% and at least one further HbA(1c) measurement within 18 months after the index date. Cases attained HbA(1c) goal (<7%) within 18 months; controls did not attain this HbA(1c) goal. Compliant cases and controls taking metformin monotherapy were included in the analyses. Dosing frequencywas dichotomized into once daily and twice daily or more frequently. In the multivariate analysis we considered oral antihyperglycaemic dose, baseline HbA(1c), first prescriber and number of HbA(1c) measurements. RESULTS: The study cohort included 3107new oral antihyperglycaemic drug users. The analyses included 753 cases and 477 controls taking metformin. Dosing twice daily or more was associated with a 71% higher probability of attaining goal (odds ratio 1.71 [95% CI 1.31, 2.24]) compared with once-daily dosing, after adjustment for baseline HbA(1c), first prescriber, sex and age. We could not distinguish between the effect of dose and dosing frequency as these were closely related. Statistical testing in the analyses stratified by dose was prohibited by small numbers. CONCLUSION: About 40% of compliant metformin users did not achieve their HbA(1c) goal within 18 months because of dosing problems. However, the strong correlation between total daily dose and dosing frequency did not permit identification of which of these dosing issues was the most important contributor to not achieving HbA(1c) goal.

(2008) "Haemoglobin A(1)(c) Goal Attainment in Relation to Dose in Patients with Diabetes Mellitus Taking Metformin : A Nested, Case-Control Study." Penning-van Beest, F.J. , B.H. Wolffenbuttel, et.al. Clin Drug Investig 28(8): 487-493   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Medicinal cannabis in oncology." Engels, F.K. , F.A. de Jong, et.al. Eur J Cancer 43(18): 2638-44

(2007) "Medicinal cannabis in oncology." Engels, F.K. , F.A. de Jong, et.al. Eur J Cancer 43(18): 2638-44 In The Netherlands, since September 2003, a legal medicinal cannabis product, constituting the whole range of cannabinoids, is available for clinical research, drug development strategies, and on prescription for patients. To date, this policy, initiated by the Dutch Government, has not yet led to the desired outcome; the amount of initiated clinical research is less than expected and only a minority of patients resorts to the legal product. This review aims to discuss the background for the introduction of legal medicinal cannabis in The Netherlands, the past years of Dutch clinical experience in oncology practice, possible reasons underlying the current outcome, and future perspectives.

(2007) "Medicinal cannabis in oncology." Engels, F.K. , F.A. de Jong, et.al. Eur J Cancer 43(18): 2638-44   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands." Penning-van Beest, F.J. , J. Koerselman, et.al. Pharm World Sci 29(6): 671-5

(2007) "Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands." Penning-van Beest, F.J. , J. Koerselman, et.al. Pharm World Sci 29(6): 671-5 OBJECTIVE: Coumarin anticoagulants are prone to potentially life-threatening drug-drug interactions due to a combination of unfavorable properties. However, real life data on the actual occurrence are scarce. The aim of this study was to quantify and qualify potential drug interactions with coumarin anticoagulants in daily practice. METHODS: A cohort study including all users of phenprocoumon or acenocoumarol during the period 1991-2003 in the PHARMO Record Linkage System. All 24 individual drugs and 11 drug groups interacting with coumarins according to central database used in the Dutch pharmacies were considered. MAIN OUTCOME MEASURE: Frequency and type of potential drug interactions during anticoagulant therapy with coumarins. RESULTS: 48,627out of 76,455 mainly acenocoumarol-users (64%) were dispensed at least one potentially interacting drug (PID) during anticoagulant therapy. About 35% of these cases were dispensed a (very) strongly interacting drug, whereas 3% were dispensed a contraindicated drug. Antibacterial drugs and NSAIDs (39% and 37% of all users, respectively) were the most frequently dispensed PIDs. CONCLUSION: Potential drug interactions with coumarins frequently occur in daily practice, confronting two-thirds of patients with an increased risk of bleeding. To a large part, this is attributable to commonly prescribed medication like antibacterial drugs and NSAIDs. This situation substantiates the need for proper monitoring or new anticoagulants with less drug-drug interactions.

(2007) "Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands." Penning-van Beest, F.J. , J. Koerselman, et.al. Pharm World Sci 29(6): 671-5   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution." Gumbs, P.D. , W.M. Verschuren, et.al. Br J Clin Pharmacol 64(5): 680-5

(2007) "Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution." Gumbs, P.D. , W.M. Verschuren, et.al. Br J Clin Pharmacol 64(5): 680-5 AIMS: To assess the potential annual savings due to generic and therapeutic substitution of statin therapy for the general Dutch population, taking the patients medical history into account. METHODS: We conducted a population-based costing study using the PHARMO Record Linkage System (RLS). PHARMO RLS contains drug dispensing records from a representative sample of pharmacies located in more than 50 regions in the Netherlands. We selected all statin users in the database since 2003. The cost-savings of generic substitution of statin therapy for all simvastatin and pravastatin users, and of therapeutic substitution of statin therapy for other statin users were calculated. Substituting current users and new users of statins were considered separately. Therapeutic substitution was based on the medical history of the individual patient. Patients were only substituted if there was an appropriate substitute available. The appropriateness of substitution was based on drug-drug interactions between statins and possible comedication and the availability of an equipotent alternative. RESULTS: Substituting (generic and therapeutic) statin therapy for all current users would lead to potential annual savings of approximately 87 million euros. Substituting (generic and therapeutic) all starters on statin therapy would lead to potential annual savings of around 51 million euros. In the case of generic substitution only, the potential annual savings for all current simvastatin and pravastatin users would be 2.4 million euros and for the new users about 1.8 million euros. CONCLUSIONS: From an economic point of view, society could gain a lot from substituting statin therapy, especially from therapeutic substitution.

(2007) "Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution." Gumbs, P.D. , W.M. Verschuren, et.al. Br J Clin Pharmacol 64(5): 680-5   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "No increased incidence of diabetes in antidepressant users." Knol, M.J. , M.I. Geerlings, et.al. Int Clin Psychopharmacol 22(6): 382-6

(2007) "No increased incidence of diabetes in antidepressant users." Knol, M.J. , M.I. Geerlings, et.al. Int Clin Psychopharmacol 22(6): 382-6 This study investigated whether the association between depression and diabetes was influenced by the presence of chronic somatic disease. To distinguish between depression and other psychosocial complaints, we studied the onset of diabetes in antidepressant (AD) users and benzodiazepine (BD) users, respectively. From the PHARMO database, which includes complete drug prescription data, we identified subjects using (i) no ADs and no BDs; (ii) AD but no BD; (iii) BD but no AD; and (iv) AD and BD. A total of 60 516 individuals (age: 45.5+/-17 years; 42.1% men) were followed from their first prescription for AD or BD until end of registration or a first prescription for antidiabetic drugs. The crude incidence rate in AD but no BD users was not increased compared with no AD and no BD users. After adjustment for age, sex and chronic diseases, the hazard ratios (95% confidence interval) were 1.05 (0.88-1.26) for AD but no BD users, 1.21 (1.02-1.43) for BD but no AD users and 1.37 (1.12-1.68) for AD andBD users compared with no AD and no BD users. We did not find an increased risk of diabetes in individuals using ADs. The association between BD use and diabetes was partly explained by chronic somatic comorbidity.

(2007) "No increased incidence of diabetes in antidepressant users." Knol, M.J. , M.I. Geerlings, et.al. Int Clin Psychopharmacol 22(6): 382-6   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Is statin use associated with a reduced incidence, a reduced Breslow thickness or delayed metastasis of melanoma of the skin?." Koomen, E.R. , A. Joosse, et.al. Eur J Cancer 43(17): 2580-9

(2007) "Is statin use associated with a reduced incidence, a reduced Breslow thickness or delayed metastasis of melanoma of the skin?." Koomen, E.R. , A. Joosse, et.al. Eur J Cancer 43(17): 2580-9 BACKGROUND: Statins show anticancer activity in melanoma cells. We investigated the association between statins and incidence and Breslow thickness of cutaneous melanoma (CM). METHODS: Data were used from PHARMO, a pharmacy database, and PALGA, a pathological database, in the Netherlands. Cases had a primary CM diagnosis between January 1st 1991 and December 14th 2004, were 18 years and had 3 years of follow up in PHARMO before CM diagnosis. Controls were matched for gender, date of birth and geographic region. Analyses were adjusted for age, gender, year of diagnosis, number of medical diagnoses and the use of NSAIDs and oestrogens. FINDINGS: Finally, 1318 cases and 6786 controls were selected. CM risk was not associated with statin use (0.5 years) (adjusted odds ratio (OR)=0.98, 95% confidence interval (CI)=0.78-1.2). However, statin use was associated with a reduced Breslow thickness (-19%, 95% CI=-33, -2.3, p=0.03). CONCLUSION: Our study suggests protective effects of statins on melanoma progression.

(2007) "Is statin use associated with a reduced incidence, a reduced Breslow thickness or delayed metastasis of melanoma of the skin?." Koomen, E.R. , A. Joosse, et.al. Eur J Cancer 43(17): 2580-9   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Effect of drug combinations on admission for recurrent myocardial infarction." van der Elst, M.E. , M.L. Bouvy, et.al. Heart 93(10): 1226-30

(2007) "Effect of drug combinations on admission for recurrent myocardial infarction." van der Elst, M.E. , M.L. Bouvy, et.al. Heart 93(10): 1226-30 OBJECTIVE: To determine the effect of the number of different drugs with adherence to medication of at least 70% on recurrent admission for myocardial infarction (MI) in patients with a history of MI. DESIGN: Nested case-control study in a dynamic cohort. SETTING: PHARMO database that contains pharmacy dispensing records and hospital discharge records of 350,000 Dutch citizens. SUBJECTS: All patients admitted to hospital for first MI (ICD-9 410) from 1991 to 2000 with at least a 30-day survival after admission. Cases were admitted for recurrent MI and were matched for age, sex, and year of admission with controls who did not have a recurrent MI. Main outcome measure(s): Odds ratio with 95% CI for admission for recurrent MI. Exposure was the numberof preventive drugs (antiplatelet agents, statins and beta blockers or ACE inhibitors) used for at least 70% of the time. RESULTS: 389 cases were matched with 2344 controls. The use of one drug was associated with a 6% odds reduction (95% CI 30% reduction to 28% increase) for admission for recurrent MI. The use of two or three drugs was associated with reductions of 26% and 41% (47% reduction to 3% increase and 6% to 63% reduction, respectively). Addition of one drug caused a 16% reduction (4% to 26%).CONCLUSIONS: Multiple drug treatment decreases admissions for recurrent MI in patients with a history of MI. Every addition of a drug, regardless of drug class, reduces the risk even further. These results support the treatment strategies as applied indaily practice.

(2007) "Effect of drug combinations on admission for recurrent myocardial infarction." van der Elst, M.E. , M.L. Bouvy, et.al. Heart 93(10): 1226-30   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Early Evidence on the Effects of Regulators' Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents." Gibbons, R.D. , C.H. Brown, et.al. Am J Psychiatry 164(9): 1356-63

(2007) "Early Evidence on the Effects of Regulators' Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents." Gibbons, R.D. , C.H. Brown, et.al. Am J Psychiatry 164(9): 1356-63 OBJECTIVE: In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression. METHOD: The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings. RESULTS: SSRI prescriptions for youths decreased byapproximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In theUnited States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in1979. CONCLUSIONS: In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents.

(2007) "Early Evidence on the Effects of Regulators' Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents." Gibbons, R.D. , C.H. Brown, et.al. Am J Psychiatry 164(9): 1356-63   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Enhanced persistence with tiotropium compared with other respiratory drugs in COPD." Breekveldt-Postma, N.S. , J. Koerselman, et.al. Respir Med 101(7): 1398-405

(2007) "Enhanced persistence with tiotropium compared with other respiratory drugs in COPD." Breekveldt-Postma, N.S. , J. Koerselman, et.al. Respir Med 101(7): 1398-405 BACKGROUND: Tiotropium is a once-daily inhaled anticholinergic maintenance treatment with demonstrated effectiveness in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To compare persistence of tiotropium-use with other inhaled respiratorydrugs in COPD in current clinical practice. METHODS: The PHARMO database includes, among others, drug-dispensing and hospital discharge records for 2 million subjects in the Netherlands. All probable COPD-patients were identified by new respiratory druguse (age >54 years) or COPD-hospitalisations. New users of tiotropium, ipratropium, long-acting beta-agonists (LABAs), or fixed combination of LABA and inhaled corticosteroids (LABA+ICS), in 1998-2003, were included in the study. Persistence was assessedquarterly during the first year of follow-up. Patients with a proportion of days covered (PDC) 80% were considered persistent. Persistence was analysed using generalised estimating equations model. RESULTS: About 37% of new users of tiotropium continuedtreatment for 1 year, compared with 14% for ipratropium, 13% for LABA, and 17% for LABA+ICS. Multivariate analyses showed that tiotropium-users were 2-3 times more persistent with their therapy than patients using ipratropium (relative risk [RR]: 2.0; 95% confidence interval [CI]: 1.8-2.3), LABA (RR: 2.9; 95% CI: 2.4-3.6), or LABA+ICS (RR: 2.4; 95% CI: 2.1-2.8), respectively. Sub-analyses in patients with a prior hospitalisation for COPD showed that 1-year persistence rates were increased for all treatments (varying from 33% for patients using LABA+ICS to 61% for patients using tiotropium), while persistence with tiotropium was again 2-3 times higher compared with other treatments. CONCLUSION: Persistence with tiotropium was higher compared to other inhaled respiratory drugs in COPD in clinical practice.

(2007) "Enhanced persistence with tiotropium compared with other respiratory drugs in COPD." Breekveldt-Postma, N.S. , J. Koerselman, et.al. Respir Med 101(7): 1398-405   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study." de Vries, F. , S. Pouwels, et.al. Pharmacoepidemiol Drug Saf 16(6): 612-9

(2007) "Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study." de Vries, F. , S. Pouwels, et.al. Pharmacoepidemiol Drug Saf 16(6): 612-9 INTRODUCTION: Administration of beta-2 agonists decreased bone mineral density in rats. But the association between bronchodilators and fracture risk has not been studied in humans. OBJECTIVES: To examine the association between use of beta-2 agonists and risk of hip/femur fracture. METHODS: We conducted a population-based case-control study (6763 cases) in the Dutch PHARMO database. Current beta-2 agonist use was compared to never use. We adjusted for severity of the underlying respiratory diseaseand disease and drug history. RESULTS: A hospitalisation for asthma/COPD in the year before index date increased risk of hip/femur fracture: crude OR 2.17 (95% CI, 1.41-3.34). Patients using higher doses of beta-2 agonists had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41-2.66) for daily dosages of >/=1600 microg albuterol equivalent. The excess fracture risk reduced after adjustment for disease severity (1.46; 95% CI, 1.02-2.08) and after exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80-2.15). Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. CONCLUSION: We found increases in the risk of hip/femur fracture in patients using higher doses of beta-2 agonists. However, the excess risk of hip/femur fracture substantially reduced after exclusion of oral glucocorticoid users and after adjustment for the underlying disease. Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. The severity of the underlying disease, rather than the use of beta-2 agonists, may play an important role in the aetiology of hip/femur fractures in patients using beta-2 agonists. Copyright (c) 2006 John Wiley & Sons, Ltd.

(2007) "Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study." de Vries, F. , S. Pouwels, et.al. Pharmacoepidemiol Drug Saf 16(6): 612-9   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "In-hospital use of opioids increases rate of coded postoperative paralytic ileus." Goettsch, W.G. , M.P. Sukel, et.al. Pharmacoepidemiol Drug Saf 16(6): 668-74

(2007) "In-hospital use of opioids increases rate of coded postoperative paralytic ileus." Goettsch, W.G. , M.P. Sukel, et.al. Pharmacoepidemiol Drug Saf 16(6): 668-74 PURPOSE: To determine the association between opioid use and the occurrence of postoperative paralytic ileus (POI) after different types of surgery. METHODS: The PHARMO database was used to perform a case control study in which intramural drug utilisation data were linked to hospital discharge diagnoses. All patients admitted for digestive, abdominal or genito-urinary surgeries were selected in 1998-2003. Cases with coded POI (ICD-9-CM 560.1 and 564.4) and controls with no POI were matched 1:10. The association between coded POI and opioid use was assessed using conditional logistic regression. RESULTS: In 0.2% of all admissions (total of 180,279), patients developed POI and in 18% of all admissions, patients received opioids. Three hundred and sixty-six cases with POI were selected with their matching controls. The use of (nico)morphine was associated with the risk for developing POI (odds ratio (OR) 12.1, 95% confidence interval (CI) 5.4-27.1). The association between opioids and POI was most obvious in patients with abdominal surgery (OR 33.8, 95%CI 6.2-184.6) and patients without colon/colorectal/rectal tumours (OR 13.2, 95%CI 5.7-30.3). CONCLUSION: This study demonstrated a distinct association between the use of opioids, in particular natural opium alkaloids, and the risk for coded POI. Copyright (c) 2006 John Wiley & Sons, Ltd.

(2007) "In-hospital use of opioids increases rate of coded postoperative paralytic ileus." Goettsch, W.G. , M.P. Sukel, et.al. Pharmacoepidemiol Drug Saf 16(6): 668-74   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Influence of initial use of serotonergic antidepressants on antiparkinsonian drug use in levodopa-using patients." Arbouw, M.E. , K.L. Movig, et.al. Eur J Clin Pharmacol 63(2): 181-7

(2007) "Influence of initial use of serotonergic antidepressants on antiparkinsonian drug use in levodopa-using patients." Arbouw, M.E. , K.L. Movig, et.al. Eur J Clin Pharmacol 63(2): 181-7 OBJECTIVE: To assess whether there is an association between initial use of serotonergic antidepressants and changes in antiparkinsonian drug treatment. METHODS: A retrospective cohort study was performed with the PHARMO record linkage system. All patients from 1994 until 2004 of 40 years or older who were first time users of an antidepressant and who had used a levodopa-containing drug at least 180 days before initiation of the antidepressant were included. The maximum follow-up time was 180 days.The first change in antiparkinsonian drug treatment, defined as an increase in the daily dosage of any antiparkinsonian drug, the start of a new antiparkinsonian drug or a change in the dosage form during the follow-up period, was taken as an endpoint.Antidepressants were classified in two ways: according to their class [selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or other antidepressants] or by the extent of their inhibition of serotonin reuptake (high, intermediate or low). RESULTS: A total of 221 patients was included in our study. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.7 (95% CI 0.3-1.5) comparing SSRI with TCA users, and it was 0.9 (95% CI 0.4-2.1) comparing users of other antidepressants with TCA users. The adjusted hazard ratio for a change in antiparkinsonian drug treatment was 0.6 (95% CI 0.3-1.4) comparing users of antidepressants with high versus low extent of inhibition of serotonin reuptake, and it was 0.7 (95%CI 0.3-1.4) comparing users of antidepressants with intermediate versus low extent of inhibition of serotonin reuptake. CONCLUSION: Based on these observations, we found no evidence to be more cautious using SSRIs or serotonergic antidepressants compared to other antidepressants in patients with Parkinson's disease.

(2007) "Influence of initial use of serotonergic antidepressants on antiparkinsonian drug use in levodopa-using patients." Arbouw, M.E. , K.L. Movig, et.al. Eur J Clin Pharmacol 63(2): 181-7   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study." de Vries, F. , S. Pouwels, et.al. J Intern Med 261(2): 170-7

(2007) "Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study." de Vries, F. , S. Pouwels, et.al. J Intern Med 261(2): 170-7 Patients using higher dosages of inhaled or oral glucocorticoids (GCs) have an increased risk of hip/femur fractures. The role of the underlying disease in the aetiology of this increased risk has not been widely studied. Objective. To evaluate thecontribution of the underlying disease to the risk of hip/femur fracture in patients using inhaled or oral GCs. Design and subjects. A case-control study within the Dutch PHARMO-RLS database was conducted. Cases (n = 6763) were adult patients with a first hip/femur fracture during enrolment. Each case was matched to four controls by age, gender and region. Results. The risk of hip/femur fracture increased with current use of inhaled GCs (crude OR 1.30, 95% CI:1.16-1.47) and with current use of oral GCs(crude OR 1.66, 95% CI: 1.46-1.90). After adjustment for disease severity, the risk of hip/femur fracture was no longer statistically significantly increased in inhaled GC users (adjusted OR 1.08, 95% CI: 0.91-1.27), whilst it remained elevated in oral GC users (adjusted OR 1.43, 95% CI: 1.22-1.67). Patients using inhaled GCs without any exposure to oral GCs had no increased risk of fracture (adjusted OR 0.98, 95% CI: 0.79-1.22). Conclusion. Inhaled GC users had no increased risk of femur/hip fracture after adjustment for underlying disease severity. Our data suggest that, even at higher dosages, inhaled GC use is not an independent risk factor for fracture. In contrast, oral GC use was associated with an increased risk of fracture, which was not fullyexplained by the underlying disease severity.

(2007) "Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study." de Vries, F. , S. Pouwels, et.al. J Intern Med 261(2): 170-7   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Use of beta-Blockers and the Risk of Hip/Femur Fracture in the United Kingdom and The Netherlands." de Vries, F. , P.C. Souverein, et.al. Calcif Tissue Int 80(2): 69-75

(2007) "Use of beta-Blockers and the Risk of Hip/Femur Fracture in the United Kingdom and The Netherlands." de Vries, F. , P.C. Souverein, et.al. Calcif Tissue Int 80(2): 69-75 Data from in vivo studies have indicated a role for beta-blockers in the prevention of bone loss. Some epidemiological studies have found protective effects of beta-blockers on fracture risk. However, there is limited information on the associationwith cumulative dose and type of beta-blockers used. We conducted two case-control studies using data from the UK General Practice Research Database (GPRD) and the Dutch PHARMO Record Linkage System (RLS). Cases were patients with a first hip or femur fracture; controls were individually matched on practice/region, gender, year of birth, and calendar time. Current use of beta-blockers was defined as a prescription in 90 days before the index date. We adjusted for medical conditions and drugs associatedwith falling or bone mineral density. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression analysis. The study population included 22,247 cases and controls in the GPRD and 6,763 cases and 26,341 controls in the PHARMO RLS. Current use of beta-blockers was associated with a reduced risk of hip/femur fracture in both the GPRD (adjusted OR = 0.82, 95% CI 0.74-0.91) and PHARMO RLS (adjusted OR = 0.87, 95% CI 0.80-0.95) study populations. However, this reduction of risk was not associated with cumulative dose, lipophilicity, or receptor selectivity of beta-blockers. The protective effect of beta-blockers was only present among patients with a history of use of other antihypertensive agents (GPRD adjusted OR = 0.72, 95% CI 0.64-0.83; PHARMO RLS adjusted OR = 0.76, 95% CI 0.67-0.86) but not in patients using beta-blockers only (GPRD adjusted OR = 0.97, 95% CI 0.82-1.14; PHARMO RLS adjusted OR = 1.01, 95% CI 0.90-1.14). Also, in patients with a history ofuse of other antihypertensive agents, no dose-response relationship with beta-blocker use was found. The effect was constant with cumulative dose and the OR was below 1.0 even among patients who just started treatment with beta-blockers. As the mechanism by which beta-blockers could influence bone mineral density is likely to need some time to exert a clinically relevant effect, all these finding suggests that the association between beta-blockers and fracture risk is not causal.

(2007) "Use of beta-Blockers and the Risk of Hip/Femur Fracture in the United Kingdom and The Netherlands." de Vries, F. , P.C. Souverein, et.al. Calcif Tissue Int 80(2): 69-75   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Developments of the incidence of osteoporosis in The Netherlands: a PHARMO study." Goettsch, W.G. , R.B. de Jong, et.al. Pharmacoepidemiol Drug Saf 16(2): 166-72

(2007) "Developments of the incidence of osteoporosis in The Netherlands: a PHARMO study." Goettsch, W.G. , R.B. de Jong, et.al. Pharmacoepidemiol Drug Saf 16(2): 166-72 PURPOSE: To assess recent and to predict future time trends in the incidence of osteoporosis using routine databases in The Netherlands in the period 1993-2015 and to compare estimations based on hip fractures versus a proxy based on pharmacy and hospitalisation data. METHODS: The incidence of hip fractures was estimated over the period 1986-2002 using information from the Dutch Medical Registry, covering more than 99% of all Dutch hospitalisations. Additionally, a proxy (hospitalisation for osteoporosis or osteoporotic fractures, treatment with glucocorticosteroids or treatment with anti-osteoporosis drugs) was constructed in order to identify osteoporotic patients in the PHARMO database. Age and gender specific incidences of hip fractures and osteoporosis were calculated and extrapolated to The Netherlands. Results of both studies were extrapolated till 2015 using a power function. RESULTS: The incidence of hip fractures decreased slightly (270 per 100 000 in 1993, 260 per 100 000 in 2002). Theincidence of osteoporosis using the constructed proxy decreased from 870 per 100 000 in 1993 to 700 per 100 000 in 2002.The incidence of hip fractures and osteoporosis remained fairly constant when modelled till 2015. Both studies showed the same time trends. CONCLUSION: Both the estimations based on the hospitalisations for hip fracture and on our proxy for osteoporosis showed that the increase in the incidence of osteoporosis as observed in the 1990s is levelling off. Due to ageing of the populationthe absolute number of hip fractures will however increase. Our definition of osteoporosis resulted in a higher estimation of the incidence of osteoporosis and may be used in future studies to follow developments in osteoporosis prevalence and incidence.Copyright (c) 2006 John Wiley & Sons, Ltd.

(2007) "Developments of the incidence of osteoporosis in The Netherlands: a PHARMO study." Goettsch, W.G. , R.B. de Jong, et.al. Pharmacoepidemiol Drug Saf 16(2): 166-72   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Changes in medication associated with epilepsy-related hospitalisation: a case-crossover study." Handoko, K.B. , J.E. Zwart-van Rijkom, et.al. Pharmacoepidemiol Drug Saf 16(2): 189-96

(2007) "Changes in medication associated with epilepsy-related hospitalisation: a case-crossover study." Handoko, K.B. , J.E. Zwart-van Rijkom, et.al. Pharmacoepidemiol Drug Saf 16(2): 189-96 AIM: To assess the association between changes in medication and epilepsy-related hospitalisation. METHODS: Data were obtained from the PHARMO Record Linkage System (Jan 1998 to Dec 2002). We conducted a case-crossover study among patients with a first epilepsy-related hospital admission who had continuously used at least one antiepileptic drug (AED) during a 28-week period before admission. For each patient, changes in medication in a 28-day window before hospitalisation were compared with changesin four earlier 28-day windows. Evaluated changes were: changes in AEDs (pattern and dosage), changes in interacting co-medication and changes in non-interacting co-medication (i.e. introduction of non-interacting drugs). The strength of the associationbetween changes in medication and epilepsy-related hospitalisation was estimated using conditional logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Out of 1185 patients with a first epilepsy-related hospitalisation, 217 patients met the inclusion criteria. Of the changes in antiepileptic therapy, discontinuation showed a trend towards an increased risk of hospitalisation (OR: 2.57; 95%CI: 0.81-8.17). Drug interactions influencing antiepileptictherapy rarely occurred. Introduction of three or more non-interacting drugs was significantly associated with epilepsy-related hospitalisation (OR: 4.80; 95%CI: 2.12-10.87). Of individual drugs, addition of antimicrobial agents was significantly associated with epilepsy-related hospitalisation (OR: 1.99; 95%CI: 1.06-3.75). CONCLUSIONS: Changes in AED therapy were not significantly associated with epilepsy-related hospitalisation and few drug interactions influencing antiepileptic therapy occurred. However, patients starting three or more new non-AEDs had a nearly five times increased risk of epilepsy-related hospital admission. Copyright (c) 2006 John Wiley & Sons, Ltd.

(2007) "Changes in medication associated with epilepsy-related hospitalisation: a case-crossover study." Handoko, K.B. , J.E. Zwart-van Rijkom, et.al. Pharmacoepidemiol Drug Saf 16(2): 189-96   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study." Penning-van Beest, F.J. , F. Termorshuizen, et.al. Eur Heart J 28(2): 154-9

(2007) "Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study." Penning-van Beest, F.J. , F. Termorshuizen, et.al. Eur Heart J 28(2): 154-9 AIMS: To investigate the 'real world' effectiveness of robust statin therapy, focusing on the effect of dose and early treatment discontinuation on the risk of hospitalization for acute myocardial infarction (AMI). METHODS AND RESULTS: In the PHARMOdatabase, including among others drug-dispensing and hospital discharge records for more than two million subjects in the Netherlands, 59 094 new users of statins in the period 1 January 1991 until 31 December 2004, >/= 18 years of age were identified.In these patients, exposure to statins, both in terms of persistence and dose, was determined over the first two treatment years. To determine the risk for AMI, patients were followed from this 2-year time point until the first hospital admission for AMI, death, or end of the study period. A total of 31 557 patients (53%) discontinued statin use within 2 years; 20 883 patients (35%) were persistent users with an average equipotent dose >/= 4. A 30% reduction in risk of hospitalization for AMI with persistent statin use was observed. The protective effect increased with a higher dose (20 and 40% risk reduction with an equipotent dose /= 4, respectively). CONCLUSION: These results show that statins are suboptimally used in real life for havingthe maximum benefit in terms of preventing AMI.

(2007) "Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study." Penning-van Beest, F.J. , F. Termorshuizen, et.al. Eur Heart J 28(2): 154-9   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Pharmacogenetics of glucose-lowering drug treatment: a systematic review." Bozkurt, O. , A. de Boer, et.al. Mol Diagn Ther 11(5): 291-302

(2007) "Pharmacogenetics of glucose-lowering drug treatment: a systematic review." Bozkurt, O. , A. de Boer, et.al. Mol Diagn Ther 11(5): 291-302 Intensive blood glucose lowering can significantly reduce the risk of micro- and macrovascular complications in patients with diabetes mellitus. However, 30% of all treated patients do not achieve optimal blood glucose levels. Genetic factors may influence the response to glucose-lowering medication. A search of MEDLINE-indexed literature published between January 1966 and July 2007 revealed 37 studies reporting data on genetic polymorphisms and response to glucose-lowering drugs. Most studies involving cytochrome P450 (CYP) genes had small sample sizes (21 studies <50 subjects) and were among healthy volunteers. Multiple studies indicated that the CYP2C9 *3 allele (Ile359Leu polymorphism) was associated with decreased clearance of sulfonylurea drugs. Supporting this, one study reported an increased insulin secretion in CYP2C9*3 allele carriers when using the sulfonylurea agent glyburide. The CYP2C9*3 allele was also associated with a decreased clearance of meglitinides, whereas the CYP2C8*3 (Arg139Lys; Lys399Arg) variant increased the clearance of meglitinides. Polymorphisms in genes encoding the inwardly rectifying potassium channel Kir6.2 (KCNJ11) and the insulin receptor substrate-1 (IRS1) were reported to be associated with an increased risk of (secondary) failure to respond to sulfonylurea therapy. A significant decrease in fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) in response to rosiglitazone was seen in subjects carrying the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma (PPARG) gene. Conversely, carriers of this polymorphism also had a higher conversion to diabetes mellitus when treated with acarbose; this effect was also seen in adiponectin (ADIPOQ) gene polymorphism carriers. Future studieswith adequate sample sizes in which several SNPs in multiple candidate genes are genotyped in patients with diabetes should provide reliable information on genetic variants and response to glucose-lowering drugs.

(2007) "Pharmacogenetics of glucose-lowering drug treatment: a systematic review." Bozkurt, O. , A. de Boer, et.al. Mol Diagn Ther 11(5): 291-302   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Verhoogde lactaatspiegels in relatie tot metforminegebuik, nierfunctie, leverfunctie en leukocytenaantal." Drabbe, N.R.G. , E.A. Van Dijk, et.al. 38(): 114-117

(2007) "Verhoogde lactaatspiegels in relatie tot metforminegebuik, nierfunctie, leverfunctie en leukocytenaantal." Drabbe, N.R.G. , E.A. Van Dijk, et.al. 38(): 114-117 No abstract available

(2007) "Verhoogde lactaatspiegels in relatie tot metforminegebuik, nierfunctie, leverfunctie en leukocytenaantal." Drabbe, N.R.G. , E.A. Van Dijk, et.al. 38(): 114-117   Ask PHARMO for copy   Sent reference to friend

(2007) "The future of postmarketing surveillance of psychotropic medications." Klein, D. , B.L. Strom, et.al. CNS Spectr 12(9 (suppl. ): 1-20

(2007) "The future of postmarketing surveillance of psychotropic medications." Klein, D. , B.L. Strom, et.al. CNS Spectr 12(9 (suppl. ): 1-20 No abstract available

(2007) "The future of postmarketing surveillance of psychotropic medications." Klein, D. , B.L. Strom, et.al. CNS Spectr 12(9 (suppl. ): 1-20   Ask PHARMO for copy   Sent reference to friend

(2007) "Effecten van statines op huidmelanomen." Koomen, E.R. , A. Joosse, et.al. 42(): 133-137

(2007) "Effecten van statines op huidmelanomen." Koomen, E.R. , A. Joosse, et.al. 42(): 133-137 No abstract available

(2007) "Effecten van statines op huidmelanomen." Koomen, E.R. , A. Joosse, et.al. 42(): 133-137   Ask PHARMO for copy   Sent reference to friend

(2007) "Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence." Menckeberg, T.T. , S.V. Belitser, et.al. BMC Health Serv Res 7(): 106

(2007) "Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence." Menckeberg, T.T. , S.V. Belitser, et.al. BMC Health Serv Res 7(): 106 BACKGROUND: In order to accurately distinguish gaps of varying length in drug treatment for chronic conditions from discontinuation without resuming therapy, short-term observation does not suffice. Thus, the use of inhalation corticosteroids (ICS)in the long-term, during a ten-year period is investigated. To describe medication use as a continuum, taking into account the timeliness and consistency of refilling, a Markov model is proposed. METHODS: Patients, that filled at least one prescription in 1993, were selected from the PHARMO medical record linkage system (RLS) containing >95% prescription dispensings per patient originating from community pharmacy records of 6 medium-sized cities in the Netherlands.The probabilities of continuous use, the refilling of at least one ICS prescription in each year of follow-up, and medication free periods were assessed by Markov analysis. Stratified analysis according to new use was performed. RESULTS: The transition probabilities of the refilling of at least one ICS prescription in the subsequent year of follow-up, were assessed for each year of follow-up and for the total study period.The change of transition probabilities in time was evaluated, e.g. the probability of continuing ICS use of starters in the first two years (51%) of follow-up increased to more than 70% in the following years. The probabilities of different patterns of medication use were assessed: continuous use (7.7%), cumulative medication gaps (1-8 years 69.1%) and discontinuing (23.2%) during ten-year follow-up for new users. New users had lower probability of continuous use (7.7%) and more variability in ICS refill patterns than previous users (56%). CONCLUSION: In addition to well-established methods in epidemiology to ascertain compliance and persistence, a Markov model could be useful to further specify the variety of possible patterns of medication use within the continuum of adherence. This Markov model describes variation in behaviour and patterns of ICS use and could also beuseful to investigate continuous use of other drugs applied in chronic diseases.

(2007) "Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence." Menckeberg, T.T. , S.V. Belitser, et.al. BMC Health Serv Res 7(): 106   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Generiek omeprazol als eerstekeuze-PPI: beleid versus praktijk." Penning-van Beest, F.J.A. , R.M.C. Herings, et.al. Modern Medicine 31(4): 163-164

(2007) "Generiek omeprazol als eerstekeuze-PPI: beleid versus praktijk." Penning-van Beest, F.J.A. , R.M.C. Herings, et.al. Modern Medicine 31(4): 163-164 No abstract available

(2007) "Generiek omeprazol als eerstekeuze-PPI: beleid versus praktijk." Penning-van Beest, F.J.A. , R.M.C. Herings, et.al. Modern Medicine 31(4): 163-164   Ask PHARMO for copy   Sent reference to friend

(2007) "Higher persistence with valsartan compared with enalapril in daily practice." Siiskonen, S.J. , N.S. Breekveldt-Postma, et.al. Vasc Health Risk Manag 3(6): 1039-44

(2007) "Higher persistence with valsartan compared with enalapril in daily practice." Siiskonen, S.J. , N.S. Breekveldt-Postma, et.al. Vasc Health Risk Manag 3(6): 1039-44 OBJECTIVE: To compare persistence with valsartan and enalapril in daily practice. METHODS: The PHARMO Record Linkage System includes various data registries including drug dispensing and hospitalizations for > or =2 million subjects in the Netherlands. Patients newly treated with valsartan or enalapril in the period of 1999-2002 were selected. Persistence was calculated by summing up the number of days of continuous treatment. Patients who remained on therapy with valsartan or enalapril for 12 or 24 months were defined as persistent at 1 or 2 years, respectively. RESULTS: 3364 patients received valsartan and 9103 patients received enalapril. About 62% of patients treated with valsartan and 55% of patients treated with enalapril remained on therapyat 12 months after the initial dispensing, while 48% of patients treated with valsartan and 43% of patients treated with enalapril were persistent at 24 months. Patients treated with valsartan were about 20% more likely to stay on treatment than patients treated with enalapril (1 year RR(adj): 1.23, 95% CI: 1.16-1.32; 2 years RR(adj): 1.16, 95% CI: 1.11-1.23). CONCLUSIONS: Real-life persistence is higher with valsartan than with enalapril. The results of this and other studies on persistence in daily practice should be taken into account when deciding upon drug treatment for hypertension.

(2007) "Higher persistence with valsartan compared with enalapril in daily practice." Siiskonen, S.J. , N.S. Breekveldt-Postma, et.al. Vasc Health Risk Manag 3(6): 1039-44   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Rates and determinants of reinitiating antihypertensive therapy after prolonged stoppage: a population-based study." van Wijk, B.L. , J. Avorn, et.al. J Hypertens 25(3): 689-697

(2007) "Rates and determinants of reinitiating antihypertensive therapy after prolonged stoppage: a population-based study." van Wijk, B.L. , J. Avorn, et.al. J Hypertens 25(3): 689-697 OBJECTIVE: To assess patterns of restarting antihypertensive drugs after a prolonged period of discontinuation. METHODS: We conducted a retrospective cohort study among new users of blood pressure-lowering medication in the PHARMO database in the Netherlands, who had a period of at least 180 days without such medication. A multivariable Cox proportional hazard analysis was used to explore the baseline variables associated with reinitiating treatment. Case-crossover analysis was used to evaluate determinants of reinitiating treatment. RESULTS: We identified 35 714 patients as initiating blood pressure-lowering treatment during the period 1 January 1999 to 30 June 2004. Of the 18 357 (51.4%) patients who discontinued blood pressure-lowering treatment, 19.3% restarted treatment within 1 year and 60.7% restarted within 6 years. With every additional year they had been on therapy, patients were more likely to restart [odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.34-1.42]. The case-crossover analysis revealed that hospitalization for cardiovascular disease (OR = 2.20; 95% CI = 1.84-2.63), as well as refilling of another cardiovascular medication (OR = 1.25; 95% CI = 1.11-1.40), were each independently associated with reinitiating treatment. Refilling non-cardiovascular medications was not associated with reinitiating treatment (OR = 1.03; 95% CI = 0.97-1.10). CONCLUSION: Physicians should be aware that many patients have prolonged periods of discontinuation during the use of blood pressure-lowering medication, and that most of these patients will eventually resume therapy. Ongoing refilling other medications is not associated with reinitiating treatment. This suggests that, for some patients, the decision to discontinue may be drug specific rather than a behavioural characteristic applicable to all chronic treatments.

(2007) "Rates and determinants of reinitiating antihypertensive therapy after prolonged stoppage: a population-based study." van Wijk, B.L. , J. Avorn, et.al. J Hypertens 25(3): 689-697   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2007) "Herstarten van antihypertensiva." Van Wijk, B.L.G. , J. Avorn, et.al. 38(): 118-120

(2007) "Herstarten van antihypertensiva." Van Wijk, B.L.G. , J. Avorn, et.al. 38(): 118-120 No abstract available

(2007) "Herstarten van antihypertensiva." Van Wijk, B.L.G. , J. Avorn, et.al. 38(): 118-120   Ask PHARMO for copy   Sent reference to friend

(2006) "Risk of ischemic complications related to the intensity of triptan and ergotamine use." Wammes-van der Heijden, E.A. , H. Rahimtoola, et.al. Neurology 67(7): 1128-34

(2006) "Risk of ischemic complications related to the intensity of triptan and ergotamine use." Wammes-van der Heijden, E.A. , H. Rahimtoola, et.al. Neurology 67(7): 1128-34 OBJECTIVE: To investigate whether the intensity of triptan and ergotamine use, in specific overuse, is associated with the risk of ischemic complications. METHODS: We conducted a retrospective nested case-control study using data from the PHARMO Record Linkage System. All patients with more than one prescription for either a triptan or ergotamine were initially identified. Cases were all patients who were admitted to the hospital for an ischemic complication. Matched controls were assigned the sameindex date as the cases. The determinant was the intensity of use of triptans and ergotamine during 1 year preceding the index date. Overuse was defined as use of > or =90 defined daily doses during that year. Conditional logistic regression was used toestimate odds ratios (ORs), adjusting for confounders. Stratified analysis was used to estimate the risk for both patients using and those not using cardiovascular drugs. RESULTS: A total of 17,439 patients received more than one prescription. A total of 188 cases and 689 controls were identified. Triptan overuse was not associated with an increased risk of ischemic complications (OR 0.96; 95% CI: 0.49 to 1.90). Overuse of triptans in patients concomitantly using cardiovascular drugs did not increase this risk. Overuse of ergotamine turned out to be a risk factor for ischemic complications (OR 2.55; 95% CI: 1.22 to 5.36). Patients overusing ergotamine and concomitantly using cardiovascular drugs were at highest risk (OR 8.52; 95% CI 2.57 to 28.2). CONCLUSIONS: In general practice, triptan overuse does not increase the risk of ischemic complications. Overuse of ergotamine may increase the risk of these complications, especially in those simultaneously using cardiovascular drugs.

(2006) "Risk of ischemic complications related to the intensity of triptan and ergotamine use." Wammes-van der Heijden, E.A. , H. Rahimtoola, et.al. Neurology 67(7): 1128-34   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2006) "Pleidooi voor het behoud van de Landelijke Medische Registratie voor betrouwbare informatie over de volksgezondheid en de gezondheidszorg." Stricker, B.H. , R.M. Herings, et.al. Ned Tijdschr Geneeskd 150(35): 1916-7

(2006) "Pleidooi voor het behoud van de Landelijke Medische Registratie voor betrouwbare informatie over de volksgezondheid en de gezondheidszorg." Stricker, B.H. , R.M. Herings, et.al. Ned Tijdschr Geneeskd 150(35): 1916-7 No abstract available

(2006) "Pleidooi voor het behoud van de Landelijke Medische Registratie voor betrouwbare informatie over de volksgezondheid en de gezondheidszorg." Stricker, B.H. , R.M. Herings, et.al. Ned Tijdschr Geneeskd 150(35): 1916-7   Ask PHARMO for copy   Sent reference to friend

(2006) "Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands." Goettsch, W. , J. Bouwes Bavinck, et.al. J Eur Acad Dermatol Venereol 20(7): 834-9

(2006) "Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands." Goettsch, W. , J. Bouwes Bavinck, et.al. J Eur Acad Dermatol Venereol 20(7): 834-9 Information on the prevalence of bacterial cellulitis (BC) and erysipelas (ER) of the leg (BCERL) is sparse and dependent on the definitions used. There is no information available on the number of hospitalized and non-hospitalized patients with BCERL, and related treatment costs. The purpose of this study was to assess the burden of illness for BCERL in the Netherlands in 2001. Data were obtained from different linked databases. Hospital information was obtained from the National Morbidity Registration (known in the Netherlands as the LMR), which includes all Dutch citizens, using ICD-9-CM codes. The number of patients not admitted to hospital was estimated using a subsample with data from general practitioners (GPs) (N = 50 000). These data wereextrapolated using age/gender and disease-specific standardization. The subsample was used to assess the location of the infection. Reimbursement costs were available for all resources. In 2001, approximately 28 000 patients presented with either BC orER of the leg. Of these patients, 2200 were admitted to the hospital and 4-6% had two or more episodes of ER/BC in 2001. The average costs per hospitalization for BCERL were 5346 euros, accumulating to more than 14 million euros in 2001. Although only 7%of all patients were hospitalized, 83% of the total treatment costs could be attributed to hospitalization. BCERL are common and serious infections in the Netherlands. Hospitalization occurs in only one in 14 patients but contributes more than 80% of the total costs, which accumulate to 17 million euros a year.

(2006) "Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands." Goettsch, W. , J. Bouwes Bavinck, et.al. J Eur Acad Dermatol Venereol 20(7): 834-9   Ask PHARMO for copy   Print abstract   Sent reference to friend

(2006) "Results from a rosuvastatin historical cohort study in more than 45,000 Dutch statin users, a PHARMO study.." Goettsch, W.G. , E.M. Heintjes, et.al. Pharmacoepidemiol Drug Saf 15(7): 435-43