Sex differences associated with adverse drug reactions resulting in hospital admissions.

BACKGROUND: Adverse drug events, including adverse drug reactions (ADRs), are responsible for approximately 5% of unplanned hospital admissions: a major health concern. Women are 1.5-1.7 times more likely to develop ADRs. The main objective was to identify sex differences in the types and number of ADRs leading to hospital admission. METHODS: ADR-related hospital admissions between 2005 and 2017 were identified from the PHARMO Database Network using hospital discharge diagnoses. Patients aged ≥ 16 years with a drug possibly responsible for the ADR and dispensed within 3 months before admission were included. Age-adjusted odds ratios (OR) with 95% CIs for drug-ADR combinations for women versus men were calculated. RESULTS: A total of 18,469 ADR-related hospital admissions involving women (0.35% of all women admitted) and 14,678 admissions involving men (0.35% of all men admitted) were included. Most substantial differences were seen in ADRs due to anticoagulants and diuretics. Anticoagulants showed a lower risk of admission with persistent haematuria (ORadj 0.31; 95%CI 0.21, 0.45) haemoptysis (ORadj 0.47, 95%CI 0.30,0.74) and subdural haemorrhage (ORadj 0.61; 95%CI 0.42,0.88) in women than in men and a higher risk of rectal bleeding in women (ORadj 1.48; 95%CI 1.04,2.11). Also, there was a higher risk of admission in women using thiazide diuretics causing hypokalaemia (ORadj 3.03; 95%CI 1.58, 5.79) and hyponatraemia (ORadj 3.33, 95%CI 2.31, 4.81) than in men. CONCLUSIONS: There are sex-related differences in the risk of hospital admission in specific drug-ADR combinations. The most substantial differences were due to anticoagulants and diuretics.

Cohort profile: the PHARMO Perinatal Research Network (PPRN) in the Netherlands: a population-based mother-child linked cohort.

PURPOSE: Observational population-based research is a very suitable non-invasive method for studies in the vulnerable populations of pregnant women and children. Therefore, the PHARMO Perinatal Research Network (PPRN) was set up as a resource for life course perinatal and paediatric research by linking population-based data from existing registrations. PARTICIPANTS: From 1999 to 2017, the PPRN captures approximately 542 900 pregnancies of 387 100 mothers ('Pregnancy Cohort'). Additionally, mother-child linkage is currently available for a quarter of these pregnancies ('Child Cohort'). The PPRN contains preconceptional information on maternal healthcare, as well as detailed pregnancy and neonatal data, extending into long-term follow-up and outcomes after birth for both mother and child up to nearly 20 years. It includes linked data from different primary and secondary healthcare settings. FINDINGS TO DATE: Through record linkage of the Netherlands Perinatal Registry and the PHARMO Database Network, we have established a large population-based research network including data on demographics, medication use, medical conditions and details concerning labour, birth and neonatal outcomes. Here, we provide an overview of record types available from the PPRN, available database follow-up and pregnancy characteristics of the PPRN cohorts. The PPRN has been used for a number of different pharmacoepidemiological studies, for example, to confirm that preterm-born infants were more likely than full-term infants to be hospitalised or use medication. Similar long-term comparisons showed that children born following spontaneous preterm labour were at increased risk of neurodevelopmental and respiratory conditions. Most recently, the PPRN provided important evidence on the trends in use of potentially harmful medication during pregnancy. FUTURE PLANS: The PPRN provides a unique and rich data set facilitating large-scale observational pharmacoepidemiological perinatal research. The patient-level linkage of many different healthcare data sources allows for long-term follow-up of mother and child, with ongoing annual updates.

Trends in mortality, cardiovascular complications, and risk factors in type 2 diabetes.

BACKGROUND: Quality of diabetes care in the Netherlands ranked second in the Euro Diabetes Index 2014, but data on outcomes are lacking. We assessed trends in cardiovascular disease and mortality among type 2 diabetes (T2DM) patients in the context of risk factor control. METHODS: Annual cohorts of adult T2DM patients were constructed from the PHARMO Database Network. Age-standardised mortality rates and incidence rates (IR) of hospitalisations for acute myocardial infarction (AMI), stroke, and congestive heart failure (CHF) were compared with a diabetes-free population matched on age, sex, and general practitioner. Life years lost (LYL) to T2DM or cardiovascular disease were determined by comparing life expectancy between matched groups. Proportions attaining glycated haemoglobin (HbA1c), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) goals were assessed annually. RESULTS: Among 53,602 T2DM patients, slight increases in IR between 2008 and 2016 were proportional to those in diabetes-free controls; on average T2DM increased the risk of mortality by 86%, hospitalisation for AMI 69%, stroke 57%, and CHF 185%. At age 55, LYL to T2DM averaged 3.5 years and established CVD added 1.8 years, irrespective of sex. HbA1c goal attainment increased from 58% to 65%, LDL-C from 56% to 65%, and systolic BP from 57% to 72%. CONCLUSION: Despite highly organised diabetes care, excess incident cardiovascular events and mortality due to T2DM did not decrease over the study period. Life expectancy of T2DM patients is significantly reduced and risk factor control is suboptimal. This suggests there is considerable room for improvement of diabetes care in the Netherlands.

Changes in glucose-lowering drug use before and after cancer diagnosis in patients with diabetes.

AIM: This study explores the changes in glucose-lowering drug (GLD) use before and after cancer diagnosis among patients with diabetes. METHODS: New GLD users (1998-2011) living in the Dutch ECR-PHARMO catchment area were selected from the PHARMO Database Network (n=52,228). Those with a primary cancer diagnosis were considered cases (n=3281) and matched with eligible controls (n=12,891) without cancer during follow-up. Conditional logistic regression analysis was used to assess changes in GLD use, such as treatment add-ons, treatments drops and initiation of insulin, for cases compared with controls associated with specific cancer types in four time windows (6-3 and 0-3months before cancer diagnosis; 0-3 and 3-6months after cancer diagnosis). RESULTS: In the 3months before cancer diagnosis, patients with upper gastrointestinal (GI) cancers (oesophageal, stomach, pancreatic, liver cancers) had higher odds of initiating insulin (OR: 9.3; 95% CI: 3.6-24.1); to a lesser extent, this was also observed in the 3months prior to that (at 6months, OR: 3.9; 95% CI: 1.3-12.1). Diagnosis of colorectal (OR: 3.4; 95% CI: 1.4-8.4), pulmonary (OR: 2.5; 95% CI: 1.1-5.4) and upper GI (OR: 13.6; 95% CI: 5.0-36.9) cancers was associated with increased odds of initiating insulin in the 3months after cancer diagnosis. During all study time windows, the odds of treatment drops were higher for patients with upper GI cancers whereas, for most other cancers, these odds were higher only after a diagnosis of cancer. CONCLUSION: The greater odds of initiating insulin during the 6months prior to diagnosis of upper GI cancers suggest reverse causation. After cancer diagnosis, drops in use of GLDs was commonly seen.

[Prevalence of diabetes mellitus in the Netherlands more than doubled in the period 1999-2014]. / Meer dan verdubbeling van de prevalentie van diabetes.

OBJECTIVE: To study the trend in the prevalence of diabetes in the Netherlands during the period 1999-2014. DESIGN: Descriptive study of prevalence. METHODS: The prevalence of diabetes during the period 1999-2014 was calculated on the basis of data from the PHARMO Database Network, a network of electronic databases that includes data from public pharmacies for 3.8 million residents of the Netherlands. A person with diabetes was defined as someone with at least two dispensings for a glucose lowering-drug within six months. Prevalence was adjusted for variation in age demographics per sex to investigate the influence of these variations on population demographics. RESULTS: The prevalence of diabetes in the Netherlands increased from 1.8% in 1999 to 4.9% in 2014. The increase was more pronounced among men as age increased. Only half of the increase was explained by changes in age demographics per sex. CONCLUSION: The study showed that the prevalence of diabetes more than doubled during the period 1999-2014. This trend can only be partly explained by changes in age demographics per sex.

Increased overall drug utilization in patients with psoriasis: a case-control study based on Dutch general practitioner data.

BACKGROUND: Medication use in patients with psoriasis has been studied mostly in the context of psoriasis comorbidities. OBJECTIVES: To investigate detailed drug utilization in patients with psoriasis compared with controls in a population-based sample. METHODS: This was a case-control study based on drug prescriptions derived from a Dutch general practitioner database where patients with psoriasis and controls without psoriasis were matched 1 : 1 for age, sex, general practitioner and duration of follow-up, between 2002 and 2012. We calculated Mantel-Haenszel odds ratios (ORs) and 95% confidence intervals (CIs) for all therapeutic groups and chemical substances. RESULTS: In total 17 627 patients with psoriasis and 17 627 controls were followed for > 4 years. Overall 20% of patients with psoriasis received no psoriasis treatment and 8% had moderate-to-severe disease. During the entire follow-up a mean of nine unique drugs were prescribed in patients with psoriasis; this was significantly higher than in controls (mean of seven). Drug use did not peak around the date of diagnosis for psoriasis, but remained constant over time. All of the most commonly prescribed therapeutic groups were significantly more often prescribed in patients with psoriasis than in controls. These included drugs associated with psoriasis symptoms and treatment (OR 2·17, 95% CI 2·07-2·28 and OR 22, 95% CI 21-25, respectively), drugs related to psoriasis comorbidities (1·46, 95% CI 1·39-1·53) and a proportion of drugs that were a priori not expected to be increased in patients with psoriasis, such as nasal preparations and laxatives. CONCLUSIONS: Patients with psoriasis received more prescriptions for all drugs, regardless of associated comorbidities. This overall increased use of drugs suggests an increased healthcare utilization in patients with psoriasis identified in routine databases.

Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study.

UNLABELLED: Analyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely ruled out. The observed tendency for decreased valvulopathy risk with cumulative duration of bisphosphonate use >6 months may even indicate a protective effect with prolonged use. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy. INTRODUCTION: A signal of cardiac valve disorders with use of bisphosphonates was identified in the literature and EudraVigilance database, which contains reports of suspected adverse drug reactions from worldwide sources. The aim of this study was to evaluate the association using population-based healthcare data. METHODS: This was a case-control study among users of bisphosphonates and other drugs for osteoporosis in six healthcare databases covering over 30 million individuals in Italy, Netherlands and the UK from 1996 to 2012. Prescriptions/dispensations were used to assess drug exposure. Newly diagnosed cases of cardiac valvulopathy were identified via disease codes/free-text search. Controls were matched to each case by age, sex, database and index date. Adjusted odds ratios (ORs) were estimated using conditional logistic regression for the pooled data and meta-analysis of individual database risk estimates. RESULTS: A small but statistically significant association was found between exposure to bisphosphonates as a class and risk of valvulopathy. Overall risk was 18 % higher (95 % CI 12-23 %) in those currently exposed to any bisphosphonate (mainly alendronate and risedronate) vs. those not exposed within the previous year. Risk of valve regurgitation was 14 % higher (95 % CI 7-22 %). Decreased valvulopathy risk was observed with longer cumulative duration of bisphosphonate use, compared to use of less than 6 months. Meta-analyses of database-specific estimates confirmed results from pooled analyses. CONCLUSIONS: The observed increased risks of cardiac valvulopathy with bisphosphonate use, although statistically significant, were quite small and unlikely to be clinically significant. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy and to investigate possible mechanisms for the association.

Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another?

BACKGROUND: Metformin, statin and aspirin use seem associated with decreased mortality in cancer patients, though, without adjusting for one another. Independent associations of these drugs with overall mortality after colorectal cancer (CRC) diagnosis within glucose-lowering drugs (GLDs) users were assessed. METHODS: Patients starting GLDs before CRC diagnosis (1998-2011) were selected from the Eindhoven Cancer Registry linked with the PHARMO Database Network. The Cox regression model, with time since CRC diagnosis, included time-dependent variables of cumulative exposure to metformin, statins and aspirin after cancer diagnosis and time-dependent ever-never terms for drug exposure. RESULTS: A total of 1043 patients used GLDs before CRC diagnosis; 666 (64%) used metformin, 639 (61%) used statins and 490 (47%) used aspirin after CRC diagnosis. Multivariable analyses revealed that longer cumulative exposure to metformin was not associated with overall mortality (HRCumulative exposure/6 months 1.02; 95% CI 0.97-1.07), whereas the favourable effect of statins increased with cumulative exposure (HRCumulative exposure/6 months 0.93; 95% CI 0.89-0.98). No association between aspirin use and overall mortality was seen (HRCumulative exposure/6 months 0.98; 95% CI 0.93-1.03). CONCLUSIONS: No independent association between cumulative exposure to metformin, aspirin and overall mortality was found. Cumulative exposure to statins after CRC diagnosis was associated with lower overall mortality, supporting a drug effect of statins among GLDs users.

Long term trends in oral antidiabetic drug use among children and adolescents in the Netherlands.

AIM: The aim of the study was to document long term trends in oral antidiabetic drug (OAD) use among children and adolescents in the Netherlands. METHODS: A population-based cohort study was conducted using the Dutch PHARMO Database Network. All patients younger than 20 years old with at least one OAD dispensing were identified. Age-adjusted and age-specific incidence (1999-2011) and prevalence (1998-2011) rates of OAD use were calculated. Trends over time were assessed using joinpoint regression software. A subset of PHARMO Database Network (including community pharmacy dispensing records linked to general practitioner data (OPD-GP database)) was used to assess indications for OADs. RESULTS: In 2011, the overall age-adjusted incidence and prevalence rates of OAD use were 20.7/100 000 (95% CI 19.2, 22.1) person-years (PY) and 53.8/100 000 (95% CI 51.5, 56.1) persons, respectively. The average annual percentage change (AAPC) in the overall age-adjusted incidence rates from 1999 to 2011 was 18.9% (95% CI 4.5, 35.2). The incidence and prevalence rates of OAD use were higher among females and older age categories. The increases in rates of OAD use were mainly driven by metformin. For only 50% of the 98 patients in the OPD-GP database, indications for OAD prescriptions were reported with type 1 diabetes (n = 20), type 2 diabetes (n = 16), and overweight/obesity (n = 10). CONCLUSIONS: Incidence and prevalence rates of OAD use in children and adolescents substantially increased in the Netherlands, especially among older age categories (10-14 and 15-19 years) and females. The main indications for use of OADs were type 1 and 2 diabetes and overweight/obesity.

Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population-based study.

OBJECTIVE: To study the dispensing of potentially teratogenic drugs in the 12-month period before as well as during pregnancy in the Netherlands. DESIGN: Population-based study. SETTING: A cohort was constructed using a linkage between the PHARMO Database Network and the Netherlands Perinatal Registry (PRN). POPULATION: A total of 203 962 Dutch pregnancies reported between 1999 and 2007 METHODS: Drug-dispensing information was identified from the PHARMO Database Network for the 12-month period before conception and during pregnancy. Drugs with either a Swedish FASS 'D' classification, an Australian ADEC or American FDA 'D' or 'X' classification were considered potentially teratogenic (n = 202). MEAN OUTCOME MEASURES: Proportion of pregnancies that received potentially teratogenic drugs in the 12-month period before and during pregnancy and specific for the risk category X drugs and newly initiated drugs. RESULTS: Sixteen percent of the pregnancies received a potentially teratogenic drug in the 12-month period before and 5.07% during pregnancy. Doxycycline and paroxetine were most frequently received during pregnancy by 1.01% and 0.85% of women, respectively; 0.66% of the women received a risk category X drug during pregnancy which most frequently consisted of triptorelin (0.25%), norethisterone (0.22%) and simvastatin (0.03%). Fifty-three percent of the women who received a potentially teratogenic drug during pregnancy received this for the first time during the study period. These percentages were heterogeneous between therapeutic drug classes. CONCLUSIONS: Five percent of the pregnancies received a potentially teratogenic drug during pregnancy and 0.66% received a drug from the risk category X. It may be possible to reduce these proportions when reasons for prescription have been explored.

Risk of fractures in patients with multiple sclerosis: a population-based cohort study.

OBJECTIVE: To examine the risk of fracture in patients with multiple sclerosis (MS) compared with population-based controls. METHODS: A population-based cohort study was performed in the Dutch PHARMO Record Linkage System (1998-2008). Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to up to 6 patients without MS (controls). We used Cox proportional hazards models to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments were made for age, history of disease, and drug use. RESULTS: During follow-up, there were 59 fractures among patients with MS (2.4%) and 227 fractures among controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic fracture (HR 1.73 [95% confidence interval (CI) 1.18-2.53]) and a 4-fold increased risk of hip fracture (HR 4.08 [95% CI 2.21-7.56]). The risk of osteoporotic fracture was significantly greater for patients with MS who had been prescribed antidepressants (HR 3.25 [95% CI 1.77-5.97]) or hypnotics/anxiolytics (HR 3.40 [95% CI 2.06-5.63]) in the previous 6 months, compared with controls. CONCLUSIONS: Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics.

Use of aspirin postdiagnosis improves survival for colon cancer patients.

BACKGROUND: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. METHODS: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998-2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure. RESULTS: In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63-0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50-0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46-0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79-1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70-2.20; P<0.001). CONCLUSION: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of a placebo-controlled trial that investigates the role of aspirin as adjuvant treatment in colon cancer patients.

Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study.

AIMS/HYPOTHESIS: Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. METHODS: Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes. RESULTS: Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified. CONCLUSION/INTERPRETATION: Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin.

Platelet aggregation inhibitors, vitamin K antagonists and risk of subarachnoid hemorrhage.

BACKGROUND: Use of platelet aggregation inhibitors and vitamin K antagonists has been associated with an increased risk of intracranial hemorrhage (ICH). Whether the use of these antithrombotic drugs is associated with an increased risk of subarachnoid hemorrhage (SAH) remains unclear, especially as confounding by indication might play a role. OBJECTIVE: The aim of the present study was to investigate whether use of platelet aggregation inhibitors or vitamin K antagonists increase the risk of SAH. METHODS: We applied population-based case-control, case-crossover and case-time-control designs to estimate the risk of SAH while addressing issues both of confounding by indication and time varying exposure within the PHARMO Record Linkage System database. This system includes drug dispensing records from community pharmacies and hospital discharge records of more than 3 million community-dwelling inhabitants in the Netherlands. Patients were considered a case if they were hospitalized for a first SAH (ICD-9-CM code 430) in the period between 1st January 1998 and 31st December 2006. Controls were selected from the source population, matched on age, gender and date of hospitalization. Conditional logistic regression was used to estimate multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of SAH during use of platelet aggregation inhibitors or vitamin K antagonists. In the case-crossover and case-time-control designs we selected 11 control periods preceding the index date in successive steps of 1 month in the past. RESULTS: In all, 1004 cases of SAH were identified. In the case-control analysis the adjusted OR for the risk of SAH in current use of platelet aggregation inhibitors was 1.32 (95% CI: 1.02-1.70) and in current use of vitamin K antagonists 1.29 (95% CI: 0.89-1.87) compared with no use. In the case-crossover analysis the ORs for the risk of SAH in current use of platelet aggregation inhibitors and vitamin K antagonists were 1.04 (95% CI: 0.56-1.94) and 2.46 (95% CI: 1.04-5.82), respectively. In the case-time-control analysis the OR for platelet aggregation inhibitors was 0.50 (95% CI: 0.26-0.98) and for vitamin K antagonists 1.98 (95% CI: 0.82-4.76). CONCLUSION: The use of platelet aggregation inhibitors was not associated with an increased SAH risk; the modest increase observed in the case-control analysis could be as a result of confounding. The use of vitamin K antagonists seemed to be associated with an increased risk of SAH. The increase was most pronounced in the case-crossover analysis and therefore cannot be explained by unmeasured confounding.

Characteristics and drug utilization patterns of new users of rosuvastatin and other statins in four countries.

AIM: This study was undertaken to increase understanding of the utilization of a newly introduced statin through evaluation of characteristics of 'real-life' patients in a pharmacoepidemiology program in the USA, the Netherlands, the UK and Canada. METHODS: This was an observational analysis of prospectively collected data from primary care patients classified as new users of rosuvastatin or any other statin. New users (naïve or switched initiators) of rosuvastatin were compared with initiators of other statins, as identified from automated healthcare databases in the first 1 to 2 years of rosuvastatin availability. Demographics, statin doses, previous statin use and other lipid-lowering therapies, and relevant comorbidities were recorded. The main outcome measure was proportion of naïve and non-naïve statin users in patients prescribed rosuvastatin or 'other statins'. RESULTS: Among 346.547 new statin users identified in the cohorts, 46.838 (13.5%) were new users of rosuvastatin and most (84.1%) were statin-naïve. Patients receiving rosuvastatin were more likely to have been previously treated with another statin or non-statin lipid-lowering therapy and tended to be younger, compared with first users of other statins. CONCLUSION: These findings suggest that rosuvastatin is preferentially prescribed to patients who have not responded satisfactorily to established treatment.

Melanoma incidence and exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

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.

Estimated age- and sex-specific incidence and prevalence of dopamine agonist-treated hyperprolactinemia.

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 and sex. 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: The incidence 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.