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Observational and intervention studies suggest that low dose aspirin use may prevent cancer. The objective of this study was to investigate the protective effect of long term low dose aspirin use (≤100 mg daily) on cancer in general and site-specific cancer among low dose aspirin users in the Dutch general population. We conducted a population-based cohort study with detailed information on aspirin exposure and cancer incidence. Only incident (new) low dose aspirin users, who were included in the linkage between PHARMO and the Eindhoven Cancer Registry (1998-2010) and free of cancer before the start of follow up were included. A Cox proportional hazard model with cumulative aspirin use as a time-varying determinant was used to obtain hazard ratios (HR). Duration of aspirin use amongst 109,276 incident low dose aspirin users was not associated with a decreased risk of any of the site-specific cancers or cancer in general (adjusted HR per year of aspirin use for all cancers: 1.02, 95% confidence interval [CI] 1.00-1.04, HR of >6 years aspirin use compared to <2 years: 1.17, 95% CI 1.02-1.34). After adjusting for current and past aspirin use, 2-6 years of low dose aspirin use was associated with a reduced colorectal cancer risk compared to <2 years of aspirin use (adjusted HR 0.75, 95% CI 0.59-0.96). However, a clear dose-response relationship was not observed (adjusted HR >6 years aspirin use 0.95, 95% CI 0.60-1.49). Our results do not support the primary prevention of cancer among long term aspirin users., (© 2013 UICC.)

Importance: Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects., Objective: To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression., Design, Setting, and Participants: A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival., Main Outcomes and Measures: Overall survival., Results: The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44)., Conclusions and Relevance: Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.

Background: Results from preclinical and observational studies suggest that β-adrenoreceptor inhibition might influence disease progression of melanoma., Patients and Methods: Patients ⩾18years with cutaneous melanoma (Breslow thickness >1mm) registered in the Eindhoven Cancer Registry between January 1, 1998 and December 31, 2010, who were also registered with PHARMO record linkage system (RLS), were eligible. Randomly selected patients using β-blockers from PHARMO record linkage system (RLS) matched on age and gender served as a control cohort. Adjusted time-dependent and time-fixed Cox proportional hazard models were employed to estimate the hazard ratio of all-cause mortality. Five-year relative survival rates for all-cause mortality were calculated to estimate disease specific survival., Results: 203 of 709 eligible patients used β-blockers after melanoma diagnosis. The use of β-blockers was not associated with the risk of dying (adjusted hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.55-1.24). Neither duration of exposure nor β-blocker dosage showed significant influence on survival. Five-year relative survival for β-blocker users was lower than in non-users amongst melanoma patients (80.9% and 83.7%, respectively) but higher among the β-blocker control group compared to the general population (101.4%)., Conclusion: Our results do not show a statistically significant impact of β-blocker exposure on overall survival of melanoma patients, regardless of the timing, duration or dosage of β-blocker use., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: In this cohort study, the rates of pulmonary embolism (PE), myocardial infarction (MI), and ischemic stroke (IS) before and after lung cancer (LC) diagnosis were compared to cancer-free controls., Methods: Patients with LC during 2000-2007 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO medical record linkage system, including drug use and hospitalizations of 3 million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. Hospitalizations for PE, MI, and IS were assessed in the 12 months before and after LC diagnosis., Results: LC patients (N = 3,717) were six times more likely than cancer-free controls to have had a PE in the 12 months before diagnosis. After LC diagnosis, patients experienced an extremely increased risk of PE in the first 6 months (hazard ratio [HR] 16.8; 95 % confidence interval [CI] 7.6-36.8) compared with controls), which decreased to a five times increased risk (HR 5.1; 95 % CI 2.7-9.4) thereafter. However, there were less than two events per 100 person years during both time periods. LC patients receiving chemotherapy were eight times more likely to develop PE, whereas surgery increased the risk on PE three times. For MI and IS, no significant difference was observed compared with cancer-free controls before or after LC diagnosis., Conclusions: LC patients have a higher risk of developing PE compared with cancer-free controls, although the frequency of PE hospitalizations was low. Surgery and chemotherapy were associated with an increased risk of PE.

There is little information available on the patterns of chemotherapy regimens administered in daily practice to patients with early stage and metastatic or recurrent breast cancer. To determine the trends in type of chemotherapy regimens used in breast cancer patients, newly diagnosed breast cancer patients in the period 2000-2008 who received chemotherapy were identified from the Eindhoven Cancer Registry (ECR) and linked to the PHARMO RLS, including data on, e.g., in- and outpatient drug use. Chemotherapy regimens were classified based on the received combinations and sequences. Trends in the distribution of adjuvant chemotherapy regimens (for early-stage breast cancer) and palliative chemotherapy regimens (for metastatic or recurrent breast cancer) were determined and stratified by Her2/neu status when possible. In this study, 422 patients diagnosed with early-stage breast cancer received adjuvant chemotherapy. The use of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) decreased from 90% in 2000 to almost none since 2005. Administration of regimens that included anthracyclines increased from 4% in 2000 to 96% in 2005, but decreased to 68% in 2008. The use of trastuzumab- and taxane-containing regimens (with or without anthracyclines) increased from 2005 onwards to 24% and 34%, respectively, in 2008. Among the 82 breast cancer patients who received palliative chemotherapy at diagnosis or after breast cancer recurrence, the use of CMF and anthracyclines (without taxanes) decreased, while the use of taxanes (with or without anthracyclines) increased (26% in 2008). Trastuzumab was used as palliative chemotherapy from 2003 onwards, with 22% of the metastatic breast cancer patients receiving trastuzumab-containing regimens in 2008, and bevacizumab was administered since 2007 with 19% of the patients receiving bevacizumab-containing regimens in 2008. In conclusion, major changes have taken place in the chemotherapeutic treatment of patients with early and recurrent breast cancer. These changes reflect the key findings from large clinical trials, as incorporated in the Dutch guidelines., (© 2013 Wiley Periodicals, Inc.)

Tamoxifen is a largely inactive pro-drug, requiring metabolism into its most important metabolite endoxifen. Since the cytochrome P450 (CYP) 2D6 enzyme is primarily involved in this metabolism, genetic polymorphisms of this enzyme, but also drug-induced CYP2D6 inhibition can result in considerably reduced endoxifen formation and as a consequence may affect the efficacy of tamoxifen treatment. Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) have been effectively used for the treatment of depression and hot flashes, both of which occur frequently in tamoxifen-treated women. Due to the drug-drug interaction considerably reduced endoxifen concentrations by inhibition of CYP2D6 will be the result. Evidence of a significant influence of strong CYP2D6-inhibiting drugs on the pharmacokinetics of tamoxifen has resulted in recommendations to avoid potent CYP2D6-inhibiting antidepressants (e.g., paroxetine, fluoxetine) in patients treated with tamoxifen for breast cancer. Nevertheless, dispensing data for tamoxifen and seven regularly used SSRIs/SNRIs in the period between 2005 and 2010, obtained from a large community pharmacy database in the Netherlands (3,000,000 people), show that the potent CYP2D6-inhibiting drug paroxetine remains one of the most frequently used antidepressants in tamoxifen-treated patients. Moreover, trends in the use of SSRIs/SNRIs in the population of all women were similar with trends in women using tamoxifen. Apparently, the recommendations to avoid paroxetine in tamoxifen-treated women have not been implemented into clinical practice. Several reasons may underlie continued use of this drug-drug combination. Contrary to CYP2D6 polymorphisms, drug-induced CYP2D6 inhibition can easily be avoided, since alternative drugs are available. In clinical practice, one should strive to avoid potent CYP2D6 inhibitors as much as possible in tamoxifen-treated patients to reduce the risk of compromising the efficacy of the hormonal therapy. Co-medication should be reviewed by both physicians and pharmacists and potent CYP2D6 inhibitors ought to be switched to weaker alternatives.

Objectives: To assess survival in relation to aspirin use after diagnosis in older adults with colon cancer., Design: Subgroup analysis of a previously published cohort and retrospective study., Setting: Individuals registered in the Eindhoven Cancer Registry (ECR) between 1998 and 2007, linked to prescriptions of low-dose aspirin (80 mg) registered in a community pharmacy database., Participants: Five hundred thirty-six individuals aged 70 and older diagnosed with colon cancer with or without aspirin use after diagnosis., Measurements: Survival was analyzed with user status as a time-dependent covariate. Multivariate Poisson regression survival models were used to study the effect of aspirin on overall survival., Results: One hundred seven participants (20.0%) started aspirin after being diagnosed with colon cancer; 429 (80.0%) were not prescribed aspirin. Three hundred thirty-nine participants (63.2%) had died by the end of follow-up. Aspirin use after diagnosis was associated with longer overall survival (rate ratio (RR) = 0.51, 95% confidence interval (CI) = 0.38-0.70, P < .001). Multivariate proportional hazards regression analysis revealed that aspirin use was associated with longer overall survival (adjusted RR = 0.59, 95% CI = 0.44-0.81, P = .001)., Conclusion: Aspirin use after the diagnosis of colon cancer in older adults was associated with longer survival. Low-dose aspirin could be used as an effective adjuvant therapy in older adults with colon cancer., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Purpose: In recent years, the number of oral anticancer agents has increased substantially. Although these agents have quickly been incorporated in the treatment of a variety of malignancies, data on their incidence, prevalence and costs are lacking. The objective of the present study was to obtain insight into the use and the costs of oral anticancer agents (with Anatomical Therapeutic Chemical classification system (World Health Organisation) code L01) in the Netherlands between 2000 and 2008., Methods: Incidence and prevalence were determined using community pharmacy dispensing records obtained from the PHARMO Record Linkage System database. The data of costs were provided by the Genees- en hulpmiddelen Informatie Project of the Dutch Health Care Insurance Board (CVZ, Diemen, The Netherlands)., Results: In the years 2000-2008, the use of oral anticancer agents has more than doubled from 64 to 140 users per 100 000 inhabitants. The increase is mainly caused by the prescription of capecitabine for various indications. There was a 50-fold rise in costs on oral anticancer agents from €2 m in 2000 to approximately €100 m in 2008. The share in the costs of tyrosine kinase inhibitors (TKIs) in 2008 was 67% (€70 m) with the oldest TKI, imatinib, having a share of more than 50% within the group of TKIs., Conclusions: The increased use of oral anticancer agents is mainly due to the frequent prescription of capecitabine. The increased costs are caused by the registration of a variety of TKIs, in particular imatinib. The costs of new agents with an orphan drug status are very high as compared with those of capecitabine, a newer agent for which there are alternative treatment options., (Copyright © 2011 John Wiley & Sons, Ltd.)

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.

Background: Limited data exist on the burden of comorbidity among patients with squamous cell head and neck cancer (SCCHN) before and during cancer treatment., Methods: The precancer prevalence and incidence rates of 8 comorbid conditions were estimated among a population-based cohort of 1499 patients with SCCHN in the Netherlands. Patients with cancer, treatments, and comorbidities were identified in the PHARMO Record Linkage System (RLS) using hospital admissions and/or dispensing codes. Prevalence proportions and incidence rates were also compared against a matched cancer-free population., Results: Cardiovascular (41%) and respiratory diseases (12%) were the most prevalent comorbidities. Incidence rates of most comorbidities were highest the first 6 months after cancer diagnosis and decreased over time. Patients receiving chemotherapy-based treatment had significantly higher incidence rates of anemia and other malignant diseases., Conclusions: High rates of acute and chronic comorbidity were observed; knowledge of comorbidity burden aids in establishing a benefit-risk profile for investigational SCCHN therapies., (Copyright © 2011 Wiley Periodicals, Inc.)

Background. Data is limited on the burden of common comorbidities, such as cardiovascular disease (CVD), respiratory disease and diabetes, or comorbidities related to cancer and its treatment, such as anemia and depression, in patients with soft tissue sarcoma (STS). Patients and Methods. From the Dutch Pathology Registry linked to the PHARMO database (including data on drug use and hospitalizations), 533 patients with STS were selected during 2000-2007 and matched 1 : 10 to cancer-free controls. The occurrences of comorbidities were assessed in the 12 months before and after STS diagnosis. Results. STS patients were 2-4 times more likely to have comorbidities at diagnosis compared with cancer-free controls. The incidence of CVD, anemia, and depression after STS diagnosis differed significantly from cancer-free controls and decreased during followup from 40-124 per 1,000 person-years (py) during the first six months to 11-38 per 1,000 py more than 12 months after diagnosis. The incidence of respiratory disease and diabetes among STS patients remained stable during followup (5-21 per 1,000 py) and did not differ significantly from cancer-free controls. Conclusions. STS patients were more likely to have comorbidities before cancer diagnosis and to develop CVD, anemia, and depression after diagnosis compared to cancer-free controls.

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.

We studied the occurrence of myocardial infarction (MI), ischaemic stroke (IS) and pulmonary embolism (PE) before and after breast cancer hospitalisation compared with cancer-free controls. For this, women with a first breast cancer hospitalisation during 2000-2007 were selected from the PHARMO Record Linkage System, including drug use and hospitalisations of three million inhabitants in the Netherlands, and matched 1:10 by age to cancer-free women. The occurrence of MI, IS and PE were assessed in the 12 months before and after breast cancer hospitalisation. The study included 11,473 breast cancer patients, with a mean (± SD) age of 59 (± 14) years. Breast cancer patients were two to three times as likely as their cancer-free controls to have had a hospitalisation for PE, MI or IS in the 12 months before diagnosis, though prevalence was <1% in all groups. Breast cancer patients experienced an extreme high risk of PE in the first six months after diagnosis (hazard ratio [HR] 23.5, 95% confidence interval [CI] 11.1-49.7 compared to controls), which declined gradually to a four times increased risk (HR 3.6, 95%CI 2.4-5.5) more than 12 months after breast cancer hospitalisation. However, incidence was low: less than five events per 1,000 person years during all time periods. For MI and IS we did not observe significant increased HRs after breast cancer hospitalisation compared to controls. Breast cancer patients seem to have a higher risk profile to develop MI and IS, and receive treatment that increases the risk of PE compared to cancer-free controls, although the frequency of hospitalisations was low.

Background: In the last decade, the number of new agents, including monoclonal antibodies, being developed to treat metastatic colorectal cancer (mCRC) increased rapidly. While improving outcomes, these new treatments also have distinct and known safety profiles with toxicities that may require hospitalizations. However, patterns and costs of hospitalizations of toxicities of these new 'targeted' drugs are often unknown., Objective: This study aimed to estimate the costs of hospital events associated with adverse events specified in the 'Special Warnings and Precautions for Use' section of the European Medicinal Agency Summary of Product Characteristics for bevacizumab, cetuximab, and panitumumab, in patients with mCRC., Methods: From the PHARMO Record Linkage System (RLS), patients with a primary or secondary hospital discharge code for CRC and distant metastasis between 2000-2008 were selected and defined as patients with mCRC. The first discharge diagnosis defining metastases served as the index date. Patients were followed from index date until end of data collection, death, or end of study period, whichever occurred first. Hospital events during follow-up were identified through primary hospital discharge codes. Main outcomes for each event were length of stay and costs per hospital admission., Results: Among 2964 mCRC patients, 271 hospital events occurred in 210 patients (mean [SD] duration of follow-up: 34 [31] months). The longest mean (SD) length of stay per hospital admission were for stroke (16 [33] days), arterial thromboembolism (ATE) (14 [21] days), wound-healing complications (WHC), acute myocardial infarction (AMI), congestive heart failure (CHF), and neutropenia (all 9 days; SD 5-15). Highest mean (SD) costs per admission were for stroke (€13,500 [€28,800]), ATE (€13,300 [€18,800]), WHC (€10,800 [€20,500])., Limitations: Although no causal link could be identified between any specific event and any specific treatment, data from this study are valuable for pharmacoeconomic evaluations of newer treatments in mCRC patients., Conclusions: Inpatient costs for events in mCRC patients are considerable and vary greatly.

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 of tamoxifen, 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.

Purpose: The use of cytochrome P450 2D6-inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in patients with breast cancer. The objectives of this study were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event-free time (EFT)., Patients and Methods: Data were from PHARMO and included a community pharmacy dispensing database; PALGA, a nationwide pathology database; and the Dutch Medical Register in the Netherlands. Patients with breast cancer treated with adjuvant tamoxifen between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for concomitant CYP2D6 inhibitor exposure was used. Adherence calculated over the first year after tamoxifen initiation was related to breast cancer events in the following period., Results: In total, 1,962 patients with breast cancer using tamoxifen were included, among whom 150 (7.6%) frequently used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed (adjusted hazard ratio [HR], 0.87; 95% CI, 0.42 to 1.79; P = .69). Poor tamoxifen adherence was associated with lower EFT (adjusted HR, 0.987; 95% CI, 0.975 to 0.999; P = .029)., Conclusion: This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen despite the strong biologic rationale. This study shows, to the best of our knowledge for the first time, that poor tamoxifen adherence is associated with an increased risk of breast cancer events.

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., (Copyright 2009 Elsevier Ltd. All rights reserved.)

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 John Wiley & Sons, Ltd.)

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.