Soest, E.M. van

Prescription of nonselective NSAIDs, coxibs and gastroprotective agents in the era of rofecoxib withdrawal - A 617 400-patient study (Article)

2012-10-01T00:00:00Z

Background Gastroprotective strategies are recommended for nonsteroidal anti-inflammatory drug (NSAID) users at risk of upper gastrointestinal (UGI) complications. Aim To compare the use of gastroprotective strategies in NSAID users in three countries, and the subsequent impact of rofecoxib withdrawal. Methods We conducted a population-based cohort study in three general practice (GP) databases: (i) United Kingdom's (UK) GP Research Database (1998-2008); (ii) Italy's (IT) Health Search/CSD Longitudinal Patient Database (2000-2007); and (iii) the Dutch (NL) Integrated Primary Care Information database (1996-2006). Study cohorts comprised incident NSAID users ≥50 years. Preventive strategies included: (i) co-prescription of gastroprotective agents; or (ii) cyclooxygenase-2-selective inhibitor use. Under-use was defined as no gastroprotection in patients with ≥1 UGI risk factor (history of UGI event, age ≥65 years, concomitant use of anticoagulants, antiplatelets or glucocorticoids). Interrupted time-series analysis was performed to assess the impact of rofecoxib withdrawal on preventive strategies. Results The study populations consisted of 384 649 UK, 177 747 IT and 55 004 NL NSAID users. In UK, under-use of preventive strategies fell from 91% to 71% [linear trend (lt) P = 0.001], in NL from 92% to 58% (lt P < 0.001) and in IT from 90% to 76% (lt P = 0.38) in high-risk NSAID users. In 2000 and 2006, under-use was significantly lower in NL compared with UK and IT (P < 0.001) in high-risk users. After rofecoxib's withdrawal, under-use increased significantly in UK and NL. Conclusions The prescription of gastropreventive strategies followed a similar pattern across countries. Despite a temporary negative effect of rofecoxib withdrawal on under-use, improvement of gastroprotection with nonsteroidal anti-inflammatory drugs was observed.

The risk of new onset heart failure associated with dopamine agonist use in Parkinson's disease (Article)

2012-03-01T00:00:00Z

The aim of present study was to investigate the risk of heart failure associated with dopamine agonist use in patients with Parkinson's disease. The data sources of this study were four different population-based, healthcare databases in United Kingdom, Italy and Netherlands. A case control study nested within a cohort of Parkinson's disease patients who were new users of either dopamine agonist or levodopa was conducted. Incident cases of heart failure were identified and validated, using Framingham criteria. Controls were matched to cases on age, gender and database. To estimate the risk of newly diagnosed heart failure with ergot and non-ergot derived dopamine agonists, as compared to levodopa, odds ratios and 95% confidence intervals were calculated through conditional logistic regression. In the cohort of 25,459 Parkinson's disease patients (11,151 new users of dopamine agonists, 14,308 new users of levodopa), 518 incident heart failure cases were identified during follow-up. Compared to levodopa, no increased risk of heart failure was found for ergot dopamine agonists (odds ratio: 1.03; 95% confidence interval: 0.69-1.55). Among non-ergot dopamine agonists, only pramipexole was associated with an increased risk of heart failure (odds ratio: 1.61; 95%confidence interval: 1.09-2.38), especially in the first three months of therapy (odds ratio: 3.06; 95% confidence interval: 1.74-5.39) and in patients aged 80 years and older (odds ratio: 3.30; 95% confidence interval: 1.62-7.13). The results of this study indicate that ergot dopamine agonist use in Parkinson's disease patients was not associated with an increased risk of newly diagnosed heart failure. Among non-ergot dopamine agonists, we observed a statistically significant association between pramipexole use and heart failure, especially during the first months of therapy and in very old patients.

Guillain-Barré syndrome: Background incidence rates in the Netherlands (Article)

2011-09-01T00:00:00Z

Guillain-Barré syndrome (GBS) is a (sub)acute polyradiculoneuropathy, which may occur following immunization. To interpret the occurrence of GBS after introduction of large-scale immunization programmes, it is important to define recent background incidence rates (IRs) of GBS. We used a general practitioner electronic medical record database to assess age-specific GBS IRs between 1996 and 2008 in The Netherlands. All possible GBS cases were manually reviewed. Validated incident cases were reviewed by a neurologist (B. J.) for diagnostic certainty using the GBS case definition of the Brighton Collaboration (BC). In a population of 638,891 persons, we identified 23 validated incident GBS cases (mean age 46 years). IR was 1.14 per 100,000 person years (95% confidence interval [CI] 0.67-1.61) and was lower for people under 50 years (0.76; 95%CI 0.41-1.32) compared with elderly of 50 years or older (1.80; 95%CI 0.98-3.05). Only six cases fulfilled level 1 or 2 of diagnostic certainty of the BC case definition. IR of GBS increases with age. As vaccinations are often targeted at specific age groups, age-specific rates should be used to monitor GBS observed versus expected rates after introduction of large-scale vaccination programmes.

Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: An observational study using three European databases (Article)

2011-06-02T00:00:00Z

Background: Gastro-protective agents (GPA) are co-prescribed with non-steroidal anti-inflammatory drugs (NSAID) to lower the risk of upper gastrointestinal (UGI) events. It is unknown to what extent the protective effect is influenced by therapy adherence. Aim: To study the association between GPA adherence and UGI events among non-selective (ns) NSAID users. Methods: The General Practice Research Database (UK 1998e2008), the Integrated Primary Care Information database (the Netherlands 1996-2007) and the Health Search/CSD Longitudinal Patient Database (Italy 2000-2007) were used. A nested case-control design was employed within a cohort of nsNSAID users aged ≥50 years, who also used a GPA. UGI event cases (UGI bleeding and/or symptomatic ulcer with/without obstruction/perforation) were matched to event-free members of the cohort for age, sex, database and calendar time. Adherence to GPA was calculated as the proportion of nsNSAID treatment days covered by a GPA prescription. Adjusted OR with 95% CI were calculated. Results: The cohort consisted of 618 684 NSAID users, generating 1 107 266 nsNSAID episodes. Of these, 117 307 (10.6%) were (partly) covered by GPA, 4.9% of which with a GPA coverage <20% (non-adherence), and 68.1% with a GPA coverage >80% (full adherence). 339 patients experienced an event. Among non-adherers, the OR was 2.39 (95% CI 1.66 to 3.44) for all UGI events and 1.89 (95% CI 1.09 to 3.28) for UGI bleeding alone, compared to full adherers. Conclusions: The risk of UGI events was significantly higher in nsNSAID users with GPA non-adherence. This underlines the importance of strategies to improve GPA adherence. Copyright Article author (or their employer) 2011.

Risk of recurrent myocardial infarction with the concomitant use of clopidogrel and proton pump inhibitors (Article)

2011-01-01T00:00:00Z

Background: The association between myocardial infarction (MI) and co-administration of proton pump inhibitors (PPIs) and clopidogrel remains controversial. Aim: To quantify the association between concomitant use of PPIs and clopidogrel and occurrence of recurrent MI. Methods: We conducted a case-control study within a cohort of acute MI patients in PHARMO Record Linkage System (1999-2008). The cases were patients readmitted for MI. PPI exposure was categorized as current (3-1 days before MI), past (30-3 days before MI), or no use (>30 days before MI). We used conditional logistic regression analyses. Results: Among 23 655 patients hospitalized following MI, we identified 1247 patients readmitted for MI. Among clopidogrel users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.62, 95% CI: 1.15-2.27) when compared with no PPI use, but not when compared with past PPI use (OR: 0.95, 95% CI: 0.38-2.41). Among clopidogrel non-users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.38, 95% CI: 1.18-1.61) when compared with no PPI use. Conclusions The apparent association between recurrent MI and use of PPIs with clopidogrel depends on the design, and is affected by confounding by indication. The association is not present when (un)measured confounding is addressed by design.

Association between calcium channel blockers and gingival hyperplasia (Article)

2010-07-01T00:00:00Z

Aim: To study the effect of the dose and type of calcium channel blockers (CCBs) on the risk of gingival hyperplasia and to quantify this association. Methods: The study was conducted within the Integrated Primary Care Information Project in The Netherlands. A nested case-control study was designed within a cohort of all patients who were new users of either CCBs or drugs interacting with the renin-angiotensin system (RAS). Cases were all individuals with a validated diagnosis of gingival hyperplasia. Controls were matched on age, gender and index date. Results: Within the study population, 103 cases of gingival hyperplasia were identified and matched to 7677 controls. The risk of gingival hyperplasia was higher in current users of CCBs [adjusted odds ratio (ORadj) 2.2, 95% confidence intervals (95% CI): 1.4-3.4], especially in dihydropyridines (ORadj2.1, 95% CI: 1.3-3.5) and benzothiazepine derivatives (ORadj2.9, 95% CI: 1.3-6.5) than in RAS drug users. The risk increased in patients using more than the recommended daily dose (ORadj3.0, 95% CI: 1.6-5.5) and when the duration of current use was <1 month (ORadj5.2, 95% CI: 2.1-12.6). Conclusion: This study shows that the risk of gingival hyperplasia is twofold higher in current users of CCBs than in users of RAS drugs. The association was dose dependent and the highest for dihydropyridines or benzothiazepine derivates.

Time-trends in gastroprotection with nonsteroidal anti-inflammatory drugs (NSAIDs) (Article)

2010-06-01T00:00:00Z

Background Preventive strategies are advocated in patients at risk of upper-gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs (NSAIDs). Aim To examine time-trends in preventive strategies. Methods In a study population comprising 50 126 NSAID users ≥50 years from the Integrated Primary Care Information database, we considered two preventive strategies: co-prescription of gastroprotective agents and prescription of a cyclooxygenase-2-selective inhibitor. In patients with ≥1 risk factor (history of upper-gastrointestinal bleeding/ulceration, age >65 years, use of anticoagulants, aspirin, or corticosteroids), correct prescription was defined as the presence of a preventive strategy and under-prescription as the absence of one. In patients with no risk factors, correct prescription was defined as the lack of a preventive strategy, and over-prescription as the presence of one. Results Correct prescription rose from 6.9% in 1996 to 39.4% in 2006 (P < 0.01) in high-risk NSAID users. Under-prescription fell from 93.1% to 59.9% (P < 0.01). In the complete cohort, over-prescription rose from 2.9% to 12.3% (P < 0.01). Conclusions Under-prescription of preventive strategies has steadily decreased between 1996 and 2006; however, 60% of NSAID users at increased risk of NSAID complications still do not receive adequate protection.

Exposure to colorectal examinations before a colorectal cancer diagnosis: A case-control study (Article)

2010-04-01T00:00:00Z

Objectives: To assess the prior exposure to colorectal examinations between colorectal cancer (CRC) patients and matched control participants to estimate the effect of these examinations on the development of CRC and to obtain insight into the background incidence of colorectal examinations. Methods: A population-based case-control study was conducted within the Dutch Integrated Primary Care Information database over the period 1996-2005. All incident CRC cases were matched with up to 18 controls (n=7790) for age, sex, index date (date of CRC diagnosis) and follow-up before diagnosis. All colorectal examinations performed in symptomatic participants in the period 0.5-5 years before index date were considered in the analyses. Results: Within the source population of 457024 persons, we identified 594 incident cases of CRC. In the period 0.5-5 years before index date 2.9% (17 of 594) of the CRC cases had undergone colorectal examinations, compared with 4.4% (346 of 7790) in the control population [odds ratio (ORadj): 0.56, 95% confidence interval (CI): 0.33-0.94]. For left-sided CRC, significantly more controls than cases had undergone a colorectal examination (4.7 vs. 2.0%, respectively, ORadj: 0.36, 95% CI: 0.17-0.76), which was not seen for right-sided CRCs (3.3 vs. 3.9%, respectively, ORadj: 0.98, 95% CI: 0.42-2.25). Conclusion: Patients diagnosed with CRC were less likely than controls to have had a colorectal examination in previous years, being more pronounced in patients diagnosed with left-sided CRCs. If diagnostic examinations have a similar protective effect as screening examinations, this finding supports the concept that colorectal examination can have a major impact on the reduction of CRC risk.

Gastro-oesophageal reflux, medical resource utilization and upper gastrointestinal endoscopy in patients at risk of oesophageal adenocarcinoma (Article)

2008-07-01T00:00:00Z

Background: Early identification of patients at risk of oesophageal adenocarcinoma (OAC) might improve survival. Aim: To assess the medical resource utilization in the 3 years before OAC diagnosis as potential markers for early identification and intervention. Methods: We identified 65 incident OAC within the Integrated Primary Care Information database. For comparison, we randomly selected 260 age- and gender-matched population controls. We abstracted the use of gastric acid inhibitors, general practitioner (GP) and specialist care, and gastroscopies in the 3 years before the detection of OAC. Results: Approximately 20% of the cases used gastric acid inhibitors in the third and second year before OAC, which increased to almost 50% in the last year, compared to approximately 10% among controls. Only in the 6 months before OAC, the proportion of patients visiting a GP (97%) or specialist (41%) increased compared to controls. Of 13 gastroscopies performed in the 3 years, six (46%) were not suspect for a malignancy. Conclusions: Only a minority of all OAC patients used acid inhibitors before diagnosis. The use of medical care between cases and controls differed only in the final year before OAC diagnosis. Detection of early neoplastic changes proves to be difficult.

The effect of anticholinergic agents on gastro-oesophageal reflux and related disorders (Article)

2008-03-01T00:00:00Z

The most important risk factor of oesophageal adenocarcinoma is gastro-oesophageal reflux disease. Gastro-oesophageal reflux disease is in itself a common disorder, giving bothersome symptoms. In daily clinical practice, anticholinergic drugs are believed to increase the risk of gastro-oesophageal reflux through effects on the lower oesophageal sphincter. In this review we discuss the available literature on the potential association between the use of drugs with anticholinergic properties and the risk of gastro-oesophageal reflux-related disorders.

Gastric acid-related disorders and drugs: An epidemiological perspective (Doctoral Thesis)

2008-02-15T00:00:00Z

Gastroesophageal reflux disease (GERD) is an important health problem for several reasons. First, GERD is highly prevalent. GERD symptoms are experienced by more than 25% of the general population on at least a monthly basis. Secondly, GERD has a substantial impact on quality of life. Thirdly, GERD may lead to complications, such as esophageal strictures, Barrettâ€™s esophagus and ultimately to esophageal adenocarcinoma (EAC). The primary goals of treatment of GERD are to achieve relief of symptoms as well as to prevent complications. The most common pharmacological treatment consists of proton pump inhibitors (PPIs). With this thesis we aimed to give insight into the epidemiology of and risk factors for GERD and associated diseases, and on usage patterns, efficacy and safety of proton pump inhibitors in daily clinical practice. We made use of the Integrated Primary Care Information (IPCI) database which is a general practitioner research database, containing the complete longitudinal electronic medical records of more than 800,000 patients in the Netherlands. The main findings of the studies described in this thesis include that the incidence of Barrettâ€™s esophagus is increasing, mainly among men under 60 years of age. The incidence of EAC is increasing as well. Furthermore we showed that the use of tricyclic antidepressants, with the exception of clomipramine, does not increase the risk of reflux esophagitis. Also for other anticholinergic drugs there is no solid evidence for such an association. With regard to PPIs, we described usage patterns in daily clincial practice and concluded that the risk of NSAID-related gastrointestinal complications is increased 4-fold in patients who are not adherent to PPI therapy. PPIs were not associated with an increased risk of colorectal cancer.

Tricyclic antidepressants and the risk of reflux esophagitis (Article)

2007-09-01T00:00:00Z

OBJECTIVE: Incompetence of the lower esophageal sphincter (LES) is a key factor in the pathogenesis of gastroesophageal reflux disease (GERD). Drugs with anticholinergic properties, such as tricyclic antidepressants (TCAs), may facilitate GERD by a relaxing effect on the LES. AIM: To investigate whether the use of TCAs is associated with an increased risk of reflux esophagitis (RE). METHOD: A population-based case-control study was conducted within a large Dutch primary care database over the period 1996-2005. Cases with endoscopy-confirmed RE were identified and matched with up to 10 controls on gender, age, GP practice, and calendar time. Exposure to TCAs was assessed in the year prior to diagnosis and categorized as current (last prescription covered or ended within one month prior to the index date), past, and no use. The relative risk of RE was estimated by odds ratios (OR) with 95% confidence intervals (95% CI) using multivariate conditional logistic regression analysis. RESULTS: During the study period, 1,462 cases with endoscopy-confirmed RE were identified. The risk of RE was increased in current TCA users (ORadj1.61, 95% CI 1.04-2.50). Drug-specific analyses revealed that only clomipramine was associated with an increased risk of RE (ORadj4.6, 95% CI 2.0-10.6) in a duration- and dose-dependent manner (ORadj7.1, 95% CI 2.7-19.2 for use >180 days and ORadj9.2, 95% CI 1.6-51.5 for >1 DDD equivalent/day). CONCLUSION: No association was observed between the risk of RE and the use of TCAs other than clomipramine. The association between RE and clomipramine might be drug-related or a result of the underlying indication.

Adherence to gastroprotection and the risk of NSAID-related upper gastrointestinal ulcers and haemorrhage (Article)

2007-07-01T00:00:00Z

Background: Upper gastrointestinal (UGI) complications are a well-recognized risk of NSAID treatment, requiring preventive measures in high-risk patients. Adherence to gastroprotective agents (GPAs) in NSAID users has been suggested to be suboptimal. Aim: To investigate the association between adherence to GPAs (proton pump inhibitors or H2-receptor antagonists) and the risk of NSAID-related UGI ulcers or haemorrhage in high-risk patients. Methods: A population-based nested case-control study was conducted within a cohort of new NSAID users with at least one risk factor for a NSAID-related UGI complication, identified in the Dutch IPCI database during 1996-2005. Adherence to GPAs was calculated as the proportion of NSAID treatment days covered (PDC) by a GPA prescription. Multivariate conditional logistic regression analysis was used to calculate odds ratios with 95% confidence intervals (95% CI). Results: Fifteen percent of the non-selective NSAID users received GPAs. The risk of a NSAID-related UGI complication among NSAID users increased 16% for every 10% decrease in adherence. Compared to patients with a PDC of >80%, patients with PDCs of 20-80% and <20% had a 2.5-fold (95% CI: 1.0-6.7) respectively 4.0-fold (95% CI: 1.2-13.0) increased risk. Conclusion: There is a strong inverse relationship between adherence to GPAs and the risk of UGI complications in high-risk NSAID users.

Increasing incidence of Barrett's oesophagus in the general population (Article)

2005-01-01T00:00:00Z

BACKGROUND: Barrett's oesophagus (BO) predisposes to oesophageal adenocarcinoma. Epidemiological data suggest that the incidence of BO is rising but it is unclear whether this reflects a true rise in incidence of BO or an increase in detection secondary to more upper gastrointestinal endoscopies performed. This study aimed to examine the changes in BO incidence relative to the number of upper gastrointestinal endoscopies performed in the general population. METHODS: We conducted a cohort study using the Integrated Primary Care Information database. This general practice research database contains the complete and longitudinal electronic medical records of more than 500,000 persons. RESULTS: In total, 260 incident cases of BO were identified during the study period. The incidence of BO increased from 14.3/100,000 person years in 1997 (95% confidence interval (CI) 8.6-22.4) to 23.1/100,000 person years (95% CI 17.2-30.6) in 2002 (r2 = 0.87). The number of upper gastrointestinal endoscopies decreased from 7.2/1000 person years (95% CI 6.7-7.7) to 5.7/1000 person years (95% CI 5.4-6.1) over the same time period. This resulted in an overall increase in detected BO per 1000 endoscopies from 19.8 (95% CI 12.0-31.0) in 1997 to 40.5 (95% CI 30.0-53.5) in 2002 (r2 = 0.93). The incidence of adenocarcinoma increased from 1.7/100,000 person years (95% CI 0.3-5.4) in 1997 to 6.0/100,000 person years (95% CI 3.3-10.2) in 2002 (r2 = 0.87). CONCLUSION: The incidence of diagnosed BO is increasing, independent of the number of upper gastrointestinal endoscopies that are being performed. This increase in BO incidence will likely result in a further increase in the incidence of oesophageal adenocarcinomas in the near future.