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Background: There is growing evidence that ergot dopamine agonists may induce cardiac valve regurgitation (CVR) in persons with Parkinson's disease. It is unclear whether the CVR risk is increased with ergot-dopamine agonist use in persons with hyperprolactinaemia, in whom the dose is much lower.Objective: The aim of the study was to explore the association between different dopamine agonists and CVR in patients with Parkinson's disease or hyperprolactinaemia.Design: Nested case-control studies conducted separately in cohorts of Parkinson's disease and hyperprolactinaemia patients. Cases were patients who developed newly diagnosed CVR. Controls were CVR-free patients from the same cohorts and were matched to cases by age, sex, database and calendar year.Setting and Patients: Study patients were identified from over 4.5 million persons in The Health Improvement Network (THIN; UK), Health Search (Italy), and Integrated Primary Care Information (IPCI; the Netherlands) general practice databases in the years 1996-2007. The Parkinson's disease cohort included new users of dopamine agonists or levodopa, while the hyperprolactinaemia cohort included new users or non-users of dopamine agonists.Main Outcome Measure: Risk of newly diagnosed CVR with dopamine agonist use compared with levodopa use in the Parkinson's disease cohort, and dopamine agonist-naïve patients in the hyperprolactinaemia cohort.Results: In the Parkinson's disease cohort (7893 dopamine agonist users, 11 766 levodopa users), 85 incident CVR cases were identified. Increased CVR risk was observed for ergot dopamine agonists (adjusted OR [OR(adj)] 3.82; 95% CI 2.14, 6.81), but not for non-ergot dopamine agonists (OR(adj) 1.20; 95% CI 0.63, 2.29). In the hyperprolactinaemia cohort (6740 dopamine agonist users and 14 299 dopamine agonist-naïve patients), 37 CVR cases were identified during a mean follow-up of 4.5 years and 3.5 years for new users and non-users of dopamine agonists, respectively. However, no association with ever use of ergot dopamine agonists was observed (OR(adj) 0.47; 95% CI 0.20, 1.19).Conclusion: Ergot-derived dopamine agonists are associated with an increased risk of CVR in Parkinson's disease but not in hyperprolactinaemia patients. [ABSTRACT FROM AUTHOR]

A 66-year-old man with seronegative, erosive rheumatoid arthritis for 12 years presented with malaise, elevated alkaline phosphatase and gamma-glutamyl transferase, and leg oedema. He subsequently developed ascites. No liver pathology was found, but cardiac analysis including right heart catheterisation revealed constrictive pericarditis. Rheumatoid constrictive pericarditis is a rare condition, but, despite current effective treatment for rheumatoid arthritis, still occurs. Diagnostic delay is frequent. Although mortality of the intervention is high, pericardiectomy is needed for most patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A 63-year-old male was seen at the rheumatology outpatient clinic because of a curved deformity of his left hand, with fixed flexion of the MCP joints and hyperextension of the PIP and DIP joints. This so-called striatal hand, a feature of Parkinson's disease, can easily be confused with rheumatoid arthritis or Dupuytren's contracture.

Background: Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA)., Aim: To identify whether and in whom either of these strategies should be preferred in daily practice., Methods: A nested case-control study was conducted using three European primary care databases. We selected a cohort including all naive nsNSAID+GPA (≥80% GPA adherence) and coxib users (without GPA use) aged ≥50 years. Cases with an UGI event (i.e. symptomatic UGI ulcer or bleeding) were matched to cohort members without an UGI event on age, sex and number of individual UGI risk factors (i.e. UGI event history, age ≥65 years, concomitant use of anticoagulants, antiplatelets, or glucocorticoids) and calendar time. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% CI, while adjusting for potential confounders., Results: Within the NSAID cohort (n = 617,220), 398 UGI cases were identified. The risk of UGI events was equivalent for coxib and nsNSAID+GPA (≥80% adherence) users (OR: 1.02; 95%CI: 0.77-1.37). In concurrent glucocorticoid users, the risk of UGI events was significantly elevated for nsNSAID+GPA (≥80% adherence) compared with coxib users (OR: 9.01; 95%CI: 1.61-50.50)., Conclusions: The risk of UGI events was similar in nsNSAID+GPA (≥80% adherence) and coxibs users. In patients concurrently using glucocorticoids, a significant increase in the risk of UGI events for nsNSAID+GPA users was observed and coxibs should be preferred., (© 2013 John Wiley & Sons Ltd.)

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., (© 2012 Blackwell Publishing Ltd.)

Objective: Guidelines recommend coprescription of gastroprotective agents (GPAs) in patients receiving cyclooxygenase 2 inhibitors (coxibs) who are at high risk of upper gastrointestinal (UGI) tract complications (i.e., patients with a previous complicated ulcer or with multiple risk factors). Suboptimal GPA adherence has been shown to diminish the gastroprotective effect during use of nonselective nonsteroidal antiinflammatory drugs, but little is known about the effect of GPA adherence during coxib treatment. We undertook this study to determine the association between GPA adherence and UGI tract events among patients receiving coxibs., Methods: Using primary care data from 3 databases, we conducted a case-control study in a cohort of patients age ≥50 years who were newly starting treatment with coxibs and concomitantly taking GPAs. Patients who had a UGI tract event (bleeding or symptomatic ulcer) were matched to event-free controls for age, sex, database, and calendar date. Coxib treatment intervals were defined as consecutive coxib prescriptions with intervening gaps not exceeding the duration of the previous coxib prescription. Adherence to GPAs was calculated as the proportion of days of coxib treatment covered by a GPA prescription. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using conditional logistic regression analysis., Results: The coxib plus GPA-treated cohort consisted of 14,416 coxib-treated patients who received GPAs for at least 1 day, yielding 16,442 coxib treatment intervals in which a GPA was coprescribed. Most patients were treated with coxibs for <30 days. Seventy-four patients had a UGI tract event during or shortly after a coxib treatment interval in which a GPA was coprescribed, with an incidence rate of 11.9 (95% CI 9.4-14.8) per 1,000 years of coxib treatment. The risk of UGI tract events was 1.97 (95% CI 0.84-4.60) for patients with <20% adherence to GPAs compared to patients with >80% adherence to GPAs. For every 10% decrease in GPA adherence, the risk of UGI tract events increased by 9% (OR 1.09 [95% CI 1.00-1.18])., Conclusion: Decreasing GPA adherence among coxib-treated patients is associated with an increased risk of UGI tract events., (Copyright © 2012 by the American College of Rheumatology.)

Purpose: Increasingly, patient information is stored in electronic medical records, which could be reused for research. Often these records comprise unstructured narrative data, which are cumbersome to analyze. The authors investigated whether text mining can make these data suitable for epidemiological studies and compared a concept recognition approach and a range of machine learning techniques that require a manually annotated training set. The authors show how this training set can be created with minimal effort by using a broad database query., Methods: The approaches were tested on two data sets: a publicly available set of English radiology reports for which International Classification of Diseases, Ninth Revision, Clinical Modification code needed to be assigned and a set of Dutch GP records that needed to be classified as either liver disorder cases or noncases. Performance was tested against a manually created gold standard., Results: The best overall performance was achieved by a combination of a manually created filter for removing negations and speculations and rule learning algorithms such as RIPPER, with high scores on both the radiology reports (positive predictive value = 0.88, sensitivity = 0.85, specificity = 1.00) and the GP records (positive predictive value = 0.89, sensitivity =0.91, specificity =0.76)., Conclusions: Although a training set still needs to be created manually, text mining can help reduce the amount of manual work needed to incorporate narrative data in an epidemiological study and will make the data extraction more reproducible. An advantage of machine learning is that it is able to pick up specific language use, such as abbreviations and synonyms used by physicians., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals., Methods: A retrospective cohort study (1996-2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases., Results: In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2-7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3-5) in 1996-2004 to 9/100,000 py in 2007/8 (95% CI, 6-16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005)., Conclusions: MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly., (Copyright © 2012 S. Karger AG, Basel.)

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 1998-2008), 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.

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., (© 2011 Peripheral Nerve Society.)

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., (© 2010 Blackwell Publishing Ltd.)

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 (OR(adj)) 2.2, 95% confidence intervals (95% CI): 1.4-3.4], especially in dihydropyridines (OR(adj) 2.1, 95% CI: 1.3-3.5) and benzothiazepine derivatives (OR(adj) 2.9, 95% CI: 1.3-6.5) than in RAS drug users. The risk increased in patients using more than the recommended daily dose (OR(adj) 3.0, 95% CI: 1.6-5.5) and when the duration of current use was <1 month (OR(adj) 5.2, 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.

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 > or =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 > or =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.

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.

Introduction: Proton pump inhibitor (PPI) use is associated with increased serum gastrin levels and bacterial overgrowth, resulting in more toxic bile salt formation. Concern has risen that these factors may increase the risk of developing colorectal neoplasia., Aim: To investigate the association between the use of PPIs and the risk of colorectal cancer., Methods: A population-based case-control study was conducted within the Dutch Primary Care Information (IPCI) database over the period 1996-2005. Cases with colorectal cancer were matched with up to 20 controls on age, gender, calendar time, and duration of follow-up prior to diagnosis. Cumulative exposure to PPIs was assessed in the 5 yr prior to diagnosis with a 1-yr lag time analysis. We calculated adjusted odds ratios (OR) with 95% confidence intervals (95% CI) using multivariate, conditional logistic regression analysis., Results: Within the source population of 457,024 persons, we identified 595 colorectal cancer cases. The odds of colorectal cancer were not increased among patients ever using PPIs compared with patients who never used PPIs (OR 0.85, 95% CI 0.63-1.16). Also, the use of PPIs for >365 days was not associated with a greater risk of colorectal cancer (OR 0.79, 95% CI 0.44-1.41) compared with nonusers. The odds of colorectal cancer in neither the right nor the left hemicolon were significantly increased in patients using PPIs., Conclusion: The present study indicates no association between PPI use and the risk of colorectal cancer. Larger numbers of long-term PPI users are needed to confirm the absence of a risk-increasing effect of long-term PPI exposure.

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.

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 (OR(adj) 1.61, 95% CI 1.04-2.50). Drug-specific analyses revealed that only clomipramine was associated with an increased risk of RE (OR(adj) 4.6, 95% CI 2.0-10.6) in a duration- and dose-dependent manner (OR(adj) 7.1, 95% CI 2.7-19.2 for use >180 days and OR(adj) 9.2, 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.

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 H(2)-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.

Background: Proton pump inhibitors are widely used, but little is known about the usage pattern in different indications., Aim: To analyse proton pump inhibitor usage patterns in the general population., Methods: A cohort of 16 311 incident proton pump inhibitor users was identified in the Integrated Primary Care Information database, a Dutch general practice research database. Persistence and adherence were calculated by indication. Risk factors were identified by logistic regression analysis., Results: One-year persistence was 31% in patients using proton pump inhibitors for gastro-oesophageal reflux. Persistence was higher in oesophagitis grade A/B (54%), grade C/D (73%) and Barrett's oesophagus (72%), compared to patients with only reflux symptoms (27%). Approximately 25% of patients with non-reflux dyspepsia or Helicobacter pylori-associated indications used proton pump inhibitors for more than 6 months. Half of all patients used proton pump inhibitors <80% of time indicating intermittent use, which was independent of indication. Exception were patients with Barrett's oesophagus, who were most adherent., Conclusions: A substantial proportion of patients with indications not requiring long-term treatment use proton pump inhibitors for an extended period. Half of the patients used proton pump inhibitors on-demand or intermittently. Such usage pattern is probably sufficient for most patients, but may be inadequate if proton pump inhibitors are used for serious diseases, such as severe oesophagitis or Barrett's oesophagus.

Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a decreased risk of colorectal tumors. Single nucleotide polymorphisms (SNPs) in target genes of NSAID action, and their haplotypes, might modulate this protective effect., Methods: A case-control study including 724 cases and 682 controls was used to evaluate the effect of NSAIDs on colorectal adenoma risk in The Netherlands, a country in which NSAID use is relatively low. Cases and controls were classified according to presence or absence of endoscopy-proven, pathology-confirmed colorectal adenomas, ever in their lives. Thirteen SNPs in four genes (PPARdelta, PPARgamma, PTGS1 and PTGS2) were genotyped in 787 subjects (384 cases and 403 controls)., Results: Compared to non-regular users (< 12 times/year), regular users of NSAIDs (> or = 12 times/year) had a lower risk of colorectal adenomas (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.56-0.99). The results were similar for aspirin only. We found an interaction between SNP c.-789C>T in PPARdelta and NSAID use (P=0.03). The protective effect of NSAIDs was strengthened for regular users with the PPARdelta CT or TT genotypes (OR: 0.35, 95%CI: 0.11-1.13), whereas a positive association was observed for non-regular users with these genotypes (OR: 2.24, 95%CI: 1.06-4.73) as compared to non-regular users with the CC genotype. Also, a statistically significant interaction between a major haplotype containing the minor allele of this SNP and NSAID use was observed., Conclusions: This study confirms the protective effect of NSAIDs and suggests a modulating effect of a SNP in the promoter of PPARdelta.

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.

Objectives: The aims of this exploratory study were to survey the prevalence of certain exposures and health problems among a group of veterinary nurses attending the International Veterinary Nurses' Conference in Brisbane, Australia, 2003 and to identify the main concerns among those veterinary nurses with regard to occupational health hazards they may face., Methods and Materials: An anonymous self-administered questionnaire was distributed among all attendees of the International Veterinary Nurses' Conference 2003, Brisbane, Australia (N=147 respondents among 215 surveyed)., Results: The prevalence of exposure to X-radiation (97%), anaesthetics (96%), disinfectants (96%) and vaccines (85%) was high. More than 70% of the nurses were exposed to formaldehyde (76%) and pesticides/insecticides (71%). For all exposures except vaccines, about 50% of the nurses exposed were worried about negative health consequences. Acute injuries were common with 98% of the nurses experiencing dog/cat bites/scratches, 71% experiencing needle stick injuries and 43% experiencing lacerations. More than half of the nurses (52%) suffered from chronic back/neck pain and 39% reported having allergy or hay fever. Sixteen cases (11%) of Cat Scratch Fever were reported. Job related affective well-being was similar to a large sample of workers in comparable level jobs., Conclusion: Among attendees of a veterinary nurses conference, the proportion of this group of nurses exposed to hazards in their work environment was high and acute and chronic injuries were common. Considering that nurses account for more than 40% of total employment in the veterinary service industry, the results of this study show that the occupational health hazards of this professional group require further study.