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Objective: To assess the effectiveness of duloxetine in addition to usual care in patients with chronic osteoarthritis (OA) pain. The cost-effectiveness and whether the presence of symptoms of centralized pain alters the response to duloxetine were secondary objectives. Methods: We conducted an open-label, cluster-randomized trial. Patients with chronic hip or knee OA pain who had an insufficient response to acetaminophen and nonsteroidal antiinflammatory drugs were included. Randomization took place at the general practice level, and patients received duloxetine (60 mg/day) in addition to usual care or usual care alone. The presence of centralized pain was defined as a modified PainDETECT Questionnaire score >12. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores (scale 0–20) at 3 months after the initiation of treatment. Our aim was to detect a difference between the groups of a clinically relevant effect of 1.9 points (effect size 0.4). We used a linear mixed model with repeated measurements to analyze the data. Results: In total, 133 patients were included, and 132 patients were randomized into treatment groups. A total of 66 patients (at 31 practices) were randomized to receive duloxetine in addition to usual care, and 66 patients (at 35 practices) were randomized to receive usual care alone. We found no differences in WOMAC pain scores between the groups at 3 months (adjusted difference –0.58 [95% confidence interval (95% CI) –1.80, 0.63]) or at 12 months (adjusted difference –0.26 [95% CI –1.86, 1.34]). In the subgroup of patients with centralized pain symptoms, we also found no effect of duloxetine compared to usual care alone (adjusted difference –0.32 [95% CI –2.32, 1.67]). Conclusion: We found no effect of duloxetine added to usual care compared to usual care alone in patients with chronic knee or hip OA pain. Another trial including patients with centralized pain symptoms should be conducted to validate our results.

textabstractAims Low-dose aspirin (LDA) and non-steroidal-anti-inflammatory drugs (NSAIDs) both increase the risk of upper gastrointestinal events (UGIEs). In the Netherlands, recommendations regarding the prescription of gastroprotective agents (GPAs) in LDA users were first issued in 2009 in the HARM-Wrestling consensus. National guidelines on gastroprotective strategies (GPSs) in NSAID users were issued in the first part of the preceding. The aim of the present study was to examine time-trends in GPSs in patients initiating LDA and those initiating NSAIDs between 2000 and 2012. Methods Within a large electronic primary healthcare database, two cohorts were selected: (i) patients newly prescribed LDA and (ii) patients newly prescribed NSAIDs between 2000 and 2012. Patients who had been prescribed a GPA in the previous six months were excluded. For both cohorts, patients risk of a UGIE was classified as low, moderate or high, based on the HARM-Wrestling consensus, and the presence of an adequate GPSwas determined. Results A total of 37 578 patients were included in the LDA cohort and 352 025 patients in the NSAID cohort. In both cohorts, an increase in GPSs was observed over time, but prescription of GPAs was lower in the LDA cohort. By 2012, an adequate GPS was present in 31.8% of high-risk LDA initiators, vs. 48.0% of high-risk NSAID initiators. Conclusions Despite a comparable risk of UGIEs, GPSs are prescribed less in high-risk LDA initiators than in high-risk NSAID initiators. For both groups of patients, there is still room for improvement in guideline adherence.

IntroductionGout is the most common inflammatory arthritis in the Dutch general practice population and is often managed with long-term uric acid lowering treatment. The clinical relevance of this treatment in preventing gout attacks is unclear.Primary research questionWhat is the frequency of self-reported gout attacks and what is the effect of allopurinol use in patients diagnosed with gout in general practice?Methods and analysisAdult patients with a diagnostic consultation code for gout in the year 2013, 2014 or 2015 will be invited to participate in this prospective observational cohort study. Patients with a limited life expectancy will be excluded. Baseline measurements will include blood pressure, body mass index and a blood sample (estimated glomerular filtration rate, serum uric acid, cholesterol (low-density lipoprotein (LDL) and high-density lipoprotein), glucose (fasting)). At the 2-year follow-up, patients will receive questionnaires every 3 months. The questionnaires at baseline, 12 months and 24 months assess the frequency of gout attacks, the presence of tophi, comorbidity, medication use, quality of life, diet and lifestyle. The questionnaires in between only assess the frequency of gout attacks and medication use for gout. Descriptive statistics will be used to calculate the mean frequency of self-reported gout attacks during the 2-year follow-up. The propensity score for each patient being offered allopurinol is estimated and used to match patients with and without allopurinol treatment. We will compare the frequency of gout attacks in these groups using multilevel Poisson regression analyses. With this type of analysis, we can calculate the corrected estimated effect of allopurinol on gout attack frequency.Ethics and disseminationThe research protocol was approved by the Medical Ethical Committee of the Erasmus Medical Centre in Rotterdam. The knowledge generated by this study will be transferred to the Dutch College of General Practitioners, conferences and to (inter)national peer-reviewed journals.Trial registration numberNTR6329; Pre-results.

Objective. To determine how often patients with musculoskeletal (MSK) complaints prescribed a non-steroidal anti-inflammatory drug (NSAID) subsequently consult their general practitioner (GP) with a non-serious adverse drug reaction (ADR). Design. Cohort study. Setting. A healthcare database containing the electronic GP medical records of over 1.5 million patients throughout the Netherlands. Patients. A total of 16 626 adult patients with MSK complaints prescribed an NSAID. Main outcome measures. The patients' medical records were manually assessed for the duration of NSAID use for a maximum of two months, and consultations for complaints predefined as potential ADRs were identified. Subsequently, the likelihood of an association with the NSAID use was assessed and these potential ADRs were categorized as likely, possible, or unlikely ADRs. Results. In total, 961 patients (6%) consulted their GP with 1227 non-serious potential ADRs. In 174 patients (1%) at least one of these was categorized as a likely ADR, and in a further 408 patients (2.5%) at least one was categorized as a possible ADR. Dyspepsia was the most frequent likely ADR, followed by diarrhoea and dyspnoea (respectively 34%, 8%, and 8% of all likely ADRs). Conclusion. Of the patients with MSK complaints prescribed an NSAID, almost one in 30 patients re-consulted their GP with a complaint likely or possibly associated with the use of this drug. The burden of such consultations for non-serious ADRs should be taken into account by GPs when deciding whether treatment with an NSAID is appropriate.

Background The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with serious adverse drug events (ADEs). Aim To determine the prevalence of over-the-counter (OTC) NSAID use in the general population and in patients with a high risk of developing a serious NSAID-related ADE. Design and setting Cross-sectional study in four general practices in the Netherlands. Method Two patient samples were selected: a random sample of adults (general population sample); and adult patients with a high risk of developing a serious ADE in case of NSAID use (high-risk sample). All included patients were sent a questionnaire regarding their use of OTC NSAIDs in the 4 weeks prior to participation. Results In the general population sample, 118 of 456 (26%) invited patients completed the questionnaire. Of these, 35 (30%) had used an OTC NSAID. In the high-risk sample, 264 of 713 (37%) invited patients completed the questionnaire, and of these high-risk patients 33 (13%) had used an OTC NSAID. Over 20% of OTC NSAID users in the general population sample and over 30% in the high-risk sample had used the OTC NSAID for >7 days. OTC NSAIDs were used in a dosage exceeding the recommended daily maximum by 9% and 3% of OTC NSAID users in the general population and the high-risk sample respectively. Conclusion OTC NSAIDs are used by almost one-third of the general population. In the high-risk patients selected, one in eight patients used an OTC NSAID. Continued efforts by health authorities and healthcare professionals to inform patients of the risks of these drugs are warranted.

Contains fulltext : 127746.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The Dutch HARM-Wrestling (HW) Task Force issued general and drug-specific recommendations aimed at reducing hospital admissions related to medication (HARMs). This study examines if the drug-specific recommendations could be converted into indicators that could be monitored in existing databases of general practitioner (GP) or community pharmacy (CP) data. The study also assesses the performance of these indicators before and during the official release of HW recommendations. METHODS: HW recommendations were divided into sub-recommendations. We studied to what extent these were measurable as indicators based on available information in both databases. For each measurable indicator, performance between 2007 and 2010 was determined and possibilities for further improvement were estimated. RESULTS: Thirty-four drug-specific HW recommendations were divided into 69 sub-recommendations, 32 of which were measurable as indicator in at least one of the databases. Application of these indicators between 2007 and 2010 showed that many of the indicators did not change over time. Possibilities for further improvement were estimated as moderate to major for 16/31 (52%) indicators measured in the GP database and 6/15 (40%) HW indicators measured in the CP database. CONCLUSIONS: Further implementation of the HW recommendations and development of additional monitoring methods are warranted to improve drug safety in outpatients.

IntroductionOsteoarthritis (OA) is a highly prevalent painful condition of the musculoskeletal system. The effectiveness of current analgesic options has proven to be limited and improved analgesic treatment is needed. Several randomised placebo-controlled trials have now demonstrated the efficacy of duloxetine, an antidepressant with a centrally acting effect, in the treatment of OA pain. The aim of the current study is to investigate if duloxetine is effective and cost-effective as a third-choice analgesic added to usual care for treating chronic pain compared with usual care alone in general practice.Methods and analysisA pragmatic open, cluster randomised trial is conducted. Patients with pain due to hip or knee OA on most days of the past 3 months with insufficient benefit of non-steroidal anti-inflammatory drugs or contraindications or intolerable side effects are included. General practices are randomised to either (1) duloxetine and usual care or (2) usual care only. Primary outcome is pain at 3 months measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes at 3 months and 1 year are pain (WOMAC, at 1 year), function (WOMAC), adverse reactions, quality of life and modification of the response to treatment by the presence of centrally sensitised pain (modified PainDETECT). At 1 year, medical and productivity costs will be assessed. Analyses will be performed following the intention-to-treat principle taking the cluster design into account.Ethics and disseminationThe study is approved by the local Medical Ethics Committee (2015–293). Results will be published in a scientific peer-reviewed journal and will be communicated at conferences.Trial registration numberDutch Trial Registry(ntr4798); Pre-results.

Background To reduce adverse drug events (ADEs), clinical guidelines recommend cautious prescription of non-steroidal anti-inflammatory drugs (NSAIDs) in patients known to be at a high risk of developing a serious ADE. General practitioners (GPs) frequently prescribe NSAIDs in the treatment of musculoskeletal complaints (MSC). Objectives To determine the extent of prescription and of potentially harmful prescription of NSAIDs in a primary care population with MSC. Methods Data were retrieved from the Integrated Primary Care Information (IPCI) database, a longitudinal GP research database containing over one million patient records1. All new episodes of MSC occurring in adult patients (≥18 years) between 2000 and 2010 were identified based on the International Classification of Primary Care (ICPC)-coding. An episode was considered new if the patient had not consulted their GP for the same complaint in the six months prior to consultation. For all episodes, NSAID prescriptions issued on the day of consultation were subsequently identified. NSAID prescriptions were considered potentially harmful if given to patients at a high risk of adverse events at the time of NSAID prescription, defined as a high renal risk (glomerular filtration rate 70 years, or two or more of the following: age 60-70 years, history of heart failure, diabetes or severe rheumatoid arthritis, use of antithrombotics, corticosteroids, selective serotonin reuptake inhibitors or high dose NSAIDs) without adequate concomitant gastroprotection (either a cox-2 selective inhibitor or a non-selective NSAID with concomitant proton pump inhibitor, misoprostol or histamine-2 receptor antagonist). Results In total, 1,632,005 episodes of MSC occurred in 474,201 adult patients between 2000 and 2010. In 401,473 (24.6%) of these episodes, concerning 221,539 (46.7%) of all patients, an NSAID was prescribed. The percentage of NSAID prescriptions decreased over time, from 29.5% in 2000 to 21.2% in 2010 (p Conclusions Although prescription rates have decreased significantly over time, GPs still routinely treat MSC with NSAIDs. Patients’ risk profiles are not sufficiently taken into account in one tenth of prescriptions, particularly in patients at a high risk of serious gastro-intestinal ADEs. References Vlug AE, et al. Postmarketing surveillance based on electronic patient records: the IPCI project. Methods Inf Med 1999;38:339-44. Disclosure of Interest None Declared

Background The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with serious adverse drug events (ADEs)1. In many countries, including the Netherlands, NSAIDs are available over-the-counter (OTC). Objectives To determine the prevalence of OTC NSAID use in the general population and in patients with a high risk of developing a serious NSAID-related ADE. Methods We conducted a cross-sectional study among adults registered with four Dutch general practitioners (GPs). In the Netherlands, all citizens are registered with a GP. Two samples of different patient populations were selected: (i) a random sample of adults (general population), and (ii) a sample of adult patients with a high risk of developing a serious ADE in case of NSAID use (high-risk population). The patients’ risk profiles were determined using their electronic medical records. Based on Dutch clinical prescription guidelines1, patients were considered at high risk if they had a history of a peptic ulcer or ulcer complication, myocardial infarction, stroke or heart failure, were aged over 70 years, had a glomerular filtration rate Results In the general population, 120 of 456 included patients chose to participate. Of these, 35 (29%) had used an OTC NSAID in the four weeks prior to participation. In the high-risk population, 265 of 713 included patients chose to participate and 33 (13%) had used an OTC NSAID. Musculoskeletal complaints formed the most common reason for OTC NSAID use in the high-risk population, with 67% of OTC NSAID users giving this as a reason for use. In the general population, 46% of OTC NSAID users reported using these drugs because of musculoskeletal complaints. Over 20% of OTC NSAID users had used the OTC NSAID for more than seven days in the general population and over 30% in the high risk-population. OTC NSAIDs were used in a dosage exceeding the recommended daily maximum by 9% and 3% of OTC NSAID users in respectively the general and the high-risk population. Conclusions OTC NSAIDs are used by around one third of the general population and by one in eight patients with a high risk of developing a serious ADE. In this high-risk group, musculoskeletal complaints form the most common reason for OTC NSAID use. Continued efforts by healthcare professionals to inform patients of the risks of these drugs is warranted, particularly when a new diagnosis is made or medication prescribed which alters the patient’s risk profile. References Warle-Van Herwaarden MF, Kramers C, Sturkenboom MC, et al. Targeting outpatient drug safety: Recommendations of the Dutch Harm-Wrestling Task Force. Drug Saf 2012;35(3):245-59 Disclosure of Interest None Declared