Nature and frequency of prescription modifications in community pharmacies: A nationwide study in the Netherlands.

AIMS: To investigate the nature and frequency of prescription modifications in Dutch community pharmacies. METHODS: In this cross-sectional study, Dutch community pharmacists documented prescription modifications in their pharmacy during 1 predetermined day. Pharmacists from all Dutch community pharmacies were invited to participate. A prescription modification was defined as any modification in a prescription for a medicine or other healthcare product because of an administrative problem, logistic issue or potential drug-related problem (DRP). All documented modifications were assessed to establish the nature and frequency of prescription modifications. RESULTS: Pharmacists in 275 pharmacies completed the study. A modification was performed in 5.5% of all prescriptions. 1.3% of the prescriptions contained an administrative problem, of which insufficient specification of the dosing regimen was most common (63.1%). A modification was performed due to a logistic issue in 2.4% of the prescriptions. The most frequently recorded issues were unavailability of medication (40.9%) and obligatory product substitutions due to reimbursement policies (33.2%). A modification was performed in 1.8% of the prescriptions to solve or prevent potential DRPs. Of these, 69.2% was potentially clinically relevant according to the pharmacist concerned. The most frequently prevented potential DRP was an incorrect strength or dose (31.9%). CONCLUSION: Dutch community pharmacists modified almost 1 in 20 prescriptions per pharmacy. The nature of the modifications reflects current community pharmacy practice, in which pharmacists frequently deal with logistic issues and intervene to solve or prevent for DRPs several times a day. The majority of the DRPs were considered to be potentially clinically relevant.

Associations between personality traits and adequate home storage of drugs in older patients.

The objective of this study was to investigate the association between personality traits of older patients and adequate home storage of drugs. Forty-four participating Dutch community pharmacists randomly selected each up to four community-dwelling elderly patients (≥65 years) who were using at least one prescription drug. The Big Five Inventory was used to assess the personality traits - 'openness', 'conscientiousness', 'extraversion', 'agreeableness' and 'neuroticism' - of patients. An assessment of adequate home storage of drugs was made using a summed composite score for each patient ranging from zero (adequate storage) to three (inadequate storage) was based on storage criteria representing quality, information and level of storage organization. A 51.2% of the patients stored drugs adequately in accordance with all quality ("Q") and information ("I") criteria. A high level of drug storage organization was found in 70.8% of patients. Forty-three patients (31.4%) stored their drugs adequately based on all storage criteria (composite storage score 0). No associations between personality dimensions and adequate drug storage were found. Having a lower number of drugs was associated with adequate drug home storage (ORadjusted 0.86; 95% CI: 0.77-0.96). In conclusion, this study suggests that personality is not associated with adequate home storage of drugs in older patients.

Development of a nomogram for the estimation of long-term adherence to clozapine therapy using neutrophil fluorescence.

AIMS: Previously, we have reported an association between clozapine use and elevated FL3 neutrophil fluorescence, a flow-cytometric parameter for cell viability. Here, we developed and evaluated a pharmacokinetic-pharmacodynamic model relating FL3-fluorescence to clozapine exposure and derived a nomogram for estimation of long-term adherence. METHODS: Data from 27 patients initiating clozapine were analysed using nonlinear mixed effects modelling. A previously described pharmacokinetic model for clozapine was coupled to a FL3 fluorescence model. For this, an effect compartment with clozapine concentrations as input and a first order decay rate as output was linked with an Emax model to FL3-fluorescence. FL3-fluorescence was simulated for clozapine doses of 50, 150 and 400 mg daily (n = 10 000) to establish the nomogram. Finally, true simulated adherence (% of daily doses taken over 100 days) was compared to nomogram-estimated adherence to evaluate the performance of the nomogram. RESULTS: The half-life of FL3-fluorescence was estimated at 228 h (coefficient of variation 35%). Median absolute prediction errors of the nomogram in case of fully random adherence for 50, 150 and 400 mg ranged from -0.193% to -0.525%. The nomogram performed slightly worse in case of nonrandom adherence (median prediction error up to 5.19%), but was still clinically acceptable. Compliance patterns containing longer drug holidays revealed that the nomogram adequately estimates compliance over approximately the last 3 weeks prior to FL3-measurement. CONCLUSION: Our nomogram could provide information regarding long-term adherence based on prescribed clozapine dose and FL3-fluorescence. Future studies should further explore the clinical value of this biomarker and nomogram.

Effects of training physicians in electronic prescribing in the outpatient setting on clinical, learning and behavioural outcomes: a cluster randomized trial.

AIMS: Electronic prescribing systems may improve medication safety, but only when used appropriately. The effects of task analysis-based training on clinical, learning and behavioural outcomes were evaluated in the outpatient setting, compared with the usual educational approach. METHODS: This was a multicentre, cluster randomized trial [EDUCATional intervention for IT-mediated MEDication management (MEDUCATE trial)], with physicians as the unit of analysis. It took place in the outpatient clinics of two academic hospitals. Participants comprised specialists and residents (specialty trainees, in the UK) and their patients. Training took the form of a small-group session and an e-learning. The primary outcome was the proportion of medication discrepancies per physician, measured as discrepancies between medications registered by physicians in the electronic prescribing system and those reported by patients. Clinical consequences were estimated by the proportion of patients per physician with at least one missed drug-drug interaction with the potential for causing adverse drug events. A questionnaire assessed physicians' knowledge and skills. RESULTS: Among 124 participating physicians, primary outcome data for 115 (93%) were available. A total of 1094 patients were included. A mean of 48% of registered medications per physician were discrepant with the medications that their patients reported in both groups (P = 0.14). Due to registration omissions, a mean of 4% of patients per physician had one or more missed drug-drug interactions with the potential to cause a clinically relevant adverse drug event in the intervention group, and 7% in controls (P = 0.11). The percentages of correct answers on the knowledge and skills test were higher in the intervention group (57%) compared with controls (51%; P = 0.01). CONCLUSION: The training equipped outpatient physicians with the knowledge and skills for appropriate use of electronic prescribing systems, but had no effect on medication discrepancies.

The Impact of Inadequate Temperature Storage Conditions on Aggregate and Particle Formation in Drugs Containing Tumor Necrosis Factor-Alpha Inhibitors.

PURPOSE: To measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes. METHODS: TNF-α inhibitors in their original primary and secondary packaging were exposed to 32 freeze-thaw cycles (-10°C for 120min/5°C for 60 min) or continuous low storage temperature (-20°C for 96 h) before thawing at 2-8°C. Non-stressed products were used as controls. The products were analyzed by high pressure size exclusion chromatography (HP-SEC), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), micro-flow imaging (MFI) and second derivative ultraviolet (UV) spectroscopy. RESULTS: Ten out of twenty-one stressed product samples (47.6%) showed increased particle numbers in the submicron and micron size range when compared to controls. For each product, DLS, MFI and NTA detected an increase in particle level in at least one stressed syringe (both continuous freezing and freeze-thaw), whereas HP-SEC and UV spectroscopy showed no differences between stressed and non-stressed products. CONCLUSION: TNF-α inhibitors are relatively resistant to freezing temperatures similar to storage conditions previously observed in patients' homes. However, almost half of the stressed product samples showed formation of particles in the submicron and micron size range.

Anti-epileptic drug changes and quality of life in the community.

OBJECTIVE: Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community-based setting. METHODS: We assessed a cohort of 248 people with epilepsy identified from community pharmacy records from whom we retrieved AED dispensing history. We assessed all changes in AED use during the 2 years prior to the index date and current QoL using the validated Dutch QOLIE-31 questionnaire. RESULTS: Thirty-one per cent had at least one AED change during the study period, either in drug type or dose. People who changed showed significantly lower QoL (QOLIE score 73 vs 79), especially those who intensified their treatment. Each additional change was associated with a further reduction of 4.9 points in QoL score. CONCLUSIONS: AED changes are common practice, even in people with long-standing epilepsy. Frequent changes, as objective measure of epilepsy severity, are associated with a progressively lower QoL. Changes, even in dose, should be monitored in daily clinical practice and used as a red flag that may require adjustments in epilepsy management. This may include earlier referral to a specialized centre for a more thorough evaluation or counselling. AED changes can also be used as an outcome marker in epilepsy research as a proxy of QoL for better translation of drug-efficacy results to general practice.

[Instructions for monitoring clinical parameters in the Summary of Product Characteristics (SmPC) for psychotropic drugs: overview and applicability for clinical practice]. / Instructies voor monitoren van klinische parameters in de registratieteksten van psychofarmaca: overzicht en toepasbaarheid voor de klinische praktijk1.

BACKGROUND: The Summary of Product Characteristics (Smpc) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm.
AIM: To evaluate which monitoring instructions are given in the Smpc and to assess the applicability in clinical practice.
METHOD: The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed.
RESULTS: An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable.
CONCLUSION: Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice.

Task analysis of information technology-mediated medication management in outpatient care.

AIMS: Educating physicians in the procedural as well as cognitive skills of information technology (IT)-mediated medication management could be one of the missing links for the improvement of patient safety. We aimed to compose a framework of tasks that need to be addressed to optimize medication management in outpatient care. METHODS: Formal task analysis: decomposition of a complex task into a set of subtasks. First, we obtained a general description of the medication management process from exploratory interviews. Secondly, we interviewed experts in-depth to further define tasks and subtasks. SETTING: Outpatient care in different fields of medicine in six teaching and academic medical centres in the Netherlands and the United States. PARTICIPANTS: 20 experts. Tasks were divided up into procedural, cognitive and macrocognitive tasks and categorized into the three components of dynamic decision making. RESULTS: The medication management process consists of three components: (i) reviewing the medication situation; (ii) composing a treatment plan; and (iii) accomplishing and communicating a treatment and surveillance plan. Subtasks include multiple cognitive tasks such as composing a list of current medications and evaluating the reliability of sources, and procedural tasks such as documenting current medication. The identified macrocognitive tasks were: planning, integration of IT in workflow, managing uncertainties and responsibilities, and problem detection. CONCLUSIONS: All identified procedural, cognitive and macrocognitive skills should be included when designing education for IT-mediated medication management. The resulting framework supports the design of educational interventions to improve IT-mediated medication management in outpatient care.

Increase in prophylaxis of glucocorticoid-induced osteoporosis by pharmacist feedback: a randomised controlled trial.

UNLABELLED: The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis would stimulate the prescribing of osteoporosis prophylaxis. The intervention did not significantly increase the prescribing of bisphosphonates in the total study population, but a significant increase was seen in men and in the elderly. However, the proportion of bisphosphonate-treated patients remained low. INTRODUCTION: The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis (GIOP) would stimulate the implementation of the Dutch GIOP guideline. METHODS: This randomised controlled trial included 695 patients who were dispensed ≥675 mg prednisone equivalents without a concomitant bisphosphonate prescription within 6 months before baseline. Pharmacists were asked to contact the physicians of GIOP-eligible patients in the intervention group to suggest osteoporosis prophylaxis. The primary endpoint was a bisphosphonate prescription. Secondary endpoints were a prescription of calcium supplements, vitamin D or any prophylactic osteoporosis drug (bisphosphonate, calcium supplements, vitamin D). RESULTS: The group assigned to the intervention was slightly younger than the control group (68.7 ± 15.4 vs. 65.9 ± 16.9 years, p = 0.02) and used hydrocortisone more often (7.0% vs. 3.1%, p = 0.02). Within 6 months, the intervention did not significantly increase the prescribing of bisphosphonates (11.4% after intervention vs. 8.0% for controls; hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.91-2.39). However, subgroup analyses showed a significant increase for the primary endpoint in men (12.8% vs. 5.1%, HR 2.53, 95% CI 1.11-5.74) and patients ≥70 years (13.4% vs. 4.9%, HR 2.88, 95% CI 1.33-6.23). The prescribing of calcium and vitamin D was not significantly altered. CONCLUSION: This study showed that active identification of patients eligible for GIOP by pharmacists did not significantly increase the prescribing of bisphosphonates in the total study population, but there was an increase in men and the elderly. However, the proportion of GIOP-treated patients remained low.

Antidepressant prescribing in five European countries: application of common definitions to assess the prevalence, clinical observations, and methodological implications.

PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases. METHODS: Annual prevalence per 10,000 person-years (PYs) was calculated for 2001-2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. RESULTS: The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15-57% and 39-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.

Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial.

It was investigated whether pharmacogenetic factors, both as single polymorphism and as gene-gene interactions, have an added value over non-genetic factors in predicting statin response. Five common polymorphisms were selected in apolipoprotein E, angiotensin-converting enzyme, hepatic lipase and toll-like receptor 4. Linear regression models were built and compared on R(2) to estimate the added value of single polymorphisms and gene-gene interactions. The selected polymorphisms and the gene-gene interactions had a small added value in predicting change in low-density lipoprotein cholesterol levels (LDL-c) as response to statins over the non-genetic predictors (P=0.104), and also in predicting LDL-c in non-treated patients (P=0.016). Moreover, four gene-gene interactions with statin therapy were identified. The added value of genetic factors over non-genetic variables is for the greater part produced by gene-gene interactions. This underlines the importance to examine gene-gene interactions in future (pharmaco)genetic research.

Occurrence and determinants of poor response to short-term pre-operative erythropoietin treatment.

BACKGROUND: This study aimed to explore the occurrence and determinants of poor response to short-term pre-operative erythropoietin treatment and the effect of such poor response on transfusion in total hip arthroplasty patients. METHODS: We studied total hip arthroplasty patients who received erythropoietin before surgery. The primary outcome was the pre-operative increase in haemoglobin (delta haemoglobin) as response to erythropoietin therapy. Additionally, patients were classified in tertiles based on this delta haemoglobin: poor responders (cases), responders and good responders (controls) to erythropoietin. Patient characteristics, comedication and co-morbidity were collected as potential determinants of erythropoietin response. Regression techniques were used to estimate the strength of the associations and to assess the effect of poor response on transfusion requirement. RESULTS: A total of 379 patients receiving erythropoietin were eligible to enter the study. Mean delta haemoglobin was 19.3 g/l (standard deviation 9.4). Factors significantly associated with delta haemoglobin were the use of angiotensin II antagonists [-3.1 g/l; 95% confidence interval (CI) -5.7 to -0.6] and vitamin K antagonists (-6.9 g/l; 95% CI -10.0 to -0.2), together with body mass index (BMI) (-0.3 g/l per unit>; 95% CI -0.5 to -0.2). The additional case-control analysis yielded comparable results. Poor response to erythropoietin was associated with an increased transfusion risk (odds ratio 4.6, 95% CI 2.0-11). CONCLUSION: Use of angiotensin II receptor antagonists and vitamin K antagonists, and having a high BMI were determinants of poor response to short-term pre-operative erythropoietin treatment in total hip arthroplasty patients. Poor responders had a higher risk for perioperative blood transfusion.

Preventing hospital admissions by reviewing medication (PHARM) in primary care: an open controlled study in an elderly population.

WHAT IS KNOWN AND OBJECTIVE: Limited and conflicting evidence exists on the effect of a multicomponent pharmaceutical care intervention (i.e. medication review, involving collaboration between general practitioners (GPs), pharmacists and patients) on medication-related hospitalizations, survival, adverse drug events (ADEs) and quality of life. We aimed to investigate the effect of a multicomponent pharmaceutical care intervention on these outcomes. METHODS: An open controlled multicentre study was conducted within primary care settings. Patients with a high risk on medication-related hospitalizations based on old age, use of five or more medicines, non-adherence and type of medication used were included. The intervention consisted of a patient interview, a review of the pharmacotherapy and the execution and follow-up evaluation of a pharmaceutical care plan. The patient's own pharmacist and GP carried out the intervention. The control group received usual care and was cared for by a GP other than the intervention GP. The primary outcome of the study was the frequency of hospital admissions related to medication within the study period of 12 months for each patient. Secondary outcomes were survival, quality of life and ADEs. RESULTS AND DISCUSSION: 364 intervention and 310 control patients were included. Less medication-related hospital admissions were found in the intervention group (n = 6; 1·6%) than in the control group (n = 10; 3·2%) but the overall effect was not statistically significant (hazard ratio (HR) 0·50, 95% confidence interval (CI) 0·12-1·59). The secondary outcomes were not statistically significantly different either. The study was underpowered, which may explain the negative results. A post hoc analysis showed that the effect of the intervention was statistically significant for patients with five diseases or more: five diseases, HR 0·28 (95% bootstrap CI: 0·056-0·73) and eight diseases, HR 0·11 (95% CI: 0·013-0·34). WHAT IS NEW AND CONCLUSION: A multicomponent pharmaceutical care intervention does not prevent medication-related hospital admissions. Whether this is true for such interventions in general is unknown, because the PHARM study was underpowered. The intervention may significantly reduce medication-related hospitalizations in patients with five or more comorbidities, but this is only based on a post hoc analysis and thus needs confirmation in large controlled trials.

Feasibility of point-of-care creatinine testing in community pharmacy to monitor drug therapy in ambulatory elderly patients.

WHAT IS KNOWN AND OBJECTIVE: It is often necessary to adjust drug therapy if renal function is impaired in elderly patients taking drugs for diabetes and/or cardiovascular disease that are cleared by the kidneys. Although clinical guidelines recommend regular monitoring of renal function in these patients, in practice adherence to these recommendations varies from 28% to 75%. To determine whether drug dosing is appropriate, pharmacists need have up-to-date information about patients' renal function. In this study, the feasibility of point-of-care creatinine testing (POCCT) in a community pharmacy was evaluated as part of monitoring the drug therapy of ambulatory elderly patients. METHODS: Elderly patients on maintenance therapy with renally excreted drugs for diabetes or cardiovascular disease were eligible for POCCT. After informed consent was obtained, POCCT was performed by trained personnel. A pharmacist assessed the clinical relevance of electronically generated drug alerts based on the patient's calculated renal function and the Dutch guidelines for adjusting drug dosage in patients with chronic kidney disease. If appropriate, the patient's general practitioner (GP) was consulted and adjustments to treatment were communicated to the patient. The feasibility of POCCT was evaluated by means of questionnaires completed by patients and healthcare professionals (GPs and pharmacists). RESULTS: Of 338 potentially eligible patients, 149 (44%) whose renal function was not known were asked, by letter, to participate in the study. Of these individuals, 46 (31%) gave their informed consent and underwent POCCT. Response rates for completing the patient and professional questionnaires were 87% and 100%, respectively. More than half of the patients who underwent POCCT had mild-to-moderate renal impairment. On the basis of information provided by patients and healthcare professionals, POCCT would appear to be feasible in community pharmacies. WHAT IS NEW AND CONCLUSION: POCCT improves the management of drug therapy by community pharmacists and is feasible in daily practice.

Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen.

Busulfan exposure has previously been linked to clinical outcomes, hence the need for therapeutic drug monitoring (TDM). Study objective was to evaluate the effect of day 1 TDM-guided dosing (regimen d1) versus days 1 + 2 TDM-guided dosing (regimen d1 + 2) on attaining adequate busulfan exposure. In this observational study, we included all children receiving busulfan-based allogeneic hematopoietic cell transplantation. Primary outcome was the percentage of patients achieving busulfan target attainment in both TDM regimens. Secondary outcomes were the variance in busulfan exposure and day-4 clearance (Clday4) estimates between both TDM regimens and dosing day 1 and 2. In regimen d1, 84.3% (n = 91/108) attained a therapeutic busulfan exposure, while in regimen d1 + 2 a proportion of 90.9% was found (n = 30/33, not-significant). Variance of Clday4 estimate based on busulfan day 2 concentrations was significantly smaller than the variance of Clday4 estimates based on day 1 concentrations (p < 0.001). Therefore, day 1-guided TDM (pharmacometric model-based) of busulfan may be sufficient for attaining optimal target exposure, provided that subsequent TDM is carried out if required. However, performing TDM on subsequent days may be beneficial, as measurements on day 2 seemed to reduce the variance in the estimated clearance as compared to day 1 sampling.

Hospital physicians' and older patients' agreement with individualised STOPP/START-based medication optimisation recommendations in a clinical trial setting.

OBJECTIVE: To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. METHODS: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. RESULTS: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9-14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30-50 ml/min/1.73 m2; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients' reluctance to discontinue or initiate medication. CONCLUSION: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations. CLINICAL TRIAL REGISTRATION: Trial Registration Number NCT02986425.

Dopaminergic drugs and the risk of hip or femur fracture: a population-based case-control study.

SUMMARY: The effect of dopaminergic medication on the risk of hip/femur fractures is not clear. Our results showed a nearly twofold increased risk of hip/femur fractures in current dopaminergic drug users. Concomitant use of antidepressants further increased this risk. Fracture risk assessment may be warranted in elderly users of dopaminergic drugs. INTRODUCTION: Dopaminergic drugs, often used in the treatment of Parkinson's disease, have several pharmacological effects that may increase or decrease the risk of falling and fractures. Thus, the effect of dopaminergic medication on the risk of hip/femur fractures is not clear. The objective of the study was to examine the effect of dopaminergic medication and concomitant use of psychotropics on the risk of hip/femur fractures taking into account the timing of dopaminergic drug use. METHODS: A population-based case-control study in the PHARMO database was conducted for the period 1991 to 2002. Cases were patients aged 18 years and older with a first hip or femur fracture and matched to four control patients by year of birth, sex and geographical region. RESULTS: The study population included 6,763 cases and 26,341 controls. Current use of dopaminergic drugs (1-30 days before the index date) was associated with an increased risk of hip/femur fractures compared to never use (OR(adj) 1.76, 95% CI = 1.39-2.22), but this excess risk rapidly dropped to baseline levels when treatment had been discontinued >1 year ago. Concomitant use of antidepressants among current dopaminergic drug users further increased the risk of hip/femur fractures (OR(adj) 3.51, 95% CI = 2.10-5.87) while there was no additional risk with concomitant use of other psychotropics. CONCLUSIONS: Although the observed association between dopaminergic drugs and fracture risk may not be entirely causal, due to absence of information on the (severity of the) underlying disease, fracture risk assessment may be warranted in elderly users of dopaminergic drugs.

Representation of people with intellectual disabilities in randomised controlled trials on antipsychotic treatment for behavioural problems.

BACKGROUND: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. AIM: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs. METHODS: A literature search in EMBASE, PubMed and Cochrane was performed and reviewed. RESULTS: People with ID participated in 27 of the 100 included RCTs. The RCTs were of good quality but smaller compared with trials in patients with dementia or schizophrenia (average sample sizes = 55, 124 and 374). In 13/27 trials no clear definition of ID was given. Over 25 different outcome measures were used to assess behavioural problems. CONCLUSIONS: Studies in which people with ID are included are of a sufficient quality, but of a small size. The heterogeneity in the characteristics of the ID population included as well as in the applied assessment instruments makes performing meta-analyses unfeasible.

Quantifying antibiotic use in paediatrics: a proposal for neonatal DDDs.

The defined daily dose (DDD) as defined by the World Health Organization (WHO) has been the most frequently used unit of measurement to measure antibiotic use. However, measuring antibiotic use in paediatrics is a problem as the WHO DDD methodology is not applicable in children (aged >1 month) due to the large variation in body weight within this population. Based on the narrow range of body weights in the neonatal population, we therefore aimed to develop a set of neonatal DDDs for antibiotics. Eight well-respected (inter)national sources for dosage recommendations of antibiotics in children and neonates were consulted for the assumed maintenance dose of the ten most frequently used antibiotics in neonatal intensive care units in its main indication for neonates. A set of neonatal DDDs for ten commonly used antibiotics in neonates based on an assumed neonatal weight of 2 kg was proposed. Primarily in children DDDs are not applicable to quantify antibiotic use since there is large variation in body weight. In the neonatal population, however, based on its narrow range of body weights and when access to patient level data is not available, neonatal DDDs can be used as a unit of measurement.

Transitions from General Practitioner to Psychiatrist Care (or vice versa) during a first antidepressant treatment episode.

INTRODUCTION: The aim of this study was to investigate how frequently patients transit from general practitioner (GP) to psychiatrist care and vice versa during a first antidepressant episode and antidepressant treatment changes associated with those transitions. METHOD: Antidepressant episodes were constructed for patients (> or =18 years) initiating SSRI use in 2000 (N=10 158). Transition in care within a first treatment episode was investigated. Changes in antidepressant treatment were compared between transiting and non-transiting patients. RESULTS: 6.0% of patients who initiate SSRI use in GP practice transited to psychiatrist care, whereas 39.1% of those initiating use in psychiatrist care transited to GP care. Patients transiting from GP to psychiatrist care were more likely to switch to other antidepressants (RR=6.16, 95% CI: 4.90, 7.75) or to other doses (RR=4.48, 95% CI: 3.76, 5.34) than non-transiting patients. No significant differences in antidepressant treatment were found for patients transiting from psychiatric to GP care. DISCUSSION: Approximately 9% of SSRI initiators transit in care. Transitions from GP to psychiatric care lead to antidepressant treatment changes and could potentially be used in observational studies as a disease severity indicator.