PhenoCaB: a new phenological model based on carbon balance in boreal conifers.

Traditional phenological models use chilling and thermal forcing (temperature sum or degree-days) to predict budbreak. Because of the heightening impact of climate and other related biotic or abiotic stressors, a model with greater biological support is needed to better predict budbreak. Here, we present an original mechanistic model based on the physiological processes taking place before and during budbreak of conifers. As a general principle, we assume that phenology is driven by the carbon status of the plant, which is closely related to environmental variables and the annual cycle of dormancy-activity. The carbon balance of a branch was modelled from autumn to winter with cold acclimation and dormancy and from winter to spring when deacclimation and growth resumption occur. After being calibrated in a field experiment, the model was validated across a large area (> 34 000 km2 ), covering multiple conifers stands in Québec (Canada) and across heated plots for the SPRUCE experiment in Minnesota (USA). The model accurately predicted the observed dates of budbreak in both Québec (±3.98 d) and Minnesota (±7.98 d). The site-independent calibration provides interesting insights on the physiological mechanisms underlying the dynamics of dormancy break and the resumption of vegetative growth in spring.

Added value of patient- and drug-related factors to stratify drug-drug interaction alerts for risk of QT prolongation: Development and validation of a risk prediction model.

AIMS: Many clinical decision support systems trigger warning alerts for drug-drug interactions potentially leading to QT prolongation and torsades de pointes (QT-DDIs). Unfortunately, there is overalerting and underalerting because stratification is only based on a fixed QT-DDI severity level. We aimed to improve QT-DDI alerting by developing and validating a risk prediction model considering patient- and drug-related factors. METHODS: We fitted 31 predictor candidates to a stepwise linear regression for 1000 bootstrap samples and selected the predictors present in 95% of the 1000 models. A final linear regression model with those variables was fitted on the original development sample (350 QT-DDIs). This model was validated on an external dataset (143 QT-DDIs). Both true QTc and predicted QTc were stratified into three risk levels (low, moderate and high). Stratification of QT-DDIs could be appropriate (predicted risk = true risk), acceptable (one risk level difference) or inappropriate (two risk levels difference). RESULTS: The final model included 11 predictors with the three most important being use of antiarrhythmics, age and baseline QTc. Comparing current practice to the prediction model, appropriate stratification increased significantly from 37% to 54% appropriate QT-DDIs (increase of 17.5% on average [95% CI +5.4% to +29.6%], padj = 0.006) and inappropriate stratification decreased significantly from 13% to 1% inappropriate QT-DDIs (decrease of 11.2% on average [95% CI -17.7% to -4.7%], padj ≤ 0.001). CONCLUSION: The prediction model including patient- and drug-related factors outperformed QT alerting based on QT-DDI severity alone and therefore is a promising strategy to improve DDI alerting.

The impact of a summative national prescribing assessment and curriculum type on the development of the prescribing competence of junior doctors.

PURPOSE: The primary aim of this study was to investigate the effect of including the Dutch National Pharmacotherapy Assessment (DNPA) in the medical curriculum on the level and development of prescribing knowledge and skills of junior doctors. The secondary aim was to evaluate the relationship between the curriculum type and the prescribing competence of junior doctors. METHODS: We re-analysed the data of a longitudinal study conducted in 2016 involving recently graduated junior doctors from 11 medical schools across the Netherlands and Belgium. Participants completed three assessments during the first year after graduation (around graduation (+ / - 4 weeks), and 6 months, and 1 year after graduation), each of which contained 35 multiple choice questions (MCQs) assessing knowledge and three clinical case scenarios assessing skills. Only one medical school used the DNPA in its medical curriculum; the other medical schools used conventional means to assess prescribing knowledge and skills. Five medical schools were classified as providing solely theoretical clinical pharmacology and therapeutics (CPT) education; the others provided both theoretical and practical CPT education (mixed curriculum). RESULTS: Of the 1584 invited junior doctors, 556 (35.1%) participated, 326 (58.6%) completed the MCQs and 325 (58.5%) the clinical case scenarios in all three assessments. Junior doctors whose medical curriculum included the DNPA had higher knowledge scores than other junior doctors (76.7% [SD 12.5] vs. 67.8% [SD 12.6], 81.8% [SD 11.1] vs. 76.1% [SD 11.1], 77.0% [12.1] vs. 70.6% [SD 14.0], p < 0.05 for all three assessments, respectively). There was no difference in skills scores at the moment of graduation (p = 0.110), but after 6 and 12 months junior doctors whose medical curriculum included the DNPA had higher skills scores (both p < 0.001). Junior doctors educated with a mixed curriculum had significantly higher scores for both knowledge and skills than did junior doctors educated with a theoretical curriculum (p < 0.05 in all assessments). CONCLUSION: Our findings suggest that the inclusion of the knowledge focused DNPA in the medical curriculum improves the prescribing knowledge, but not the skills, of junior doctors at the moment of graduation. However, after 6 and 12 months, both the knowledge and skills were higher in the junior doctors whose medical curriculum included the DNPA. A curriculum that provides both theoretical and practical education seems to improve both prescribing knowledge and skills relative to a solely theoretical curriculum.

Determinants for under- and overdosing of direct oral anticoagulants and physicians' implementation of clinical pharmacists' recommendations.

AIMS: To analyse the appropriateness of direct oral anticoagulant (DOAC) dosing and determinants for under-and overdosing as well as acceptance and implementation rates of pharmacists' interventions. METHODS: Cross-sectional study in a tertiary hospital in hospitalized patients with atrial fibrillation on DOACs in 2019 (n = 1688). Primary outcome was the proportion of patients with inappropriate DOAC prescribing with identification of determinants for under-and overdosing. Secondary outcomes included acceptance and implementation rates of pharmacists' recommendations and determination of reasons for nonacceptance/nonimplementation. RESULTS: Inappropriate prescribing was observed in 16.9% of patients (n = 286) with underdosing (9.7%) being more prevalent than overdosing (6.9%). For all DOACs considered together, body weight<60 kg (odds ratio [OR] 0.46 [0.27-0.77]), edoxaban use (OR 0.42 [0.24-0.74]), undergoing surgery (OR 0.57 [0.37-0.87]) and being DOAC naïve (OR 0.45 [0.29-0.71]) were associated with significantly lower odds of underdosing. Bleeding history (OR 1.86 [1.24-2.80]) and narcotic use (OR 1.67 [1.13-2.46]) were associated with significantly higher odds for underdosing. Determinants with a significantly higher odds of overdosing were renal impairment (OR 11.29 [6.23-20.45]) and body weight<60 kg (OR 2.34 [1.42-3.85]), whereas dabigatran use (OR 0.24 [0.08-0.71]) and apixaban (OR 0.18 [0.10-0.32]) were associated with a significantly lower odds of overdosing compared to rivaroxaban. Physicians accepted the pharmacists' advice in 179 cases (79.2%) consisting of 92 (51.4%) recommendations for underdosing, 82 (45.8%) for overdosing and 5 (2.8%) for contraindications. CONCLUSION: Inappropriate DOAC prescribing remains common, although there is a slight improvement compared to our study of 2016. Clinical services led by pharmacists help physicians to reduce the number of inadequate prescriptions for high-risk medications such as DOACs.

Assessment of adherence, treatment satisfaction and knowledge of direct oral anticoagulants in atrial fibrillation patients.

AIMS: Direct oral anticoagulants (DOACs) are increasingly used for stroke prevention in atrial fibrillation. However, little is known about the association between medication adherence, patient satisfaction and treatment knowledge. The objective was to determine patients' DOAC adherence and their treatment satisfaction over time. Furthermore, we respectively investigated possible associations of treatment satisfaction and treatment knowledge in relation to adherence. METHODS: Longitudinal study conducted in atrial fibrillation patients hospitalized in 2019 in a tertiary university hospital. DOAC adherence, treatment satisfaction and knowledge were assessed with validated questionnaires. Mixed effects logistic regression was modelled to investigate the effect of both treatment satisfaction and knowledge on DOAC adherence over time. RESULTS: In total, 164 patients participated of whom 128 and 101 patients could be recontacted after a period of, respectively, 3 (first contact) and 6 months (second contact) to assess adherence and treatment satisfaction. Suboptimal adherence was observed in 40.6% of the patients after 3 months and in 42.6% after 6 months (P = .78). There was no significant difference (P = .29) in the total score for treatment satisfaction between the first (79.2%) and the second contact (80.6%). DOAC adherence was not affected by time (P = .71) nor by total knowledge score (P = .61) or treatment satisfaction score (P = .34). Nonetheless, a strong correlation between treatment satisfaction and knowledge was found (P = .004). CONCLUSION: DOAC adherence was suboptimal. Treatment satisfaction and knowledge were not associated with DOAC adherence over a 6-month period. Knowledge gaps were identified that could be remediated through patient education and follow-up.

Do we become better prescribers after graduation: A 1-year international follow-up study among junior doctors.

AIM: The aim of this study was to investigate how the prescribing knowledge and skills of junior doctors in the Netherlands and Belgium develop in the year after graduation. We also analysed differences in knowledge and skills between surgical and nonsurgical junior doctors. METHODS: This international, multicentre (n = 11), longitudinal study analysed the learning curves of junior doctors working in various specialties via three validated assessments at about the time of graduation, and 6 months and 1 year after graduation. Each assessment contained 35 multiple choice questions (MCQs) on medication safety (passing grade ≥85%) and three clinical scenarios. RESULTS: In total, 556 junior doctors participated, 326 (58.6%) of whom completed the MCQs and 325 (58.5%) the clinical case scenarios of all three assessments. Mean prescribing knowledge was stable in the year after graduation, with 69% (SD 13) correctly answering questions at assessment 1 and 71% (SD 14) at assessment 3, whereas prescribing skills decreased: 63% of treatment plans were considered adequate at assessment 1 but only 40% at assessment 3 (P < .001). While nonsurgical doctors had similar learning curves for knowledge and skills as surgical doctors (P = .53 and P = .56 respectively), their overall level was higher at all three assessments (all P < .05). CONCLUSION: These results show that junior doctors' prescribing knowledge and skills did not improve while they were working in clinical practice. Moreover, their level was under the predefined passing grade. As this might adversely affect patient safety, educational interventions should be introduced to improve the prescribing competence of junior doctors.

Machine Learning Techniques Outperform Conventional Statistical Methods in the Prediction of High Risk QTc Prolongation Related to a Drug-Drug Interaction.

In clinical practice, many drug therapies are associated with prolongation of the QT interval. In literature, estimation of the risk of prescribing drug-induced QT prolongation is mainly executed by means of logistic regression; only one paper reported the use of machine learning techniques. In this paper, we compare the performance of both techniques on the same dataset. High risk for QT prolongation was defined as having a corrected QT interval (QTc) ≥ 450 ms or ≥ 470 ms for respectively male and female patients. Both conventional statistical methods (CSM) and machine learning techniques (MLT) were used. All algorithms were validated internally and with a hold-out dataset of respectively 512 and 102 drug-drug interactions with possible drug-induced QTc prolongation. MLT outperformed the best CSM in both internal and hold-out validation. Random forest and Adaboost classification performed best in the hold-out set with an equal harmonic mean of sensitivity and specificity (HMSS) of 81.2% and an equal accuracy of 82.4% in a hold-out dataset. Sensitivity and specificity were both high (respectively 75.6% and 87.7%). The most important features were baseline QTc value, C-reactive protein level, heart rate at baseline, age, calcium level, renal function, serum potassium level and the atrial fibrillation status. All CSM performed similarly with HMSS varying between 60.3% and 66.3%. The overall performance of logistic regression was 62.0%. MLT (bagging and boosting) outperform CSM in predicting drug-induced QTc prolongation. Additionally, 19.2% was gained in terms of performance by random forest and Adaboost classification compared to logistic regression (the most used technique in literature in estimating the risk for QTc prolongation). Future research should focus on testing the classification on fully external data, further exploring potential of other (new) machine and deep learning models and on generating data pipelines to automatically feed the data to the classifier used.

Impact of health technology assessment and managed entry schemes on reimbursement decisions of centrally authorised medicinal products in Belgium.

PURPOSE: Centrally authorised medicinal products (CAMPs) in the European Union may offer added therapeutic value (ATV) but may be linked to high prices and limited efficiency. Health technology assessment (HTA) and managed entry schemes (MES) may facilitate the reimbursement decision by providing reliable estimates of the medicinal product's value and costs and by controlling the remaining uncertainty, respectively. We investigated the impact of HTA criteria and the initiation of a MES on the reimbursement decision of CAMPs in Belgium. METHODS: We selected all reimbursement submissions for new centrally authorised medicinal products in the 2010-2015 period. We retrieved data relating to the reimbursement decision, the HTA outcome and the use of a managed entry scheme. RESULTS: The decision of the Minister was available for 115 dossiers, covering 36 (31.3%) orphan medicinal products (OMPs) and 79 ATV products. A MES was used in 41 submissions. A positive reimbursement decision was obtained in 65% of cases. The significant factors affecting the reimbursement decision were the approval of ATV, the medical need if it was considered 'important or major' and the use of a managed entry scheme. Price, budget impact and efficiency had no significant impact. CONCLUSIONS: Added therapeutic value and high medical need increase the odds for a positive reimbursement decision. No impact could be demonstrated of the cost-related HTA criteria. Cost elements may be biased by the use of a confidential MES. Without a MES, only 53% of the centrally authorised medicinal products, including OMPs, are reimbursed in Belgium.

Clinical Decision Support Systems for Drug Allergy Checking: Systematic Review.

BACKGROUND: Worldwide, the burden of allergies-in particular, drug allergies-is growing. In the process of prescribing, dispensing, or administering a drug, a medication error may occur and can have adverse consequences; for example, a drug may be given to a patient with a documented allergy to that particular drug. Computerized physician order entry (CPOE) systems with built-in clinical decision support systems (CDSS) have the potential to prevent such medication errors and adverse events. OBJECTIVE: The aim of this review is to provide a comprehensive overview regarding all aspects of CDSS for drug allergy, including documenting, coding, rule bases, alerts and alert fatigue, and outcome evaluation. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed as much as possible and searches were conducted in 5 databases using CPOE, CDSS, alerts, and allergic or allergy as keywords. Bias could not be evaluated according to PRISMA guidelines due to the heterogeneity of study types included in the review. RESULTS: Of the 3160 articles considered, 60 met the inclusion criteria. A further 9 articles were added based on expert opinion, resulting in a total of 69 articles. An interrater agreement of 90.9% with a reliability Κ=.787 (95% CI 0.686-0.888) was reached. Large heterogeneity across study objectives, study designs, study populations, and reported results was found. Several key findings were identified. Evidence of the usefulness of clinical decision support for drug allergies has been documented. Nevertheless, there are some important problems associated with their use. Accurate and structured documenting of information on drug allergies in electronic health records (EHRs) is difficult, as it is often not clear to healthcare providers how and where to document drug allergies. Besides the underreporting of drug allergies, outdated or inaccurate drug allergy information in EHRs poses an important problem. Research on the use of coding terminologies for documenting drug allergies is sparse. There is no generally accepted standard terminology for structured documentation of allergy information. The final key finding is the consistently reported low specificity of drug allergy alerts. Current systems have high alert override rates of up to 90%, leading to alert fatigue. Important challenges remain for increasing the specificity of drug allergy alerts. We found only one study specifically reporting outcomes related to CDSS for drug allergies. It showed that adverse drug events resulting from overridden drug allergy alerts do not occur frequently. CONCLUSIONS: Accurate and comprehensive recording of drug allergies is required for good use of CDSS for drug allergy screening. We found considerable variation in the way drug allergy are recorded in EHRs. It remains difficult to reduce drug allergy alert overload while maintaining patient safety as the highest priority. Future research should focus on improving alert specificity, thereby reducing override rates and alert fatigue. Also, the effect on patient outcomes and cost-effectiveness should be evaluated.

Development and Pilot Testing of 24/7 In-Ambulance Telemedicine for Acute Stroke: Prehospital Stroke Study at the Universitair Ziekenhuis Brussel-Project.

BACKGROUND: In-ambulance telemedicine is a recently developed and a promising approach to improve emergency care. We implemented the first ever 24/7 in-ambulance telemedicine service for acute stroke. We report on our experiences with the development and pilot testing of the Prehospital Stroke Study at the Universitair Ziekenhuis Brussel (PreSSUB) to facilitate a wider spread of the knowledge regarding this technique. METHODS: Successful execution of the project involved the development and validation of a novel stroke scale, design and creation of specific hardware and software solutions, execution of field tests for mobile internet connectivity, design of new care processes and information flows, recurrent training of all professional caregivers involved in acute stroke management, extensive testing on healthy volunteers, organisation of a 24/7 teleconsultation service by trained stroke experts and 24/7 technical support, and resolution of several legal issues. RESULTS: In all, it took 41 months of research and development to confirm the safety, technical feasibility, reliability, and user acceptance of the PreSSUB approach. Stroke-specific key information can be collected safely and reliably before and during ambulance transportation and can adequately be communicated with the inhospital team awaiting the patient. CONCLUSION: This paper portrays the key steps required and the lessons learned for successful implementation of a 24/7 expert telemedicine service supporting patients with acute stroke during ambulance transportation to the hospital.

Hypotensive and sympathoinhibitory responses to selective central AT2 receptor stimulation in spontaneously hypertensive rats.

The type 2 angiotensin receptor (AT2R) has been suggested to counterbalance the type 1 angiotensin receptor (AT1R) in the central regulation of blood pressure and sympathetic tone. In the present study we investigated the blood pressure responses to stimulation of central AT2Rs by the selective agonist Compound 21 in conscious spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKY rats). We also assessed the impact on noradrenaline [norepinephrine (NE)] plasma levels, autonomic function, spontaneous baroreflex sensitivity, and the possible involvement of the nitric oxide (NO) pathway and the AT1Rs. Chronic intracerebroventricular Compound 21 infusion lowered blood pressure and NE plasma levels in both rat strains. The night-time hypotensive effect was greater in SHRs compared with WKY rats. Compound 21 improved spontaneous baroreflex sensitivity more in SHRs than in WKY rats. These effects were abolished by co-administration of the AT2R antagonist PD123319 or the NO synthase inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Central AT1R blockade did not enhance the hypotensive response to Compound 21. Chronic selective stimulation of central AT2Rs lowers blood pressure through sympathoinhibition, and improves spontaneous baroreflex sensitivity more in SHRs than in WKY rats. These responses appear to require a functioning central NO pathway, but are not modified by central AT1R blockade. Collectively, the data demonstrate specific beneficial effects of stimulation of central AT2Rs in hypertension associated with increased sympathetic tone, and suggest that central AT2Rs may represent a potential new therapeutic target for the treatment of neurogenic hypertension.

Determinants of medication use in a multi-ethnic population of pregnant women: a cross-sectional study.

OBJECTIVES: To investigate determinants of medication use among multi-ethnic pregnant women. METHODS: A total of 641 pregnant women participated in this cross-sectional study in a Brussels university hospital. A questionnaire was used to obtain data on socio-demographic characteristics and medication use. Chi-squared tests and binary logistic regression analyses were performed using SPSS 19. RESULTS: Medication use during pregnancy (37%) was positively associated with age older than 35 years, Western origin, being born in Belgium, high education and employment status. Highly educated Western women had a greater exposure to drugs with an unknown safety profile than Arab/Turkish and 'Other (non-Western) origins' women. In the latter two groups, low education and nulliparity were the most important determinants of lower drug use. Nulliparous Arab/Turkish women used significantly less medications (17%) during pregnancy than parous women with the same ethnic background (34%; p = 0.024). CONCLUSIONS: Medication use during pregnancy is considerable but differs according to ethnicity. Age, parity, educational level, occupational status and duration of stay in Belgium are important determinants that should be taken into account for risk assessment and preventive measures targeting pregnant women.

Usability of Graphical User Interfaces With Semiautomatic Delabeling Feature to Improve Drug Allergy Documentation.

BACKGROUND: The quality of allergy documentation in electronic health records is frequently poor. OBJECTIVE: To compare the usability of 3 graphical user interfaces (GUIs) for drug allergy documentation. METHODS: Physicians tested 3 GUIs by means of 5 fictional drug allergy scenarios: the current GUI (GUI 0), using mainly free-text, and 2 new coded versions (GUI 1 and GUI 2) asking information on allergen category, specific allergen, symptom(s), symptom onset, timing of initial reaction, and diagnosis status with a semiautomatic delabeling feature. Satisfaction was measured by the System Usability Scale questionnaire, efficiency by time to complete the tasks, and effectiveness by a task completion score. Posttest interviews provided more in-depth qualitative feedback. RESULTS: Thirty physicians from 7 different medical specialties and with varying degrees of experience participated. The mean System Usability Scale scores for GUI 1 (77.25, adjective rating "Good") and GUI 2 (78.42, adjective rating "Good") were significantly higher than for GUI 0 (56.58, adjective rating "OK") (Z, 6.27, Padj < .001 and Z, 6.62, Padj < .001, respectively). There was no significant difference in task time between GUIs. Task completion scores of GUI 1 and GUI 2 were higher than for GUI 0 (Z, 9.59, Padj < .001 and Z, 11.87, Padj < .001, respectively). Quantitative and qualitative findings were combined to propose a GUI 3 with high usability. CONCLUSIONS: The usability and quality of allergy documentation was higher for the newly developed coded GUIs with a semiautomatic delabeling feature without being more time-consuming.

Discrepancies in medication information for the primary care physician and the geriatric patient at discharge.

BACKGROUND: Medication discrepancies in discharge medication lists can lead to medication errors and adverse drug events following discharge. OBJECTIVE: To determine the incidence and type of discrepancies between the discharge letter for the primary care physician and the patient discharge medication list as well as identify possible patient-related determinants for experiencing discrepancies. METHODS: A retrospective, single-center, cohort study of patients discharged from the acute geriatric department of a Belgian university hospital between September 2009 and April 2010 was performed. Medications listed in the discharge letter for the primary care physician were compared with those in the patient discharge medication list. Based on the clinical pharmacist-acquired medication list at hospital admission and the medications administered during hospitalization, we determined for every discrepancy whether the medication listed in the discharge letter or the patient discharge medication list was correct. RESULTS: One hundred eighty-nine discharged patients (mean [SD] age 83.9 [5.7] years, 64.0% female) were included in the study. Almost half of these patients (90; 47.6%) had 1 or more discrepancies in medication information at discharge. The discharge letters were often more complete and accurate than the patient discharge medication lists. The most common discrepancies were omission of a brand name in the patient discharge medication list and omission of a drug in the discharge letter. Increasing numbers of drugs in the discharge medication list (OR 1.19; 95% CI 1.07 to 1.32; p = 0.001) and discharge letter (OR 1.18; 95% CI 1.07 to 1.32; p = 0.001) were associated with a higher risk for discrepancies. CONCLUSIONS: Discrepancies between the patient discharge medication list and the medication information in the discharge letter for the primary care physician occur frequently. This may be an important source of medication errors, as confusion and uncertainty about the correct discharge medications can originate from these discrepancies. Increasing numbers of drugs involve a higher risk for discrepancies. Medication reconciliation between both lists is warranted to avoid medication errors.

Effect of medication reconciliation at hospital admission on medication discrepancies during hospitalization and at discharge for geriatric patients.

BACKGROUND: Medication discrepancies have the potential to cause harm. Medication reconciliation by clinical pharmacists aims to prevent discrepancies and other drug-related problems. OBJECTIVE: To determine how often discrepancies in the physician-acquired medication history result in discrepancies during hospitalization and at discharge. Secondary objectives were to determine the influence of clinical pharmacists' interventions on discrepancies and to investigate possible patient-related determinants for experiencing discrepancies. METHODS: This was a retrospective, single-center, cohort study of patients who were admitted to the acute geriatric department of a Belgian university hospital and followed up by clinical pharmacists between September 2009 and April 2010. Patients were limited to those 65 years or older who were taking 1 or more prescription drug. Medication reconciliation at admission, during hospitalization, and at discharge was conducted by an independent pharmacist who gathered information via chart reviews. RESULTS: The reconciliation process at admission identified 681 discrepancies in 199 patients. Approximately 81.9% (163) of patients had at least 1 discrepancy in the physician-acquired medication history. The clinical pharmacists performed 386 interventions, which were accepted in 279 cases (72.3%). A quarter of the medication history discrepancies (165; 24.2%) resulted in discrepancies during hospitalization, mostly because the intervention was not accepted. At discharge, 278 medication history discrepancies (40.8%) resulted in discrepancies in the discharge letter, accounting for 50.2% of all 554 discrepancies identified in the discharge letters. The likelihood for experiencing discrepancies at admission increased by 47% for every additional drug listed in the medication history. CONCLUSIONS: Discrepancies in the physician-acquired medication history at admission do not always correlate with discrepancies during hospitalization because of clinical pharmacists' interventions; however, discrepancies at admission may be associated with at least half of the discrepancies at discharge. Clinical pharmacist-conducted medication reconciliation can reduce these discrepancies, provided the erroneous information in the physician-acquired medication history is corrected and each intentional change in the medication plan is well documented during hospitalization and at discharge.

Stroke prevention in atrial fibrillation: current status and emerging therapies.

Stroke is the most common cardiovascular disorder after heart disease, with a high mortality and often poor quality of life in survivors. Atrial fibrillation (AF), the most commonly occurring sustained cardiac arrhythmia increases the risk of stroke by five. However, stroke risk is not homogeneous and varies with associated morbidities and risk factors. Risk assessment scores have been developed and according to the calculated level of risk, guidelines recommend treatment with antithrombotic agents, preferably vitamin K antagonists (VKA). Despite these recommendations many patients with AF do not receive adequate thromboprophylaxis. The presence of AF is often not recognized and VKA are underused due to doctor- or patient-related factors and intrinsic disadvantages of these drugs. An awareness campaign for the diagnosis of AF is warranted, highlighting the risk of stroke. Novel anticoagulants that largely overcome many of the limitations of vitamin K antagonists are becoming available.

Interdisciplinary knowledge gaps on intravenous fluid management in adult patients: Survey among physicians and nurses of a university hospital.

RATIONALE: Intravenous (IV) fluids are frequently involved in iatrogenic complications in hospitalized patients. Knowledge of IV fluids seems inadequate and is not covered sufficiently in standard medical education. METHODS: Two surveys were developed, based on the 2016 British National Institute for Health and Care Excellence guideline 'IV fluid therapy in adults in hospital', to provide insight on the learning needs and expectations of physicians and nurses. Each survey focused on profession-specific practice and consisted of three parts: demographics, knowledge questions and evaluation of current habits. Physicians and nurses practicing in a Belgian university hospital were invited to complete the survey electronically, respectively, in January and May 2018. RESULTS: A total of 103 physicians (19%) and 259 nurses (24%) participated. Although every indication for fluid therapy may require a specific fluid and electrolyte mixture, and hence, knowledge of their exact composition, most physicians and nurses did not know the composition of commonly prescribed solutions for IV infusion. Senior physicians did not score better than juniors did on questions concerning the daily needs of a nil-by-mouth patient. The availability of an IV fluid on the ward guides physicians to prescribe IV fluids (17%). Nurses (56%) feel they share responsibility in fluid management as they frequently intervene in urgent situations. More than half of participants (70% of physicians, 79% of nurses) indicated a need for additional information. CONCLUSIONS: A clear need for more structured information on IV fluids was identified. Both physicians and nurses struggle with fluid therapy. Continuing education on IV fluid management, emphasizing multidisciplinary collaboration, and monitoring evidence-based practice is essential to support the clinical decision process in daily practice.

Access to orphan drugs despite poor quality of clinical evidence.

AIM: We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS: Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French 'Haute Autorité de Santé', including the five-point scale parameter 'Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS: Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P= 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS: Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states.

Determinants of folic acid use in a multi-ethnic population of pregnant women: a cross-sectional study.

AIMS: To investigate the possible differences in folic acid use and to identify the determinants of antenatal folic acid use among multi-ethnic pregnant women. METHODS: Three hundred and fifty pregnant women participated in this cross-sectional study in a university hospital in Brussels, Belgium. A questionnaire was used to obtain data on socio-demographic characteristics and folic acid use. χ(2)-tests and binary logistic regression analyses were performed using SPSS 17. RESULTS: In the overall cohort, 59.2% used folic acid supplements during pregnancy. This supplement use was associated with an age of 26-35 years, being of Western origin, with high education and employment status, understanding physician's instructions, and early booking for antenatal care. Education (odds ratio, OR: 2.24; 95% confidence interval, CI: 1.08-4.63) and early booking for antenatal care OR: 2.45; 95% CI: 1.11-5.40) were the most important determinants. In particular for Arab/Turkish women, a lower employment status OR: 0.42; 95% CI: 0.24-0.73) was associated with a higher risk of not using folic acid supplements. CONCLUSIONS: The lower use of folic acid supplements in Arab/Turkish ethnicities, which may be associated with an increased risk of neural tube defects, is related to socio-economic factors rather than to lower educational attainment. As recommended by other studies, fortification of ethnic minority food may be warranted to reduce the risk of neural tube defects.

Evaluation of an optimized context-aware clinical decision support system for drug-drug interaction screening.

OBJECTIVE: Evaluation of the effect of six optimization strategies in a clinical decision support system (CDSS) for drug-drug interaction (DDI) screening on alert burden and alert acceptance and description of clinical pharmacist intervention acceptance. METHODS: Optimizations in the new CDSS were the customization of the knowledge base (with addition of 67 extra DDIs and changes in severity classification), a new alert design, required override reasons for the most serious alerts, the creation of DDI-specific screening intervals, patient-specific alerting, and a real-time follow-up system of all alerts by clinical pharmacists with interventions by telephone was introduced. The alert acceptance was evaluated both at the prescription level (i.e. prescription acceptance, was the DDI prescribed?) and at the administration level (i.e. administration acceptance, did the DDI actually take place?). Finally, the new follow-up system was evaluated by assessing the acceptance of clinical pharmacist's interventions. RESULTS: In the pre-intervention period, 1087 alerts (92.0 % level 1 alerts) were triggered, accounting for 19 different DDIs. In the post-intervention period, 2630 alerts (38.4 % level 1 alerts) were triggered, representing 86 different DDIs. The relative risk forprescription acceptance in the post-intervention period compared to the pre-intervention period was 4.02 (95 % confidence interval (CI) 3.17-5.10; 25.5 % versus 6.3 %). The relative risk for administration acceptance was 1.16 (95 % CI 1.08-1.25; 54.4 % versus 46.7 %). Finally, 86.9 % of the clinical pharmacist interventions were accepted. CONCLUSION: Six concurrently implemented CDSS optimization strategies resulted in a high alert acceptance and clinical pharmacist intervention acceptance. Administration acceptance was remarkably higher than prescription acceptance.