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AIM: Inappropriate anticoagulant use increases the risk of bleeding and thrombotic events. We implemented clinical decision rules to promote judicious medication use, as part of the 'Check of Medication Appropriateness' (CMA). The CMA concerns a pharmacist-led review service, targeting potentially inappropriate prescriptions (PIPs). In this analysis, we aimed to evaluate the impact of the CMA on anticoagulant prescribing. METHODS: The number of anticoagulant-related PIPs was evaluated before and after implementation of the intervention in a quasi-experimental interrupted time series analysis. The pre-implementation cohort received usual care. The anticoagulant-focused CMA, comprising 13 clinical rules pertaining to anticoagulation therapies, was implemented in the post-implementation cohort. Segmented regression analysis was used to assess the impact of the intervention on the number of residual PIPs. A residual PIP was defined as a PIP which persisted up to 48h after the CMA intervention. Total number of recommendations and acceptance rate were documented for the 2-year post-implementation period. RESULTS: Pre-implementation, we observed 501 PIPs in 466 inpatients on 36 days, with a median proportion of 78.5% (range: 46.2%-100%) residual PIPs per day. Post-implementation, 538 PIPs were detected in 485 patients over the same number of days. The CMA intervention reduced the median proportion to 18.2% (range: 0-100%) per day. The effect coincided with an immediate relative reduction of 70% (95%CI 0.19-0.46) in anticoagulant-related residual PIPs. Post-implementation, 2778 recommendations were provided and 75.1% were accepted. CONCLUSION: Our CMA approach significantly reduced anticoagulant-related PIPs. Implementing a pharmacist-led intervention, based on clinical rules, may support safer prescribing of anticoagulants. ispartof: British Journal Of Clinical Pharmacology vol:88 issue:6 pages:2959-2968 ispartof: location:England status: accepted

Portable infusion pumps are an interesting solution to continue outpatient parenteral antimicrobial therapy (OPAT) at the patient's home. However, the use of ceftazidime for such applications is challenging in view of its relatively poor stability in solution. In this study, elastomeric infusion pumps with 6 or 7 g of ceftazidime were deflated over 24 h in an oven at 33°C while ceftazidime and its degradation product, pyridine, were regularly monitored. Hereto, a fast and sensitive liquid chromatographic (LC) method has been developed using a Kinetex® C18 (150 × 3 mm, 2.6 μm) column with gradient elution. Ammonium formate 20 mM and acetonitrile (ACN) were mixed in a ratio of 98:2 v/v for mobile phase A and 85:15 v/v for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was set at 0.4 mL/min. The solution with a starting dose of 6 g ceftazidime was found to be degraded 10% after an average of 19 h 11 min so that an administration of 6 g to the patient was not reached. For the solution with a starting dose of 7 g of ceftazidime, 10% degradation was observed after an average of 18 h 42 min. However, by starting from a higher dose, an average of 6.56 g of ceftazidime could be administered over 24 h. In addition, 1.0% of pyridine versus ceftazidime pentahydrate with sodium carbonate (=mixture for injection) was formed over 24 h.

Objectives Inappropriate prescribing of antimicrobials in hospitals contributes to the emergence of resistance and adverse drug events. To support antimicrobial stewardship (AMS), clinical decision rules focusing on antimicrobial therapy were implemented in the ‘Check of Medication Appropriateness’ (CMA). The CMA is a hospital-wide pharmacist-led medication review service consisting of a clinical rule-based screening for potentially inappropriate prescriptions (PIPs). We aimed to investigate the impact of the CMA on antimicrobial prescribing. Methods An interrupted time series study was performed at the University Hospitals Leuven. The pre-implementation cohort was exposed to standard-of-care AMS. Afterwards, an AMS-focused CMA comprising 41 specific clinical rules, targeting six AMS objectives, was implemented in the post-implementation period. A regression model was used to assess the impact of the intervention on the number of AMS-related residual PIPs between both periods. The total number of recommendations and acceptance rate was recorded for the 2 year post-implementation period. Results Pre-implementation, a median proportion of 75% (range: 33%–100%) residual PIPs per day was observed. After the CMA intervention, the proportion was reduced to 8% (range: 0%–33%) per day. Use of clinical rules resulted in an immediate relative reduction of 86.70% (P Conclusions We proved that the CMA approach reduced the number of AMS-related residual PIPs in a highly significant and sustained manner, with the potential to further expand the service to other AMS objectives.

BACKGROUND Pain therapy in inpatients is regularly suboptimal and might be improved by clinical pharmacy services. In our hospital, we have implemented a software-supported 'Check of Medication Appropriateness' (CMA), which is a centralized pharmacist-led service consisting of a clinical rule-based screening for potentially inappropriate prescriptions (PIPs), and a subsequent medication review by pharmacists. We aimed to investigate the impact of the CMA on pain-related prescribing. METHODS A quasi-experimental study was performed in a large teaching hospital, using an interrupted time series design. Pre-implementation, patients were exposed to standard of care. Afterwards, a pain-focused CMA comprising 12 specific clinical rules pertaining to analgesic prescribing were implemented in the post-implementation period. A regression model was used to assess the impact of the intervention on the number of pain-related residual PIPs between both periods. The total number of recommendations and acceptance rate was recorded for the post-implementation period. RESULTS At baseline, a median number of 13.1 (range: 9.5-15.8) residual PIPs per day was observed. After the CMA intervention, the number was reduced to 2.2 (range: 0-9.5) per day. Clinical rules showed an immediate relative reduction of 66% (p

Background Adverse drug events following inappropriate prescribing in the hospital cause a substantial and avoidable medical and economic burden to hospitals, payers and patients alike. A clinical rule-based, pharmacist-led medication-review service, the 'Check of Medication Appropriateness' (CMA) was implemented in the University Hospitals Leuven. The CMA is shown to be effective in reducing potentially inappropriate prescriptions. Aim This study investigated whether this centralised clinical pharmacy service is cost-effective. Method We performed a cost-effectiveness analysis of three clinical rules of the CMA, targeting adverse drug events at three levels of severity: A) persistent opioid-induced constipation, B) ketorolac-induced gastrointestinal bleeding and C) drug-induced Torsade de Pointes. A decision tree was developed for each clinical rule. Both intervention costs as well as total costs associated with the occurrence of an adverse drug event were considered. The outcomes were reported in the form of an incremental cost-effectiveness ratio, expressed as an incremental cost per adverse drug event avoided. Results Applying clinical rules to avoid persistent opioid-induced constipation and ketorolac-induced gastrointestinal bleeding were cost-saving. Implementation of a medication check to avoid drug-induced Torsade de Pointes costed €8,846 per Torsade de Pointes avoided. Conclusion Our study provides strong indications that the CMA is worth its investment for clinical rules targeting (very) common adverse drug events, that can be avoided with limited expenses. Further research is required to assess the full CMA. The proposed model may be useful to perform cost-effectiveness analyses of other centralised clinical pharmacy services targeting inappropriate prescribing, at the level of individual adverse drug events.

Objective Anticoagulation is highly effective for stroke prevention in atrial fibrillation (AF), reducing the risk by about 64%. Despite overwhelming evidence in support of anticoagulation, up to 40% of AF patients remain untreated. We aimed to develop and validate STEWARxD-AF: a Screening Tool to Evaluate and Warrant Anticoagulation Treatment prior to Discharge in Atrial Fibrillation. Materials and methods STEWARxD-AF was developed by integrating information extracted from the electronic health record (EHR). A stepwise decision process was applied, based on AF diagnosis, estimated CHA2DS2-VASc-score and anticoagulant use. A priority score was assigned accordingly, ranging from 0 (no risk) to 5 (highest risk of undertreatment). A cross-sectional study was performed to assess the accuracy of STEWARxD-AF. Criterion and tool validity were ascertained by determining sensitivity and specificity, compared to a manual check of the EHR in an inpatient sample (n = 800). Consistency regarding the priority score was determined by estimating Cohen’s kappa. Results A tool to screen for un(der)treated AF was developed and embedded into the EHR. Sensitivity and specificity for AF diagnosis were 98.4% and 87.6%, respectively. Overall sensitivity and specificity for identification of a CHA2DS2-VASc-score ≥ 2 was 97.7% and 72.7%. Sensitivity and specificity to determine the presence of anticoagulant treatment was at least 87.8% and 97.1% There was good agreement for the priority score (κ 0.74 (unweighted); 0.66 (weighted)). Conclusions STEWARxD-AF was able to identify untreated AF inpatients reliably and with a high sensitivity. Nearly no patients were missed. We will now implement this AF-screening tool in clinical practice to improve the use of anticoagulation and reduce the risk of stroke.

Background and importance Stroke prevention in atrial fibrillation (AF) is a major indication for oral anticoagulants. Appropriate use of anticoagulants reduces the relative risk of stroke by approximately 66%. Despite an abundance of evidence for this treatment, up to 40% of AF patients do not receive anticoagulant therapy. Decision support systems have shown promise in increasing guideline adherence to reduce therapeutic omissions. Aim and objectives We aimed to develop and validate a screening tool to identify untreated AF inpatients. Material and methods A computerised screening tool was developed integrating the following data from the patient’s electronic health record (EHR): demographic, laboratory and medication data, ECG reports and allocation to specific care programmes. A decision process was applied, which consisted of (1) determining whether AF was present, (2) calculating the CHA2DS2-VASc score and (3) determining whether anticoagulant treatment was present during hospitalisation and/or in the pre-admission therapy. Subsequently, based on these three steps, a priority score was assigned to the patient, from 0 (no risk) to 5 (highest level of risk). A validation study was done to assess the accuracy of this approach. Criterion and tool validity were ascertained by determining specificity and sensitivity, compared with a manual check of the EHR. Consistency regarding the priority score was determined by estimating Cohen’s kappa (κ). Results For the validation, 800 inpatients were included. The specificity and sensitivity of the tool for identification of patients with AF were 87.6% and 95.1%, respectively. Overall specificity and sensitivity for identification of AF patients with a CHA2DS2-VASc score ≥2 was 72.7% and 97.7%, respectively. Specificity and sensitivity to determine the presence of anticoagulants was 97% and 87%, respectively. There was good agreement between the priority score obtained by the pharmacist after EHR review and the one generated by the screening tool (κ unweighted 0.74; κ equal weighted 0.66). Conclusion and relevance This screening tool to identify untreated AF inpatients was found to be reliable and valid with a high sensitivity. To further improve specificity, future investigations might focus on better digital structuring of patient data. Our future goal is to implement the AF screening tool in clinical practice to improve the use of preventative therapy and reduce the significant burden of stroke. References and/or acknowledgements Conflict of interest No conflict of interest

Background and importance Pain therapy in inpatients is regularly suboptimal and might be improved by clinical pharmacy services with the aim of optimising pain control and reducing iatrogenic harm related to adverse drug events and overuse. In our hospital, we have implemented a software supported check of medication appropriateness (CMA), which is a centralised pharmacist led service consisting of a clinical rule based screening for potentially inappropriate prescriptions (PIPs) and a subsequent medication review by pharmacists. Aim and objectives We aimed to investigate the impact of the CMA on pain related prescribing. Material and methods A quasi-experimental study was performed in a 1995 bed tertiary hospital, using an interrupted time series design. Pre-implementation, patients were exposed to standard of care. Afterwards, a pain focused CMA comprising 12 clinical rules pertaining to analgesic prescribing were implemented in the post-implementation period. A regression model was used to assess the impact of the intervention on the number of pain related residual PIPs. For the pre-implementation period, data collection was performed retrospectively (January 2016 to December 2018). Post-implementation (January 2019 to July 2020), an initial PIP was identified prospectively in the CMA. The total number of recommendations and acceptance rate were recorded for the post-implementation period. Results At baseline, the median proportion of residual PIPs was 69.0% (range 50.0–83.3%) with a median number of 13.1 (range 9.5–15.8) residual PIPs per day. After the CMA intervention, the median proportion and median number decreased to 11.8% (range 0–50%) and 2.2 (range 0–9.5), respectively. Clinical rules showed an immediate relative reduction of 66% (p Conclusion and relevance We proved that the CMA approach improved analgesic prescribing, as the number of pain related residual PIPs was reduced in a highly significant and sustained manner. The downward trend in the post-implementation period might indicate a learning effect on physicians, resulting in a higher acceptance rate of recommendations over time. More pharmacist involvement and the use of clinical rules during hospital stay should be further promoted to optimise appropriate prescribing of analgesics. References and/or acknowledgements Conflict of interest No conflict of interest

ObjectivesEarly switch from intravenous to oral therapy of bioequivalent drugs has major advantages but remains challenging. At our hospital, a basic clinical rule was designed to automatically alert the physician to review potential intravenous to oral switch (IVOS). A rather low acceptance rate was observed. In this study, we aimed to develop, validate and investigate the effect of more advanced clinical rules for IVOS, as part of a centralised pharmacist-led medication review service.Design and settingA quasi-experimental study was performed in a large teaching hospital in Belgium using an interrupted time series design.InterventionA definite set of 13 criteria for IVOS, focusing on the ability of oral absorption and type of infection, was obtained by literature search and validated by a multidisciplinary expert panel. Based on these criteria, we developed a clinical rule for paracetamol and one for ten bioequivalent antibiotics to identify patients with potentially inappropriate intravenous prescriptions (PIVs). Postintervention, the clinical rule alerts were reviewed by pharmacists, who provided recommendations to switch in case of eligibility.Primary and secondary outcome measuresA regression model was used to assess the impact of the intervention on the number of persistent PIVs between the preintervention and the postintervention period. The total number of recommendations, acceptance rate and financial impact were recorded for the 8-month postintervention period.ResultsAt baseline, a median number of 11 (range: 7–16) persistent PIVs per day was observed. After the intervention, the number reduced to 3 (range: 1–7) per day. The advanced IVOS clinical rules showed an immediate relative reduction of 79% (incidence rate ratio=0.21, 95% CI 0.13 to 0.32; pConclusionsWe showed the efficacy of advanced clinical rules combined with a pharmacist-led medication review for IVOS of bioequivalent drugs.

Background and importance Continuous infusion of high dose piperacillin/tazobactam (16/2 g in 264 mL NaCl 0.9%) has been included in the UZ Leuven outpatient parenteral antimicrobial therapy (OPAT) protocol. Elastomeric pumps (Infusor LV10, Baxter) were selected as the drug delivery device, as the patient’s mobility and comfort are maintained. Unfortunately, incomplete infusions after 24 hours were observed, related to a reduced flow rate. A mean daily residual volume of 50 mL, corresponding to a dose of 3/0.38 g piperacillin/tazobactam, was detected, resulting in substantial underdosing with the risk of treatment failure. Aim and objectives To analyse two hypotheses: a reduced flow rate could be the result of particulate formation of piperacillin dimers due to the absence of stabilising excipients (hypothesis 1) or a result of high viscosity (hypothesis 2). Material and methods Hypothesis 1: particulate formation was detected by comparing the flow rate of tazocillin (with stabilising excipients) versus generic piperacillin/tazobactam (without this excipients), by measuring light absorbance (600 nm) by spectrophotometry and by measuring total piperacillin content at different concentrations after storage for 24 hours at 33°C. Hypothesis 2: the effect of concentration on the density and viscosity at 33°C was measured. Additionally, the relation between viscosity and flow rate was evaluated. Results Hypothesis 1: no difference was observed in the flow rate between Tazocillin and generic piperacillin/tazobactam. No difference was observed in absorbance between Tazocillin and generic piperacillin/tazobactam, and no difference was observed in absorbance between piperacillin/tazobactam and a blank. Generic piperacillin/tazobactam seemed to be stable for 24 hours at 33°C. Hypothesis 2: a linear relationship was observed between concentration and viscosity. An inverted linear relationship was observed between viscosity and flow rate of piperacillin/tazobactam solutions. Conclusion and relevance The in vitro experiments suggest that the reduced flow rate is a result of high viscosity, related to the concentration of piperacillin/tazobactam. As it is impossible to lower the concentration, the final volume of the solution should be adjusted. Before being used in clinical practice for OPAT, this mode of administration will first be validated in five patients during hospitalisation. In general, healthcare teams need to be aware of factors which may lead to longer flow durations with these infusion devices. References and/or acknowledgements No conflict of interest.

Evidence supports the implementation of outpatient parenteral antimicrobial therapy (OPAT) as standard of care. Until 2015 the overall experience with OPAT in Belgium remained limited. The aim of this study was to evaluate the efficacy and safety of a Belgian ‘OPAT at home’ program, which was implemented in University Hospitals Leuven starting from January 2017. A mono-centric, prospective, observational study was carried out. All OPAT cases discharged between 10 January 2017 and 10 January 2019 were included in the study. Relevant demographic and clinical patient data were collected. The outcomes were clinical cure rate, OPAT related readmission rate, adverse event rate and patients’ satisfaction. Over the two-year study period, 152 OPAT episodes were started in 130 patients, resulting in 3153 avoided hospitalization days which corresponds to 5.4 freed hospital beds. Urinary tract infections accounted for 40.8% of OPAT courses and temocillin was the most frequently used antibiotic (24.3%). Cure was achieved in 97.9% of the OPAT episodes. During 22 (14.5%) OPAT episodes, patients experienced adverse events, including line related adverse events (7.9%) and adverse drug events (6.6%). An OPAT related readmission rate of 9.2% was observed, mostly related to line-associated adverse events. All patients who completed the satisfaction survey (n = 23) were very satisfied with their OPAT course. The University Hospitals Leuven OPAT program is associated with a high level of clinical cure and low all-cause readmission and adverse event rates. Improvement actions are described to further reduce the readmission rate to less than 5.0%.

Background To improve medication surveillance and provide pharmacotherapeutic support in University Hospitals Leuven, a back-office clinical service, called “Check of Medication Appropriateness” (CMA), was developed, consisting of clinical rule based screening for medication inappropriateness. The aim of this study is twofold: 1) describing the development of CMA and 2) evaluating the preliminary results, more specifically the number of clinical rule alerts, number of actions on the alerts and acceptance rate by physicians. Methods CMA focuses on patients at risk for potentially inappropriate medication and involves the daily checking by a pharmacist of high-risk prescriptions generated by advanced clinical rules integrating patient specific characteristics with details on medication. Pharmacists’ actions are performed by adding an electronic note in the patients’ medical record or by contacting the physician by phone. A retrospective observational study was performed to evaluate the primary outcomes during an 18-month study period. Results 39,481 clinical rule alerts were checked by pharmacists for which 2568 (7%) electronic notes were sent and 637 (1.6%) phone calls were performed. 37,782 (96%) alerts were checked within four pharmacotherapeutic categories: drug use in renal insufficiency (25%), QTc interval prolonging drugs (11%), drugs with a restricted indication or dosing (14%) and overruled very severe drug-drug interactions (50%). The emergency department was a frequently involved ward and anticoagulants are the drug class for which actions are most frequently carried out. From the 458 actions performed for the four abovementioned categories, 69% were accepted by physicians. Conclusions These results demonstrate the added value of CMA to support medication surveillance in synergy with already integrated basic clinical decision support and bedside clinical pharmacy. Otherwise, the study also highlighted a number of limitations, allowing improvement of the service. Electronic supplementary material The online version of this article (10.1186/s12911-019-0748-5) contains supplementary material, which is available to authorized users.

This narrative review aims to describe barriers of outpatient parenteral antimicrobial therapy at home (OPAT), potentially compromising general standards of antibiotic stewardship (ABS) and facilitators of OPAT for ABS. After a literature review, five authors determined the barriers and facilitators to discuss in this review. Sixty-six publications were included in the narrative review and seven barriers and five facilitators are discussed in this article. The impracticability of multiple daily dosing during OPAT, the impact of real-life temperature variations, deviations of the infusion rates of elastomeric devices, access to prolonged intravenous antibiotic therapy, not administering loading doses before the initiation of extended or continuous infusions and the transmural nature of care associated with OPAT, can lead to deviations of recommended treatment regimens and sub-optimal clinical and laboratory follow-up, with a risk of inferior clinical outcomes, adverse events, drug-resistance and higher costs. On the other hand, OPAT provides access to treatments with intravenous antibiotics and simultaneously avoids prolonged hospitalization. Implementing ABS guidelines in OPAT programs, e.g., by using a multidisciplinary team approach and facility-specific protocols for OPAT with patient selection criteria and instructions for selection, storage, preparation and administration of antibiotics, can improve appropriate antibiotic use. Additionally, further research should examine the effectiveness of these interventions on outcomes of OPAT.

Background During the last decade, healthcare shifted from a disease-focused approach towards a more patient-focused approach. Hospital pharmacy services experienced a similar development. Traditional drug-oriented services expanded towards patient-oriented services by imbedding computerised clinical decision support systems (CDSSs) in the prescribing process and implementing bedside clinical pharmacy services. However, due to limited resources, clinical pharmacy services are not implemented on a hospital-wide basis in Belgian hospitals. Purpose To guarantee patient safety, a central check of medication appropriateness (COMA) was developed and implemented since March 2016 in the University Hospitals Leuven. Materials and Methods Based on a risk analysis, high-risk prescriptions are checked by a hospital pharmacist for appropriateness. A daily check (0.5 FTE) of automatically generated queries is performed using standardised algorithms. The queries are a result of the screening of all new prescriptions in the electronic prescribing system of the last 24 hours. Interventions are performed via electronic warnings in the patient’s file or phone calls to the treating physician. Results Twelve hospital pharmacists are now involved in the COMA and 79 specific algorithms were developed, covering five pharmacotherapeutic areas of interest: drugs with restrictive indication; overruled interventions raised by CDSS; medication-related biochemical changes; sequential therapy for bio-equivalent drugs; and reimbursement of drugs. During a 18 month period, 92 050 prescriptions were checked for which 24 943 (27%) electronic warnings were sent and 637 (1%) phone calls were carried out. When analysed without automatic warnings for sequential therapy, 39 481 prescriptions were checked for which 2568 (7%) electronic warnings were sent and 637 (2%) phone calls were carried out. Conclusion For the future we obtain the next goals: Evaluation of the acceptance of the current COMA process. Fine–tuning the screening queries with an emphasis on improving specificity. Determining inter–rater validity. Development of new algorithms, also expanding to other areas of interest. Development of an easy access training tool for hospital pharmacists to perform COMA.