Prevalence and predictors of inappropriate prescribing in outpatients with severe mental illness.

Background: Potentially inappropriate prescribing (PIP) is frequent in geriatrics and results in an increased risk for adverse effects, morbidity, mortality and reduced quality of life. Research on PIP in psychiatry has mainly focused on elderly patients and inpatients. Objectives: To determine the prevalence and the predictors of PIP of psychotropic medication in outpatients with severe mental illness. Design: This study is part of the Muva study, a pragmatic open Stepped Wedge Cluster Randomized Trial of a physical activity intervention for patients (age ⩾ 16 years) with severe mental illness. Methods: A structured medication interview, questionnaires on social functioning, quality of life and psychiatric symptoms, and BMI and waist circumference measurements were performed followed by a structured medication review. Patients were divided into groups: PIP versus no PIP. Between-group differences were calculated and a multivariate binary logistic regression was performed to examine predictors for PIP. A receiver operating characteristics analysis was performed to determine the area under the curve (AUC). Results: In 75 patients, an average of 5.2 medications of which 2.5 psychotropic medication was used. 35 (46.7%) patients were identified with PIP. Unindicated long-term benzodiazepine use was the most frequently occurring PIP (34.1%). Predictors of PIP were female gender [odds ratio (OR) = 4.88, confidence interval (CI) = 1.16-20.58, p = 0.03], number of medications (OR = 1.41, CI = 1.07-1.86, p = 0.02) and lower social functioning (OR = 1.42, CI = 1.01-2.00, p = 0.05). The AUC was 0.88 for the combined prediction model. Conclusion: The prevalence of PIP of psychotropic medication in outpatients with severe mental illness is high. It is therefore important to identify, and where possible, resolve PIP by frequently performing a medication review with specific attention to females, patients with a higher number of medications and patients with lower social functioning. Trial registration: This trial was registered in The Netherlands Trial Register (NTR) as NTR NL9163 on 20 December 2020 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9163).

Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients.

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU). Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05). Discussion: This study underlines the importance to consider phenoconversion when looking at a patient's genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.

Medical Residents' Informal Learning from Pharmacists in the Clinical Workplace.

Workplace-based interactions between residents and pharmacists, though relatively underexplored, might contribute substantially to learning. This international study sought to investigate the affordances residents use for informal learning about medications, their interactions with pharmacists and patterns of resident-pharmacist engagement, as well as residents' perceived impact of these interactions on their learning. Contextual differences between US and Dutch residency training and electronic health record (EHR) may impact informal learning about medications. We conducted a cross-sectional, online, 25-item survey study, including closed-format and open-response questions among current resident physicians (post-graduate years 1-6, from a variety of residency programs n = 803) from the University of California San Francisco, the University of Minnesota, and the University Medical Center Utrecht. Responses from 173 residents in both countries revealed that these physician trainees were afforded opportunities to engage in a wide variety of pharmacotherapy-related activities but engaged differently with social and environmental resources for support. Residents from the United States (US) utilized pharmacists and Up-To-Date, whereas Dutch residents preferentially utilized the online Dutch medication information site and EHR-embedded medication resources. US residents interacted with pharmacists significantly more frequently than Dutch residents. Pharmacists provided residents with a wide range of useful information, much of which is integrated into the medication resources in the Dutch EHR-based decision-support system. While US residents reported overwhelmingly that informal interactions with pharmacists contribute to their learning about medications, Dutch residents' responses did not confirm this. Intentionally designing residents' training to include opportunities for interactions with pharmacists could potentially positively impact residents' informal workplace learning. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01784-1.

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.

INTRODUCTION: Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. OBJECTIVE: The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. METHODS: Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. RESULTS: In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. CONCLUSION: MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. REGISTRATION: ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. FUNDING: European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF).

Performance of a trigger tool for detecting adverse drug reactions in patients with polypharmacy acutely admitted to the geriatric ward.

PURPOSE: Adverse drug reactions (ADRs) account for 10% of acute hospital admissions in older people, often under-recognised by physicians. The Dutch geriatric guideline recommends screening all acutely admitted older patients with polypharmacy with an ADR trigger tool comprising ten triggers and associated drugs frequently causing ADRs. This study investigated the performance of this tool and the recognition by usual care of ADRs detected with the tool. METHODS: A cross-sectional study was performed in patients ≥ 70 years with polypharmacy acutely admitted to the geriatric ward of the University Medical Centre Utrecht. Electronic health records (EHRs) were screened for trigger-drug combinations listed in the ADR trigger tool. Two independent appraisers assessed causal probability with the WHO-UMC algorithm and screened EHRs for recognition of ADRs by attending physicians. Performance of the tool was defined as the positive predictive value (PPV) for ADRs with a possible, probable or certain causal relation. RESULTS: In total, 941 trigger-drug combinations were present in 73% (n = 253/345) of the patients. The triggers fall, delirium, renal insufficiency and hyponatraemia covered 86% (n = 810/941) of all trigger-drug combinations. The overall PPV was 41.8% (n = 393/941), but the PPV for individual triggers was highly variable ranging from 0 to 100%. Usual care recognised the majority of ADRs (83.5%), increasing to 97.1% when restricted to possible and certain ADRs. CONCLUSION: The ADR trigger tool has predictive value; however, its implementation is unlikely to improve the detection of unrecognised ADRs in older patients acutely admitted to our geriatric ward. Future research is needed to investigate the tool's clinical value when applied to older patients acutely admitted to non-geriatric wards.

Impulse control disorders associated with dopaminergic drugs: A disproportionality analysis using vigibase.

BACKGROUND: Dopamine receptor agonist drugs, which are used, for example, to treat Parkinson's disease (PD), increase the risk for impulse control disorders (ICDs), potentially resulting in devastating psychosocial consequences. It is unknown whether other drugs with dopaminergic properties also increase the risk for ICDs. This study assesses the disproportionality of reporting ICDs between drugs with dopaminergic properties and selected non-dopaminergic drugs. METHODS: A case/non-case disproportionality analysis was performed, using data from VigiBase (1968-2020). Reports on ICDs as suspected adverse drug reactions (ADRs) were cases (n=852), and those with ADRs other than ICDs were non-cases (n=281,720). Relative reporting frequencies were expressed as adjusted reporting odds ratios (aRORs). Within the dopamine receptor agonists, the relationship between reporting odds ratios and dopamine receptor occupancy was explored. RESULTS: A high disproportionality was found for reporting ICDs for all dopaminergic drugs (aROR 20.4 [95% CI 17.4-24.1]) compared to non-dopaminergic drugs. In pharmacotherapeutic subgroups, a high disproportionality was found for primary dopaminergic agents used in PD (aROR 52.1 [95% CI 44.1-61.5]), and to a lesser extent for ADHD psychostimulants and antidepressants (aROR 5.8 [95% 4.1-8.3] and aROR 3.9 [95% CI 2.9-5.6], respectively). There was no difference in reporting by consumers and healthcare professionals. The highest disproportionality was found for the dopamine receptor agonists pramipexole and ropinirole. CONCLUSIONS: A signal of disproportion in ICD occurrence was found among all investigated drugs with dopaminergic properties, highlighting the importance of counselling and monitoring for ICDs when prescribing dopaminergic drugs.

Performance of a trigger tool for detecting drug-related hospital admissions in older people: analysis from the OPERAM trial.

BACKGROUND: identifying drug-related hospital admissions (DRAs) in older people is difficult. A standardised chart review procedure has recently been developed. It includes an adjudication team (physician and pharmacist) screening using 26 triggers and then performing causality assessment to determine whether an adverse drug event (ADE) occurred (secondary to an adverse drug reaction, overuse, misuse or underuse) and whether the ADE contributed to hospital admission (DRA). OBJECTIVE: to assess the performance of those triggers in detecting DRA. DESIGN: retrospective study using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people) trial. SETTINGS: four European medical centres. SUBJECTS: multimorbid (≥ 3 chronic medical conditions) older (≥ 70 years) inpatients with polypharmacy (≥ 5 chronic medications) were enrolled in the OPERAM trial (N = 2,008) and followed for 12 months. We included patients with ≥1 adjudicated hospitalisation during the follow-up. METHODS: the positive predictive value (PPV; number of DRAs identified by trigger/number of triggers) was calculated for each trigger and for the tool as a whole. RESULTS: of 1,235 hospitalisations adjudicated for 832 patients, 716 (58%) had at least one trigger; an ADE was identified in 673 (54%) and 518 (42%) were adjudicated as DRAs. The overall PPV of the trigger tool for detecting DRAs was 0.66 [0.62-0.69]. CONCLUSIONS: this tool performs well for identifying DRAs in older people. Based on our results, a revised version of the tool was proposed but will require external validation before it can be incorporated into research and clinical practice.

Frequency and Acceptance of Clinical Decision Support System-Generated STOPP/START Signals for Hospitalised Older Patients with Polypharmacy and Multimorbidity.

BACKGROUND: The Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) instrument is used to evaluate the appropriateness of medication in older people. STOPP/START criteria have been converted into software algorithms and implemented in a clinical decision support system (CDSS) to facilitate their use in clinical practice. OBJECTIVE: Our objective was to determine the frequency of CDSS-generated STOPP/START signals and their subsequent acceptance by a pharmacotherapy team in a hospital setting. DESIGN AND METHODS: Hospitalised older patients with polypharmacy and multimorbidity allocated to the intervention arm of the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) trial underwent a CDSS-assisted structured medication review in four European hospitals. We evaluated the frequency of CDSS-generated STOPP/START signals and the subsequent acceptance of these signals by a trained pharmacotherapy team consisting of a physician and pharmacist after evaluation of clinical applicability to the individual patient, prior to discussing pharmacotherapy optimisation recommendations with the patient and attending physicians. Multivariate linear regression analysis was used to investigate potential patient-related (e.g. age, number of co-morbidities and medications) and setting-related (e.g. ward type, country of inclusion) determinants for acceptance of STOPP and START signals. RESULTS: In 819/826 (99%) of the patients, at least one STOPP/START signal was generated using a set of 110 algorithms based on STOPP/START v2 criteria. Overall, 39% of the 5080 signals were accepted by the pharmacotherapy team. There was a high variability in the frequency and the subsequent acceptance of the individual STOPP/START criteria. The acceptance ranged from 2.5 to 75.8% for the top ten most frequently generated STOPP and START signals. The signal to stop a drug without a clinical indication was most frequently generated (28%), with more than half of the signals accepted (54%). No difference in mean acceptance of STOPP versus START signals was found. In multivariate analysis, most patient-related determinants did not predict acceptance, although the acceptance of START signals increased in patients with one or more hospital admissions (+ 7.9; 95% confidence interval [CI] 1.6-14.1) or one or more falls in the previous year (+ 7.1; 95% CI 0.7-13.4). A higher number of co-morbidities was associated with lower acceptance of STOPP (- 11.8%; 95% CI - 19.2 to - 4.5) and START (- 11.0%; 95% CI - 19.4 to - 2.6) signals for patients with more than nine and between seven and nine co-morbidities, respectively. For setting-related determinants, the acceptance differed significantly between the participating trial sites. Compared with Switzerland, the acceptance was higher in Ireland (STOPP: + 26.8%; 95% CI 16.8-36.7; START: + 31.1%; 95% CI 18.2-44.0) and in the Netherlands (STOPP: + 14.7%; 95% CI 7.8-21.7). Admission to a surgical ward was positively associated with acceptance of STOPP signals (+ 10.3%; 95% CI 3.8-16.8). CONCLUSION: The involvement of an expert team in translating population-based CDSS signals to individual patients is essential, as more than half of the signals for potential overuse, underuse, and misuse were not deemed clinically appropriate in a hospital setting. Patient-related potential determinants were poor predictors of acceptance. Future research investigating factors that affect patients' and physicians' agreement with medication changes recommended by expert teams may provide further insight for implementation in clinical practice. REGISTRATION: ClinicalTrials.gov Identifier: NCT02986425.

Prevalence of drug-drug interactions in older people before and after hospital admission: analysis from the OPERAM trial.

BACKGROUND: Drug-drug interactions (DDIs) are highly prevalent in older patients but little is known about prevalence of DDIs over time. Our main objective was to assess changes in the prevalence and characteristics of drug-drug interactions (DDIs) during a one-year period after hospital admission in older people, and associated risk factors. METHODS: We conducted a sub-study of the European OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people), which assessed the effects of a structured medication review (experimental arm) compared to usual care (control arm) on reducing drug-related hospital readmissions. All OPERAM patients (≥70 years, with multimorbidity and polypharmacy, hospitalized in four centers in Bern, Brussels, Cork and Utrecht between December 2016 and October 2018, followed over 1 year) who were alive at hospital discharge and had full medication data during the index hospitalization (at baseline i.e., enrolment at admission, and at discharge) were included. DDIs were assessed using an international consensus list of potentially clinically significant DDIs in older people. The point-prevalence of DDIs was evaluated at baseline, discharge, and at 2, 6 and 12 months after hospitalization. Logistic regression models were performed to assess independent variables associated with changes in DDIs 2 months after baseline. RESULTS: Of the 1950 patients (median age 79 years) included, 1045 (54%) had at least one potentially clinically significant DDI at baseline; point-prevalence rates were 58, 57, 56 and 57% at discharge, and 2, 6 and 12 months, respectively. The prevalence increased significantly from baseline to discharge (P < .001 [significant only in the control group]), then remained stable over time (P for trend .31). The five most common DDIs -all pharmacodynamic in nature- accounted for 80% of all DDIs and involved drugs that affect potassium concentrations, centrally-acting drugs and antithrombotics. At 2 months, DDIs had increased in 459 (27%) patients and decreased in 331 (19%). The main factor predictive of a change in the prevalence of DDIs was hyperpolypharmacy (≥10 medications). CONCLUSIONS: DDIs were very common; their prevalence increased during hospitalization and tended to remain stable thereafter. Medication review may help control this increase and minimize the risk of adverse drug events.

Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial.

OBJECTIVE: To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. DESIGN: Cluster randomised controlled trial. SETTING: 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. PARTICIPANTS: 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). INTERVENTION: Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. MAIN OUTCOME MEASURE: Primary outcome was first drug related hospital admission within 12 months. RESULTS: 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). CONCLUSIONS: Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02986425.

The effect of prednisolone on symptom severity in schizophrenia: A placebo-controlled, randomized controlled trial.

OBJECTIVE: Immune dysregulation may be involved in the pathophysiology of schizophrenia. Given the need for new treatment options in schizophrenia, anti-inflammatory medication could be a potential treatment in this illness. METHODS: In this double-blind, placebo-controlled clinical trial, patients with schizophrenia, schizoaffective disorder or psychosis NOS were randomized 1:1 to either prednisolone or placebo, in addition to their regular antipsychotic medication. Patients diagnosed with schizophrenia for less than 7 years and on antipsychotics, were treated with prednisolone or placebo, tapered-off within six weeks in the following schedule: 40 mg/day for 3 days and 30 mg/day for 4 days, followed by a decrease of 5 mg/day per week during the remaining 5 weeks. Change in symptom severity relative to baseline was compared between treatment arms, as measured through the Positive and Negative Syndrome Scale total score. RESULTS: In total, 68 patients signed informed consent and were screened on eligibility criteria, of whom 42 patients were randomized to either prednisolone or placebo, with 39 patients completing the treatment and tapering phase. Due to recruitment difficulties, the study was terminated prematurely. Symptom severity decreased significantly in both the prednisone and placebo treatment arm (p < 0.001). The degree of improvement was not significantly different between treatment arms (p = 0.96). No serious adverse events occurred during the treatment phase. DISCUSSION: There is no indication that prednisolone has a beneficial effect on symptom severity, as adjunctive treatment in patients with schizophrenia, as compared to placebo. CONCLUSION: Adjunctive treatment with prednisolone did not improve symptom severity compared to placebo in patients with schizophrenia.

Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial.

BACKGROUND: Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. METHODS: In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000 mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. DISCUSSION: The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem. TRIAL REGISTRATION: This trial was registered in the Netherlands Trial Register (NTR) at  https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020.

Alignment of CanMEDS-based Undergraduate and Postgraduate Pharmacy Curricula in The Netherlands.

In this article the design of three master programs (MSc in Pharmacy) and two postgraduate specialization programs for community or hospital pharmacist is described. After a preceding BSc in Pharmacy, these programs cover the full pharmacy education capacity for pharmacists in primary and secondary health care in the Netherlands. All programs use the CanMEDS framework, adapted to pharmacy education and specialization, which facilitates the horizontal integration of pharmacists' professional development with other health care professions in the country. Moreover, it is illustrated that crossing the boundary from formal (university) education to experiential (workplace) education is eased by a gradual change in time spent in these two educational environments and by the use of comparable monitoring, feedback, and authentic assessment instruments. A reflection on the curricula, based on the principles of the Integrative Pedagogy Model and the Self-determination Theory, suggests that the alignment of these educational programs facilitates the development of professional expertise and professional identity of Dutch pharmacists.

Reporting Patterns of Sialorrhea Comparing Users of Clozapine to Users of Other Antipsychotics: A Disproportionality Analysis Using VigiBase.

BACKGROUND: Sialorrhea is a non-life-threatening, but potentially invalidating adverse drug reaction (ADR) in patients using clozapine. In light of the very serious ADRs (agranulocytosis and myocarditis), sialorrhea is at risk to be overlooked by health care professionals. In this study, the sialorrhea reporting patterns of clozapine compared with other antipsychotics were assessed by evaluating differences in relative reporting frequency and reporter type. METHODS: A case/noncase disproportionality analysis using data from VigiBase (1968-2016) was performed. Reports of antipsychotics with "salivary hypersecretion" as ADR were considered as cases, and those with ADRs other than salivary hypersecretion were defined as noncases. Relative reporting frequencies were expressed as reporting odds ratios (RORs), and multivariate logistic regression was performed with the drug-ADR pair as unit of analysis to estimate RORs with 95% confidence intervals (CIs). RESULTS: A total of 1,169,254 drug-ADR pairs from 425,304 unique Individual Case Safety Reports were identified. Sialorrhea was relatively more frequently reported in clozapine (n = 2732 [1.1%]) compared with other antipsychotics (n = 2911 [0.31%]; ROR, 3.60; 95% CI, 3.41-3.79) and was reported relatively more often by consumers (ROR, 19.8; 95% CI, 15.1-25.9) compared with health care professionals (ROR, 2.44; 95% CI, 2.27-2.63). CONCLUSIONS: Sialorrhea was reported almost 4 times more often with clozapine use than with other antipsychotic use and was reported 8 times more often by patients than by health care professionals. This provides a signal of disproportion in sialorrhea occurrence among clozapine compared with other antipsychotics and in light of the disproportionality between reporter and an underreporting by health care professionals, underlining the importance to incorporate sialorrhea into the shared decision process when commencing clozapine therapy.

Intervention protocol: OPtimising thERapy to prevent avoidable hospital Admission in the Multi-morbid elderly (OPERAM): a structured medication review with support of a computerised decision support system.

BACKGROUND: Several approaches to medication optimisation by identifying drug-related problems in older people have been described. Although some interventions have shown reductions in drug-related problems (DRPs), evidence supporting the effectiveness of medication reviews on clinical and economic outcomes is lacking. Application of the STOPP/START (version 2) explicit screening tool for inappropriate prescribing has decreased inappropriate prescribing and significantly reduced adverse drug reactions (ADRs) and associated healthcare costs in older patients with multi-morbidity and polypharmacy. Therefore, application of STOPP/START criteria during a medication review is likely to be beneficial. Incorporation of explicit screening tools into clinical decision support systems (CDSS) has gained traction as a means to improve both quality and efficiency in the rather time-consuming medication review process. Although CDSS can generate more potential inappropriate medication recommendations, some of these have been shown to be less clinically relevant, resulting in alert fatigue. Moreover, explicit tools such as STOPP/START do not cover all relevant DRPs on an individual patient level. The OPERAM study aims to assess the impact of a structured drug review on the quality of pharmacotherapy in older people with multi-morbidity and polypharmacy. The aim of this paper is to describe the structured, multi-component intervention of the OPERAM trial and compare it with the approach in the comparator arm. METHOD: This paper describes a multi-component intervention, integrating interventions that have demonstrated effectiveness in defining DRPs. The intervention involves a structured history-taking of medication (SHiM), a medication review according to the systemic tool to reduce inappropriate prescribing (STRIP) method, assisted by a clinical decision support system (STRIP Assistant, STRIPA) with integrated STOPP/START criteria (version 2), followed by shared decision-making with both patient and attending physician. The developed method integrates patient input, patient data, involvement from other healthcare professionals and CDSS-assistance into one structured intervention. DISCUSSION: The clinical and economical effectiveness of this experimental intervention will be evaluated in a cohort of hospitalised, older patients with multi-morbidity and polypharmacy in the multicentre, randomized controlled OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multi-morbid elderly), which will be completed in the last quarter of 2019. TRIAL REGISTRATION: Universal Trial Number: U1111-1181-9400 Clinicaltrials.gov: NCT02986425, Registered 08 December 2016. FOPH (Swiss national portal): SNCTP000002183. Netherlands Trial Register: NTR6012 (07-10-2016).

Evaluation of clarity of the STOPP/START criteria for clinical applicability in prescribing for older people: a quality appraisal study.

OBJECTIVES: Appropriate prescribing in older people continues to be challenging. Studies still report a high prevalence of inappropriate prescribing in older people. To reduce the problem of underprescribing and overprescribing in this population, explicit drug optimisation tools like Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) have been developed. The aim of this study was to evaluate the clinical applicability of STOPP/START criteria in daily patient care by assessing the clarity of singular criteria. DESIGN: Quality appraisal study. METHODS: For each of the 114 STOPP/START criteria V.2, elements describing the action (what/how to do), condition (when to do) and explanation (why to do) were identified. Next, the clarity of these three elements was quantified on a 7-point Likert scale using tools provided by the Appraisal of Guidelines for Research and Evaluation (AGREE) Consortium. PRIMARY AND SECONDARY OUTCOMES: The primary outcome measure was the clarity rating per element, categorised into high (>67.7%), moderate (33.3%-67.7%) or low (<33.3%). Secondary, factors that positively or negatively affected clarity most were identified. Additionally, the nature of the conditions was further classified into five descriptive components: disease, sign, symptom, laboratory finding and medication. RESULTS: STOPP recommendations had an average clarity rating of 64%, 60% and 69% for actions, conditions and explanations, respectively. The average clarity rating in START recommendations was 60% and 57% for actions and conditions, respectively. There were no statements present to substantiate the prescription of potential omissions for the 34 START criteria. CONCLUSIONS: Our results show that the clarity of the STOPP/START criteria can be improved. For future development of explicit drug optimisation tools, such as STOPP/START, our findings identified facilitators (high clarity) and barriers (low clarity) that can be used to improve the clarity of clinical practice guidelines on a language level and therefore enhance clinical applicability.

Prescribing medicines to older people-How to consider the impact of ageing on human organ and body functions.

Ageing is associated with several changes in human organs, which result in altered medication pharmacokinetics and pharmacodynamics. Ageing is also associated with changes in human body functions, such as impaired vision, hearing, swallowing, motor and cognitive functions, which can affect the adequate intake and administration of drugs. As a consequence, older people, and especially patients older than 75 years, are the main users of many drugs and they frequently use 5 drugs or more long-term (i.e. polypharmacy). All this increases the complexity of adequate drug intake, administration and adherence. However, there is a lack of evidence on the considerations that should be taken into account to ensure appropriate drug prescribing to older people. This review article summarizes the most clinically relevant changes in human organ and body functions and the consequential changes in pharmacokinetics and pharmacodynamics in older people, along with possible dosing consequences or alternatives for drugs frequently prescribed to this patient population. Recommendations are given on how ageing could be considered in clinical drug development, drug authorization and appropriate prescribing.

High levels of several antipsychotics and antidepressants due to a pharmacogenetic cause: a case report.

Pharmacogenetic analysis to explain or predict the response of a specific patient to drug therapy is increasingly used in clinical practice. This holds especially true for CYP genotyping in psychiatry. We present a patient with genetic polymorphisms in more than one CYP450 enzyme, resulting in reduced effectiveness of CYP enzymes, explaining the high drug serum trough levels of antipsychotics and antidepressants and difficulty in optimizing therapy and dosing. Mrs X was found to be a CYP1A2, CYP2D6, CYP3A4 intermediate and in addition a CYP2C19 poor metabolizer. For Mrs X, pharmacogenetic analysis has contributed to reconsider choice and use of medication. Prior knowledge of the genetic polymorphisms in this patient might have avoided treatment delay and discomfort.