Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report.

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient's pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.

Inappropriate prescribing: a systematic overview of published assessment tools.

BACKGROUND: Criteria to assess the appropriateness of prescriptions might serve as a helpful guideline during professional training and in daily practice, with the aim to improve a patient's pharmacotherapy. OBJECTIVE: To create a comprehensive and structured overview of existing tools to assess inappropriate prescribing. METHOD: Systematic literature search in Pubmed (1991-2013). The following properties of the tools were extracted and mapped in a structured way: approach (explicit, implicit), development method (consensus technique, expert panel, literature based), focused patient group, health care setting, and covered aspects of inappropriate prescribing. RESULTS: The literature search resulted in 46 tools to assess inappropriate prescribing.Twenty-eight (61%) of 46 tools were explicit, 8 (17%) were implicit and 10 (22%) used a mixed approach. Thirty-six (78%) tools named older people as target patients and 10 (22%) tools did not specify the target age group. Four (8.5%) tools were designed to detect inappropriate prescribing in hospitalised patients, 9 (19.5%) focused on patients in ambulatory care and 6 (13%) were developed for use in long-term care. Twenty-seven (59%) tools did not specify the health care setting. Consensus methods were applied in the development of 19 tools (41%), the others were based on either simple expert panels (13; 28%) or on a literature search (11; 24%). For three tools (7%) the development method was not described. CONCLUSION: This overview reveals the characteristics of 46 assessment tools and can serve as a summary to assist readers in choosing a tool, either for research purposes or for daily practice use.

Overcoming Barriers: Strategies for Implementing Pharmacist-Led Pharmacogenetic Services in Swiss Clinical Practice.

There is growing evidence that pharmacogenetic analysis can improve drug therapy for individual patients. In Switzerland, pharmacists are legally authorized to initiate pharmacogenetic tests. However, pharmacogenetic tests are rarely conducted in Swiss pharmacies. Therefore, we aimed to identify implementation strategies that facilitate the integration of a pharmacist-led pharmacogenetic service into clinical practice. To achieve this, we conducted semi-structured interviews with pharmacists and physicians regarding the implementation process of a pharmacist-led pharmacogenetic service. We utilized the Consolidated Framework for Implementation Research (CFIR) to identify potential facilitators and barriers in the implementation process. Additionally, we employed Expert Recommendations for Implementing Change (ERIC) to identify strategies mentioned in the interviews and used the CFIR-ERIC matching tool to identify additional strategies. We obtained interview responses from nine pharmacists and nine physicians. From these responses, we identified 7 CFIR constructs as facilitators and 12 as barriers. Some of the most commonly mentioned barriers included unclear procedures, lack of cost coverage by health care insurance, insufficient pharmacogenetics knowledge, lack of interprofessional collaboration, communication with the patient, and inadequate e-health technologies. Additionally, we identified 23 implementation strategies mentioned by interviewees using ERIC and 45 potential strategies using the CFIR-ERIC matching tool. In summary, we found that significant barriers hinder the implementation process of this new service. We hope that by highlighting potential implementation strategies, we can advance the integration of a pharmacist-led pharmacogenetic service in Switzerland.

Recurrent high creatine kinase levels under clozapine treatment - a case report assessing a suspected adverse drug reaction.

Suspected adverse drug reactions (ADRs) during treatment with clozapine often prompt therapeutic drug monitoring (TDM) in clinical practice. Currently, there is no official recommendation for pharmacogenetic (PGx) testing in the context of clozapine therapy. In this case report, we demonstrate and discuss the challenges of interpreting PGx and TDM results highlighting the possibilities and limitations of both analytical methods. A 36-year-old male patient with catatonic schizophrenia was treated with clozapine. He experienced multiple hospitalizations due to elevated creatine kinase (CK) levels (up to 9000 U/L, reference range: 30-200 U/L). With no other medical explanation found, physicians suspected clozapine-induced ADRs. However, plasma levels of clozapine were consistently low or subtherapeutic upon admission, prompting us to conduct a PGx analysis and retrospectively review the patient's TDM data, progress notes, and discharge reports. We investigated two possible hypotheses to explain the symptoms despite low clozapine plasma levels: Hypothesis i. suggested the formation and accumulation of a reactive intermediate metabolite due to increased activity in cytochrome P450 3A5 and reduced activity in glutathione S-transferases 1, leading to myotoxicity. Hypothesis ii. proposed under-treatment with clozapine, resulting in ineffective clozapine levels, leading to a rebound effect with increased catatonic symptoms and CK levels. After considering both data sources (PGx and TDM), hypothesis ii. appeared more plausible. By comprehensively assessing all available TDM measurements and examining them in temporal correlation with the drug dose and clinical symptoms, we observed that CK levels normalized when clozapine plasma levels were raised to the therapeutic range. This was achieved through hospitalization and closely monitored clozapine intake. Therefore, we concluded that the symptoms were not an ADR due to altered clozapine metabolism but rather the result of under-treatment. Interpreting TDM and PGx results requires caution. Relying solely on isolated PGx or single TDM values can result in misinterpretation of drug reactions. We recommend considering the comprehensive patient history, including treatment, dosages, laboratory values, clinic visits, and medication adherence.

Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study.

Purpose: Pharmacogenetics (PGx) is an emerging aspect of personalized medicine with the potential to increase efficacy and safety of pharmacotherapy. However, PGx testing is still not routinely integrated into clinical practice. We conducted an observational case series study where PGx information from a commercially available panel test covering 30 genes was integrated into medication reviews. The aim of the study was to identify the drugs that are most frequently object of drug-gene-interactions (DGI) in the study population. Patients and Methods: In out-patient and in-patient settings, we recruited 142 patients experiencing adverse drug reaction (ADR) and/or therapy failure (TF). Collected anonymized data from the individual patient was harmonized and transferred to a structured database. Results: The majority of the patients had a main diagnosis of a mental or behavioral disorder (ICD-10: F, 61%), of musculoskeletal system and connective tissue diseases (ICD-10: M, 21%), and of the circulatory system (ICD-10: I, 11%). The number of prescribed medicines reached a median of 7 per person, resulting in a majority of patients with polypharmacy (≥5 prescribed medicines, 65%). In total, 559 suspected DGI were identified in 142 patients. After genetic testing, an association with at least one genetic variation was confirmed for 324 suspected DGI (58%) caused by 64 different drugs and 21 different genes in 141 patients. After 6 months, PGx-based medication adjustments were recorded for 62% of the study population, whereby differences were identified in subgroups. Conclusion: The data analysis from this study provides valuable insights for the main focus of further research in the context of PGx. The results indicate that most of the selected patients in our sample represent suitable target groups for PGx panel testing in clinical practice, notably those taking drugs for mental or behavioral disorder, circulatory diseases, immunological diseases, pain-related diseases, and patients experiencing polypharmacy.

The impact of pharmacist-led medication reconciliation and interprofessional ward rounds on drug-related problems at hospital discharge.

BACKGROUND: During transitions of care, including hospital discharge, patients are at risk of drug-related problems (DRPs). AIM: To investigate the impact of pharmacist-led services, specifically medication reconciliation at admission and/or interprofessional ward rounds on the number of DRPs at discharge. METHOD: In this retrospective, single-center cohort study, we analyzed routinely collected data of patients discharged from internal medicine wards of a regional Swiss hospital that filled their discharge prescriptions in the hospital's community pharmacy between June 2016 and May 2019. Patients receiving one of the two or both pharmacist-led services (Study groups: Best Care = both services; MedRec = medication reconciliation at admission; Ward Round = interprofessional ward round), were compared to patients receiving standard care (Standard Care group). Standard care included medication history taken by a physician and regular ward rounds (physicians and nurses). At discharge, pharmacists reviewed discharge prescriptions filled at the hospital's community pharmacy and documented all DRPs. Multivariable Poisson regression analyzed the independent effects of medication reconciliation and interprofessional ward rounds as single or combined service on the frequency of DRPs. RESULTS: Overall, 4545 patients with 6072 hospital stays were included in the analysis (Best Care n = 72 hospital stays, MedRec n = 232, Ward Round n = 1262, and Standard Care n = 4506). In 1352 stays (22.3%) one or more DRPs were detected at hospital discharge. The combination of the two pharmacist-led services was associated with statistically significantly less DRPs compared to standard care (relative risk: 0.33; 95% confidence interval: 0.16, 0.65). Pharmacist-led medication reconciliation alone showed a trend towards fewer DRPs (relative risk: 0.75; 95% confidence interval: 0.54, 1.03). CONCLUSION: Our results support the implementation of pharmacist-led medication reconciliation at admission in combination with interprofessional ward rounds to reduce the number of DRPs at hospital discharge.

Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy.

Patients suffering from chronic pain may respond differently to analgesic medications. For some, pain relief is insufficient, while others experience side effects. Although pharmacogenetic testing is rarely performed in the context of analgesics, response to opiates, non-opioid analgesics, and antidepressants for the treatment of neuropathic pain can be affected by genetic variants. We describe a female patient who suffered from a complex chronic pain syndrome due to a disc hernia. Due to insufficient response to oxycodone, fentanyl, and morphine in addition to non-steroidal anti-inflammatory drug (NSAID)-induced side effects reported in the past, we performed panel-based pharmacogenotyping and compiled a medication recommendation. The ineffectiveness of opiates could be explained by a combined effect of the decreased activity in cytochrome P450 2D6 (CYP2D6), an increased activity in CYP3A, and an impaired drug response at the µ-opioid receptor. Decreased activity for CYP2C9 led to a slowed metabolism of ibuprofen and thus increased the risk for gastrointestinal side effects. Based on these findings we recommended hydromorphone and paracetamol, of which the metabolism was not affected by genetic variants. Our case report illustrates that an in-depth medication review including pharmacogenetic analysis can be helpful for patients with complex pain syndrome. Our approach highlights how genetic information could be applied to analyze a patient's history of medication ineffectiveness or poor tolerability and help to find better treatment options.

Case report: Non-response to fluoxetine in a homozygous 5-HTTLPR S-allele carrier of the serotonin transporter gene.

We report the case of a 50-year-old male with major depressive disorder (MDD) to illustrate the challenge of finding effective antidepressant pharmacotherapy and the role that the patient's genetic makeup may play. Recent treatment attempts before clinic admission included venlafaxine and fluoxetine. Venlafaxine was discontinued due to lack of response, and subsequently switched to fluoxetine based on pharmacogenotyping of the P-glycoprotein transporter (P-gp, encoded by ABCB1) by the outpatient psychiatrist. Despite steady state serum levels within the therapeutic range, the patient did not benefit from fluoxetine either, necessitating admission to our clinic. Here a clinical pharmacist-led medication review including additional pharmacogenetic (PGx) analysis resulted in the change of the antidepressant therapy to bupropion. Under the new regimen, established in the in-patient-setting, the patient remitted. However, based on the assessed pharmacokinetics-related gene variants, including CYPs and ABCB1, non-response to fluoxetine could not be conclusively explained. Therefore, we retrospectively selected the serotonin transporter (SERT1, encoded by SLC6A4) for further genetic analysis of pharmacodynamic variability. The patient presented to be a homozygous carrier of the short allele variant in the 5-HTTLPR (S/S) located within the SLC6A4 promoter region, which has been associated with a reduced expression of the SERT1. This case points out the potential relevance of panel PGx testing considering polymorphisms in genes of pharmacokinetic as well as pharmacodynamic relevance.

A Guide to a Pharmacist-Led Pharmacogenetic Testing and Counselling Service in an Interprofessional Healthcare Setting.

Genetic predisposition is one factor influencing interindividual drug response. Pharmacogenetic information can be used to guide the selection and dosing of certain drugs. However, the implementation of pharmacogenetics (PGx) in clinical practice remains challenging. Defining a formal structure, as well as concrete procedures and clearly defined responsibilities, may facilitate and increase the use of PGx in clinical practice. Over 140 patient cases from an observational study in Switzerland formed the basis for the design and refinement of a pharmacist-led pharmacogenetics testing and counselling service (PGx service) in an interprofessional setting. Herein, we defined a six-step approach, including: (1) patient referral; (2) pre-test-counselling; (3) PGx testing; (4) medication review; (5) counselling; (6) follow-up. The six-step approach supports the importance of an interprofessional collaboration and the role of pharmacists in PGx testing and counselling across healthcare settings.

Drug use problems with self-injected low-molecular-weight heparins in primary care.

PURPOSE: Outpatient subcutaneous therapies are becoming increasingly common. A literature search failed to find produced any studies on application problems pertaining to the self-injection of low-molecular-weight heparins (LMWH) in a heterogeneous outpatient population under daily-life conditions. We therefore designed a study with the aim of recording drug use problems, patient satisfaction, compliance, problems arising from the injection site (abdomen vs. thigh), and residual drug volumes in pre-filled syringes used in self-injection therapy. METHODS: Patients were recruited in community pharmacies by 95 trained Master's students in pharmacy. Data were collected during recruitment and by means of structured questionnaire-based telephone interviews that were carried out at the beginning and the end of the LMWH treatment. RESULTS: The median age of the 213 patients enrolled in the study was 54 years [interquartile range (IQR) 39-70 years]; of these, 15.5% had their injections administered by a third person. The rate of self-reported non-compliance was 17.1%. At least one relevant problem was recorded in 85.0% of the cases. At the end of the treatment, 38.9% of the patients stated self-administration of the injections required some effort. The preferred injection site was the thigh (68.5%). An overall mean residual drug volume ≥ 10.0% was detected for 3.9% of the patients. If residual drug was present, a median of 11.2% (IQR 8.6-17.6%) of the total drug volume had not been injected. Patients injecting into the thigh showed a higher risk of leaving residual medication (odds ratio 2.16, 95% confidence interval 1.04-4.51). CONCLUSIONS: Most patients had drug use problems, whereas no clear factors were associated with non-compliance, the injection site (apart from residual drug), and discomfort or effort required (apart from prior injection use).

Pharmaceutical Discharge Management: Implementation in Swiss Hospitals Compared to International Guidelines.

Readmissions to the hospital are frequent after hospital discharge. Pharmacist-led interventions have been shown to reduce readmissions. The objective of this study was to describe pharmacist-led interventions to support patients' medication management at hospital discharge in Switzerland and to compare them to international guidelines. We conducted a national online survey among chief hospital pharmacists focusing on medication management at hospital discharge. To put our findings in perspective, Cochrane reviews and guidelines were searched for summarised evidence and recommendations on interventions. Based on answers in the survey, hospitals with implemented models to support patients at discharge were selected for in-depth interviews. In semi-structured interviews, they were asked to describe pharmacists' involvement in the patients' pathway throughout the hospital stay. In Swiss hospitals (n = 44 survey participants), interventions to support patients at discharge were frequently implemented, mostly "patient education" (n = 40) and "communication to primary care provider" (n = 34). These interventions were commonly recommended in guidelines. Overall, pharmacists were rarely involved in the interventions on a regular basis. When pharmacists were involved, the services were provided by hospital pharmacies or collaborating community pharmacies. In conclusion, interventions recommended in guidelines were frequently implemented in Swiss hospitals, however pharmacists were rarely involved.

Pharmacist-guided pre-emptive pharmacogenetic testing in antidepressant therapy (PrePGx): study protocol for an open-label, randomized controlled trial.

BACKGROUND: It is known that only 50% of patients diagnosed with major depressive disorders (MDD) respond to the first-line antidepressant treatment. Accordingly, there is a need to improve response rates to reduce healthcare costs and patient suffering. One approach to increase rates of treatment response might be the integration of pharmacogenetic (PGx) testing to stratify antidepressant drug selection. The goal of PGx assessments is to identify patients who have an increased risk to experience adverse drug reactions or non-response to specific drugs. Especially for antidepressants, there is compiling evidence on PGx influencing drug exposure as well as response. METHODS: This study is an open-label, randomized controlled trial conducted in two study centers in Switzerland: (1) the Psychiatric Clinic of Solothurn and (2) the Private Clinic Wyss in Münchenbuchsee. Adult inpatients diagnosed with a unipolar moderate or severe depressive episode are recruited at clinic admission and are included in the study. If the adjustment to a new antidepressant pharmacotherapy is necessary, the participants are randomized to either Arm A (intervention group) or Arm B (control group). If no new antidepressant pharmacotherapy is introduced the participants will be followed up in an observational arm. The intervention is the service of pharmacist-guided pre-emptive PGx testing to support clinical decision making on antidepressant selection and dosing. As a comparison, in the control group, the antidepressant pharmacotherapy is selected by the treating physician according to current treatment guidelines (standard of care) without the knowledge of PGx test results and support of clinical pharmacists. The primary outcome of this study compares the response rates under antidepressant treatment after 4 weeks between intervention and control arm. DISCUSSION: The findings from this clinical trial are expected to have a direct impact on inter-professional collaborations for the handling and use of PGx data in psychiatric practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04507555 . Registered on August 11, 2020. Swiss National Clinical Trials Portal SNCTP000004015 . Registered August 18, 2020.

Pharmacogenetic-Guided Antidepressant Selection as an Opportunity for Interprofessional Collaboration: A Case Report.

In the herein reported case of a 42-year-old woman diagnosed with anxiety and depression, a long history of antidepressant ineffectiveness and adverse drug reactions was decisive for an in-depth medication review including pharmacogenetic panel testing. In detail, treatment attempts with paroxetine and escitalopram were ineffective and discontinued due to subjective gastrointestinal intolerance. Due to the worsening of the depression after the failed treatment attempts, admission to our clinic became necessary. Herein, owing to the collaboration of psychiatrists with clinical pharmacists, individualized incorporation of pharmacogenetic data into the process of antidepressant selection was enabled. We identified vortioxetine as a suitable therapeutic, namely for being most likely pharmacokinetically unaffected as predicted by pharmacogenetic panel testing and taking into account the current comedication, as well as for its favorable action profile. Herein, our collaborative effort proved to be successful and resulted in the patient's depression remission and clinic discharge with the interprofessionally selected pharmacotherapy. This exemplary case not only highlights the potential benefits and challenges of pre-emptive pharmacogenetic testing in antidepressant prescription, but also proposes an approach on how to put pharmacogenetics into practice.

Pharmacogenetics in Pharmaceutical Care-Piloting an Application-Oriented Blended Learning Concept.

To enable application-oriented training of Swiss pharmacists on pharmacogenetic (PGx) testing, an advanced, digital training program was conceptualized based on the Miller's Pyramid framework, using a blended learning approach. The PGx advanced training program included an asynchronous self-study online module, synchronous virtual classroom sessions with lectures and workshops, and a follow-up case study for in-depth applied learning including the analysis of the participants' PGx profile. The evaluation of the training program consisted of (a) an assessment of the participants' development of knowledge, competencies and attitudes towards PGx testing in the pharmacy setting; (b) a satisfaction survey including; (c) questions about their future plans for implementing a PGx service. Twenty-one pharmacists participated in this pilot program. The evaluation showed: (a) a significant improvement of their PGx knowledge (mean score in the knowledge test 75.3% before to 90.3% after training completion) and a significant increase of their self-perceived competencies in applying PGx counselling; (b) a high level of satisfaction with the training program content and the format (at least 79% expressed high/very high agreement with the statements in the questionnaire); (c) a mixed view on whether participants will implement PGx testing as a pharmacy service (indecisive 8; agreed/completely agreed to implement 7/1; disagreed 3 (n = 19)). We consider ongoing education as an important driver for the implementation of PGx in pharmacy practice.

Enriching Medication Review with a Pharmacogenetic Profile - A Case of Tamoxifen Adverse Drug Reactions.

Pharmacogenotyping is applied to determine the hereditable component of a patient's susceptibility to experience therapy failure and/or adverse drug reactions (ADRs). We present the case of a female patient diagnosed with breast cancer and treated with tamoxifen as recurrence therapy who experienced various ADRs. Pharmacogenotyping revealed variants in the cytochrome P450 (CYP) enzymes CYP2D6, CYP2C9, and CYP2C19. The observed genotype was associated with a risk for lower tamoxifen efficacy. Aside from the tamoxifen therapy, the comedication was reviewed for the influence of the patient's pharmacogenetic profile. As a result of this pharmacist-led medication review with pharmacogenetic analyses, concrete genotype-driven recommendations for the treating gynecologist were compiled. This case revealed the added value of a large pharmacogenetic panel and the complexity of integrating a pharmacogenetic profile into a recommendation.

Detection and resolution of drug-related problems at hospital discharge focusing on information availability - a retrospective analysis.

BACKGROUND: Hospital stays are often associated with medication changes, which may lead to drug-related problems (DRPs). Medication reconciliation and medication reviews are strategies to detect and resolve DRPs. METHODS: A descriptive cohort study was conducted using DRPs collected during routine pharmacist-led medication reconciliation and medication reviews in the hospital's community pharmacy at discharge (Zug Cantonal Hospital, Switzerland). In a simulation experiment, we retrospectively analysed the detection and resolution possibilities of these DRPs and their dependency on different information sources. RESULTS: Overall, 6,087 prescriptions were filled in the hospital's community pharmacy (between June 2016 and May 2019). Among 1,352 prescriptions (with ≥ 1 documented DRP) a total of 1,876 DRPs were detected. The retrospective assessment showed that 1,115 DRPs could have been detected by performing simple medication reviews (based on the discharge prescription and the medication history), whereas in the remaining cases, additional clinical and/or patient-specific information would have been needed. In 944 (84.7 %) DRPs, which are detectable by simple medication reviews, the pharmacist would need to consult the prescriber for resolution. CONCLUSION: The detection of DRPs is strongly influenced by the information available. These results support models with pre-discharge medication reconciliation and pharmacist-led medication review procedures enabling both comprehensive detection and facilitated resolution of DRPs.

Classification of drug-related problems with new prescriptions using a modified PCNE classification system.

OBJECTIVES: To explore and classify drug-related problems (DRPs) with new prescriptions detected in community pharmacies using a modified PCNE (Pharmaceutical Care Network Europe) classification system. SETTING: Sixty-four Swiss community pharmacies offering internships for pharmacy students. MAIN OUTCOME MEASURES: Occurrence, nature and pharmacist's management of DRPs. METHODS: Fifth-year pharmacy students collected consecutively hospital discharge and primary care prescriptions. After training, they documented clinical and technical DRPs, causes and interventions. RESULTS: Prescriptions of 616 patients (43.0% discharged from hospital) were analysed. The patients' median age was 56 years and they received a median of 3 (range 2-19) different drugs. In 121 (19.6%) prescriptions 141 clinical DRPs were detected. The most frequent clinical DRPs were potential drug-drug interactions (DDIs) (37.6%), drug choice (24.8%) and drug use problems (15.6%). These clinical DRPs led to a total of 299 interventions. There were 222 prescriptions (36.0%) that showed 278 technical DRPs, resulting in a total of 417 interventions. Most frequent technical DRPs were missing or unclear package size or therapy duration (32.7%) and missing or unclear dosing/application instructions (30.9%). Most DRPs (75.4%) could be managed by the pharmacist alone. The number of prescribed drugs was the main factor with an influence on the frequency of clinical and technical DRPs. CONCLUSION: Clinical and technical DRPs are frequently observed in primary care as well as in hospital discharge prescriptions. The modified PCNE classification system, especially the amendment with a technical DRP category, proved to be useful and allowed the classification of all DRPs. Neither the setting (hospital discharge vs. primary care) nor the quality of electronically printed prescriptions, but only the number of prescribed drugs influenced the occurrence of clinical or technical DRPs.

Clinical Pharmacy Activities in Swiss Hospitals: How Have They Evolved from 2013 to 2017?

The role of pharmacists is changing; in many countries, pharmacists have acquired new competencies. A survey conducted in 2013 mapped the clinical pharmacy services in Swiss hospitals by quantifying full-time equivalents (FTE) and depicting clinical pharmacy activities. The aim of this survey was to update these results and analyze the development in Swiss hospitals. An online questionnaire was sent to chief hospital pharmacists (n = 60). The questionnaire was developed based on the previous survey and on a literature search. The survey took place from June to September 2017. In the survey, 44 hospital pharmacies participated (return rate 73%). They counted 265.8 FTE for pharmacists; 31 offered clinical pharmacy services. Hospitals participating in both surveys (n = 32) showed a significant increase in FTE for hospital (+24.5%) and clinical (+62.7%) pharmacists. The number of training positions available for the certificate of proficiency in "clinical pharmacy" has increased by 5.5. Patient-related services are less commonly implemented in comparison to treatment and process-related services. In conclusion, the increase in FTE of clinical pharmacists was more pronounced than of hospital pharmacists in general. For further development and broader implementation of clinical pharmacy services, however, hospital pharmacies should increase the number of training positions and should direct more activities towards patient-related services.

Lessons Learned From Three Months of Pharmaceutical-Care Digital-Education at the University of Basel, Switzerland.

An acceptable degree of digital literacy has always been present among the pharmacy teaching staff in Basel, with PowerPoint being the main vehicle to present teaching materials in front of full or half classes. Because cell phones became inseparable from students over the past years, mobile voting (movo.ch) or e-quizzes (mentimeter.com) have been regularly used to hold the attention of all students during collective teaching. Moreover, e-assessment on iPad® with the software BeAxi (www.k2prime.com) was introduced in 2012 and is currently used for all evaluations and exams. Suddenly over the night of March 16, 2020, our university, as all universities around the world, had to transfer all courses to an online format and to empower lecturers to teach from their home. This paper offers one perspective for how this digitial experiment unfolded at the University of Basel in Basel, Switzerland.

Nonresponse to high-dose bupropion for depression in a patient carrying CYP2B6*6 and CYP2C19*17 variants: a case report.

We report the case of a patient with major depression treated with high-dose bupropion due to prior detected subtherapeutic blood concentrations at standard dosing. Pharmacogenetic panel testing identified the patient as a carrier of the CYP2B6*6 allele, which has been associated with reduced bupropion metabolism and decreased concentrations of the pharmacologically active metabolite hydroxybupropion. Interestingly, we also found the patient to be homozygous for the CYP2C19*17 allele, predicting an ultra rapid metabolizer phenotype. We propose a combined effect of the detected CYP2C19 and CYP2B6 genetic variants on bupropion metabolism. This case underlines the potential benefit of pre-emptive pharmacogenotyping but also the yet still fragmentary evidence making precise pharmacogenotype guided antidepressant selection and dosing challenging.