Adherence Monitoring Package (AMoPac) in patients suspected of non-response to antihypertensive treatment: perceived usefulness by general practitioners.

BACKGROUND: Non-adherence to antihypertensive agents is common, mainly because of the low perceived burden of high blood pressure. General practitioners (GPs) are unable to predict whether patients are adhering to a recommended treatment. Knowledge about adherence might be of clinical interest in patients non-responding to antihypertensive treatment. AIM: To assess the usefulness of an Adherence Monitoring Package (AMoPac) to identify non-adherence in patients non-responding to antihypertensive treatment. METHODS: AMoPac consists of (1) 4 weeks of electronic adherence monitoring, (2) pharmacist's feedback on patient's intake behaviour and (3) adherence metrics including clinical-pharmaceutical recommendations to the GP. AMoPac-HYP ('Adherence Monitoring Package to identify non-adherence in ambulatory HYPertensive patients') is an observational study among GPs and ambulatory patients with hypertension in a real-world setting. The primary outcome was GPs' perceived usefulness of AMoPac. Secondary outcomes were (1) frequency of medication problems and prescribing errors; (2) types of pharmacist's' recommendations; (3) acceptance of the recommendations by GPs; (4) medication adherence and (5) patients' satisfaction. Outcomes are reported descriptively. Data were collected with questionnaires and electronic monitoring of medicine intake. RESULTS: Fifteen GPs and 15 patients with hypertension participated in the AMoPac-HYP Study. Patients were on average 62 years old, and mean blood pressure was 137/83 mmHg. All GPs rated AMoPac as useful. The most frequently mentioned use was excluding non-adherence in patients with hypertension (93%). Medication problems and prescribing errors were observed in 80% of the patients. The study pharmacist recommended adherence support (N=9 patients) and treatment optimisation (N=8 patients). The recommendations were accepted and implemented in 10 of 17 cases by the GP. Patients' mean taking and timing adherence were 90% and 86%, respectively. Satisfaction with the study procedures among patients was high. CONCLUSION: AMoPac was rated as useful for identifying and excluding non-adherence in patients with hypertension and was highly accepted among patients. Including adherence data in clinical decision-making could contribute to optimising patient care.

Intake reminders are effective in enhancing adherence to direct oral anticoagulants in stroke patients: a randomised cross-over trial (MAAESTRO study).

BACKGROUND: Direct oral anticoagulants (DOAC) effectively prevent recurrent ischaemic events in atrial fibrillation (AF) patients with recent stroke. However, excellent adherence to DOAC is mandatory to guarantee sufficient anticoagulation as the effect quickly subsides. AIM: To investigate the effect of intake reminders on adherence to DOAC. METHODS: MAAESTRO was a randomised, cross-over study in DOAC-treated AF patients hospitalised for ischaemic stroke. Adherence was measured by electronic monitoring for 12 months. After an observational phase, patients were randomised to obtain an intake reminder either in the first or the second half of the subsequent 6-month interventional phase. The primary outcome was 100%-timing adherence. Secondary outcomes were 100%-taking adherence, and overall timing and taking adherence. We analysed adherence outcomes using McNemar's test or mixed-effects logistic models. RESULTS: Between January 2018 and March 2022, 130 stroke patients were included, of whom 42 dropped out before randomisation. Analysis was performed with 84 patients (mean age: 76.5 years, 39.3% women). A 100%-timing adherence was observed in 10 patients who were using the reminder, and in zero patients without reminder (p = 0.002). The reminder significantly improved adherence to DOAC, with study participants having 2.7-fold increased odds to achieve an alternative threshold of 90%-timing adherence (OR 2.65; 95% CI 1.05-6.69; p = 0.039). A similar effect was observed for 90%-taking adherence (OR 3.06; 95% CI 1.20-7.80; p = 0.019). Overall timing and taking adherence increased significantly when using the reminder (OR 1.70; 95% CI 1.55-1.86, p < 0.01; and OR 1.67; 95% CI 1.52-1.84; p < 0.01). CONCLUSION: Intake reminders increased adherence to DOAC in patients with stroke attributable to atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03344146.

Severe systemic adverse reactions to ophthalmic timolol in a CYP2D6 homozygous *4 allele carrier: a case report.

A woman with ocular hypertension suffered from severe bradycardia, hypotension and syncope attacks in temporal relation with ophthalmic timolol application. Topically applied timolol is nasally absorbed and has been shown to reach potentially relevant systemic concentrations. Timolol is mainly metabolized by CYP2D6, which exhibits interindividual metabolic capacity due to genetic variations. A reactive pharmacogenetic panel test identified the patient as a CYP2D6 homozygous *4 allele carrier, which has been associated with a poor metabolizer phenotype and lacking enzyme activity. Thus, the adverse drug reactions possibly resulted from increased systemic timolol exposure. This case report highlights that pharmacogenetic panel testing can contribute to safe and effective pharmacotherapy, even for topically applied drugs.

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.

Pharmacogenetic testing and counselling in the community pharmacy: mixed-methods study of a new pharmacist-led service.

BACKGROUND: Pharmacogenetic (PGx) testing and counselling (short: PGx service) in the community pharmacy is not routinely practiced. We propose a comprehensive pharmacist-led service where PGx information is integrated into medication reviews. AIM: To evaluate the pharmacist-led service comprising PGx testing and counselling (PGx service) from the perspective of patients. METHOD: For this mixed-methods study, we conducted two follow-up interviews F1 and F2 with patients recruited for the PGx service in a community pharmacy after 1st of January 2020. The semi-structured interviews were held by phone call and covered understanding of PGx, the implementation of recommendations, handling of PGx documents (list of concerned substances and PGx recommendation), gain in medication knowledge, and willingness to pay for the PGx service. RESULTS: We interviewed 25 patients in F1 and 42 patients in F2. Patients were generally able to understand and use results of the PGx service. At least one PGx recommendation was implemented for 69% of the patients. Handling of PGx documents ranged from patients having forgotten about the PGx results to patients consulting the list for every medication-related decision; the latter often expecting negative effects. Finally, 62% of the patients were willing to pay for the PGx service. CONCLUSION: For future PGx testing and counselling, HCPs should consider the patients' health literacy in a standardized way and use adequate communication skills to enhance the patient's understanding in PGx and to attenuate potential negative expectations.

Hepatitis C virus screening in community pharmacies: results on feasibility from a Swiss pilot.

BACKGROUND: Hepatitis C virus (HCV) infections are a public health burden worldwide and often go undetected until sequelae develop. Offering HCV screening for the different vulnerable populations in community pharmacies could help prevent further undetected HCV infections. This pilot aimed to assess the feasibility and pharmacist acceptance of HCV rapid antibody saliva testing in community pharmacies. METHODS: A structured pharmaceutical care intervention was developed that included addressing, informing, and screening clients, as well as referral and reporting to subsequent health care providers. Participating pharmacies from French-, German- and Italian-speaking parts of Switzerland were trained to provide this service to local vulnerable populations. Information on client recruitment, feasibility, and acceptability of HCV screening was collected. RESULTS: Of 36 pharmacies initially recruited, 25 started the pilot and approached 435 clients, 145 of whom (33%) were interested in screening. Eight of these rapid antibody tests returned positive (prevalence rate: 5.5%). Facilitators were being able to offer a free rapid test (73%), followed by having training prior to the project (67%) and having a new service to offer (67%). The possibility of clients reacting dismissively (53%) and of unsettling clients (47%) were reported to be the main barriers. CONCLUSIONS: This pilot demonstrated the general feasibility of an HCV screening service with rapid antibody saliva testing in Swiss community pharmacies, which achieved a higher prevalence rate than national estimates. With appropriate communication training and remuneration, Swiss community pharmacies could be an important partner in implementing HCV elimination strategies.

Rescue Analgesia for Opioid-Dependent Individuals on Opioid Agonist Treatment during Hospitalization: Adherence to Guideline Treatment.

INTRODUCTION: Opioid agonist treatment (OAT) is the first-line treatment for opioid use disorder (OUD). Simultaneously, opioids are essential medicines in acute pain management. The literature is scarce on acute pain management in individuals with OUD, and guidelines are controversial for patients on OAT. We aimed at analyzing rescue analgesia in opioid-dependent individuals on OAT during hospitalization in the University Hospital Basel, Switzerland. METHODS: Patient hospital records were extracted from the database over 6 months (Jan-Jun) in 2015 and 2018. Of the 3,216 extracted patient records, we identified 255 cases on OAT with full datasets. Rescue analgesia was defined according to established principles of acute pain management, e.g., i) the analgesic agent is identical to the OAT medication, and ii) the opioid agent is dosed above 1/6th morphine equivalent dose of the OAT medication. RESULTS: The patients were on average 51.3 ± 10.5 years old (range: 22-79 years), of which 64% were men. The most frequent OAT agents were methadone and morphine (34.9% and 34.5%). Rescue analgesia was not documented in 14 cases. Guideline-concordant rescue analgesia was observed in 186 cases (72.9%) and consisted mostly of NSAIDs, including paracetamol (80 cases), and identical agents such as the OAT opioid (70 cases). Guideline-divergent rescue analgesia was observed in 69 (27.1%) cases, predominantly due to an underdosed opioid agent (32 cases), another agent other than the OAT (18 cases), or contraindicated agents (10 cases). DISCUSSION: Our analysis suggests that rescue analgesia in hospitalized OAT patients was predominantly concordant with guidelines, while divergent prescriptions seemed to follow common principles of pain medicine. Clear guidelines are needed to appropriately treat acute pain in hospitalized OAT patients.

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.

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.

Is Pharmacogenetic Panel Testing Applicable to Low-Dose Methotrexate in Rheumatoid Arthritis? - A Case Report.

Purpose: Pharmacogenetic (PGx) panel testing could help to determine the heritable component of a rheumatoid arthritis (RA) patient's susceptibility for therapy failure and/or adverse drug reactions (ADRs) from methotrexate (MTX). Considering the literature mentioning the potential applicability of PGx panel testing within MTX regimens, we discuss the case of a patient who was treated with MTX, suffered from ADRs, and obtained a reactive PGx panel testing. Genotyping: We used a commercial PGx panel test involving the ABC-transporters P-glycoprotein (P-gp; gene: ABCB1), and breast cancer resistance protein (BCRP; gene: ABCG2), the solute carriers reduced folate carrier 1 (RFC1; gene: SLC19A1), and organic anion transporting polypeptide 1B1 (OATP1B1; gene: SLCO1B1), and the enzymes inosine triphosphatase (ITPA), and glutathione transferase P1 (GSTP1). In addition, we genotyped the patient for the enzymes 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR)/inosine monophosphate (IMP) cyclohydrolase (gene name: ATIC), gamma-glutamyl hydrolase (gene name: GGH) and methylenetetrahydrofolate reductase (gene name: MTHFR). Results: The PGx profile of the patient revealed genetic variants in SLC19A1, ABCB1, and MTHFR, which may explain the ADRs experienced during the treatment with MTX and a potentially lower efficacy of MTX. Based on our interpretation of the PGx profile, we recommended the patient to avoid MTX in the future. Conclusion: The MTX pathway is complex, which makes the interpretation of genetic variants affecting metabolism challenging. A reactive PGx panel test was applicable to explain ADRs experienced during MTX treatment for a patient with RA. However, the clinical utility of PGx-guided MTX treatment in a primary care setting is still limited. In order to base a recommendation for MTX on PGx data, we need genome-wide association studies, large prospective multicenter studies and PGx studies, which analyze different multi-gene haplotypes and gene-drug-drug interactions for MTX.

Development and testing of a framework for defining a strategy to address medication adherence during patient encounters in community pharmacies.

Background: Counseling patients on medication adherence could be ameliorated in pharmacy practice. There is a lack of simple and practical strategies to address medication adherence with patients in daily practice. The goal was to develop and test a framework that allows pharmacy teams to define and apply a strategy to address medication adherence in community pharmacies. Methods: A framework based on the principles of social marketing was developed. It consisted of 3 items: the target patient ("Who"), the target plan ("How"), and the target goal ("How many"). To test the framework, each participating pharmacy team developed their strategy by defining the 3 items and applied them during one pilot day. A master student observed the encounters between patients and pharmacy team members and used a structured checklist to document the patient's characteristics, counseling content, and strategy use. Pharmacy teams answered a feedback questionnaire at the end of the pilot day. Results: Ten pharmacy teams were included. During a brainstorming session that lasted on average 31 ± 8 min, unique strategies comprised 18 different target patients and 20 different target plans. The planned target goal was a mean of 31 patients (range: 1 to "all"). A total of 325 encounters were observed, of which 208 patients (64%) corresponded to the predefined target patients. Medication adherence was addressed with 73 patients (22.5%), and adherence counseling was performed with 50 patients (15%). The pharmacy teams accepted the framework and judged it feasible and adaptable to their needs. Conclusion: The proposed framework represents a simple tool that enables pharmacy teams to develop a strategy for addressing medication adherence in community pharmacies. Its adoption by pharmacy teams occurred without additional training and its integration into daily practice without difficulties. A further study is now needed to investigate if pharmacy teams can successfully engage patients in discussion on medication adherence and ultimately propose targeted adherence interventions.

Delta T, a Useful Indicator for Pharmacy Dispensing Data to Monitor Medication Adherence.

INTRODUCTION: Calculating patients' medication availability from dispensing or refill data is a common method to estimate adherence. The most often used measures, such as the medication possession ratio (MPR), average medication supplies over an arbitrary period. Averaging masks the variability of refill behavior over time. GOAL: To derive a new absolute adherence estimate from dispensing data. METHOD: Dispensing histories of patients with 19 refills of direct oral anticoagulants (DOAC) between 1 January 2008 and 31 December 2017 were extracted from 39 community pharmacies in Switzerland. The difference between the calculated and effective refill day (ΔT) was determined for each refill event. We graphed ΔT and its dichotomized version (dΔT) against the MPR, calculated mean ΔT and mean dΔT per refill, and applied cluster analysis. RESULTS: We characterized 2204 refill events from 116 DOAC patients. MPR was high (0.975 ± 0.129) and showed a positive correlation with mean ΔT. Refills occurred on average 17.8 ± 27.9 days "too early", with a mean of 75.8 ± 20.2 refills being "on time". Four refill behavior patterns were identified including constant gaps within or at the end of the observation period, which were critical. CONCLUSION: We introduce a new absolute adherence estimate ΔT that characterizes every refill event and shows that the refill behavior of DOAC patients is dynamic.

How do elderly outpatients manage polypharmacy including DOAC - A qualitative analysis highlighting a need for counselling.

BACKGROUND: Patients with polypharmacy are challenged with the management of their daily medication. Medication management strategies for direct oral anticoagulants (DOAC) are especially important to guarantee medication adherence and to prevent thromboembolic events. Patients are often left alone with finding an appropriate strategy. OBJECTIVE(S): To explore medication management strategies, to measure adherence to DOAC with the aim of deducing recommendations for practice. METHODS: Face-to-face semi-structured interviews were conducted at the home of outpatients who were taking ≥4 medications daily including a DOAC, and self-managing their medication. A small electronic device (Time4Med™) was given to record medication intake during the four following weeks. During a second home visit, participants saw a graph of their medication intake as dot chart, and obtained a feedback. Interviews were transcribed verbatim and thematically analysed. Medication adherence was calculated with electronic data. RESULTS: Eighteen individuals (61.1% female; median age 77.5 years) were interviewed and reported 30 different medication management strategies, together with triggers, advantages and limitations. They combined at least five strategies, composed of internal (memory-based) and external (packaging-based or intake-based) strategies. The number of strategies was neither associated with the number of medications nor with medication adherence. Taking adherence was <100% for eight patients (44.4%). The inability of any medication management strategy to adapt to ageing and cognitive decline emerged as its most dramatic limitation, especially because individuals would fail to notice when their strategy became unsuited. CONCLUSIONS: Elderly patients develop manifold medication management strategies, which can inspire future medication users. Limitations are present such as forgetting medication intake in spite of a management strategy. The moment to adapt the strategy to ageing or cognitive decline is crucial and often goes unnoticed. It is therefore decisive that healthcare professionals regularly re-evaluate the appropriateness of the medication management strategies during counselling or ideally during home visits.

Impact of the COVID-19 lockdown on the adherence of stroke patients to direct oral anticoagulants: a secondary analysis from the MAAESTRO study.

BACKGROUND: The negative impact of the COVID-19 outbreak on stroke care has been reported, but no data exist on the influence of the lockdown on medication adherence to antithrombotic treatment for stroke prevention. We present a comparison of electronic adherence data of stroke patients treated with direct oral anticoagulants (DOAC) prior to and during the COVID-19 lockdown in spring 2020 in Switzerland. METHODS: This is a secondary analysis using data from the ongoing MAAESTRO study, in which stroke patients with atrial fibrillation electronically monitor their adherence to DOAC treatment. Eligible patients for this analysis had at least four weeks of adherence data prior to and during the COVID-19 lockdown. Three adherence metrics (taking adherence, timing adherence, drug holidays) were calculated and compared descriptively. RESULTS: The analysis included eight patients (median age 81.5 years, IQR 74.8-84.5). Five patients had a pre-lockdown taking adherence over 90% (mean 96.8% ± 2.9), with no change during lockdown, high timing adherence in both periods and no drug holidays. The remaining three patients had pre-lockdown taking and timing adherence below 90%. Of those, two patients showed a moderate decline either in taking or timing adherence compared to pre-lockdown. One showed a substantial increase in taking and timing adherence during lockdown (both + 25.8%). CONCLUSION: Our data suggest that a major disruption of social life (i.e., the imposed COVID-19 lockdown) is unlikely to relevantly affect the medication intake behaviour of patients with high pre-established adherence, but might have an impact in patients with previously suboptimal adherence. TRIAL REGISTRATION NUMBER: MAAESTRO: electronic Monitoring and improvement of Adherence to direct oral Anticoagulant treatment-a randomized crossover study of an Educational and reminder-based intervention in ischaemic STROke patients under polypharmacy, NCT03344146.

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.

Communicating Electronic Adherence Data to Physicians-Consensus-Based Development of a Compact Reporting Form.

Information on medication adherence is missing in patient files, although it might be helpful to optimize treatment. An adherence report that presents data from electronic adherence monitoring and provides recommendations regarding pharmacological treatment could close this gap. We aimed to develop an adherence reporting form that combines suitable calculations and graphical representations to facilitate the physicians' interpretation of (non-)adherence. Two consensus development panels were conducted. First, pharmacists with expertise in adherence monitoring debated the items needed to calculate and illustrate electronic adherence data. Second, physicians discussed the items they would need for an adherence report and were encouraged to propose new items. Preference was indicated by raising a green or red card. Voting was repeated until consensus was obtained. Third, first drafts of the adherence reporting form were created by two pharmacists. Seven pharmacists agreed on four metrics to express medication adherence and three graphical representations. Five physicians approved the four metrics and rated the dot chart as the most useful illustration for judging the patient's adherence patterns. Additionally, they required a clinical-pharmaceutical evaluation of the adherence estimates considering drug-related properties. We developed an adherence reporting form for the first time in a compact format and based on the recommendations of experts. In addition, we considered the preferences of physicians, who appreciated the clarity of the reporting form.

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.

Vitamin D oral intermittent treatment (DO IT) study, a randomized clinical trial with individual loading regimen.

Comparison of several regimens of oral vitamin D including an individually calculated loading regimen with the aim of achieving serum values > 75 nmol/l. Interventional, randomized, 3-arm study in vitamin D-deficient outpatients. Participants were allocated to supplementation of 24,000 IU vitamin D monthly over three months, using either a monthly drinking solution (Vi-De 3) or capsule (D3 VitaCaps), or an individualized loading regimen with the capsules taken weekly. For the loading regimen, the cumulative dose was calculated according to baseline 25-hydroxy-vitamin D (25(OH)D) serum value and body weight. Main inclusion criteria were age ≥ 18 years and 25(OH)D serum concentration < 50 nmol/l. The primary outcome was 25(OH)D serum concentration one week after treatment termination. Secondary endpoints were patient's preferences and adverse events. Full datasets were obtained from 52 patients. Mean 25(OH)D values were statistically significant higher after a loading regimen compared to a monthly administration of 24,000 IU vitamin D (76.4 ± 15.8 vs 61.4 ± 10.8 nmol/l; p < 0.01). All patients treated with the loading regimen reached sufficient 25(OH)D values > 50 nmol/l. Serum 25(OH)D values > 75 nmol/l were observed more frequently in patients taking the loading regimen (47% vs 11% drinking solution vs 12% capsules). Vitamin D-related adverse effects did not occur in any treatment groups. Capsules were preferred by 88.5% of the patients. Compared to treatments with monthly intake of 24,000 IU vitamin D, the intake of an individually calculated weekly loading regimen was able to raise serum concentrations > 50 nmol/l in all cases within a safe range.

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.