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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.

Abstract Background Knowledge, attitudes and substitution laws of biosimilars are not consistent across countries. Biosimilar acceptance among patients and healthcare professionals may be suffering from gaps in knowledge and understanding about biosimilars and their regulatory approval process. Pharmacists' roles and responsibilities changed considerably during the COVID-19 pandemic. Thus, they might have gained new skills and self-confidence in counseling and substitution of biosimilars. Aims To examine and compare the knowledge, perceptions and information needs of German and Swiss pharmacists regarding original biologicals and biosimilars in 2020 and 2022. Methods We conducted an online survey among Swiss and German community pharmacies in February 2020 (before) and August 2022 (after the COVID-19 pandemic). Descriptive statistics were calculated and the Chi-Square test was used for comparisons among categorical variables. Results A total of 764 pharmacists took part in the survey (390 in 2020 and 374 in 2022) with comparable demographics. The frequency of dispensing biologicals remained similar between German and Swiss pharmacists in 2020 and 2022, but the Swiss dispensation of biosimilars increased significantly in 2022 compared to 2020. Concerning the understanding of the term biosimilars, knowledge remained moderate in both countries in both years. Participants were equally familiar with the term and most felt sufficiently informed. In both countries, substitution with a biosimilar showed the least confidence of all attitudes. A third of the participants indicated correct substitution rules in their country. In both years, around 85% of the participants were highly interested in additional training on this topic. Discussion/Conclusion The results indicate that similarities and differences between Germany and Switzerland regarding knowledge and attitudes towards biologicals and biosimilars remained unchanged before and after the COVID-19 pandemic. An influence of the pandemic is unlikely. There is still a clear lack of knowledge among community pharmacists on biosimilars, especially regarding the substitution rules. Due to a rising market with many benefits but also big challenges to overcome, the topic of biosimilars should receive more attention in the future. This requires additional training for pharmacists.

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.

Abstract Background and Aims The World Health Organization has set a goal to eradicate hepatitis C virus (HCV) by the year 2030. Nonadherence to HCV treatment has substantial economic implications due to high treatment costs, among others. Barriers to start HCV treatment may be critical. The aim of this study was to assess pertinent barriers to HCV treatment in ambulatory patients with a history of illicit substance use and to compare them to the literature. Methods Barriers to HCV treatment mentioned by the key risk group (i.e., people who inject drugs) were retrieved from literature through a pragmatic literature search. From 34 published articles, we identified 80 modifiable barriers that were bundled in 23 items within the four topics “Personal difficulties and barriers to treatment,” “Personal motivation to be treated,” “Knowledge about the disease,” and “Received information about the medicine.” In‐depth semistructured interviews were performed face‐to‐face with ambulatory patients from the University Psychiatric Clinics in Basel, Switzerland. Transcripts were coded inductively. Results Interviews were performed with seven individuals (mean age: 48.3 years; range: 38–63 years; one woman) treated with oral direct‐acting antivirals between 2014 and 2022. Thirteen barriers to start HCV treatment were mentioned that corresponded to the five categories: information, attitudes, swallowing difficulties, social environment, and unfavorable lifestyle. The barrier “swallowing difficulties” emerged exclusively from the statements provided by the interviewees. Conclusion Barriers to the initiation of HCV treatment indicated by our interviewees clearly differed from the literature. Notably, the challenge of swallowing medicines may be particularly relevant for physicians prescribing and pharmacists dispensing HCV medication.

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.

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.

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.

Abstract Background Patients with substance use disorders grow older thanks to effective treatments. Together with a high prevalence of comorbidities, psychological problems, and low social support, these patients are at high risk for medication non-adherence. Established treatment facilities face challenges to accommodate these complex patients within their setting. Electronic medication management aids (e-MMAs) might be appropriate to simultaneously monitor and improve adherence for these patients. Case presentation We report the first long-term experiences with a novel remote electronic medication supply model for two opioid-dependent patients with HIV. John (beginning dementia, 52 years, 6 tablets daily at 12 am) and Mary (frequent drug holidays, 48 years, 5–6 tablets daily at 8 pm) suffered from disease progression due to non-adherence. We electronically monitored adherence and clinical outcomes during 659 (John) and 953 (Mary) days between July 2013 and April 2016. Both patients retrieved over 90% of the pouches within 75 min of the scheduled time. Technical problems occurred in 4% (John) and 7.2% (Mary) of retrievals, but on-site support was seldom required. Viral loads fell below detection limits during the entire observation period. Conclusions Continuous medication supply and persistence with treatment of over 1.7 years, timing adherence of more than 90%, and suppressed HIV viral load are first results supporting the feasibility of the novel supply model for patients on opioid-assisted treatment and polypharmacy.

Background: The description of adherence based on medication refill histories relies on the estimation of continuous medication availability (CMA) during an observation period. Thresholds to distinguish adherence from non-adherence typically refer to an aggregated value across the entire observation period, disregarding differences in adherence over time. Sliding windows to divide the observation period into smaller portions, estimating adherence for these increments, and classify individuals with similar trajectories into clusters can retain this temporal information. Optimal methods to estimate adherence trajectories to identify underlying patterns have not yet been established. This simulation study aimed to provide guidance for future studies by analyzing the effect of different longitudinal adherence estimates, sliding window parameters, and sample characteristics on the performance of a longitudinal clustering algorithm.Methods: We generated samples of 250–25,000 individuals with one of six longitudinal refill patterns over a 2-year period. We used two longitudinal CMA estimates (LCMA1 and LCMA2) and their dichotomized variants (with a threshold of 80%) to create adherence trajectories. LCMA1 assumes full adherence until the supply ends while LCMA2 assumes constant adherence between refills. We assessed scenarios with different LCMA estimates and sliding window parameters for 350 independent samples. Individual trajectories were clustered with kml, an implementation of k-means for longitudinal data in R. We compared performance between the four LCMA estimates using the adjusted Rand Index (cARI).Results: Cluster analysis with LCMA2 outperformed other estimates in overall performance, correct identification of groups, and classification accuracy, irrespective of sliding window parameters. Pairwise comparison between LCMA estimates showed a relative cARI-advantage of 0.12–0.22 (p < 0.001) for LCMA2. Sample size did not affect overall performance.Conclusion: The choice of LCMA estimate and sliding window parameters has a major impact on the performance of a clustering algorithm to identify distinct longitudinal adherence trajectories. We recommend (a) to assume constant adherence between refills, (b) to avoid dichotomization based on a threshold, and (c) to explore optimal sliding windows parameters in simulation studies or selecting shorter non-overlapping windows for the identification of different adherence patterns from medication refill data.

BackgroundPatients with atrial fibrillation (AF) have a high risk for recurrent clinical events after an ischemic stroke. Direct oral anticoagulants (DOAC) are prescribed for secondary prevention. Adherence to DOAC is crucial mainly because of their short elimination half-life. Non-adherence to DOAC can negatively impact patients' outcomes. The relationship between (non-)adherence and recurrent clinical events is unknown in AF patients after initial stroke. We investigated adherence to DOAC in stroke survivors with AF who were included in the MAAESTRO study at the University Hospital Basel, Switzerland, between 2008 and 2022.MethodsThis study is a secondary analysis of data from MAAESTRO with a matched nested case-control design and 1:2 ratio. DOAC intake was measured with a small electronic device (Time4MedTM). We defined two arbitrary intervals of 17 days and 95 days as the longest time spans with electronic monitoring data per patient to maximize the number of participants with adequate amount of observation time available for analysis. Taking and timing adherence were calculated retrospectively i.e., prior to the recurrent event for cases. Trendline analysis of adherence over 95 days was calculated. Linear regression analysis was performed after adjusting for the co-variables age and daily pill burden. Sensitivity analysis was performed with controls for intervals in the reverse direction (prospectively).ResultsWe analyzed 11 cases and 22 matched controls (mean age: 75.9 ± 9.2 years vs. 73.1 ± 8.4 years; n.s.) with similar stroke characteristics (NIHSS, mRS, MoCA) and 36.4% women in each group. Mean adherence values were high and similar between cases and controls (95 days taking: 87.0 ± 18.9% (cases) vs. 90.8 ± 9.8% (controls), n.s.; similar values for timing adherence). Six hemorrhagic and five ischemic events had occurred. Compared to controls, a significantly higher 95 days taking adherence was observed for hemorrhagic events (96.0 ± 5.0% (cases) vs. 88.1 ± 11.5% (controls); pConclusionBecause recurrent ischemic events after an AF-related stroke were associated with low adherence to DOAC 96%.Trial registrationClinicalTrials.gov NCT03344146.

Background: A considerable proportion of drugs administered to children are not authorised for this purpose, and consequently off-label use is common in paediatric care. Our aims were to quantify systematically the number of drugs authorised in Switzerland for use in children based on their current summary of product characteristics (SmPC) and to assess the quality of this information., Methods: We used natural language processing to screen all Swiss SmPCs, available in German language in the open-source drug database, for information about use in children. Based on the SmPCs of the most frequently used drugs in Swiss children's hospitals, 10 search terms were defined to retrieve this information., Results: Of the analysed 4214 drugs corresponding to 1553 active substances, 2322 (55.1%) drugs were authorised for use in children. In only 639 (15.2%) SmPCs, information about authorisation for children was found in the section 'Therapeutic indications'. 320 (13.8%) SmPCs of drugs authorised for use in children contained only verbal age indications such as 'children' and 'adolescents' without a clear definition of the age or an age range., Conclusions: Most Swiss SmPCs contain information about children, but only a minority refer to an official indication. Even if some SmPCs clearly indicate that use in children is authorised, a clear statement of the age at which the drug may be administered is missing. Standardisation of information about use in children in SmPCs is needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Electronic health care databases are increasingly used for informing clinical decision-making. In long-term care, linking and accessing information on health care delivered by different providers could improve coordination and health outcomes. Several methods for quantifying and visualizing this information into data-driven care delivery pathways (CDPs) have been proposed. To be integrated effectively and sustainably into routine care, these methods need to meet a range of prerequisites covering 3 broad domains: clinical, technological, and behavioral. Although advances have been made, development to date lacks a comprehensive interdisciplinary approach. As the field expands, it would benefit from developing common standards of development and reporting that integrate clinical, technological, and behavioral aspects., Objective: We aimed to describe the content and development of long-term CDP quantification and visualization methods and to propose recommendations for future work., Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. We searched peer-reviewed publications in English and reported the CDP methods by using the following data in the included studies: long-term care data and extracted data on clinical information and aims, technological development and characteristics, and user behaviors. The data are summarized in tables and presented narratively., Results: Of the 2921 records identified, 14 studies were included, of which 13 (93%) were descriptive reports and 1 (7%) was a validation study. Clinical aims focused primarily on treatment decision-making (n=6, 43%) and care coordination (n=7, 50%). Technological development followed a similar process from scope definition to tool validation, with various levels of detail in reporting. User behaviors (n=3, 21%) referred to accessing CDPs, planning care, adjusting treatment, or supporting adherence., Conclusions: The use of electronic health care databases for quantifying and visualizing CDPs in long-term care is an emerging field. Detailed and standardized reporting of clinical and technological aspects is needed. Early consideration of how CDPs would be used, validated, and implemented in clinical practice would likely facilitate further development and adoption., Trial Registration: PROSPERO CRD42019140494; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=140494., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2019-033573., (©Luiza Siqueira do Prado, Samuel Allemann, Marie Viprey, Anne-Marie Schott, Dan Dediu, Alexandra Lelia Dima. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.12.2023.)

Background: Adherence to pharmacotherapy is crucial to prevent symptom deterioration in chronic diseases. However, non-adherence to chronic treatments is prevalent, especially in polypharmacy. Practical tools to assess adherence to polypharmacy in primary care are missing., Aims: We aimed to develop an Adherence Monitoring Package (AMoPac) for general practitioners (GPs) to identify patient non-adherence. We tested the feasibility and acceptance of AMoPac in the primary healthcare setting., Methods: AMoPac was developed based on peer-reviewed literature. It consists in (1) electronic monitoring of patients' medication intakes for 4 weeks, (2) receiving feedback on intake behaviour by the pharmacist and (3) generating an adherence report to communicate to the GPs. A feasibility study was conducted with heart failure patients. GPs' acceptance of AMoPac was explored with semistructured interviews. Electronic transmission of the reports into the GP's electronic health record along with laboratory reports stating N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels was analysed., Results: We developed AMoPac and tested its feasibility with six GPs and seven heart failure patients. GPs were satisfied with the adherence report including the pharmaceutical-clinical recommendations. Integrated transmission of adherence reports to GPs was not feasible due to technical incompatibilities. Mean taking adherence was 86.4%±12.8% and three patients had low correct dosing-days (69%, 38% and 36%, respectively). NT-proBNP ranged from 102 to 8561 pg/mL and four patients had elevated values (>1000 pg/mL)., Conclusion: AMoPac is feasible in the primary healthcare setting, excluding the integrated transmission of adherence reports to GPs. The procedure was highly accepted by GPs and patients. AMoPac fills a gap by combining clinical values with adherence data, and therefore, delivers a multifaceted picture of the patient's behaviour. In case of unmet adherence, our tool might facilitate the selection of patient-centred approaches to optimise pharmacological therapies in chronic heart failure patients., Trial Registration Number: NCT04326101., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

(1) Background: Pharmacists are often challenged with situations where women are already on hormonal contraceptives (HC) but have no valid prescription. By Swiss law, pharmacists are allowed to supply prescription-only drugs in exceptional situations without a physician's prescription. Because eligibility for HC can change, women at risk for complications, such as serious side effects, need to be identified. We aimed to develop a protocol to assist pharmacists in clarifying and documenting eligibility for HC. (2) Methods : We conducted a survey using the Delphi method to identify relevant clarifications and develop a protocol for pharmacists. Proposed material was created based on the literature and existing toolkits/protocols aimed at verifying eligibility for HC. A multidisciplinary expert panel, consisting of gynecologists and pharmacists, reviewed the proposed material and provided anonymized feedback over two survey cycles. (3) Results: This Delphi survey revealed items essential to the clarification of eligibility for HC in pharmacies for women who are already using it. This resulted in a protocol that maps "best practices" regarding these ad interim supplies of HC given without a prescription in Switzerland. (4) Conclusions : This survey, made using the Delphi method, allowed us to create a protocol for pharmacists that aims to verify and document eligibility for HC in Switzerland, where HC is frequently supplied without a prescription.

Purpose: In Switzerland 167 drugs on the market contain information about pharmacogenetics in their drug label (PGx drug). Preemptive pharmacogenetic testing is reimbursed by health care insurance for only seven drugs (abacavir, carbamazepine, 6-mercaptopurine, azathioprine, 5-fluorouracil, capecitabine, and irinotecan) although, it is proposed to be a cost-effective approach to personalized medicine. The aim of this study was to describe the use of PGx drugs and their corresponding genes in Switzerland., Methods: We identified 90 drugs with dosing recommendations from the Pharmacogenetic Knowledgebase involving 24 genes. We assessed the utilization of those drugs between 2016 and 2020, using claims data from a large Swiss insurance company (Helsana)., Results: Of 841 491 persons with drug claims during the whole study period, 78.7% were exposed to PGx drugs. Ibuprofen, pantoprazole, and tramadol had the highest number of users. Seven genes ( CYP2C19, CYP2C9, CYP2D6, SLCO1B1, HLA-B, MT-RNR1 , and VKORC1 ) were responsible for over 95% of all potential drug-gene interactions., Conclusion: The prevalence of PGx drug prescriptions is high in the Swiss population. Therefore, intensified preemptive testing may be a useful option as a substantial amount of the Swiss population might benefit., Competing Interests: The authors report no conflicts of interest in this work. This research received no external funding., (© 2022 Wittwer et al.)

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.

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., (© 2021. The Author(s).)

(1) Background : Access to hormonal contraceptives (HC) strongly differs between countries and varies from over the counter (OTC) to prescription-only availability. This study aimed to identify opinions among physicians in Switzerland regarding extended access to HC. (2) Methods : Web-based survey among physicians (gynecologists, general practitioners, and pediatricians) in Switzerland. (3) Results : Hundred sixty-three physicians, mainly gynecologists, participated in this survey and 147 (90%) were included for analysis. A total of 68% ( n = 100) answered that prescription-only status could be extended under certain conditions but physicians were concerned about patients' safety (97%, n = 142). Moreover, there was concern about insufficient patient education on HC (93%, n = 136) and that women may forego preventive examinations (80%, n = 118). Participants did not support OTC availability (93%, n = 136). Pharmacists prescribing (including initiation of HC) revealed controversial results, but a combined access model (initial prescription from physician and follow-up prescriptions by pharmacists) found acceptance in 70% ( n = 103). (4) Conclusions : Participating physicians stated that prescription-only status for HC could be lifted under certain conditions but also some concerns, e.g., patients' safety or neglection of preventive examinations, were raised. Future research should focus on specific conditions in which extended access to HC could be agreed on.

Background: Worldwide the availability to Hormonal Contraceptives (HC) varies from over the counter (OTC) to prescription-only access. In various countries pharmacists are allowed to prescribe HC, although conditions may be different. In Switzerland, HC require a prescription from a physician, although Swiss law allows pharmacists to dispense prescription-only medications in justified exceptional cases without a valid physician's prescription. This study aimed to identify current dispensing practices for HC in Swiss pharmacies, pharmacists' knowledge about HC, and their opinion and interest about expanding access to HC., Methods: Web-based survey among Swiss pharmacists., Results: This survey was completed by 397 registered pharmacists and 331 (83%) were included for analysis. The survey showed that 21% of respondents regularly dispense HC without prescription and that a high number of participants are either very interested (57%, n = 189) or rather interested (33%, n = 110) in extended pharmacy access to HC. The majority did not or rather not support physician's prescription-only status (77%, n = 256) or OTC availability (94%, n = 310). Furthermore, surveyed pharmacists are willing to train for contraception services (90%, n = 299). According to participants, resistance of physicians is the most relevant barrier to this service (88%, n = 292)., Conclusion: Surveyed pharmacists are interested in extended access to HC.

Introduction: Chronic conditions require long periods of care and often involve repeated interactions with multiple healthcare providers. Faced with increasing illness burden and costs, healthcare systems are currently working towards integrated care to streamline these interactions and improve efficiency. To support this, one promising resource is the information on routine care delivery stored in various electronic healthcare databases (EHD). In chronic conditions, care delivery pathways (CDPs) can be constructed by linking multiple data sources and extracting time-stamped healthcare utilisation events and other medical data related to individual or groups of patients over specific time periods; CDPs may provide insights into current practice and ways of improving it. Several methods have been proposed in recent years to quantify and visualise CDPs. We present the protocol for a systematic review aiming to describe the content and development of CDP methods, to derive common recommendations for CDP construction., Methods and Analysis: This protocol followed the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. A literature search will be performed in PubMed (MEDLINE), Scopus, IEEE, CINAHL and EMBASE, without date restrictions, to review published papers reporting data-driven chronic CDPs quantification and visualisation methods. We will describe them using several characteristics relevant for EHD use in long-term care, grouped into three domains: (1) clinical (what clinical information does the method use and how was it considered relevant?), (2) data science (what are the method's development and implementation characteristics?) and (3) behavioural (which behaviours and interactions does the method aim to promote among users and how?). Data extraction will be performed via deductive content analysis using previously defined characteristics and accompanied by an inductive analysis to identify and code additional relevant features. Results will be presented in descriptive format and used to compare current CDPs and generate recommendations for future CDP development initiatives., Ethics and Dissemination: Database searches will be initiated in May 2019. The review is expected to be completed by February 2020. Ethical approval is not required for this review. Results will be disseminated in peer-reviewed journals and conference presentations., Prospero Registration Number: CRD42019140494., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cystic fibrosis (CF) is a life-shortening genetic condition that usually affects several organs and involves significant treatment burden. Adherence to medication is important for successful CF management., Objective: To describe medication adherence according to age, therapeutic class, and pharmaceutical form in adults and children followed in four regional CF centers in France., Methods: We conducted a cross-sectional study with non-transplanted patients followed in two adult and two pediatric centers during 2015 who were covered by the French National Health Insurance (NHI). Sociodemographic, clinical, hospitalization, and prescription data were collected from patient medical records. Medication dispensations were extracted from the regional French NHI database. Adherence was calculated over 12 months using continuous medication availability (CMA) accounting for dose adjustments and hospitalizations. Drug-specific CMA was computed in R with the AdhereR package for each medication prescribed more than 3 months, which was averaged to obtain a composite CMA score (cCMA) for all treatments and per therapeutic class as well as pharmaceutical form for each patient., Results: A total of 228 patients were included. The number of chronic medications increased with age ( r =0.50, p <0.001): a median of 7 medications per patient were prescribed. The mean±SD cCMA was significantly different between age groups ( p =0.0098): it was 0.71±0.20 for the 0-5 years age group, 0.73±0.16 for 6-11 years, 0.64±0.17 for 12-17 years, 0.57±0.23 for 18-25 years, and 0.65±0.20 for the over 25 years age group. cCMA varied significantly according to pharmaceutical forms: the mean±SD cCMA was 0.70±0.21 for oral medications and 0.54±0.28 for inhaled medications ( p <0.001)., Conclusion: This study suggests that adherence to medication regimens in CF patients remains suboptimal and varies substantially between age groups and pharmaceutical forms. These variations in adherence should be considered when developing effective strategies to improve adherence., Competing Interests: Alexandra Lelia Dima report grants and non-financial support from Respiratory Effectiveness Group, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2019 Rouzé et al.)

Adherence to medications is a key performance indicator and behavioral outcome in healthcare. Electronic healthcare databases represent rich data sources for estimating adherence in both research and practice. To build a solid evidence base for adherence management across clinical settings, it is necessary to standardize adherence estimation and facilitate its appropriate use. We present the recent development and oportunities offered by AdhereR, an R package for visualisation of medication histories and computation of adherence.