Inconclusiveness of psychometric testing of medication adherence questionnaires.

PURPOSE: To propose a paradigm change for the validation procedures of medication adherence questionnaires. METHODS: A total of 121 validation procedures of unique questionnaires for medication adherence were analyzed. RESULTS: "Construct validity" and "internal consistency" were most often assessed, and test results varied largely. A more in-depth analysis indicated that the assessment of medication non-adherence included distinct but related constructs, such as the extent to which doses are missed, and the attempt to identify different facets of medication-taking behavior. Consequently, each construct requires a different measurement approach with different psychometric tests for establishing its validity and reliability. CONCLUSION: Results show that assessing the validity and reliability of adherence questionnaires with standard procedures including statistical tests is inconclusive. Refinement of the constructs of non-adherence is needed in pharmacy and medical practice. We suggest a distinction between the (i) extent of missed doses over the past 2 weeks, (ii) modifiable reasons for non-adherence behavior, and (iii) unmodifiable factors of non-adherence. Validation procedures and corresponding statistical methods should be selected according to the specific single constructs.

Relationship between electronically monitored adherence to direct oral anticoagulants and ischemic or hemorrhagic events after an initial ischemic stroke-A case control study.

BACKGROUND: Patients 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. METHODS: This 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). RESULTS: We 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); p<0.01) and a significantly lower 95 days taking adherence was observed for ischemic events (75.7 ± 24.8% (cases) vs. 94.2 ± 6.2% (controls), p = 0.024). Values for timing adherence were similar. A non-significant downward linear trend of adherence was observed over 95 days independently of the clinical events. The sensitivity analysis showed that the direction of the interval had negligible impact on the 95 days adherence. CONCLUSION: Because recurrent ischemic events after an AF-related stroke were associated with low adherence to DOAC <76%, adherence enhancing interventions seem crucial in anticoagulated AF-patients. However, AF-patients with high adherence might benefit from a regular re-assessment of the bleeding risk as hemorrhagic complications were associated with adherence to DOAC >96%. TRIAL REGISTRATION: ClinicalTrials.gov NCT03344146.

Information in summaries of product characteristics about use in children is limited and needs standardisation: a systematic analysis in Switzerland.

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.

Initiation of oral hepatitis C virus treatment: Which barriers are pertinent for ambulatory individuals with a history of illicit substance use? A qualitative interview study.

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.

Toward an Interdisciplinary Approach to Constructing Care Delivery Pathways From Electronic Health Care Databases to Support Integrated Care in Chronic Conditions: Systematic Review of Quantification and Visualization Methods.

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_record.php?RecordID=140494. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-033573.

Knowledge and attitudes of German and Swiss community pharmacists towards biologicals and biosimilars - a prospective survey before and after the COVID-19 pandemic.

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.

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.

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.

Development and acceptance of a new adherence monitoring package to identify non-adherent patients with polypharmacy in primary care: a feasibility study.

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.

Adherence patterns in antiseizure medications influencing risk of sudden unexplained death in epilepsy: A data linkage study using dispensed prescriptions.

OBJECTIVE: Medication adherence is considered an important risk factor for sudden unexpected death in epilepsy (SUDEP), although measurement accuracy is difficult. Using prescription dispensations, this study aims to estimate antiseizure medication (ASM) adherence and identify adherence patterns that influence epilepsy mortality. METHODS: This is a retrospective cohort study of tertiary epilepsy outpatients seen at St Vincent's Hospital Melbourne, Victoria, Australia, from January 1, 2012 until December 31, 2017. Privacy-preserving data linkage with the Australian national prescription, death, and coroner's databases was performed. We fitted a four-cluster longitudinal group-based trajectory model for ASM adherence from recurring 90-day windows of prescription dispensations during a 3-year "landmark period" from January 1, 2012 to December 31, 2014, using the AdhereR package. We estimated the risk of SUDEP and all-cause death for each adherence pattern during an "observation period" from January 1, 2015 to December 31, 2017. The Cox proportional hazards and logistic regression models were adjusted for age, sex, socioeconomic status, epilepsy duration, comorbidity, drug resistance, and inadequate seizure control. RESULTS: One thousand one hundred eighty-seven participants were observed for a median of 3.2 years (interquartile range = 2.4-4.0 years). We observed 66 deaths with 10 SUDEP cases during the observation period. We identified four patterns of ASM adherence: good, 51%; declining, 24%; poor, 16%; and very poor, 9%. Declining adherence was associated with an increased risk for SUDEP, with hazard ratio (HR) = 8.43 (95% confidence interval [CI] = 1.10-64.45) at 1 year and HR = 9.17 (95% CI = 1.16-72.21) at 3 years. Compared to no ASM therapeutic change, the addition of a second to fourth ASM offered increased protection against SUDEP in patients with continuing drug-resistant epilepsy. SIGNIFICANCE: ASM nonadherence was observed in half of outpatients with epilepsy. A declining pattern of adherence, observed in a quarter of patients, was associated with more than eight times increased risk of SUDEP. Any ongoing medication interventions must include strategies to maintain and improve ASM adherence if we are to reduce the risk of SUDEP.

Methodological considerations on estimating medication adherence from self-report, electronic monitoring and electronic healthcare databases using the TEOS framework.

AIMS: Measuring adherence to medication is complex due to the diversity of contexts in which medications are prescribed, dispensed and used. The Timelines-Events-Objectives-Sources (TEOS) framework outlined a process to operationalize adherence. We aimed to develop practical recommendations for quantification of medication adherence using self-report (SR), electronic monitoring (EM) and electronic healthcare databases (EHD) consistent with the TEOS framework for adherence operationalization. METHODS: An adherence methodology working group of the International Society for Medication Adherence (ESPACOMP) analysed implications of the process of medication adherence for all data sources and discussed considerations specific to SR, EM and EHD regarding the information available on the prescribing, dispensing, recommended and actual use timelines, the four events relevant for distinguishing the adherence phases, the study objectives commonly addressed with each type of data, and the potential sources of measurement error and quality criteria applicable. RESULTS: Four key implications for medication adherence measurement are common to all data sources: adherence is a comparison between two series of events (recommended and actual use); it refers to one or more specific medication(s); it applies to regular repeated events coinciding with known recommended dosing; and it requires separate measurement of the three adherence phases for a complete picture of patients' adherence. We propose recommendations deriving from these statements, and aspects to be considered in study design when measuring adherence with SR, EM and EHD using the TEOS framework. CONCLUSION: The quality of medication adherence estimates is the result of several design choices that may optimize the data available.

Renal insufficiency and magnesium deficiency correlate with a decreased formation of biologically active cholecalciferol: a retrospective observational study.

BACKGROUND: Vitamin D is synthesized in the skin or supplied. Cholecalciferol is hydroxylated in the liver to 25(OH) vitamin D [25D]. 25D is further hydroxylated in the kidney to 1,25(OH) vitamin D [1,25D]. Catabolism occurs by further hydroxylation. Magnesium is a cofactor of all involved hydroxylases. AIM: To investigate the association between renal function and serum magnesium levels, and the biologically active hormone 1,25D. METHOD: Anonymised serum values of 25D, 1,25D, magnesium and creatinine measured in an outpatient cohort over 2 years were analysed. RESULTS: Renal function and magnesium level did not influence 25D values (r = - 0.144 and 0.030, respectively). Mean serum 1,25D values decreased from 106.5 ± 44.3 pmol/l in individuals with normal renal function to 51.7 ± 18.9 pmol/l in those with severe renal insufficiency (p < 0.01). A weak positive correlation was observed between 1,25D and eGFR (r = 0.317), and between 1,25D and serum magnesium (r = 0.217). CONCLUSION: Impaired renal function and low magnesium serum levels are slightly associated with low 1,25D concentrations. Measuring 25D, but not 1,25D, may overestimate the patient's vitamin D status. In patients with renal insufficiency adequate magnesium supply should be ensured.

Clinical relevance and implementation into daily practice of pharmacist-prescribed medication for the management of minor ailments.

Background: Autonomous pharmacist prescribing was legally introduced in Switzerland in 2019 with the reclassification from prescription medication to pharmacist prescribing of 105 medications for sixteen indications. Its aim was to limit medical consultations and healthcare costs. Objectives: To evaluate the clinical relevance of the pharmacy prescribing medications compared to the over-the-counter medications (OTCs) and to evaluate its implementation into daily practice. Methods: A comparison was undertaken by clinical pharmacists to evaluate chemical and galenical equivalences between pharmacy prescribing medications and OTCs using compendium. ch and pharmavista. ch. Then, a scoping review was carried out in October 2021 to determine clinical relevance according to clinical guidelines' recommendations. Clinical relevance was completed by determining if pharmacy prescribing medications were part of a homogeneous therapeutic class (no differences in efficacy and safety considered in clinical guidelines, but rather inter-molecular differences) that included an OTC medication. To identify the most clinically relevant pharmacy prescribing medications, first-line treatments were considered. The implementation into daily practice in Swiss community pharmacies was evaluated through an online questionnaire distributed via e-mail from the national pharmacists' association and LinkedIn®. It included 15 questions divided in: pharmacy demographics, experience on pharmacy prescribing, use of prescribing medications and opinion about the them. Results: Of the 105 pharmacy prescribing medications, 20 (19.0%) were first-line treatments without OTC equivalences. Six of them were OTCs reclassified for safety reasons. Ten medications (9.5%) showed a negative clinical relevance (they were not first-line therapeutic options to support pharmacist when managing patients or considered as to be avoided) compared to the OTCs available. For the questionnaire, 283 pharmacists from the German (40.3%), French (37.1%) and Italian-speaking regions (16.9%) answered. In the previous 6 months, 41.7% pharmacies had delivered 10-50 medications and 30.0% between 1 and 10 medications. In situations where patients could be equally treated with a pharmacy prescribing medication or OTC (with an identical OTC, similar OTC or an OTC for the same therapeutic group): 75.6%, 74.9% and 84.8% of pharmacists, respectively, would have chosen OTCs because it required less documentation and it did not require patients' payment for the service. In addition, pharmacists' lack of training was also mentioned as barrier for providing the service. Conclusion: Most pharmacist prescribing medications do not present clinical advantages compared to OTCs. In addition, other barriers for implementation were also pharmacists' training and patient medications costs.

Development of a Protocol Using the Delphi Method for the ad interim Supply of Hormonal Contraceptives in Swiss Pharmacies.

(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.

Utilization of Drugs with Pharmacogenetic Dosing Recommendations in Switzerland: A Descriptive Study Using the Helsana Database.

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.

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.