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.

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.

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.

Development and validation of the 15-STARS - A novel self-report pharmacy-based questionnaire to screen for medication non-adherence.

BACKGROUND: Published scales measuring medication adherence are myriad. There is a need for a tool that guides towards downstream adherence interventions. OBJECTIVE: To develop and validate a self-report questionnaire able to detect modifiable determinants of medication non-adherence. METHODS: Workshops, surveys and meetings were used to identify items. Validation was performed in French and German (Switzerland) between March and April 2022. Face validation, content validation, construct validation, internal consistency and test-retest reliability were assessed. The questionnaire was finalized in August 2022. RESULTS: The first draft in English included 13 items divided into four areas. Following translation, validation was performed with 144 patients (63 German-, 81 French-speaking) who were recruited in 35 community pharmacies. Acceptability was good (<5% missing data). Psychometric properties were acceptable with good content validity and moderate construct validity. Internal consistency was acceptable for the French version (Cronbach's alpha = 0.71 [item 1-5] - 0.61 [item 6-9]) and less acceptable for the German version (Cronbach's alpha = 0.43 [item 1-5] - 0.45 [item 6-9]). Test-retest was given for all items (r = 0.52 to 1.0) except item 10 in French (r = 0.25). The final instrument is a 15-item questionnaire called the 15-STARS (Screening Tool for AdheRence to medicineS) that assesses practical difficulties with medicine use, reasons for non-adherence, doses missed, and need for further help. CONCLUSIONS: Our findings support the validity and clinical utility of the 15-STARS questionnaire. Reliability was inconclusive due to incoherent internal consistency, but explainable by the single-item nature of the scale. This new tool will enable the detection of patients who experience difficulties that negatively influence medication adherence. Pharmacists will be able to propose specific and tailored adherence interventions to the patients. Next steps will focus on evaluating its usefulness for developing targeted interventions that optimize medication adherence in routine care and research settings.

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.

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.

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.

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.

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.

Towards better reporting of the proportion of days covered method in cardiovascular medication adherence: A scoping review and new tool TEN-SPIDERS.

Although medication adherence is commonly measured in electronic datasets using the proportion of days covered (PDC), no standardized approach is used to calculate and report this measure. We conducted a scoping review to understand the approaches taken to calculate and report the PDC for cardiovascular medicines to develop improved guidance for researchers using this measure. After prespecifying methods in a registered protocol, we searched Ovid Medline, Embase, Scopus, CINAHL Plus and grey literature (1 July 2012 to 14 December 2020) for articles containing the terms "proportion of days covered" and "cardiovascular medicine", or synonyms and subject headings. Of the 523 articles identified, 316 were reviewed in full and 76 were included (93% observational studies; 47% from the USA; 2 grey literature articles). In 45 articles (59%), the PDC was measured from the first dispensing/claim date. Good adherence was defined as 80% PDC in 61 articles, 56% of which contained a rationale for selecting this threshold. The following parameters, important for deriving the PDC, were often not reported/unclear: switching (53%), early refills (45%), in-hospital supplies (45%), presupply (28%) and survival (7%). Of the 46 articles where dosing information was unavailable, 59% reported how doses were imputed. To improve the transparent and systematic reporting of the PDC, we propose the TEN-SPIDERS tool, covering the following PDC parameters: Threshold, Eligibility criteria, Numerator and denominator, Survival, Presupply, In-hospital supplies, Dosing, Early Refills, and Switching. Use of this tool will standardize reporting of the PDC to facilitate reliable comparisons of medication adherence estimates between studies.

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.

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.

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.

Assessing Medication Adherence Barriers to Short-Term Oral Antibiotic Treatment in Primary Care-Development and Validation of a Self-Report Questionnaire (BIOTICA).

BACKGROUND: Pharmacists are increasingly involved in strategies to fight antimicrobial resistance by ensuring optimised antibiotic (AB) use, including adherence support. Successful adherence interventions should be tailored to patients' barriers and validated instruments are needed. This study aimed to identify adherence barriers to AB treatment, develop a self-report questionnaire, and validate it in outpatients. METHOD: Adherence barriers were identified through a systematic literature search and focus group discussion. Unmodifiable and irrelevant barriers were excluded from further processing. A validation study assessed the questionnaire's internal reliability and construct validity by comparing the questionnaire's score with electronically monitored adherence data. RESULTS: A 15-item questionnaire was created. Overall, 68 patients were included in the construct validation analysis (60.3% female). The mean consecutive taking adherence was 88% and the most frequently reported barriers were "worries about side-effects" (37%) and "having swallowing difficulties" (19%). Three items were excluded from the questionnaire, which was supported by an increase of Cronbach's alpha (0.69 to 0.70). The 12-item version's score correlated significantly with medication adherence rate (r = -0.34, p < 0.01). CONCLUSION: The self-report questionnaire is a reliable and valid tool to pre-emptively assess adherence barriers in outpatients prescribed ABs. In the future, appropriate adherence interventions can be matched to barriers and tested in a pilot intervention study.

Identification of Patients with Cobalamin Deficiency Crucially Depends on the Diagnostic Strategy.

BACKGROUND: Our goal was to determine vitamin B12 (cobalamin) deficiency with different diagnostic strategies, to propose the best possible laboratory strategy, and to synthesize the relevance of biomarkers in the diagnosis of a cobalamin deficiency. METHODS: We performed a secondary data analysis. The testing strategies were (i) vitamin B12 solely, (ii) holotranscobolamin solely, (iii) vitamin B12 and holotranscobolamin, and (iv) reflex testing of holotranscobalamin in samples with vitamin B12 < 300 pmol. A set of 3,044 laboratory samples with vitamin B12 and holotranscobalamin serum values from unselected in- and outpatients from a secondary care hospital. A sample was classified as cobalamin deficient when low values of vitamin B12 < 137 pmol/L or holotranscobalamin ≤ 37 pmol/L were measured. RESULTS: Low cobalamin values were identified in 591 (19.4%) samples either according to low vitamin B12 values (305; 10.0%) or low holotranscobalamin values (436; 14.3%). For 2,404 values with vitamin B12 < 300 pmol/L, the additional measurement of holotranscobalamin (reflex-testing) enabled the detection of an additional 278 (9.1%) deficiencies. When the grey zone was decreased to 138 - 219 pmol/L, the reflex testing of an additional 1,240 samples identified a total of 511 (16.8%) samples as cobalamin deficient. CONCLUSIONS: The identification of cobalamin deficiency or sufficiency highly depends on the diagnostic strategy. A reflex testing with a grey zone for vitamin B12 < 220 pmol/L identifies cobalamin deficiency cost efficiently in 86.5% cases (511 out of 591). Physicians should apply a uniform strategy on how to address the diagnosis of cobalamin deficiency and indication for treatment. In-hospital guidelines, which describe methodology and sensitivity of the locally used assays for vitamin B12 and holotranscobalamin could guide them.

Community pharmacists' preparedness for substituting biologics and dispensing biosimilars - Lessons learned from a multinational survey.

Interchangeability between biological medicines and biosimilars, and subsequent substitution by pharmacists represent an important opportunity for costs savings for health care systems. Because biological medicines are complex products, the expert role of the pharmacist to inform patients and support physicians is indispensable. However, regulations on substitution of biosimilars differ around the globe, such that a substitution that is allowed in one country may be forbidden in another. Overall, pharmacists' knowledge of biosimilar medicines is incomplete and hesitancy to engage in substitutions is perceptible. As counter-balancing remedy, continued education about biosimilars is needed among practicing community pharmacists.