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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. 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.

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.

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.

BackgroundPoor medication-adherence is common in chronic lung patients, resulting in reduced health-outcomes and increased healthcare-costs. This study aimed to investigate the impact of an acoustic reminder and support calls on adherence to inhaled therapy in asthma and COPD patients and to determine their effect on exacerbations.MethodsThis single-blinded randomized controlled trial investigated asthma and COPD patients during 6 months in an ambulatory setting. The intervention consisted of daily alarm clock and support phone calls, whenever use of rescue medication doubled or inhaled medication was not taken as prescribed. Primary outcome was time to next exacerbation. Frequency of exacerbations, adherence to inhaled medication and quality of life scores were secondary outcomes. Cox and Poisson regression were used to determine intervention effect on time to exacerbation and frequency of exacerbations, respectively.ResultsSeventy-five participants were assigned to the intervention group and 74 to usual follow-up care. During a median follow-up of 6.2 months, 22 and 28% in the intervention and control groups respectively, experienced at least one exacerbation. Intervention had no effect on time to first exacerbation (HR 0.65, 95% CI 0.21 to 2.07,P = .24), but showed a trend toward a 39% decreased frequency of exacerbations (RR = 0.61, 95% CI 0.35 to 1.03,P = .070) for the adjusted models, respectively. The intervention group had significantly more days with 80–100% taking adherence regarding puff inhalers (82 ± 14% vs. 60 ± 30%,P P = .01). Timing adherence in participants using puff inhalers was higher in the intervention group (69 ± 25% vs. 51 ± 33%,P ConclusionParticipants assigned to the intervention group had significantly better taking and timing adherence of inhaled medication resulting in a trend towards a decreased frequency of exacerbations. However, no effect on time to next exacerbation was observed.Trial registrationClinicalTrials.gov:NCT02386722, Registered 14 February 2014.

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 &lt, 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.

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

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.

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

ObjectivesParticularly at transitions of care points information concerning current medication tends to be incomplete. A medication chart that contains all essential information on current therapy is likely to be a helpful tool for patients and healthcare providers. We aimed to investigate any type of benefits associated with medication charts provided at transition points.MethodsA systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases, two online journals and two association websites dedicated to biomedicine and pharmacy issues were consulted to identify studies for the review using the search term ‘medication chart’ and synonyms. We run our search from database inception up to March 2019. Studies of any study design, intervention and population which examined the effect of paper-based medication charts were included. We extracted study results narratively and coded and classified them by themes and categories inductively by using the ‘framework method’ with content analysis. The methodological quality of the studies was assessed using the Effective Public Health Practice Project (EPHPP) tool.ResultsFrom the 846 retrieved articles, 30 studies met the inclusion criteria, mostly from Germany (18 studies) and the USA (5 studies). Thirteen studies reported a statistically significant result. In the ‘patient theme’, the most obvious benefits were an increase in medication knowledge, a reduction of medication errors and higher medication adherence. In the ‘interdisciplinary theme’, a medication chart represented a helpful tool to increase communication and inter-sectoral cooperation between healthcare providers. In the ‘theme of terms and conditions’, accuracy and currency of data are prerequisites for any positive effect. The quality of the studies was classified predominantly weak mainly due to unmet good quality criteria (no randomised controlled trials study design, no reported dropouts).ConclusionOverall, the reviewed studies suggested some benefits when using medication charts. Healthcare providers could consider using medication charts in their counselling practice. However, it is unknown whether the reported benefits lead to measurable improvement in clinical outcomes.PROSPERO registration number

Background To assess adherence to and preference for vitamin D substitution with different pharmaceutical forms and frequencies of administration. Methods A focus group of stakeholders aimed at preparing the design of an interventional, randomized, cross-over study with 2 × 2 groups obtaining monthly or weekly vitamin D products in liquid or solid form for 3 months each. Dosage corresponds to cumulated amount of recommended 800 IU daily (5.600 IU weekly / 24.000 IU monthly). Main inclusion criteria were a vitamin D serum value 75 nmol/l was achieved by 32% after 3 months and by 50% after 6 months. Preferred formulation was solid form (tablets, capsules) for 71% of participants, and preferred dosage frequency was monthly for 39% of participants. Conclusions Monthly oral vitamin D in solid form lead to the highest adherence, and is preferred by the participants. However, only one third of study participants achieved values in the optimal range of > 75 nmol/l cholecalciferol using weekly or monthly administration providing an average daily cholecalciferol dose of 800 IU. Trial registration NCT03121593 | SNCTP000002251 . Registered 30. May 2017,. Prospectively registered.

Due to the negative outcomes of medication nonadherence, interventions to improve adherence have been the focus of countless studies. The congruence between adherence-related patient characteristics and interventions may partly explain the variability of effectiveness in medication adherence studies. In their latest update of a Cochrane review reporting inconsistent effects of adherence interventions, the authors offered access to their database for subanalysis. We aimed to use this database to assess congruence between adherence-related patient characteristics and interventions and its association with intervention effects.We developed a congruence score consisting of six features related to inclusion criteria, patient characteristics at baseline, and intervention design. Two independent raters extracted and scored items from the 190 studies available in the Cochrane database. We correlated overall congruence score and individual features with intervention effects regarding adherence and clinical outcomes using Kruskal-Wallis rank sum test and Fisher's exact test.Interrater reliability for newly extracted data was almost perfect with a Cohen's Kappa of 0.92 [95% confidence interval (CI) = 0.89-0.94; P 0.001]. Although present in only six studies, the inclusion of nonadherent patients was the single feature significantly associated with effective adherence interventions (P = 0.003). Moreover, effective adherence interventions were significantly associated with improved clinical outcomes (odds ratio = 6.0; 95% CI = 3.1-12.0; P 0.0001). However, neither the overall congruence score nor any other individual feature (i.e., "determinants of nonadherence as inclusion criteria," "tailoring of interventions to the inclusion criteria," "reasons for nonadherence assessed at baseline," "adjustment of intervention to individual patient needs," and "theory-based interventions") was significantly associated with intervention effects.The presence of only six studies that included nonadherent patients and the interdependency of this feature with the remaining five might preclude a conclusive assessment of congruence between patient characteristics and adherence interventions. In order to obtain clinical benefits from effective adherence interventions, we encourage researchers to focus on the inclusion of nonadherent patients.

We translated the ABC adherence taxonomy (i.e., seven terms and their corresponding definitions) published by Vrijens et al. (2012) into French (F) and German (G) without changing the original meaning with the aim to promote a standardised taxonomy for medication adherence to French- and German-speaking researchers and clinicians.; A Delphi survey was performed. To generate round one, we identified French and German synonyms for the seven adherence terms through a literature search in Pubmed. Investigators translated the original English definitions into French and German. Panellists were members of ESPACOMP - the International Society for Patient Medication Adherence; experts suggested by ESPACOMP members and first authors of medication adherence publications in French and German. Google forms were used to create online questionnaires. Delphi rounds were performed until consensus was reached. The consensus was defined according to the acceptance rate as moderate consensus (50-75%), consensus (>75-95%), and strong consensus (>95%).; The literature search resulted in four to six (F) and four to seven (G) items per English term. Delphi rounds were launched between November 2016 and April 2018. Three rounds sufficed to reach consensus on all terms and definitions from 26 French-speaking and 25 German-speaking panellists. Preferred terms for medication adherence are "adhesion medicamenteuse" (82%) in French and "Medikamentenadharenz" (88%) in German.; The use of a common terminology for medication adherence with translations in French and German will contribute to standardise the vocabulary, to harmonise research projects and ultimately ease comparison of study results among researchers and clinicians.

Adherence to cardioprotective medications following myocardial infarction (MI) is commonly assessed using a binary threshold of 80%. We investigated the relationship between medication adherence as a continuous measure and outcomes in MI survivors using restricted cubic splines (RCS). We identified all patients aged ≥65 years hospitalised for MI from 2003–2008 who survived one-year post-discharge (n = 5938). Adherence to statins, beta-blockers, renin angiotensin system inhibitors (RASI) and clopidogrel was calculated using proportion of days covered to one-year post-discharge (landmark date). Outcomes were 1-year all-cause death and major adverse cardiac events (MACE) after the landmark date. Adherence-outcome associations were estimated from RCS Cox regression models. RCS analyses indicated decreasing risk for both outcomes above 60% adherence for statins, RASI and clopidogrel, with each 10% increase in adherence associated with a 13.9%, 12.1% and 18.0% decrease respectively in adjusted risk of all-cause death (all p

Objectives: Since 2002, Swiss community pharmacists have dispensed emergency contraception (EC) as pharmacist-only medicine ideally using the official Swiss protocol. Our study aimed to determine pharmacists' resolution of an imaginary EC case, compliance with the protocol, and provision of information on the risk of sexually transmitted infections (STIs). Methods: We conducted a simulated patient study with 69 students who each visited a community pharmacy. The scenario started with the student requesting the 'morning after pill'. Current practice was assessed using an online evaluation form adapted from the Medication-Related Consultation Framework. Descriptive and statistical analyses were carried out. Results: All pharmacists correctly identified that the person needed EC. All pharmacists used an EC protocol and asked on average 10.9 (standard deviation 0.68) of 11 compulsory EC assessment questions. In total, 93% of pharmacists addressed EC counselling items and 56% addressed the risk of STIs, mainly by mentioning that condoms offered the best protection (76%). Conclusions: Community pharmacists correctly issued the EC, complied with the dispensing protocol and used their professional judgement to ensure optimal EC use. There is nevertheless room for improvement regarding pharmacists' STI counselling. Finally, the protocol's STI section could be enriched with specific information to guide counselling.

Objectives To describe how stroke survivors with atrial fibrillation implement direct oral anticoagulant treatment and propose appropriate metrics to describe adherence. Materials and Methods Stroke patients with atrial fibrillation electronically recorded their self-administered direct oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban) during a 6-month observation phase after hospitalisation for ischemic stroke. Taking and timing adherence, correct dosing days, drug holidays, time of the day and day of the week subsets, dose-to-dose intervals and longest intervals between two consecutive doses were calculated from electronic monitoring data to describe and discuss the implementation phase of adherence. Results Data from 41 patients were analysed. Median age was 77 (IQR = 69–84), 63.4% were male and the majority suffered a mild stroke (median NIHSS: 1). Mean taking and timing adherence exceeded 90%. Correct dosing occurred in 86.6% of the days. Seven patients (17.1%) had intake pauses of three or more consecutive days. Patients with twice-daily regimen (70.7%) had higher taking adherence in the morning than in the evening (94.4% versus 89.9%; p = 0.001). No therapy- or anamneses-related characteristic was associated with taking adherence. Conclusions Although adherence to direct oral anticoagulants of stroke patients with atrial fibrillation exceeded 90%, deviant intake patterns such as drug holidays and missed evening doses were common and raise concerns. Appropriate adherence metrics calculated from electronic monitoring data may guide healthcare professionals elucidating patient-tailored adherence-enhancing interventions. ClinicalTrials.gov registration number: NCT03344146

ObjectivesTo translate the SWAMECO from German into English; to complete content and face validity with healthcare professionals (HCPs) and with patients from the target population that is, community-dwelling adult patients taking three or more medicines for three or more months.DesignThe process followed guidance from Sousa et al and included translation and cross-cultural adaptation, and cognitive testing among selected HCPs and patients. As the SWAMECO questionnaire is a screening instrument, pilot testing was performed in the target population.SettingThree community pharmacies in and around Cork (Ireland) recruited patients for interviews and pilot testing.ParticipantsCommunity-dwelling patients with ≥3 oral medications for ≥3 months, aged ≥18 years.Outcome measuresAnswers to the SWAMECO questionnaire; clarity of each question, each instruction and each response format.ResultsIssues related to cultural and conceptual differences were resolved by rewording some items. Ten HCPs and 11 patients completed the questionnaire and gave their feedback and opinions on criteria according to Fitzpatrick et al. Revisions included rewording; deleting of two questions; using of colour to signpost that is, where to skip questions that were not applicable to the participants; and replacement of the A-14 medication adherence scale with three validated items. Of the 66 patients enrolled for pilot testing, eight (12.1%) indicated swallowing difficulties. Difficulties with ingesting foods or liquids correlated with swallowing difficulties (p=0.001). All patients perceived discomfort (mean 6.9 on a Visual Analogue Scale from 0 to 10). Patients with swallowing difficulties were significantly more likely to report modifying their medicines (p=0.004) and having poorer medication adherence (p=0.028) than those who had no swallowing difficulties.ConclusionsThe version of the SWAMECO questionnaire in English contains 28 items and is ready for use in adults with polypharmacy.

Background: Pharmacist-led cognitive services (PLCS) are increasingly necessary in primary care as a response to patient-centered care. However, the implementation rate and remuneration models of PLCS are either absent or superficially described in the literature. Objective: The aim of this study is to review the implementation of PLCS in primary care across Europe and explore the associated third-party paid remuneration models. Methods: A cross-sectional study was conducted using an online survey sent to representatives of 44 European countries. The survey listed 21 PLCS and asked respondents to report the availability of the service, the rate of implementation and the existence of remuneration. To ensure credible data, data triangulation was sought using three representatives per country, representing backgrounds of community pharmacy, pharmacy practice research and health policy. Subsequently, data was validated, and consensus sought. Results: Data were collected between November 2016 and October 2017 from 34 different countries across Europe (79%). Provision of medicines’ information (94.1%), generic substitution (85.3%), provision of emergency oral contraception (70.6%) and point-of-care testing (67.7%) were the services reported as the most widely disseminated in European primary care. Medication review was the most disseminated among advanced services (55.9%). Medication review, adherence support and monitoring, prescription renewal, opioid substitution and travel medicine had the highest implementation rates reported. Half of the participating countries mentioned models of remuneration, predominantly based on a fee-for-service, with less frequent reports of pay-for-performance or mixed models of remuneration. Conclusions: The availability of PLCS is increasing and varying in scope across Europe. There is wide variation in the implementation level of services across Europe and a lack of valid data. Remuneration of PLCS is also spreading but no clear pattern was found that relates service provision to payment. info:eu-repo/semantics/publishedVersion

Background Oral anticoagulation therapy has proven beneficial impact on the prevention of thromboembolic events. However, the use of antocoagulatns also increases the risk of bleeds. To maximize the benefits and minimize the risks of the treatment, guidance on appropriate use of oral anticoagulants is essential. An international guideline describing relevant components and requirements for pharmaceutical care for patients receiving a therapy woth oral antocoagulants would increase the quality of care. However, recommendations on pharmaceutical care for patients on anticoagulation is lacking. Objective This study aims to develop an interprofessional guideline to support patients in their use of oral anticoagulation therapy. Method Two systematic literature searches were performed on existing guidelines on the management and interventions to improve-oral anticoagulant use, to generate possible recommendations. Subsequently, an international expert panel with 26 pharmacists with extensive experience in clinical and/or scientific work on anticoagulation from a total of 22 European and 4 non-European countries was constituted. With this (geographically well distributed) expert panel, a four-round internet-based Delphi technique was conducted to reach consensus on their relevance. Items were ranked on a 1–10 scale of agreement. A median agreement score of ≥ 7.5 was considered the threshold for consensus. Levels of importance were rated on a 1–3 scale. Setting A global network of 26 pharmacists specialized in oral antocoagulation therapy. Main outcome measure Development of inter-professional guideline. Results After the four Delphi rounds 18 guideline recommendations were formulated. Consensus of opinion was achieved for all recommendations (median agreement: 8.5–10.0), whereas mean levels of importance were between 1.1 and 2.0 (SD: 0.2–0.7). The following domains were rated as most important targets for improving the care around oral anticoagulation: ‘INR-monitoring’, ‘Transfer of care between health care settings’, ‘Adherence to medication’, ‘Patient communication and engagement’, and ‘Medication reconciliation and medication review’. Conclusion The 18 recommendations included in this guideline provide the base for optimization of anticoagulation care across different countries/healthcare systems. Future work involves translating the guideline recommendations into clinical practice. Once implemented, the recommendations of the guideline will support health care providers with the pharmaceutical care for patients on, oral anticoagulation which will improve the effective and safe use of these medicines. Electronic supplementary material The online version of this article (10.1007/s11096-019-00844-0) contains supplementary material, which is available to authorized users.

Background The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations. There are numerous reasons for the lack of disease control in asthma and COPD patients. It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient. This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence. Methods For this cross-sectional analysis, 165 asthma and COPD patients were analyzed. Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type. QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT). Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). Results Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (P = .02). Moreover, COPD patients with incorrect device application were more likely to suffer from cough (P = .03) and were more breathless while walking uphill or a flight of stairs (P = .02). While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (P = .04). Conclusions Correct inhalation of prescribed medication is associated with improved health status and lung function. These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients’ inhalation technique. Trial registration ClinicalTrials.gov: NCT0238672, Registered 14 February 2014.

Background. Prescription of fragmented tablets is useful for individualisation of dose but includes several drawbacks. Although without score lines, the antipsychotic drug quetiapine was in 2011 the most often prescribed 1/2 tablet in discharge prescriptions at the University Hospital in Basel (USB, 671 beds). We aimed at analysing the prescription patterns of split tablets in general and of quetiapine in particular in Switzerland.Methods. All orders of community pharmacies for unit-of-use soft pouch blisters placed at Medifilm AG, the leader company in Switzerland for repackaging into pouch blisters, were analysed.Results. Out of 4,784,999 tablets that were repacked in 2012 in unit-of-use pouch blisters, 8.5% were fragmented, mostly in half (87.6%), and were predominantly psycholeptics (pipamperone 15.8%). Prescription of half quetiapine appears to be a Basel specificity (highest rates of fragments and half quetiapine).Conclusions. Prescription of fragmented tablet is frequent. It represents a safety issue for the patient, and a pharmaceutical care issue for the pharmacist. In ambulatory care, the patient’s cognitive and physical capacities must be clarified, suitability of the splitting of the tablet must be checked, appropriate aids must be offered, like a pill-splitting device in order to improve accuracy, and safe use of the drug must be ensured.

Objective To assess chlamydia knowledge, willingness to undertake pharmacy-based chlamydia testing, and facilitators and barriers to such testing in consumers and community pharmacists, in Australia (AUS) and Switzerland (CH). Methods Statements of interest were retrieved from literature and assembled into a 12-item online survey (English and German versions). Survey was disseminated through Facebook, pharmacies’ publicly available emails and professional websites (March 2015). Results Consumers and pharmacists (AUS: ncons = 198, npharm = 162; CH: ncons = 209, npharm = 223) were predominantly female (>65%). Mean chlamydia knowledge scores (maximum of 8) were higher in Australia in consumers (AUS: 6.8 ± 1.5 vs CH: 4.2 ± 2.4; p Conclusion The majority of consumers and pharmacists support pharmacy-based chlamydia testing. There is now emerging evidence that the policy makers in Australia and Switzerland need to develop pharmacy-based chlamydia testing as core business.

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: Vitamin B12 (VB12) deficiency can be treated with oral high-dose substitution or intramuscular (i.m.) injection of VB12. Whenever alternative routes of administration exist, patient prefer-ences should be considered when choosing the treatment. We aimed to assess outpatient preferences towards oral or IM VB12 substitution and confirm noninferiority of early biomarker response with oral treat-ment, in a typical primary care population. METHODS: Prospective randomised nonblinded parallel-group trial. Patients were recruited by their general practitioner and randomly as-signed to oral or IM treatment. Group O-oral was given 28 tablets of 1000 μg cyanocobalamin in a monthly punch card fitted with an elec-tronic monitoring system. Group I-IM received four, weekly injections of 1000 μg hydroxocobalamin. Blood samples were drawn before the first administration and after 1, 2 and 4 weeks of treatment, and ana-lysed for VB12, holotranscobalamin (HoloTc), homocysteine (Hcy) and methylmalonic acid (MMA). For group O-oral, treatment adherence and percentage of days with 2 dosing events were calculated. Before and after 28 days of treatment, patients were asked to fill in a ques-tionnaire about their preference for the therapy options and associ-ated factors. RESULTS: Between November 2013 and December 2015, 37 patients (age: 49.5 ± 18.5 years; women: 60.5%) were recruited for oral (19) or IM (18) treatment. Baseline values with 95% confidence intervals for serum VB12, HoloTc, Hcy and MMA were 158 pmol/l [145-172], 49.0 pmol/l [40.4-57.5], 14.8 µmol/l [12.0-17.7] and 304 nmol/l [219-390], respective-ly, in group O-oral and 164 pmol/l [154-174], 50.1 pmol/l [38.7-61.6], 13.0 µmol/l [11.0-15.1] and 321 nmol/l [215-427], respectively, in group I-IM (not significant). After 1 month of treatment, levels of VB12 and HoloTc showed a significant increase compared with baseline (group O-oral: VB12 354 pmol/l [298-410] and HoloTc 156 pmol/l [116-196]; group I-IM: VB12 2796 pmol/l [1277-4314] and HoloTc 1269 pmol/l [103-2435]). Hcy and MMA levels showed a significant decrease compared with baseline (group O-oral: Hcy 13.8 µmol/l [10.7-16.8] and MMA 168 nmol/l [134-202]; group I-IM: Hcy 8.5 µmol/l [7.1-9.8] and MMA 156 nmol/l [121-190]). HoloTc and MMA levels were normalised in all patients after 4 weeks of treatment, whereas normalisation of VB12 and Hcy was reached by all patients in group I-IM only. Response of VB12, HoloTc and Hcy was more pronounced in group I-IM (p

Objectives: To compare the pharmaceutical quality of original and generic ceftriaxone sodium preparations for injection produced in Eastern Asia.Methods: Standard physical and chemical laboratory tests were performed.Participants/material: Ceftriaxone (Rocephin®, Roche, Switzerland) was the reference material. Generics produced in China, India, and Indonesia were sampled in China and Myanmar within their expiration dates.Results: Eight generics obtained from Eastern Asia markets in January 2013 were analysed. All eight generics failed the specifications in three or more tests. Residues of solvents and metals were detected in all generics, four were not particle free, and two were not sterile.Conclusions: All tested generic ceftriaxone products failed to meet the pharmaceutical quality standards of the branded original. The high levels of impurities and the identified contamination of particles and residues are of clinical concern, as they could impact tolerability and safety in patients in need of an effe...

Background Several measures for calculating adherence to one medication from dispensing data records have been proposed, but the nomenclature is inconsistent and computations vary. The same measures, like the medication possession ratio (MPR), have been used for multiple medication regimens, and have tended to over- or under-estimate adherence rates. Objective To demonstrate the impact of varying elements in MPR to a single medication regimen; to define standards for the estimation of adherence to polypharmacy; to propose a new method for calculating adherence to polypharmacy; to face validate it. Setting Face validity of the proposed method. Method Variations in the MPR formula were simulated. Standards for the estimation of adherence to polypharmacy were defined. A new method to calculate adherence to polypharmacy was established. Its face validity with three illustrative cases obtained from a pharmacy refill database was assessed. Main outcome measure Adherence rate to polypharmacy from refill data records. Results MPR to a single medication is operationalized in the numerator and denominator and is influenced by the parameters like observation period, medication gaps, overlap. For polypharmacy, an average MPR is commonly used, which is not accounting for the specificity of multiple medications, and hence overestimating adherence rate. We propose the daily polypharmacy possession ratio (DPPR) as an index of adherence to polypharmacy. It estimates the proportion of time a patient had medication available for use by considering the presence or absence of multiple medications on each day in the observation period. We calculated possession rates from refill histories over 31 months (January 1, 2011–July 31, 2013) for three illustrative patients. The average MPR estimates were 80 % for a patient with 6 medications/20 refill dates, 90 % for a patient with 4 medications/11 refill dates, and 89 % for a patient with 3 medications/17 refill dates. The corresponding DPPRs were 75, 88 and 99 %, indicating overestimations by 5 and 2 %, and underestimation by 10 %, respectively. Conclusion The DPPR accounts for the specificity of polypharmacy including number of medications, medication switching, duplication, overlapping. Research is needed to further confirm the validity of this new index.

OBJECTIVE: To compare the pharmaceutical quality of Xenical (chemically produced orlistat) with nine generic products, each produced by fermentation processes. METHODS: Xenical 120 mg capsules (Roche, Basel, Switzerland) were used as reference material. Generic products were from India, Malaysia, Argentina, Philippines, Uruguay, and Taiwan. Colour, melting temperature, crystalline form, particle size, capsule fill mass, active pharmaceutical ingredient content, amount of impurities, and dissolution were compared. Standard physical and chemical laboratory tests were those developed by Roche for Xenical. RESULTS: All nine generic products failed the Xenical specifications in four or more tests, and two generic products failed in seven tests. A failure common to all generic products was the amount of impurities present, mostly due to different by-products, including side-chain homologues not present in Xenical. Some impurities were unidentified. Two generic products tested failed the dissolution test, one product formed a capsule-shaped agglomerate on storage and resulted in poor (≤15%) dissolution. Six generic products were powder formulations. CONCLUSIONS: All tested generic orlistat products were pharmaceutically inferior to Xenical. The high levels of impurities in generic orlistat products are a major safety and tolerability concern.

Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE.

We report on the first polypharmacy adherence monitoring over 371 days, integrated into a pharmaceutical care service (counselling, electronic multidrug punch cards, feedback on recent electronic records) for a 65-year-old man with diabetes after hospital discharge. The initial daily regimen of four times per day with 15 pills daily changed after 79 days into a daily regimen of two times per day with 9 pills daily for the next 292 days. The patient removed all medication from the multidrug punch cards (taking adherence 100%) and had 96.9% correct dosing intervals (timing adherence). The 57 evening doses showed the least variation in intake times at 17 h 45 min±8 min. Over the observation year, the patient was clinically stable. He was very satisfied with the multidrug punch card and the feedback on electronic records. In conclusion, long-term monitoring of polypharmacy was associated with the benefit of successful disease management.

To translate in German the 8-item Morisky Medication Adherence Scale (MMAS-8D). To validate it against objective and subjective measures of adherence in cardiovascular patients with polypharmacy.A standard forward-backward procedure was used to translate the MMAS-8 into German. Validation took place on a convenience sample of ambulatory patients on chronic antiplatelet therapy between June 2010 and June 2011. Objective adherence was obtained from electronically monitored multi-drug punch cards. Internal consistency was assessed using Cronbach's alpha coefficient, construct validity using exploratory factor analyses and correlations between MMAS-8D and related measures. Convergent validity was assessed with a subjective questionnaire about beliefs about medicines (BMQ Specific, two sub-scales).A total of 70 patients were included (mean age 65.7 ± 9.9 years; 31.4% women). The mean score of the MMAS-8D was 7.5 (SD 0.8; range 4.5-8). Moderate internal consistency (alpha = 0.31) was observed due to multidimensionality of the scale. Factor analysis yielded four components that accounted for 71.7% of the total variance. Convergent validity was supported by significant correlations with BMQ Necessity (r = 0.31, P 0.01), BMQ Concerns (r = -0.16, P 0.05) and with electronic adherence reports (U-values 44 and 471, P 0.05). Platelet aggregation values were within therapeutic range for 80% of the patients. Blood values of the antiplatelet agent within therapeutic range were associated with a higher MMAS-8D score (U-value 125, P 0.05).The German MMAS-8 appears to be a reliable instrument to catch medication adherence in cardiovascular patients. It may be useful in patients with chronic therapy for detecting non-adherence.

An important initial step in the medication process is prescription writing. The more perfect it is, the more successfully can a therapy be performed. Imprecisions and missing information lead to unnecessary queries or to errors which are often randomly discovered during a later consultation. A "perfect prescription" serves every individual involved in the medication process. The prescription document contains the instructions for the patient, the pharmacist, the nurse, and other health professionals involved in the therapy. The prescription writing process is regulated by several laws and decrees which were enacted to assure the greatest possible drug safety. Deviations from the norm may be necessary in individual cases, which require an even more responsible prescribing and explicit indication.Ärztliches Rezeptieren ist ein wichtiger erster Schritt im Medikationsprozess. Je perfekter dies ausgeführt wird, umso erfolgreicher kann die Therapie ausgeführt werden. Ungenauigkeiten und fehlende Angaben führen zu unnötigen Rückfragen oder können Anlass für Fehler sein, welche oft erst zufällig bei Folgekonsultationen aufgedeckt werden. Ein „perfektes Rezept“ dient allen Beteiligten im Medikationsprozess und ist als Dokument die Anweisung für Patienten, Apotheker, Pflegefachleute und andere in der Therapie eingebundene Fachpersonen. Der Verordnungsprozess wird durch vielfältige Gesetze und Verordnungen geregelt, welche allesamt im Hinblick auf größtmögliche Arzneimittelsicherheit erlassen werden. Im Einzelfall können Abweichungen von den Normen nötig werden, welche eine umso sorgfältigere Verordnung und explizite Kennzeichnung erfordern.

Background Electronic compliance monitoring has provided new variables to describe drug intake behavior and new strategies to improve compliance. However, as evaluated in this study, the recording of opening events of pill bottles does not necessarily mean drug intake. Methods In an open 3-week trial with an oral vitamin combination, drug intake was recorded with use of an electronic pill box that contained 25 capsules and that registered each opening of the bottle. Thirty-seven patients were asked to take one capsule every morning for 21 days. Opening and closing events were related to the results of pill counts and patient interviews at the end of the trial. Results Drug consumption was 101.8% (663 recorded opening and closing events) in the 31 patients who completed the trial. Pill boxes were opened more than once by 10 patients on at least one monitored day. For seven patients the total number of openings was >25 (range, 26 to 29) and thus exceeded the number of capsules provided. A third interview of these patients revealed real overconsumption in only two patients. Six patients remembered that they had shown the device to relatives or friends or that they had checked to see whether they had closed the pill box well, thus turning a “curiosity event” into a drug intake event. Conclusion In short-term studies particularly, such curiosity events may substantially modify the electronic assessment of compliance surrogates. In these trials the combined evaluation of electronic openings, pill counts, and interviews may be a suitable way to reveal such openings without pill intake. Clinical Pharmacology & Therapeutics (2000) 67, 44–47; doi: 10.1067/mcp.2000.103821

Antiplatelet resistance with aspirin and clopidogrel has been associated with clinical, cellular and pharmacogenetic factors; and non-adherence has been considered as a major contributor to resistance in outpatients. We aimed at assessing factors to resistance when adherence to the antiplatelet drugs and all other oral solid drugs was controlled for. In a pilot study, we tested arachidonic acid and/or ADP-induced in vitro platelet aggregation of 82 outpatients with chronic aspirin and/or clopidogrel treatment before and after a one-week period of measuring the patient's adherence with the polymedication electronic monitoring system (POEMS). Resistance was found in 20% (aspirin; n = 69) and 25% (clopidogrel; n = 32) of the patients after monitored adherence. Mean platelet aggregation was not (aspirin) or non-significantly (clopidogrel) lowered when compared to baseline. Diabetes mellitus and inflammation were consistently associated with resistance to both drugs, but CYP2C19 polymorphisms could not be confirmed as predictors of clopidogrel response. Electronically compiled multidrug dosing histories allowed the concomitant intake of high-dose lipophilic statins to be identified as a risk factor of impaired response to clopidogrel and revealed that exposure to further potential drug-drug interactions (DDIs) was too low for analysis. Multidrug adherence monitoring allowed thus dismissing non-adherence as a major contributor to resistance and inter-individual response variability in an outpatient setting. Additionally, it allowed analysing the impact of DDIs according to the actual exposure to the potentially interfering drugs. Further studies based on this methodology are essential to prevent misleading results due to incomplete adherence and gain additional insight into the impact of timing adherence on antiplatelet drug response.

Background By definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson’s disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians. Methods Madopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original “shelf-life” specifications in use by Roche. Results Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to −7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers. Conclusions Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.

QUESTION UNDER STUDY / PRINCIPLES: Scored tablets are often split to facilitate swallowing or to fractionate the dose. In the latter case, the fragments of the tablet should comply with the content or mass uniformity requirements of the European Pharmacopoeia. For health professionals the splitting information is expected to be in the Summary of Product Characteristics (SPCs), the package leaflets (PLs) or Hospital Drug Formularies. We investigated the accuracy of splitting statements in these three sources of drug information.We selected the tablets mentioned as "scored" in the Swiss Compendium Online and in the Drug Formulary of Basel University Hospital, and screened the corresponding SPCs and PLs for information on divisibility and fractional dosing. Missing information was obtained from the drug marketing licence holder.The Swiss Compendium Online contained 698 different scored tablets whose SPCs mentioned fractional dosing for 43.8% and explicitly forbade it for 2.7%. The Hospital Drug Formulary indexed 188 items as scored tablets. The corresponding SPCs mentioned fractional dosing for 107 (59.4%) and a sentence forbidding it for 5 (2.8%). The manufacturers' answers permitted fractional dosing for 49 (27.2%) of the remaining tablets and forbade it for 19 (10.5%). Lack of dosage uniformity or presence of "historic decorative" score-lines were the reasons given.For the majority of scored tablets the official sources of drug information contained no explicit indication on fractional dosing. Improvement of splitting information is necessary to avoid potential medication errors.

To evaluate the time lapse between sexual intercourse and request for emergency hormonal contraception (EHC) from pharmacies and to analyse the profiles of EHC users shortly after deregulation and three years later, assuming EHC became better-known and more easily accessed.Official EHC written assessment forms were collected from pharmacies in Switzerland.Written assessment forms from 729 women aged 15-49 years (380 forms pertaining to the 2003 period and 349 for the 2006 period) were collected in 18 pharmacies. Due to the presence of more women aged less than 18, women in Group 2006 were significantly younger than those in Group 2003 (p = 0.014). Nearly one quarter (23.6%) of the women went to a pharmacy for EHC within 6 h of unprotected sexual intercourse. The median access time was 12 h in 2003 and 14 h in 2006 (p0.05). Variance analysis showed a relationship between time to access and the contraceptive methods used (p0.001) with male condom users going to a pharmacy the earliest after unprotected intercourse, followed by pill users and by women without any contraception. The number of women who did not use any contraception doubled from 2003 to 2006.Dispensing EHC through Swiss community pharmacies allows women to seek EHC easily and rapidly after unprotected sex. The observed changes in user profiles do not support the concern regarding enhanced sexually risky behaviour, more frequent use or misuse due to free access to EHC. The findings support a more liberal access to EHC.

Background: This was a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Evidence mapping was used to reveal the effect of drug reminder packaging on medication adherence, to identify research gaps and to make suggestions for future research. Methods: PubMed, Embase, CINAHL and PsycINFO were searched with an end date of September 2013 using the Medical Subject Headings (MeSH) term ‘medication adherence’ and 20 different search terms for ‘drug reminder packaging’, limited to the English and German languages. Additional references were identified through cross-referencing. All prospective controlled trials with an intervention using drug reminder packaging for patients taking at least one medication without the assistance of a health-care professional were included in the evidence mapping of the effect of drug reminder packaging on adherence and outcomes according to the Economic, Clinical and Humanistic Outcomes (ECHO) model. Results: A total of 30 studies met the inclusion criteria: 10 randomized controlled trials, 19 controlled clinical trials and 1 cohort study. Drug reminder packaging had a significant effect on at least one adherence parameter in 17 studies (57%). The methodological quality was strong in five studies. Two studies provided complete information. Clear research gaps emerged. Conclusions: Overall, the studies showed a positive effect of drug reminder packaging on adherence and clinical outcomes. However, poor reporting and important gaps like missing humanistic and economic outcomes and neglected safety issues limit the drawing of firm conclusions. Suggestions are made for future research.

Co-medication unknown to the treating physician, including self-medication, may compromise drug safety by increasing the risk of duplicate therapy, drug interactions and adverse drug reactions that are not recognised as such. The aim of the current study was to estimate exposure to unknown co-medication during hospitalisation by performing an analytical screening for a broad range of drugs and drug classes in urine of patients admitted to a general internal medicine ward. Urine samples of 44 patients were analysed with REMEDiHS (high-performance liquid chromatography) and six different immunoassays. Positive results were compared with drug history and documented drug prescription. If appropriate, gas chromatographic-mass spectrometric confirmatory analyses were performed on drugs classified at least once as possible unknown co-medication. Nine (20%) of the patients tested positive for a compound detected by two independent analytical methods and 18 (41%) for a compound detected by at least one analytical method. Unknown co-medication consisted mostly of analgesics, benzodiazepines or ranitidine. At least one in five patients exhibits at least once during hospitalisation exposure to drugs not documented in the patient record, which may compromise patient safety.