Several methods exist for measuring medication adherence. The Time4Med^TM device (Adherence Innovations, Hong Kong) is a small, electronic card to affix on medication packaging that records date and time of intakes when a button is pushed. We aimed to validate the device with an emphasis on polypharmacy. Twenty volunteers used Time4Med^TM devices with a virtual thrice daily intake over 14 days. Diary-recorded date and time were compared to electronically-stored events. Functionality, reliability and recovery for different stress conditions were calculated. User‘s acceptability was assessed with the System Usability Scale (SUS). Eleven elderly outpatients (mean age 80.2 ± 8.1 years) taking >3 medications daily used the device over 4 weeks. Volunteers logged 847 events. Functionality (100%), sensitivity (94.9%), specificity (99.4%) and recovery (100%) were high. Dropping the smart card and storing it in a refrigerator caused either the recording of false events or no recording at all. The mean SUS score was 82.6 (SD 14.8), demonstrating excellent acceptability. Satisfaction was very high for volunteers and patients, except for pushing the button. Time4Med^TM devices are highly accurate in recording, retaining and delivering electronic data of multiple medication intake. They are well accepted by elderly patients. They can be recommended in clinical studies and for practitioners who desire to elucidate adherence patterns of ambulatory patients.

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 < 50 nmol/l and age ≥ 18 years. Primary endpoint was adherence, secondary endpoints were preferences and vitamin D serum levels. Results: The focus group reached consensus for preference of a monthly administration of solid forms to adults. Full datasets were obtained from 97 participants. Adherence was significantly higher with monthly (79.5–100.0%) than weekly (66.4–98.1%) administration. Vitamin D levels increased significantly (p < 0.001) in all participants. An optimal value of > 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.

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.

Background: Our goal was to determine vitamin B-12 (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 B-12 solely, (ii) holotranscobolamin solely, (iii) vitamin B-12 and holotranscobolamin, and (iv) reflex testing of holotranscobalamin in samples with vitamin B-12 < 300 pmol. A set of 3,044 laboratory samples with vitamin B-12 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 B-12 < 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 B-12 values (305; 10.0%) or low holotranscobalamin values (436; 14.3%). For 2,404 values with vitamin B-12 < 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 B-12 < 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 B-12 and holotranscobalamin could guide them.

The 15-STARS questionnaire (Screening Tool for AdheRence to medicineS) is a validated self-report screening tool that assesses modifiable determinants of medication non-adherence. It was applied in the 5C-study with chronic inflammatory bowel diseases (IBD) patients in Basel, Switzerland during the winters 2022/23 and 2023/24. Its usefulness, defined as data quality, actionability, and accuracy has not yet been fully explored. The aims of this study were to assess i) which determinants are captured by the 15-STARS questionnaire in IBD patients, ii) corresponding adherence-enhancing interventions, and iii) the positive predictive value (PPV) of the questionnaire. We performed a subset-analysis of the 5C-study using a mixed-method analysis. Data were analyzed quantitatively, and participants with presumed non-adherence were interviewed between November 2023 and April 2024. Interviews were analyzed inductively using thematic analysis. Interventions were defined, missing data and PPV were calculated. Of 144 participants, 139 returned the 15-STARS questionnaire. Presumed non-adherence was identified in 71 participants (49.3 %) and 55 interviews (38.2 %) were performed and analyzed. Forgetfulness (31.0 %) was the most frequently reported determinant, followed by problems with medicine use (26.8 %), difficulties with medication recognition or preparation (14.1 %). Interviews revealed unsuspected aspects such as patients focusing on on-demand therapy. The PPV was 68.5 % (item-based) respective 67.3 % (participant-based), and adherence-enhancing interventions were developed for all 55 patients. Our results confirm the high data quality, the accuracy and the possibility to develop specific patient-centered interventions with the 15-STARS questionnaire, demonstrating its usefulness in clinical practice with IBD patients. The tool might represent a real practical aid to detect relevant adherence barriers to chronic medicines use in daily practice. Future research could investigate its implementation in community and clinic pharmacy sites and explore its applicability with broader populations.