User Acceptability and Technical Robustness Evaluation of a Novel Smart Pill Bottle Prototype Designed to Support Medication Adherence

Purpose: Smart medication adherence monitoring devices can provide objective and granular drug utilization data and help patients engaging with their treatment. In this proof-of-concept study, the acceptability and technical robustness of a novel smart pill bottle prototype (SPBP) were assessed in order to allow further optimization. Methods: The SPBP is an app-controlled automatic dispense system, capturing real-time data on a web-based platform, which sends text reminders and measures storage conditions. A heterogeneous group of ten volunteers was asked to dispense placebo capsules with the SPBP and to follow a predefined dosing schedule for a trial period of 2 weeks. Afterwards, a questionnaire was filled out during a short interview. Primary outcome was dispense adherence as measured by the bottle. Other study outcomes included system acceptability (System Usability Scale [SUS]), self-reported adherence (MARS) and technical robustness of the bottle’s mechanics (electronic pill dispenser) and sensors (bottle temperature). Results: The overall dispense adherence rate as measured by the SPBP was 88%. All participants completed the study and four participants had an adherence rate of 100% during the study. The dispense adherence rates corresponded well with participants’ self-reported adherence with an average MARS total score of 23.6 (out of 25). Participants judged the system easy to use, with a mean SUS score of 79.3 (range: 57.5– 97.5). The overall mean temperature difference between the bottle sensor and calibrated external sensor was − 0.82°C (range: − 1.37°C to − 0.21°C). Conclusion: The SPBP was well accepted and this study provides data for further optimization and follow-up studies. Smart adherence technologies such as these may change the way healthcare professionals, trialists and patients manage medication adherence

Ultra-high throughput dual channel liquid chromatography with tandem mass spectrometry for quantification of four immunosuppressants in whole blood for therapeutic drug monitoring

Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the golden standard for immunosuppressants analyses, where optimising throughput by parallel chromatography can reduce costs and turnaround time. We aimed to double our system throughput using a dual LC-MS/MS setup. Therefore, two independent UPLC systems were hyphenated to one triple quadrupole MS, with staggered injections from one autosampler on alternating columns. The method simultaneously measured the analytes tacrolimus, sirolimus, everolimus, and cyclosporin A in whole blood using isotope dilution, with a run time of 1.5 min. Using the dual LC-MS/MS system, net run-to-run time improved from 2.3 to 0.98 min per injection, where throughput increased from 26 to 61 injections per hour. For Performance Qualification, 1101 clinical samples were measured on the dual LC-MS/MS system in addition to the standard system, during a period of one month, and the results were compared using Passing Bablok regression and Bland Altman analysis. There was excellent agreement for all four analytes, with regression slopes of 0.98-1.02x and intercepts of -0.11-0.88 µg/L. Minor bias was demonstrated between the systems with mean differences from -0.93 to 1.43%. In conclusion, the throughput was doubled and idle MS time was reduced with good agreement to the standard system. Currently, the method is applied for clinical routine with frequent peak intensities of &gt;180 injections per day.</p

"Never Regard Yourself As Already So Thoroughly Informed": The Withdrawal of its Invitation to Rodney Syme to Address its 2015 Congress by the Royal Australasian College of Physicians

In 1628, William Harvey presented his revolutionary theory of the circulation to ears at the Royal College of Physicians that had been deafened by the unquestionable authority of Galen’s teachings, from one and a half millennia in the past. Harvey’s theory was initially rejected, despite his faith in his colleagues being eager for truth and knowledge, and never regarding themselves as so well informed that they would not welcome “further information”. Recently Rodney Syme, the retired Melbourne urologist who for a long time has agitated for the legalisation of assisted dying, and also challenged the authorities to apply the current law in response to his admitted assistance to a number of individuals, was invited to address the 2015 Congress of the Royal Australasian College of Physicians. At the eleventh hour, the invitation to speak was withdrawn. In this column, we trace the course of events leading to this withdrawal of the invitation, and describe some of the correspondence to and from the College in response to the withdrawal. We draw parallels between the experiences of Harvey and Syme, and point to lessons to be learnt from the recent episode of apparent unwillingness, on the part of an institution that seeks to present itself as outward-looking, progressive and socially aware, to fulfil this promise in the increasingly important area of the end-of-life

Clinical Value of Emerging Bioanalytical Methods for Drug Measurements:A Scoping Review of Their Applicability for Medication Adherence and Therapeutic Drug Monitoring

INTRODUCTION: Direct quantification of drug concentrations allows for medication adherence monitoring (MAM) and therapeutic drug monitoring (TDM). Multiple less invasive methods have been developed in recent years: dried blood spots (DBS), saliva, and hair analyses. AIM: To provide an overview of emerging drug quantification methods for MAM and TDM, focusing on the clinical validation of methods in patients prescribed chronic drug therapies. METHODS: A scoping review was performed using a systematic search in three electronic databases covering the period 2000-2020. Screening and inclusion were performed by two independent reviewers in Rayyan. Data from the articles were aggregated in a REDCap database. The main outcome was clinical validity of methods based on study sample size, means of cross-validation, and method description. Outcomes were reported by matrix, therapeutic area and application (MAM and/or TDM). RESULTS: A total of 4590 studies were identified and 175 articles were finally included; 57 on DBS, 66 on saliva and 55 on hair analyses. Most reports were in the fields of neurological diseases (37%), infectious diseases (31%), and transplantation (14%). An overview of clinical validation was generated of all measured drugs. A total of 62 drugs assays were applied for MAM and 131 for TDM. CONCLUSION: MAM and TDM are increasingly possible without traditional invasive blood sampling: the strengths and limitations of DBS, saliva, and hair differ, but all have potential for valid and more convenient drug monitoring. To strengthen the quality and comparability of future evidence, standardisation of the clinical validation of the methods is recommended

Photocatalysed (Meth)acrylate Polymerization by (Antimony-Doped) Tin Oxide Nanoparticles and Photoconduction of Their Crosslinked Polymer Nanoparticle Composites

In the absence of another (photo)radical initiator Sb:SnO 2 nanoparticles (0 ≤ Sb ≤ 13 at %) photocatalyze during irradiation with UV light the radical polymerization of (meth)acrylate monomers. When cured hard and transparent (&gt;98%) films with a low haze (&lt;1%) are required, when these particles are grafted in advance with 3-methacryloxypropyltrimethoxysilane (MPS) and doped with Sb. Public knowledge about the photocatalytic properties of Sb:SnO 2 nanoparticles is hardly available. Therefore, the influence of particle concentration, surface groups, and Sb doping on the rate of C=C (meth)acrylate bond polymerization was determined with aid of real-time FT-IR spectroscopy. By using a wavelength of irradiation with a narrow bandgab (315 ± 5 nm) the influence of these factors on the quantum yield (Φ) and on polymer and particle network structure formation was determined. It is shown that Sb doping and MPS grafting of the particles lowers Φ. MPS grafting of the particles also influences the structure of the polymer network formed. Without Sb doping of these particles unwanted, photocatalytic side reactions occur. It is also shown that cured MPS-Sb:SnO 2 /(meth)acrylate nanocomposites have photoconduction properties even when the particle concentration is as low as 1 vol.%. The results suggest that the Sb:SnO 2 (Sb &gt; 0 at %) nanoparticles can be attractive fillers for other photocatalytic applications photorefractive materials, optoelectronic devices and sensors

Digital spacer data driven COPD inhaler adherence education:The OUTERSPACE proof-of-concept study

Pressurized metered dose inhalers are recommended to be used in combination with spacers, yet inhaler technique and adherence are poor. A novel digital "smart" spacer can record spacer use and technique errors and could facilitate personalized education. In this proof-of-concept study, we assessed the usability of the digital spacer and explored its effects on inhaler technique, adherence, long-term systemic drug exposure and clinical outcomes in COPD. Usability was deemed high. One month after personalized digital spacer inhaler education, the mean number of errors per patient per day decreased with 36%, from 6.40 errors/day to 4.07 errors/day (p = 0.038). Drug exposure was confirmed by bioanalytical scalp hair analysis of formoterol. No significant change in clinical outcomes was observed. This study demonstrates the digital spacer's potential value in inhaler education, but larger, longer-term studies are required

Enantiomer-specific pharmacokinetics of D,L-3-hydroxybutyrate:Implications for the treatment of multiple acyl-CoA dehydrogenase deficiency

D,L-3-hydroxybutyrate (D,L-3-HB, a ketone body) treatment has been described in several inborn errors of metabolism, including multiple acyl-CoA dehydrogenase deficiency (MADD; glutaric aciduria type II). We aimed to improve the understanding of enantiomer-specific pharmacokinetics of D,L-3-HB. Using UPLC-MS/MS, we analyzed D-3-HB and L-3-HB concentrations in blood samples from three MADD patients, and blood and tissue samples from healthy rats, upon D,L-3-HB salt administration (patients: 736-1123 mg/kg/day; rats: 1579-6317 mg/kg/day of salt-free D,L-3-HB). D,L-3-HB administration caused substantially higher L-3-HB concentrations than D-3-HB. In MADD patients, both enantiomers peaked at 30 to 60 minutes, and approached baseline after 3 hours. In rats, D,L-3-HB administration significantly increased Cmax and AUC of D-3-HB in a dose-dependent manner (controls vs ascending dose groups for Cmax: 0.10 vs 0.30-0.35-0.50 mmol/L, and AUC: 14 vs 58-71-106 minutes*mmol/L), whereas for L-3-HB the increases were significant compared to controls, but not dose proportional (Cmax: 0.01 vs 1.88-1.92-1.98 mmol/L, and AUC: 1 vs 380-454-479 minutes*mmol/L). L-3-HB concentrations increased extensively in brain, heart, liver, and muscle, whereas the most profound rise in D-3-HB was observed in heart and liver. Our study provides important knowledge on the absorption and distribution upon oral D,L-3-HB. The enantiomer-specific pharmacokinetics implies differential metabolic fates of D-3-HB and L-3-HB