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

Empathy Gaps Between Helpers and Help-Seekers: Implications for Cooperation

Help-seekers and potential helpers often experience an “empathy gap” – an inability to understand each other’s unique perspectives. Both parties are concerned about their reputation, self-esteem, and relationships, but these concerns differ in ways that lead to misinterpretation of the other party’s actions, and, in turn, missed opportunities for cooperation. In this article, we review research that describes the role-specific concerns of helpers and help-seekers. We then review studies of emotional perspective-taking, which can help explain why help-seekers and helpers often experience empathy gaps. We go on to discuss recent work that illustrates the consequences of empathy gaps between helpers and help-seekers—social prediction errors that prevent helping and misguided intentions that can lead to unhelpful help. Finally, we discuss some promising directions for future research

Better use of inhaled medication in asthma and COPD through training, preparation and counselling:the On TRACk study protocol for a cluster randomised controlled trial

Introduction About 70% of patients with asthma and/or chronic obstructive pulmonary disease (COPD) use their inhaled medication incorrectly, leading to reduced disease control, higher healthcare use and costs. Adequate guidance from the pharmacy team from first dispense onwards can benefit patients in the long run. We propose an intervention ('On TRACk') to improve medication adherence and inhaler technique of adult patients with asthma and/or COPD. This intervention focuses on training pharmacy technicians (PTs) in patient-centred communication and inhalation instruction skills. In addition, patients are actively involved in refill consultations at the pharmacy. The aim of this study is to improve inhaler technique and better inhaled medication adherence among patients with asthma and/or COPD. This paper describes the study protocol. Methods and analysis A cluster randomised controlled trial (RCT) with an intervention and control group of 15 pharmacies each will be conducted. Per intervention pharmacy, two PTs will be trained online. Each PT will include five patients who will prepare their second and third dispense counselling sessions by selecting three topics they wish to discuss. Pharmacies in the control cluster provide usual care. In total, 300 patients (150 per group) will be included. Up to 12 months after inclusion, patients complete 3-monthly follow-up questionnaires. Both a process evaluation and a cost-effectiveness analysis will be performed alongside the trial. Trial effectiveness on the patient level will be evaluated after the 12-month follow-up period. Patient data will be collected through questionnaires and pharmacy refill data. Patients' inhaler technique will be visually assessed by PTs. Semistructured interviews with PTs and patients will be conducted regarding implementation and fidelity. Direct and indirect health costs will be collected to assess cost-effectiveness. The primary outcome is adherence to inhalation maintenance medication measured with pharmacy refill data. Secondary outcomes are inhaler technique, persistence, patients' attitudes towards medication, self-efficacy in medication use and communication with their PTs. Ethics and dissemination The study was approved by the Vrije Universiteit Amsterdam Ethics Committee (number: 2020.358). Results will be presented at (inter)national conferences and published in peer-reviewed journals. If proven to be (cost-)effective, the intervention should be considered for reimbursement and implementation in Dutch community pharmacies

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

A novel doxorubicin-glucuronide prodrug DOX-GA3 for tumour-selective chemotherapy: distribution and efficacy in experimental human ovarian cancer

The doxorubicin (DOX) prodrug N -[4-doxorubicin- N -carbonyl (oxymethyl) phenyl] O -β-glucuronyl carbamate (DOX-GA3) was synthesised for specific activation by human β-glucuronidase, which is released in necrotic areas of tumour lesions. This novel prodrug was completely activated to the parent drug by human β-glucuronidase with V max= 25.0 μmol min–1mg–1and K m= 1100 μM. The pharmacokinetics and distribution of DOX-GA3 in nude mice bearing human ovarian cancer xenografts (OVCAR-3) were determined and compared with DOX. Administration of DOX at 8 mg kg–1i.v. (maximum tolerated dose, MTD) to OVCAR-3-bearing mice resulted in a peak plasma concentration of the drug of 16.4 μM (t = 1 min). A 7.6-times lower peak plasma concentration of DOX was measured after injection of DOX-GA3 at 250 mg kg–1i.v. (50% of MTD). In normal tissues the prodrug showed peak DOX concentrations that were up to 5-fold (heart) lower than those found after DOX administration. DOX-GA3 activation by β-glucuronidase in the tumour yielded an almost 5-fold higher DOX peak concentration of 9.57 nmol g–1(P< 0.05) than the peak concentration of only 2.14 nmol g–1observed after DOX. As a consequence, the area under the curve of DOX calculated in tumour tissue after DOX-GA3 (13.1 μmol min–1g–1) was 10-fold higher than after DOX (1.31 μmol min–1g–1). The anti-tumour effects of DOX-GA3 and DOX were compared at equitoxic doses in OVCAR-3 xenografts at a mean tumour size of 125 mm3. The prodrug given i.v. at 500 mg kg–1weekly × 2 resulted in a maximum tumour growth inhibition of 87%, while the standard treatment with DOX at a dose of 8 mg kg–1i.v. weekly × 2 resulted in a maximum tumour growth inhibition of only 56%. Treatment with DOX-GA3 was also given to mice with larger tumours containing more necrosis. For tumours with a mean size of 400 mm3the specific growth delay by DOX-GA3 increased from 2.7 to 3.9. Our data indicate that DOX-GA3 is more effective than DOX and suggest that the prodrug will be specifically advantageous for treatment of advanced disease. © 2001 Cancer Research Campaign http://www.bjcancer.co

Strategies for the prevention, diagnosis and treatment of COPD in low- and middle- income countries:the importance of primary care

INTRODUCTION: Low- and middle-income countries (LMICs) bear a high proportion of the global morbidity and mortality caused by COPD. Increased exposure to risk factors throughout life (e.g. malnutrition, indoor and outdoor air pollution, smoking) is associated with higher COPD prevalence in LMICs and the lack of treatment availability increases avoidable harm. AREAS COVERED: This review covers the epidemiology and burden of COPD in LMICs, and challenges and recommendations related to healthcare systems, prevention, diagnosis and treatment. Main challenges are related to under-resourced healthcare systems (such as limited availability of spirometry, rehabilitation and medicines). Lack of policy and practical local guidelines on COPD diagnosis and management further contribute to the low diagnostic and treatment rates. In the absence of, or limited number of respiratory specialists, primary care practitioners (general practitioners, nurses, pharmacists, physiotherapists and community health workers) play an even more pivotal role in COPD management in LMICs. EXPERT OPINION: Raising awareness on COPD, educating healthcare workers, patients and communities on cost-effective preventive measures as well as improving availability, affordability and proper use of diagnostic and pharmacological and non-pharmacologic treatment in primary care are the key interventions needed to improve COPD prevention, diagnosis and care in LMICs

Long-term cost-effectiveness of digital inhaler adherence technologies in difficult-to-treat asthma

BACKGROUND: Digital inhalers can monitor inhaler usage, support difficult-to-treat asthma management and inform step-up treatment decisions yet their economic value is unknown, hampering wide-scale implementation.OBJECTIVE: We aimed to assess the long-term cost-effectiveness of digital inhaler-based medication adherence management in difficult-to-treat asthma.METHODS: A model-based cost-utility analysis was performed. The Markov model structure was determined by biological and clinical understanding of asthma and was further informed by guideline-based assessment of model development. Internal and external validation was performed using the AdViSHE tool. The INCA Sun randomized clinical trial data were incorporated into the model to evaluate the cost-effectiveness of digital inhalers. Several long-term clinical case scenarios were assessed (reduced number of exacerbations, increased asthma control, introduction of biosimilars [25% price-cut on biologics]).RESULTS: The long-term modelled cost-effectiveness based on a societal perspective indicated 1-year per-patient costs for digital inhalers and usual care (i.e., regular inhalers) of €7,546 and €10,752, respectively, reflecting cost savings of €3,207 for digital inhalers. Using a 10-year intervention duration and time horizon resulted incost savings of €26,309 for digital inhalers. In the first year, add-on biologic therapies accounted for 69% of the total costs in the usual care group, and for 49% in the digital inhaler group. Scenario analyses indicated consistent cost savings ranging from €2,287 (introduction biosimilars) to €4,581 (increased control, decreased exacerbations).CONCLUSION: In patients with difficult-to-treat asthma, digital inhaler based interventions can be cost-saving on the long-term by optimizing medication adherence and inhaler technique and reducing add-on biologic prescriptions.</p