DIGIPREDICT: physiological, behavioural and environmental predictors of asthma attacks-a prospective observational study using digital markers and artificial intelligence-study protocol.

INTRODUCTION: Asthma attacks are a leading cause of morbidity and mortality but are preventable in most if detected and treated promptly. However, the changes that occur physiologically and behaviourally in the days and weeks preceding an attack are not always recognised, highlighting a potential role for technology. The aim of this study 'DIGIPREDICT' is to identify early digital markers of asthma attacks using sensors embedded in smart devices including watches and inhalers, and leverage health and environmental datasets and artificial intelligence, to develop a risk prediction model to provide an early, personalised warning of asthma attacks. METHODS AND ANALYSIS: A prospective sample of 300 people, 12 years or older, with a history of a moderate or severe asthma attack in the last 12 months will be recruited in New Zealand. Each participant will be given a smart watch (to assess physiological measures such as heart and respiratory rate), peak flow meter, smart inhaler (to assess adherence and inhalation) and a cough monitoring application to use regularly over 6 months with fortnightly questionnaires on asthma control and well-being. Data on sociodemographics, asthma control, lung function, dietary intake, medical history and technology acceptance will be collected at baseline and at 6 months. Asthma attacks will be measured by self-report and confirmed with clinical records. The collected data, along with environmental data on weather and air quality, will be analysed using machine learning to develop a risk prediction model for asthma attacks. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the New Zealand Health and Disability Ethics Committee (2023 FULL 13541). Enrolment began in August 2023. Results will be presented at local, national and international meetings, including dissemination via community groups, and submission for publication to peer-reviewed journals. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12623000764639; Australian New Zealand Clinical Trials Registry.

Cost-Effectiveness and Impact on Health Care Utilization of Interventions to Improve Medication Adherence and Outcomes in Asthma and Chronic Obstructive Pulmonary Disease: A Systematic Literature Review.

BACKGROUND: Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence and persistence are not yet in regular widespread use. Implementation costs are a potential barrier to uptake of such programs. OBJECTIVE: We undertook a systematic literature review and narrative synthesis of studies investigating the cost-effectiveness of treatment adherence-promoting programs or that determined their impact on health care budget directly or via health care resource use (HCRU). METHODS: We identified relevant publications using Medline and PreMEDLINE (PubMed), Embase (Embase.com, Elsevier), and EconLit for publications between January 2000 and July 2021. We also searched clinical trial databases and selected conference proceedings. RESULTS: Of 1,910 potentially relevant articles, 26 met prespecified inclusion criteria and underwent data extraction. Eleven reported a direct assessment of adherence, 15 included economic evaluations, and 17 described HCRU. None included an analysis of biologic medication use. When they were studied, interventions were often found to be highly cost-effective, with dominant incremental cost-effectiveness ratios in some cases. Reductions in direct costs and HCRU (health care visits, hospital admissions, and/or the use of medications, including add-on/reliever treatment and antibiotics) were frequently reported. Reported use of maintenance treatments improved in some studies. Counseling and/or digitally informed programs were used in all cases in which favorable outcomes were observed. CONCLUSIONS: Adherence-promoting interventions are mostly cost-effective and often result in reduced HCRU and associated costs. Multidisciplinary care involving one-to-one advice and digitally enhanced communications appear to offer the greatest benefit.

Factors Associated with Patient Trust in the Pharmacy Team: Findings from a Mixed Method Study Involving Patients with Asthma & COPD.

Purpose: The pharmacy team has been shifting its role from primarily dispensing medications to providing patient-centred pharmaceutical care. Establishing a trust relation between the pharmacy team and their patients is fundamental for this new role. This study aimed to (i) identify the level of trust in the pharmacy team among patients with asthma and/or COPD, (ii) assess whether the level of trust patients have in pharmacists differs from their trust in pharmacy technicians, and (iii) identify factors that contribute to building trust in the pharmacy team. Patients and Methods: First, a focus group with six patients with asthma and/or COPD was conducted to explore which aspects they considered significant for establishing trust in the pharmacy team. Subsequently, these insights were used to develop an online questionnaire. A link to the online questionnaire was distributed among patients with asthma and/or COPD. Data were analysed using exploratory factor analyses to identify underlying constructs for trust. Regression analyses were conducted to evaluate whether these constructs affected trust (scale 1-10) in the pharmacy team. Results: A total of 290 patients completed the questionnaire. On average, they rated their trust in the pharmacy team with a score of 7.4 out of 10 (SD: 1.5), almost identical to their trust in the pharmacist and pharmacy technician. Patient trust in pharmacy teams is influenced by their perception of engagement, expertise in medication-related matters, and effective communication. Conclusion: Trust in the pharmacy team was observed as moderately high, indicating that there is room for improvement. Due to the changing role of the pharmacy team, its members should strive to enhance their patient-centred skills ensuring ongoing efforts to build and maintain trust with patients.

Multidisciplinary tuberculosis care: leveraging the role of hospital pharmacists.

INTRODUCTION: Optimal pharmacological treatment of tuberculosis (TB) requires a multidisciplinary team, yet the hospital pharmacist's role is unclear. We aimed to analyse hospital pharmacist-provided clinical pharmacy services (CPS) implementation in TB care. METHOD: A nationwide survey-based online cross-sectional study was conducted on hospital pharmacists in Indonesia from 1 November 2022 to 22 November 2022. Outcomes were the extent of pharmacists' involvement in multidisciplinary TB care, TB-related CPS provided and views on TB-related CPS. The probability of pharmacists' involvement in multidisciplinary TB teams was assessed using logistic regression. RESULTS: In total, 439 pharmacists (mean age 31.2±6.22 years, 78% female) completed the survey. Thirty-six per cent were part of multidisciplinary TB care, and 23% had TB-related tasks. Adherence monitoring (90%) and drug use evaluation (86%) were the most conducted TB-related CPS. Pharmacists' views on TB-related CPS implementation were generally positive, except for financial incentives. Work experience (OR 1.99, 95% CI 1.09 to 3.61), ever received TB-related training (OR 3.51, 95% CI 2.03 to 6.14) and specific assignments to provide TB-related CPS (OR 8.42, 95% CI 4.99 to 14.59) significantly increased pharmacist involvement in multidisciplinary TB care. CONCLUSION: Around one-third of hospital pharmacists are part of multidisciplinary TB care, with medication adherence and drug use monitoring as primary tasks. Pharmacists' experience, training, assignment to provide TB-related CPS and financial incentives are key elements for further implementation in multidisciplinary TB care. Pharmacists should proactively support current TB care and conduct operational research, sharing data with healthcare peers and fostering a collaborative multidisciplinary TB care team.

Shared decision making and medication adherence in patients with COPD and/or asthma: the ANANAS study.

Background: Medication adherence to inhalation medication is suboptimal in patients with COPD and asthma. Shared decision making (SDM) is proposed as an intervention to improve medication adherence. Despite its wide promotion, evidence of SDM's association with greater medication adherence is scarce. Also, it is unknown to what degree patients presently experience SDM and how it is associated with medication adherence. Objective: To (i) assess the level of SDM and (ii) medication adherence, (iii) explore the relation between SDM and medication adherence and iv) investigate possible underlying mechanisms. Methods: Cross-sectional observational study. A survey was distributed among Dutch patients with COPD and/or asthma using inhaled medication. Medication adherence was measured using the Test of Adherence to Inhalers (TAI-10), and SDM by the 9-item Shared Decision-Making questionnaire (SMD-Q-9). Feeling of competence, relatedness and feeling of autonomy from the Self-Determination Theory (SDT) were considered as possible mechanisms. The primary outcome was adherence. Results: A total of 396 patients with complete information on relevant covariates were included. Mean SDM-Q-9 score was 26.7 (SD 12.1, range 0-45) and complete adherence was 41.2%. The odds ratio for the association of SDM with adherence was 1.01 (95% CI: 0.99, 1.02). This only changed minimally when adjusted for mediators (mediating effect <3%). Conclusion: The patient experienced level of SDM in daily practice and medication adherence have room for improvement. No association between SDM and medication adherence was observed. Factors related to feeling of competence, relatedness and feeling of autonomy did not meaningfully explain this finding.

New terminology of medication adherence enabling and supporting activities: ENABLE terminology.

Introduction: Medication non-adherence negatively affects the effectiveness of evidence-based therapies and sustainability of healthcare systems. Lack of agreed terminology of medication adherence enabling and supporting activities leads to underuse of the available tools. The ENABLE COST Action was aimed at proposing a new terminology for these activities in order to help both scientific research and its clinical application. Methods: Initial discussions within the ENABLE Working Groups allowed for the conceptualization of four interlinked terms related to adherence, i.e., "medication adherence technology", "medication adherence enhancing intervention", "best practice" and "reimbursement". The iterative process of internal discussion was structured around two dedicated international workshops. Moreover, extensive stakeholder consultations have been organised, including an interactive online survey used to assess the level of agreement with, and the clarity of relevant terms and definitions proposed. Results: Detailed analysis of the results of this process allowed for fine-tuning of the items, and finally, for proposing the final set of definitions. Across all the three phases of this process, the definitions were substantially modified to better reflect the concepts, simplify the language, and assure completeness and cohesiveness of terminology. Feedback obtained from the stakeholders helped this process and confirmed that the final terms and definitions were well received by the experts active in the field of medication adherence. Discussion: Covering the gap in the existing terminology, this work proposes a cohesive set of terms and definitions applicable to medication adherence enabling and supporting activities. Promoting evidence-based approach to this field, this terminology may help research, clinical practice and policy.

Adult Severe Asthma Registries: A Global and Growing Inventory.

Aim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests. Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR's Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised. Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting >90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases. Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.

The impact of trust in healthcare and medication, and beliefs about medication on medication adherence in a Dutch medication-using population.

INTRODUCTION: Trust in healthcare and medication, defined as feelings of reassurance and confidence in the healthcare system or medication, may be a key prerequisite before engaging in the use of medication. However, earlier studies have focussed on beliefs about medication rather than trust as predictors of medication adherence. This study therefore aims to simultaneously explore the relationship of trust in healthcare, medication and beliefs about medication, with medication adherence. METHODS: In a cross-sectional study, an online questionnaire was sent out to 1500 members of the Dutch Health Care Consumer Panel of Nivel in November 2018. Respondents were asked to grade their level of trust in healthcare and medication (scale 1-10). The Beliefs About Medicines Questionnaire (BMQ) for general and specific medication beliefs was used to address beliefs, the Medication Adherence Report Scale (MARS-5) to measure medication adherence. Data were analysed using structural equation modelling (SEM) with a backward stepwise approach. Out of 753 people that completed the questionnaire, 407 people used prescription medication and were included in the analyses. RESULTS: A positive association between trust in medication and medication adherence was found (0.044, p < 0.05). BMQ subscales Overuse (-0.083, p < 0.05), Necessity (0.075, p < 0.05) and Concerns (-0.134, p < 0.01) related with medication adherence. BMQ subscale Harm did not relate to medication adherence. CONCLUSION: Trust in medication and beliefs about medication were both individually associated with medication adherence. Healthcare providers should therefore not only focus on patients' medication beliefs, but also on strengthening patients' trust in medication to improve medication adherence.

Implementing an Evidence-Based COPD Hospital Discharge Protocol: A Narrative Review and Expert Recommendations.

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation.

Electronic monitoring with a digital smart spacer to support personalized inhaler use education in patients with asthma: The randomized controlled OUTERSPACE trial.

BACKGROUND: Poor adherence to inhaled medication has been associated with poor outcomes. Smart spacers can monitor inhaler use and technique, yet their feasibility in adults with asthma and their potential benefits are unknown. OBJECTIVE: Assessing the feasibility of undertaking a definitive randomized controlled trial (RCT) of smart spacer-based inhaler education and explore potential clinical benefits in adults with asthma. METHODS: Two-month randomized controlled feasibility OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE (OUTERSPACE) trial comparing personalized smart spacer-based inhaler education versus usual care. Patients were recruited in four Dutch primary care centres. Outcomes were feasibility (inclusion speed, patient acceptance), medication adherence, inhaler technique, clinical effects (lung function, ACQ, FeNO) and usability (System Usability Scale [SUS]). RESULTS: 42 patients were randomized and all completed the study. The feasibility of performing a larger trial focusing on asthma patient education using a smart spacer was demonstrated with all patients included in four months and a participation rate of 86%. In the intervention group, inhalation errors per day decreased by 26.2% while in the usual care group inhalation errors increased by 14.6% (p = 0.021). Adherence decreased slightly in the intervention group as opposed to improvement in the control group (difference 12%, p = 0.028). No changes in lung function, ACQ or FeNO were observed. Usability was deemed high (SUS patients 71, nurses 89). CONCLUSION: This RCT showed that smart spacer-driven education in patients with asthma is feasible and in this short-term study reduced inhaler errors. Longer-term and larger studies are required to assess clinical effects.

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 Assessment of the Validation Status of Health-Economic (AdViSHE) tool. The INCA (Inhaler Compliance Assessment) 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 (ie, regular inhalers) of €7,546 ($7,946) and €10,752 ($11,322), respectively, reflecting cost savings of €3,207 ($3,377) for digital inhalers. Using a 10-year intervention duration and time horizon resulted in cost savings of €26,309 ($27,703) 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 ($2,408) (introduction biosimilars) to €4,581 ($4,824) (increased control, decreased exacerbations). CONCLUSIONS: In patients with difficult-to-treat asthma, digital inhaler-based interventions can be cost-saving in the long-term by optimizing medication adherence and inhaler technique and reducing add-on biologic prescriptions.

Self-reported medication adherence instruments and their applicability in low-middle income countries: a scoping review.

Introduction: Medication non-adherence is an important public health issue, associated with poor clinical and economic outcomes. Globally, self-reported instruments are the most widely used method to assess medication adherence. However, the majority of these were developed in high-income countries (HICs) with a well-established health care system. Their applicability in low- and middle-income countries (LMICs) remains unclear. The objective of this study is to systematically review the applicability of content and use of self-reported adherence instruments in LMICs. Method: A scoping review informed by a literature search in Pubmed, EBSCO, and Cochrane databases was conducted to identify studies assessing medication adherence using self-reported instruments for patients with five common chronic diseases [hypertension, diabetes, dyslipidemia, asthma, or Chronic Obstructive Pulmonary Disease (COPD)] in LMICs up to January 2022 with no constraints on publication year. Two reviewers performed the study selection process, data extraction and outcomes assessment independently. Outcomes focused on LMIC applicability of the self-reported adherence instruments assessed by (i) containing LMIC relevant adherence content; (ii) methodological quality and (iii) fees for use. Findings: We identified 181 studies that used self-reported instruments for assessing medication adherence in LMICs. A total of 32 distinct types of self-reported instruments to assess medication adherence were identified. Of these, 14 self-reported instruments were developed in LMICs, while the remaining ones were adapted from self-reported instruments originally developed in HICs. All self-reported adherence instruments in studies included presented diverse potential challenges regarding their applicability in LMICs, included an underrepresentation of LMIC relevant non-adherence reasons, such as financial issues, use of traditional medicines, religious beliefs, lack of communication with healthcare provider, running out of medicine, and access to care. Almost half of included studies showed that the existing self-reported adherence instruments lack sufficient evidence regarding cross cultural validation and internal consistency. In 70% of the studies, fees applied for using the self-reported instruments in LMICs. Conclusion: There seems insufficient emphasis on applicability and methodological rigor of self-reported medication adherence instruments used in LMICs. This presents an opportunity for developing a self-reported adherence instrument that is suitable to health systems and resources in LMICs. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022302215.

Real-World Dispensing Patterns of Inhalation Medication in Young Adult Asthma: An Inception Cohort Study.

Purpose: The Global Initiative for Asthma (GINA) suggests a step-wise approach for pharmacological treatment of asthma. Valid study of real-world treatment patterns using dispensing databases includes proper measurement of medication adherence. We aim to explore such patterns by applying a time-varying proportion of days covered (tPDC)-based algorithm. Patients and Methods: We designed a retrospective inception cohort study using the University of Groningen IADB.nl community pharmacy dispensing database. Included were 19,184 young adults who initiated asthma medication anywhere between 1994 and 2021, in the Netherlands. Main treatment steps were defined as: 1 - SABA/ICS-formoterol as needed, 2 - low dose ICS, 3 - low dose ICS + LABA or tiotropium, or intermediate dose ICS, 4 - intermediate to high dose ICS + LABA or tiotropium, triple therapy, or high dose ICS, 5 - treatment prescribed by a specialist. Changes in treatment steps were determined using a time-varying proportion of days covered (tPDC)-based algorithm. Individual drug treatment trajectories were visualized over time using a lasagna plot. Results: At initiation, of the 19,184 included individuals, 52%, 7%, 15%, 16%, and 10% started treatment in steps 1 to 5, respectively. The median (IQR) follow-up time was 3 (1-7) years. Median (IQR) number of switches was 1 (0-3). Comparing starting step to last observed step, 37% never switched between treatment steps, 20% of individuals stepped down and 22% stepped up. Conclusion: The low proportion of treatment switches between steps indicates that tailoring of treatment to patients' needs might be suboptimal. The tPDC-based algorithm functions well in translating dispensing data into continuous drug-utilization data, enabling a more granular assessment of treatment patterns among asthma patients.

Implementation of digital home monitoring and management of respiratory disease.

PURPOSE OF REVIEW: Digital respiratory monitoring interventions (e.g. smart inhalers and digital spirometers) can improve clinical outcomes and/or organizational efficiency, and the focus is shifting to sustainable implementation as an approach to delivering respiratory care. This review considers key aspects of the technology infrastructure, discusses the regulatory, financial and policy context that influence implementation, and highlights the over-arching societal themes of equity, trust and communication. RECENT FINDINGS: Technological requirements include developing interoperable and connected systems; establishing stable, wide internet coverage; addressing data accuracy and monitoring adherence; realising the potential of artificial intelligence; and avoiding clinician data overload. Policy challenges include concerns about quality assurance and increasingly complex regulatory systems. Financial barriers include lack of clarity over cost-effectiveness, budget impact and reimbursement. Societal concerns focus on the potential to increase inequities because of poor e-health literacy, deprivation or lack of available infrastructure, the need to understand the implications for patient/professional interactions of shifting care to remote delivery and ensuring confidentiality of personal data. SUMMARY: Understanding and addressing the implementation challenges posed by gaps in policy, regulatory, financial, and technical infrastructure is essential to support delivery of equitable respiratory care that is acceptable to patients and professionals.

Anticipated barriers and facilitators for implementing smart inhalers in asthma medication adherence management.

Smart inhalers are electronic monitoring devices which are promising in increasing medication adherence and maintaining asthma control. A multi-stakeholder capacity and needs assessment is recommended prior to implementation in healthcare systems. This study aimed to explore perceptions of stakeholders and to identify anticipated facilitators and barriers associated with the implementation of smart digital inhalers in the Dutch healthcare system. Data were collected through focus group discussions with female patients with asthma (n = 9) and healthcare professionals (n = 7) and through individual semi-structured interviews with policy makers (n = 4) and smart inhaler developers (n = 4). Data were analysed using the Framework method. Five themes were identified: (i) perceived benefits, (ii) usability, (iii) feasibility, (iv) payment and reimbursement, and (v) data safety and ownership. In total, 14 barriers and 32 facilitators were found among all stakeholders. The results of this study could contribute to the design of a tailored implementation strategy for smart inhalers in daily practice.