|
1
|
Fan Z, Han Y, Sun G, Dong Z. Immunosuppressant adherence after heart transplantation: a review on detection, prevention, and intervention strategies in a multidisciplinary. Front Cardiovasc Med 2025; 12:1558082. [PMID: 40129763 PMCID: PMC11931065 DOI: 10.3389/fcvm.2025.1558082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/13/2025] [Indexed: 03/26/2025] Open
Abstract
Heart transplantation is an effective treatment for end-stage heart disease, and postoperative patients' medication adherence is crucial for transplantation outcomes and long-term survival. By reviewing a large amount of related literature, this review summarizes the current status, evaluation methods, influencing factors, and intervention strategies of medication adherence after heart transplantation, emphasizes the important role of multidisciplinary teams in improving medication adherence, and discusses the importance of transplantation multidisciplinary teams and holistic management. By integrating the research results from various fields such as medicine, pharmacy, psychology, and sociology, it provides a more comprehensive theoretical support and practical guidance for improving medication adherence in heart transplant patients.
Collapse
Affiliation(s)
- Ziying Fan
- Institute of Pharmaceutical Preparations, Department of Pharmacy, Zhejiang University of Technology, Hangzhou, China
| | - Yong Han
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guojun Sun
- Institute of Pharmaceutical Preparations, Department of Pharmacy, Zhejiang University of Technology, Hangzhou, China
| | - Zuojun Dong
- Institute of Pharmaceutical Preparations, Department of Pharmacy, Zhejiang University of Technology, Hangzhou, China
| |
Collapse
|
|
2
|
Corr M, Walker A, Maxwell AP, McKay GJ. Non-adherence to immunosuppressive medications in kidney transplant recipients- a systematic scoping review. Transplant Rev (Orlando) 2025; 39:100900. [PMID: 39642406 DOI: 10.1016/j.trre.2024.100900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 11/29/2024] [Accepted: 12/01/2024] [Indexed: 12/08/2024]
Abstract
BACKGROUND Rejection and graft failure remain common in kidney transplant recipients. Non-adherence to immunosuppressive medications is considered a major contributary factor to reduced long-term graft survival, particularly in younger people. Improvements in clinical practice based on adherence studies has been minimal. METHODS Joanna Briggs' Institute Methodology was used. MedlineALL, Embase, Web of Science Core Collection and Scopus databases were searched from January 2000 through to December 2023. Abstract and full text reviews were undertaken independently by two reviewers. Data was collated using a pre-designed extraction tool. RESULTS 359 articles met the inclusion criteria. Non-adherence was commonly defined using self-reported questionnaires or pharmacy re-fill rates. Prevalence of non-adherence varied widely. There was little correlation between method of measurement and reported rates of non-adherence. Despite younger age being identified as a risk factor for non-adherence, pooled reported prevalence did not differ significantly in studies reporting prevalence in children, adolescents, or young adults vs. older adults (36.0 % vs. 34.0 %). Interventional studies to detect or improve adherence are highly heterogenous, often report small effects and are limited by the lack of gold-standard methods to measure adherence. DISCUSSION This scoping review outlines the complexities of non-adherence to immunosuppressive medications among kidney transplant recipients, highlighting significant variability in adherence definitions, measurements, and intervention efficacy. Reported non-adherence rates vary widely (2-89 %), underscoring the need for standardisation of the definition of non-adherence in research. Findings suggest that non-adherence to immunosuppressive medication is driven by a mix of demographic, psychosocial, and transplant-specific factors. Future research should prioritise standardised definitions of adherence, validated tools to measure adherence, and focus on clinically significant outcomes in non-adherent populations to develop meaningful, impactful interventions for long-term patient benefit.
Collapse
Affiliation(s)
- Michael Corr
- Centre for Public Health- Queen's University Belfast, Belfast. UK.
| | | | | | - Gareth J McKay
- Centre for Public Health- Queen's University Belfast, Belfast. UK
| |
Collapse
|
|
3
|
Gackowski M, Jasińska-Stroschein M, Osmałek T, Waszyk-Nowaczyk M. Innovative Approaches to Enhance and Measure Medication Adherence in Chronic Disease Management: A Review. Med Sci Monit 2024; 30:e944605. [PMID: 39012851 DOI: 10.12659/msm.944605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2024] Open
Abstract
Medication non-adherence is a problem that affects up to 50% of patients with chronic diseases. The result is a failure to achieve therapeutic goals and an increased burden on the healthcare system. It is, therefore, highly appropriate to develop models to assess patient adherence to prescribed therapy. To date, there are many methods for doing this. However, several tools have been developed that subjectively or objectively, directly or indirectly, assess the level of patient adherence. Electronic medication packaging devices are among the most rapidly evolving methods of measuring adherence. Other emerging technologies include the use of artificial intelligence algorithms and ingestible biosensors. The former is being used to create applications for mobile phones and laptops. The latter appears to be the least susceptible to the risk of overestimating adherence but remains very expensive. Here, we present recent developments in measuring patient adherence, and provide details of achievements in objective methods for assessing adherence, such as electronic monitoring devices, video-observed therapy, and ingestible biosensors. A dedicated section on using artificial intelligence and machine learning in adherence measurement and reviewing questionnaires and scales used in specific diseases is also included. Methods are discussed along with their advantages and potential limitations. This article aimed to review current measures and future initiatives to improve patient medication adherence.
Collapse
Affiliation(s)
- Michał Gackowski
- Chair and Department of Pharmaceutical Technology, Poznań University of Medical Sciences, Poznań, Poland
| | | | - Tomasz Osmałek
- Chair and Department of Pharmaceutical Technology, Poznań University of Medical Sciences, Poznań, Poland
| | - Magdalena Waszyk-Nowaczyk
- Pharmacy Practice and Pharmaceutical Care Division, Chair and Department of Pharmaceutical Technology, Poznań University of Medical Sciences, Poznań, Poland
| |
Collapse
|
|
4
|
Thwaites PA, Yao CK, Halmos EP, Muir JG, Burgell RE, Berean KJ, Kalantar‐zadeh K, Gibson PR. Review article: Current status and future directions of ingestible electronic devices in gastroenterology. Aliment Pharmacol Ther 2024; 59:459-474. [PMID: 38168738 PMCID: PMC10952964 DOI: 10.1111/apt.17844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/15/2023] [Accepted: 12/13/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Advances in microelectronics have greatly expanded the capabilities and clinical potential of ingestible electronic devices. AIM To provide an overview of the structure and potential impact of ingestible devices in development that are relevant to the gastrointestinal tract. METHODS We performed a detailed literature search to inform this narrative review. RESULTS Technical success of ingestible electronic devices relies on the ability to miniaturise the microelectronic circuits, sensors and components for interventional functions while being sufficiently powered to fulfil the intended function. These devices offer the advantages of being convenient and minimally invasive, with real-time assessment often possible and with minimal interference to normal physiology. Safety has not been a limitation, but defining and controlling device location in the gastrointestinal tract remains challenging. The success of capsule endoscopy has buoyed enthusiasm for the concepts, but few ingestible devices have reached clinical practice to date, partly due to the novelty of the information they provide and also due to the challenges of adding this novel technology to established clinical paradigms. Nonetheless, with ongoing technological advancement and as understanding of their potential impact emerges, acceptance of such technology will grow. These devices have the capacity to provide unique insight into gastrointestinal physiology and pathophysiology. Interventional functions, such as sampling of tissue or luminal contents and delivery of therapies, may further enhance their ability to sharpen gastroenterological diagnoses, monitoring and treatment. CONCLUSIONS The development of miniaturised ingestible microelectronic-based devices offers exciting prospects for enhancing gastroenterological research and the delivery of personalised, point-of-care medicine.
Collapse
Affiliation(s)
- Phoebe A. Thwaites
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Chu K. Yao
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Emma P. Halmos
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Jane G. Muir
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Rebecca E. Burgell
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| | - Kyle J. Berean
- Atmo BiosciencesMelbourneVictoriaAustralia
- School of Engineering, RMIT UniversityMelbourneVictoriaAustralia
| | - Kourosh Kalantar‐zadeh
- Faculty of Engineering, School of Chemical and Biomolecular EngineeringThe University of SydneyCamperdownNew South WalesAustralia
| | - Peter R. Gibson
- Department of Gastroenterology, Central Clinical SchoolMonash University and Alfred HealthMelbourneVictoriaAustralia
| |
Collapse
|
|
5
|
Wingfield LR, Salaun A, Khan A, Webb H, Zhu T, Knight S. Clinical Decision Support Systems Used in Transplantation: Are They Tools for Success or an Unnecessary Gadget? A Systematic Review. Transplantation 2024; 108:72-99. [PMID: 37143191 DOI: 10.1097/tp.0000000000004627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Although clinical decision support systems (CDSSs) have been used since the 1970s for a wide variety of clinical tasks including optimization of medication orders, improved documentation, and improved patient adherence, to date, no systematic reviews have been carried out to assess their utilization and efficacy in transplant medicine. The aim of this study is to systematically review studies that utilized a CDSS and assess impact on patient outcomes. A total of 48 articles were identified as meeting the author-derived inclusion criteria, including tools for posttransplant monitoring, pretransplant risk assessment, waiting list management, immunosuppressant management, and interpretation of histopathology. Studies included 15 984 transplant recipients. Tools aimed at helping with transplant patient immunosuppressant management were the most common (19 studies). Thirty-four studies (85%) found an overall clinical benefit following the implementation of a CDSS in clinical practice. Although there are limitations to the existing literature, current evidence suggests that implementing CDSS in transplant clinical settings may improve outcomes for patients. Limited evidence was found using more advanced technologies such as artificial intelligence in transplantation, and future studies should investigate the role of these emerging technologies.
Collapse
Affiliation(s)
- Laura R Wingfield
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Achille Salaun
- Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Aparajita Khan
- Department of Neurosurgery, Stanford University, Stanford, CA
| | - Helena Webb
- School of Computer Science, University of Nottingham, Nottingham, United Kingdom
| | - Tingting Zhu
- Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Simon Knight
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| |
Collapse
|
|
6
|
Vrijens B, Pironet A, Tousset E. The Importance of Assessing Drug Exposure and Medication Adherence in Evaluating Investigational Medications: Ensuring Validity and Reliability of Clinical Trial Results. Pharmaceut Med 2024; 38:9-18. [PMID: 38135800 PMCID: PMC10824809 DOI: 10.1007/s40290-023-00503-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2023] [Indexed: 12/24/2023]
Abstract
The objective of this current opinion paper is to draw global attention to medication adherence, emphasizing its crucial role in drug trials. Frequently, trialists lean on traditional approaches to assess medication adherence, which, while comfortable, may only reveal what trialists desire rather than offering the essential insights needed for informed decision making in drug development. Understanding drug exposure and medication adherence is paramount when evaluating the effectiveness and safety of investigational medications. Without a comprehensive understanding of how patients adhere to their prescribed treatment regimens, the integrity and dependability of clinical trial results can be compromised. This paper emphasizes the need for measures that accurately and reliably assess medication intake behaviors, enabling the differentiation between minor dosing errors and significant deviations that may impact the drug's efficacy and safety. Accurate knowledge of drug exposure empowers researchers to make informed decisions, identify potential confounding factors, and appropriately interpret study outcomes, ultimately ensuring the validity and reliability of the research findings. By prioritizing drug exposure assessment and medication adherence measurement, clinical trials can enhance their scientific rigor, contribute to more accurate evaluations of investigational medications, and ultimately speed up the development process.
Collapse
Affiliation(s)
- Bernard Vrijens
- AARDEX Group, 15/1, Rue Bois St Jean, 4102, Liège, Belgium.
- Department of Public Health, Liège University, Liège, Belgium.
| | | | - Eric Tousset
- AARDEX Group, 15/1, Rue Bois St Jean, 4102, Liège, Belgium
| |
Collapse
|
|
7
|
Pauklin P, Marandi T, Kals M, Ainla T, Martinson K, Eha J, Kampus P. Lifeday coverage of oral anticoagulants and one-year relative survival in patients with atrial fibrillation: a population-based study in Estonia. BMC Cardiovasc Disord 2023; 23:398. [PMID: 37568101 PMCID: PMC10422845 DOI: 10.1186/s12872-023-03415-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 07/24/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Routine oral anticoagulation (OAC) is recommended for almost all high-risk patients with atrial fibrillation, yet registries show that OACs are still underused. Our aim was to study the lifeday coverage (LDC) of OAC prescriptions and its relationship with one-year mortality rates of AF patients aged ≥ 65 in Estonia for the years 2019 and 2020. METHODS Medical data for AF patients aged ≥ 65 years from 2018 and alive as of 01.01.2019 (cohort I) and new AF documentation from 2019 and alive as of 01.01.2020 (cohort II) was obtained from the Health Insurance Fund's electronic database. The data was linked to the nationwide Estonian Medical Prescription Centre's database of prescribed OACs. For LDC analysis, daily doses of guideline-recommended OACs were used. The patients were categorized into three LDC groups: 0%, 1-79%, and ≥ 80%. The data was linked to the Estonian Causes of Death Registry to establish the date of death and mortality rate for the whole Estonian population aged ≥ 65. RESULTS There were 34,018 patients in cohort I and 9,175 patients with new AF documentation (cohort II), previously not included in cohort I. Of the patients, 77.7% and 68.6% had at least one prescription of OAC in cohorts I and II respectively. 57.4% in cohort I and 44.5% in cohort II had an LDC of ≥ 80%. The relative survival estimates at 1 year for LDC lifeday coverage groups 0%, 1-79%, and ≥ 80% were 91.2%, 98.2%, and 98.5% (cohort I), and 91.9%, 95.2%, and 97.6% (cohort II), respectively. CONCLUSIONS Despite clear indications for OAC use, LDC is still insufficient and anticoagulation is underused for stroke prevention in Estonia. Further education of the medical community and patients is needed to achieve higher lifeday coverage of prescribed OACs.
Collapse
Affiliation(s)
- Priit Pauklin
- Department of Cardiology, Institute of Clinical Medicine, University of Tartu, 8 Puusepa Street, 50406, Tartu, Estonia.
- Heart Clinic, Tartu University Hospital, 8 Puusepa Street, 50406, Tartu, Estonia.
| | - Toomas Marandi
- Department of Cardiology, Institute of Clinical Medicine, University of Tartu, 8 Puusepa Street, 50406, Tartu, Estonia
- Centre of Cardiology, North Estonia Medical Centre, 19 Sütiste Street, 13419, Tallinn, Estonia
| | - Mart Kals
- Estonian Genome Center, Institute of Genomics, University of Tartu, 23b Riia Street, 51010, Tartu, Estonia
| | - Tiia Ainla
- Department of Cardiology, Institute of Clinical Medicine, University of Tartu, 8 Puusepa Street, 50406, Tartu, Estonia
- Centre of Cardiology, North Estonia Medical Centre, 19 Sütiste Street, 13419, Tallinn, Estonia
| | - Katrin Martinson
- Linnamõisa Family Medicine Center, 16 Koskla Street, 10615, Tallinn, Estonia
| | - Jaan Eha
- Department of Cardiology, Institute of Clinical Medicine, University of Tartu, 8 Puusepa Street, 50406, Tartu, Estonia
- Heart Clinic, Tartu University Hospital, 8 Puusepa Street, 50406, Tartu, Estonia
| | - Priit Kampus
- Department of Cardiology, Institute of Clinical Medicine, University of Tartu, 8 Puusepa Street, 50406, Tartu, Estonia
- Centre of Cardiology, North Estonia Medical Centre, 19 Sütiste Street, 13419, Tallinn, Estonia
| |
Collapse
|
|
8
|
Stewart SJF, Moon Z, Horne R. Medication nonadherence: health impact, prevalence, correlates and interventions. Psychol Health 2023; 38:726-765. [PMID: 36448201 DOI: 10.1080/08870446.2022.2144923] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 11/01/2022] [Accepted: 11/02/2022] [Indexed: 12/05/2022]
Abstract
Nonadherence to medicines is a global problem compromising health and economic outcomes for individuals and society. This article outlines how adherence is defined and measured, and examines the impact, prevalence and determinants of nonadherence. It also discusses how a psychosocial perspective can inform the development of interventions to optimise adherence and presents a series of recommendations for future research to overcome common limitations associated with the medication nonadherence literature. Nonadherence is best understood in terms of the interactions between an individual and a specific disease/treatment, within a social and environmental context. Adherence is a product of motivation and ability. Motivation comprises conscious decision-making processes but also from more 'instinctive', intuitive and habitual processes. Ability comprises the physical and psychological skills needed to adhere. Both motivation and ability are influenced by environmental and social factors which influence the opportunity to adhere as well as triggers or cues to actions which may be internal (e.g. experiencing symptoms) or external (e.g. receiving a reminder). Systematic reviews of adherence interventions show that effective solutions are elusive, partly because few have a strong theoretical basis. Adherence support targeted at the level of individuals will be more effective if it is tailored to address the specific perceptions (e.g. beliefs about illness and treatment) and practicalities (e.g. capability and resources) influencing individuals' motivation and ability to adhere.
Collapse
Affiliation(s)
- Sarah-Jane F Stewart
- Centre for Behavioural Medicine, Research Department of Practice and Policy, UCL School of Pharmacy, University College London, London, UK
| | - Zoe Moon
- Centre for Behavioural Medicine, Research Department of Practice and Policy, UCL School of Pharmacy, University College London, London, UK
| | - Rob Horne
- Centre for Behavioural Medicine, Research Department of Practice and Policy, UCL School of Pharmacy, University College London, London, UK
| |
Collapse
|
|
9
|
Erras A, Shahrvini B, Weinreb RN, Baxter SL. Review of glaucoma medication adherence monitoring in the digital health era. Br J Ophthalmol 2023; 107:153-159. [PMID: 33858837 PMCID: PMC8517037 DOI: 10.1136/bjophthalmol-2020-317918] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 02/19/2021] [Accepted: 04/05/2021] [Indexed: 02/03/2023]
Abstract
Current glaucoma treatments aim to lower intraocular pressure, often with topical ocular hypotensive medications. Unfortunately, the effectiveness of these medications depends on sustained patient adherence to regimens which may involve instilling multiple medications several times daily. Patient adherence to glaucoma medications is often low. Recent innovations in digital sensor technologies have been leveraged to confirm eyedrop medication usage in real-time and relay this information back to providers. Some sensors have also been designed to deliver medication reminders and notifications as well as assist with correct eyedrop administration technique. Here, we review recent innovations targeted at improving glaucoma medication adherence and discuss their limitations.
Collapse
Affiliation(s)
- Alaa Erras
- Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California, USA
| | - Bita Shahrvini
- Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California, USA
| | - Robert N Weinreb
- Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California, USA
| | - Sally L Baxter
- Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California San Diego, La Jolla, California, USA
- Health Department of Biomedical Informatics, University of California San Diego, La Jolla, California, USA
| |
Collapse
|
|
10
|
Litvinova O, Klager E, Yeung AWK, Tzvetkov NT, Kimberger O, Kletecka-Pulker M, Willschke H, Atanasov AG. Bibliometric analysis and evidence of clinical efficacy and safety of digital pills. Front Pharmacol 2023; 14:1023250. [PMID: 36755951 PMCID: PMC9899979 DOI: 10.3389/fphar.2023.1023250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 01/12/2023] [Indexed: 01/24/2023] Open
Abstract
Objectives: Digital pills are new technologies that aim to improve healthcare by increasing medication adherence. The aim of the work was a bibliometric analysis of clinical studies of digital pills and an assessment of the level of evidence of their effectiveness, safety, and prospects for the future. Materials and Methods: The studies were conducted using online databases such as ClinicalTrials.gov, Dimensions, and Web of Science for the period January 2012 to July 2022. The VOSviewer tool for building and visualizing bibliometric networks was used. Results: Bibliometric analysis of the scientific literature revealed that over the past 10 years, the number of publications about digital pills has noticeably increased, which indicates the increasing importance of this field of knowledge. The leading positions in this area are occupied by scientists from the United States, the United Kingdom, and India. Sources of financial support for authors of publications in the field of digital pills are funds from leading developer companies, budget allocations, and funds from non-commercial organizations. Public-private partnerships are an important path to develop and implement digital pills. The four main clusters of digital pill studies were highlighted and visualized: efficacy and safety analysis for serious mental disorders; treatment and costs of tuberculosis therapy; features of the treatment of diabetes, cardiovascular diseases, and AIDS; and usage monitoring. Available publications demonstrate the efficacy potential and safety of digital pills. Nevertheless, the effects of digital pills have not yet been fully studied. Conclusion: Priority areas for future research are further randomized controlled clinical trials and meta-analyses, which are necessary for a high level (I level) of evidence for therapeutic applications of digital pills, as well as pharmacoeconomic studies.
Collapse
Affiliation(s)
- Olena Litvinova
- National University of Pharmacy of the Ministry of Health of Ukraine, Kharkiv, Ukraine,*Correspondence: Olena Litvinova, ; Atanas G. Atanasov,
| | - Elisabeth Klager
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria
| | - Andy Wai Kan Yeung
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria,Division of Oral and Maxillofacial Radiology, Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Nikolay T. Tzvetkov
- Department of Biochemical Pharmacology and Drug Design, Bulgarian Academy of Sciences, Institute of Molecular Biology “Roumen Tsanev, Sofia, Bulgaria
| | - Oliver Kimberger
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria,Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Maria Kletecka-Pulker
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria,Institute for Ethics and Law in Medicine, University of Vienna, Vienna, Austria
| | - Harald Willschke
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria,Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Atanas G. Atanasov
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Vienna, Austria,Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Poland,*Correspondence: Olena Litvinova, ; Atanas G. Atanasov,
| |
Collapse
|
|
11
|
Liu H, Wang Y, Huang Y, Xiong D, Shen J, Siqueiros L, Bala V, Savage GM, Guerrero M, Corado K, Rosen MI, Fletcher CV, Daar ES. Ingestible sensor system for measuring, monitoring and enhancing adherence to antiretroviral therapy: An open-label, usual care-controlled, randomised trial. EBioMedicine 2022; 86:104330. [PMID: 36372731 PMCID: PMC9782816 DOI: 10.1016/j.ebiom.2022.104330] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 09/10/2022] [Accepted: 10/14/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. We evaluated the acceptability, effectiveness, and sustainability of the IS system with real-time text reminders. METHODS Participants were recruited from HIV clinics in Los Angeles and were randomised 1:1 to IS or usual care (UC) group. Adherence to ARVs (primary outcome) was measured by IS system (IS group only), plasma ARV concentration, and self-report. IS-measured adherence was clustered by group-based trajectory model and was validated by ARV concentration summarized by integrated pharmacokinetic adherence measure (IPAM) score. HIV RNA viral load (VL) was compared between IS and UC group. FINDINGS A total of 112 (IS = 54, UC = 58) participants who completed baseline with at least one follow-up data collection were included in analyses. Overall satisfaction rate for the IS system was >90%. The IPAM score was higher (0.018, 95% CI: -0.098-0.134, p = 0.75) and VL decayed faster (-0.020, 95% CI: -0.042-0.002, p = 0.08) in the IS group compared with the UC group. The ingestible sensor system was well tolerated by study participants. INTERPRETATION The IS system was well accepted by participants and its use was associated with improved adherence and lower HIV RNA VL. The findings provide a potentially effective strategy for improving adherence. FUNDING This work was supported by grant R01-MH110056 from the National Institute of Mental Health (NIMH)/National Institutes of Health (NIH). Y. Wang was in part supported by the NIMH/NIH award T32MH080634. E. Daar was in part supported by the National Center for Advancing Translational Sciences through UCLACTSI Grant UL1TR001881. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Collapse
Affiliation(s)
- Honghu Liu
- Section of Public and Population Health, School of Dentistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA, USA.
| | - Yan Wang
- Section of Public and Population Health, School of Dentistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Division of Infectious Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Yilan Huang
- Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA, USA
| | - Di Xiong
- Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA, USA
| | - Jie Shen
- Section of Public and Population Health, School of Dentistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Lisa Siqueiros
- Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Veenu Bala
- Center for Drug Discovery, University of Nebraska Medical Center, Omaha, NE, USA; Jounce Therapeutics, Inc. Cambridge, MA, USA
| | - George M Savage
- Proteus Digital Health, Redwood City, CA, USA; Windmill Partners LLC, Portola Valley, CA, USA
| | - Mario Guerrero
- Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Katya Corado
- Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Marc I Rosen
- Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA
| | - Courtney V Fletcher
- Center for Drug Discovery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Eric S Daar
- Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
| |
Collapse
|
|
12
|
Brothers J, Hosek S, Keckler K, Anderson PL, Xiong D, Liu H, Huhn G. The ATEAM study: Advances in technology to enhance PrEP adherence monitoring (ATEAM) among young men who have sex with men. Clin Transl Sci 2022; 15:2947-2957. [PMID: 36106611 PMCID: PMC9747125 DOI: 10.1111/cts.13414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 07/14/2022] [Accepted: 08/17/2022] [Indexed: 01/26/2023] Open
Abstract
Young age has consistently correlated with lower adherence to pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Digital medicine, a dynamic healthcare platform of wearable physiological sensors and mobile communication technology that can respond to medication nonadherence rapidly, has the potential in promoting PrEP adherence. We evaluated the feasibility and acceptability of Proteus Discover, a digital monitoring adherence system, to measure PrEP adherence and provide real-time feedback among cisgender YMSM and transgender women. One hundred HIV-negative young men and transgender women ages 16-24 years were enrolled in a 24-week randomized controlled crossover study to tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) coencapsulated with Proteus Discover versus TDF/FTC standard-of-care. Participants in the 12-week Proteus Discover arm received weekly SMS text messages to promote pill taking based on Proteus Discover adherence data. Dried blood spots (DBS) were collected at 4-week intervals for tenofovir diphosphate (TFV-DP) in red blood cells as the referent and questionnaires were completed to assess acceptability, usability, and patterns of use. Linear mixed models analyzed the relationship between 30-day adherence measured by DBS and Proteus Discover. PrEP adherence was high overall. Adherence, as measured by DBS, was correlated with adherence as measured by Proteus Discover (p value = 0.03). Most participants reported that Proteus Discover helped them take their PrEP daily and that the system was easy to use. However, a majority (53.5%-60.5%) disagreed with the statement that wearing the patch was not an issue. There was an incremental increase in TFV-DP in DBS with adherence by Proteus Discover. More research is warranted to explore optimizing PrEP adherence for youth through real-time monitoring.
Collapse
Affiliation(s)
- Jennifer Brothers
- Hektoen Institute of MedicineChicagoIllinoisUSA,Cook County Department of Public HealthChicagoIllinoisUSA
| | - Sybil Hosek
- Stroger Hospital of Cook CountyChicagoIllinoisUSA
| | | | - Peter L. Anderson
- University of Colorado Skaggs School of Pharmacy and Pharmaceutical SciencesAuroraColoradoUSA
| | - Di Xiong
- Division of Oral and Systemic Health Sciences, School of DentistryUniversity of CaliforniaLos AngelesCaliforniaUSA,Departments of Biostatistics, Fielding School of Public HealthUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Honghu Liu
- Division of Oral and Systemic Health Sciences, School of DentistryUniversity of CaliforniaLos AngelesCaliforniaUSA,Departments of Biostatistics, Fielding School of Public HealthUniversity of CaliforniaLos AngelesCaliforniaUSA,Department of Health Policy and Management, Fielding School of Public HealthUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Gregory Huhn
- Stroger Hospital of Cook CountyChicagoIllinoisUSA,Ruth M. Rothstein CORE CenterChicagoIllinoisUSA
| |
Collapse
|
|
13
|
Litvinova O, Klager E, Tzvetkov NT, Kimberger O, Kletecka-Pulker M, Willschke H, Atanasov AG. Digital Pills with Ingestible Sensors: Patent Landscape Analysis. Pharmaceuticals (Basel) 2022; 15:ph15081025. [PMID: 36015173 PMCID: PMC9415622 DOI: 10.3390/ph15081025] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 11/16/2022] Open
Abstract
The modern healthcare system is directly related to the development of digital health tools and solutions. Pills with digital sensors represent a highly innovative class of new pharmaceuticals. The aim of this work was to analyze the patent landscape and to systematize the main trends in patent protection of digital pills with ingestible sensors worldwide; accordingly, to identify the patenting leaders as well as the main prevailing areas of therapy for patent protection, and the future perspectives in the field. In July 2022, a search was conducted using Internet databases, such as the EPO, USPTO, FDA and the Lens database. The patent landscape analysis shows an increase in the number of patents related to digital pills with ingestible sensors for mobile clinical monitoring, smart drug delivery, and endoscopy diagnostics. The leaders in the number of patents issued are the United States, the European Patent Office, Canada, Australia, and China. The following main areas of patenting digital pills with ingestible sensors were identified: treatment in the field of mental health; HIV/AIDS; pain control; cardiovascular diseases; diabetes; gastroenterology (including hepatitis C); oncology; tuberculosis; and transplantology. The development of scientific and practical approaches towards the implementation of effective and safe digital pills will improve treatment outcomes, increase compliance, reduce hospital stays, provide mobile clinical monitoring, have a positive impact on treatment costs and will contribute to increased patient safety.
Collapse
Affiliation(s)
- Olena Litvinova
- Department of Management, Economy and Quality Assurance in Pharmacy, National University of Pharmacy, The Ministry of Health of Ukraine, 61002 Kharkiv, Ukraine
- Correspondence: (O.L.); (A.G.A.); Tel.: +380-67-300-78-49 (O.L.); +43-1401-6036-250 (A.G.A.)
| | - Elisabeth Klager
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, 1180 Vienna, Austria
| | - Nikolay T. Tzvetkov
- Institute of Molecular Biology “Roumen Tsanev”, Department of Biochemical Pharmacology and Drug Design, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Oliver Kimberger
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, 1180 Vienna, Austria
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Maria Kletecka-Pulker
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, 1180 Vienna, Austria
- Institute for Ethics and Law in Medicine, University of Vienna, 1090 Vienna, Austria
| | - Harald Willschke
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, 1180 Vienna, Austria
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Atanas G. Atanasov
- Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, 1180 Vienna, Austria
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland
- Correspondence: (O.L.); (A.G.A.); Tel.: +380-67-300-78-49 (O.L.); +43-1401-6036-250 (A.G.A.)
| |
Collapse
|
|
14
|
Mason M, Cho Y, Rayo J, Gong Y, Harris M, Jiang Y. Technologies for Medication Adherence Monitoring and Technology Assessment Criteria: Narrative Review. JMIR Mhealth Uhealth 2022; 10:e35157. [PMID: 35266873 PMCID: PMC8949687 DOI: 10.2196/35157] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/23/2022] [Accepted: 01/28/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Accurate measurement and monitoring of patient medication adherence is a global challenge because of the absence of gold standard methods for adherence measurement. Recent attention has been directed toward the adoption of technologies for medication adherence monitoring, as they provide the opportunity for continuous tracking of individual medication adherence behavior. However, current medication adherence monitoring technologies vary according to their technical features and data capture methods, leading to differences in their respective advantages and limitations. Overall, appropriate criteria to guide the assessment of medication adherence monitoring technologies for optimal adoption and use are lacking. OBJECTIVE This study aims to provide a narrative review of current medication adherence monitoring technologies and propose a set of technology assessment criteria to support technology development and adoption. METHODS A literature search was conducted on PubMed, Scopus, CINAHL, and ProQuest Technology Collection (2010-present) using the combination of keywords medication adherence, measurement technology, and monitoring technology. The selection focused on studies related to medication adherence monitoring technology and its development and use. The technological features, data capture methods, and potential advantages and limitations of the identified technology applications were extracted. Methods for using data for adherence monitoring were also identified. Common recurring elements were synthesized as potential technology assessment criteria. RESULTS Of the 3865 articles retrieved, 98 (2.54%) were included in the final review, which reported a variety of technology applications for monitoring medication adherence, including electronic pill bottles or boxes, ingestible sensors, electronic medication management systems, blister pack technology, patient self-report technology, video-based technology, and motion sensor technology. Technical features varied by technology type, with common expectations for using these technologies to accurately monitor medication adherence and increase adoption in patients' daily lives owing to their unobtrusiveness and convenience of use. Most technologies were able to provide real-time monitoring of medication-taking behaviors but relied on proxy measures of medication adherence. Successful implementation of these technologies in clinical settings has rarely been reported. In all, 28 technology assessment criteria were identified and organized into the following five categories: development information, technology features, adherence to data collection and management, feasibility and implementation, and acceptability and usability. CONCLUSIONS This narrative review summarizes the technical features, data capture methods, and various advantages and limitations of medication adherence monitoring technology reported in the literature and the proposed criteria for assessing medication adherence monitoring technologies. This collection of assessment criteria can be a useful tool to guide the development and selection of relevant technologies, facilitating the optimal adoption and effective use of technology to improve medication adherence outcomes. Future studies are needed to further validate the medication adherence monitoring technology assessment criteria and construct an appropriate technology assessment framework.
Collapse
Affiliation(s)
- Madilyn Mason
- School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Youmin Cho
- School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Jessica Rayo
- School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Yang Gong
- School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Marcelline Harris
- School of Nursing, University of Michigan, Ann Arbor, MI, United States
| | - Yun Jiang
- School of Nursing, University of Michigan, Ann Arbor, MI, United States
| |
Collapse
|
|
15
|
Gandolfini I, Palmisano A, Fiaccadori E, Cravedi P, Maggiore U. Detecting, preventing, and treating non-adherence to immunosuppression after kidney transplantation. Clin Kidney J 2022; 15:1253-1274. [PMID: 35756738 PMCID: PMC9217626 DOI: 10.1093/ckj/sfac017] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Indexed: 11/12/2022] Open
Abstract
Medication non-adherence (MNA) is a major issue in kidney transplantation and it is associated with increased risk of rejection, allograft loss, patients’ death and higher healthcare costs. Despite its crucial importance, it is still unclear what are the best strategies to diagnose, prevent and treat MNA. MNA can be intentional (deliberate refusal to take the medication as prescribed) or unintentional (non-deliberate missing the prescribed medication). Its diagnosis may rely on direct methods, aiming at measuring drug ingestions, or indirect methods that analyse the habits of patients to adhere to correct drug dose (taking adherence) and interval (time adherence). Identifying individual risk factors for MNA may provide the basis for a personalized approach to the treatment of MNA. Randomized control trials performed so far have tested a combination of strategies, such as enhancing medication adherence through the commitment of healthcare personnel involved in drug distribution, the use of electronic reminders, therapy simplification or various multidisciplinary approaches to maximize the correction of individual risk factors. Although most of these approaches reduced MNA in the short-term, the long-term effects on MNA and, more importantly, on clinical outcomes remain unclear. In this review, we provide a critical appraisal of traditional and newer methods for detecting, preventing and treating non-adherence to immunosuppression after kidney transplantation from the perspective of the practising physician.
Collapse
Affiliation(s)
- Ilaria Gandolfini
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Nephrology Unit, University Hospital of Parma, Parma, Italy
| | | | - Enrico Fiaccadori
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Nephrology Unit, University Hospital of Parma, Parma, Italy
| | - Paolo Cravedi
- Department of Medicine, Division of Nephrology and Translational Transplant Research Center, Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Umberto Maggiore
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Nephrology Unit, University Hospital of Parma, Parma, Italy
| |
Collapse
|
|
16
|
Chai PR, Vaz C, Goodman GR, Albrechta H, Huang H, Rosen RK, Boyer EW, Mayer KH, O’Cleirigh C. Ingestible electronic sensors to measure instantaneous medication adherence: A narrative review. Digit Health 2022; 8:20552076221083119. [PMID: 35251683 PMCID: PMC8891880 DOI: 10.1177/20552076221083119] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/30/2022] [Indexed: 12/03/2022] Open
Abstract
OBJECTIVE Medication nonadherence contributes to significant morbidity and mortality worldwide. While many techniques to measure adherence exist, digital pill systems represent a novel, direct method of measuring adherence and a means of providing instantaneous adherence supports. In this narrative review, we discuss digital pill system research based on clinical trials and qualitative investigations conducted to date and potential future applications of digital pill system in medication adherence measurement. METHODS We conducted a literature search in PubMed of English language peer-reviewed articles describing the use of digital pill system for medication adherence measurement between 2000 and 2021. We included all articles that described the deployment of ingestible sensors and those involving qualitative investigations of digital pill system with human subjects. RESULTS A total of 95 articles were found on initial search; 75 were removed based on exclusion criteria. Included articles were categorized as investigations that deployed an ingestible sensor in human populations (n = 18), or those that conducted qualitative work (n = 3). For pilot studies, the mean accuracy of the sensor to successfully detect a medication ingestion event ranged from 68% to 100%. When digital pill systems were deployed in real-world clinical settings, accuracy ranged from 68% to 90% with lower accuracy due to nonadherence to digital pill system technology. Qualitative studies demonstrated that providers and patients perceive the digital pill system as a facilitator for improving adherence and as a potential platform for delivering adherence interventions. Additionally, ingestion data from digital pill system was viewed as useful in facilitating adherence discussions between clinicians and patients. CONCLUSIONS This narrative review demonstrates that the use of digital pill system is broadly feasible across multiple disease states including human immunodeficiency virus, hepatitis C infection, solid organ transplants, tuberculosis, schizophrenia, cardiovascular disease, and acute fractures, where adherence is closely linked to significant morbidity and mortality. It also highlights key areas of research that are still needed prior to broad-scale clinical deployment of such systems.
Collapse
Affiliation(s)
- Peter R Chai
- Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- The Fenway Institute, Fenway Health, Boston, MA, USA
- Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute, Boston, MA, USA
- The Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Clint Vaz
- Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute, Boston, MA, USA
| | - Georgia R Goodman
- Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- The Fenway Institute, Fenway Health, Boston, MA, USA
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
| | | | - Henwei Huang
- The Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Rochelle K Rosen
- The Centers for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI, USA
- Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI, USA
| | - Edward W Boyer
- Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- The Fenway Institute, Fenway Health, Boston, MA, USA
| | - Kenneth H Mayer
- The Fenway Institute, Fenway Health, Boston, MA, USA
- Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Conall O’Cleirigh
- The Fenway Institute, Fenway Health, Boston, MA, USA
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
| |
Collapse
|
|
17
|
Ribaut J, De Geest S, Leppla L, Gerull S, Teynor A, Valenta S. Exploring Stem Cell Transplanted Patients' Perspectives on Medication Self-Management and Electronic Monitoring Devices Measuring Medication Adherence: A Qualitative Sub-Study of the Swiss SMILe Implementation Science Project. Patient Prefer Adherence 2022; 16:11-22. [PMID: 35023905 PMCID: PMC8747798 DOI: 10.2147/ppa.s337117] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 11/22/2021] [Indexed: 01/08/2023] Open
Abstract
PURPOSE Little is known about allogeneic stem cell transplant (alloSCT) patients' medication adherence strategies. Acceptability and preferences regarding electronic monitoring (EM) systems to assess all three phases of medication adherence (ie, initiation, implementation, persistence) are crucial to allow their successful implementation in clinical or research settings but have not yet been evaluated. We therefore aimed to explore: 1) alloSCT patients' medication adherence and self-management strategies; and 2) their acceptability and preferences of three different EM systems (MEMS Cap, Helping Hand, Button) as part of the Swiss SMILe study. PATIENTS AND METHODS Respecting anti-pandemic measures, we used a purposive sample of six adult alloSCT patients from the University Hospital Basel, Switzerland (USB)-6 weeks to 2 years post-alloSCT-to conduct three focus group sessions with two patients each. Using a semi-structured outline, we explored 1) patients' medication adherence strategies and medication self-management; and 2) their acceptance and preferences regarding EM use. The three tested EM systems were available for testing during each session. Discussions were audio-recorded, visualized using mind-mapping and analyzed using Mayring's qualitative content analysis. RESULTS Patients (33% females; mean age 54.6±16.3 years; 10.4±8.4 months post-alloSCT) used medication adherence enhancing strategies (eg, preparing pillbox, linking intake to a habit). Still, they indicated that post-alloSCT medication management was challenging (eg, frequent schedule changes). All participants preferred the MEMS Button. Participants said its small size and the possibility to combine it with existing pillboxes (eg, putting it into/next to them) made them more confident about implementing it in their daily lives. CONCLUSION Regarding EM systems for medication adherence, end-user preferences and acceptability influence adoption and fidelity. Of the three systems tested, our sample found the MEMS Button most acceptable and most preferable. Therefore, we will use it for our USB SMILe study.
Collapse
Affiliation(s)
- Janette Ribaut
- Institute of Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Basel, Switzerland
- Department of Theragnostic, Hematology, University Hospital of Basel, Basel, Switzerland
| | - Sabina De Geest
- Institute of Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Basel, Switzerland
- Academic Center for Nursing and Midwifery, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Lynn Leppla
- Institute of Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Basel, Switzerland
- Departments of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg, Germany
| | - Sabine Gerull
- Department of Theragnostic, Hematology, University Hospital of Basel, Basel, Switzerland
- Department of Hematology, Cantonal Hospital of Aarau, Aarau, Switzerland
| | - Alexandra Teynor
- Department of Computer Science, University of Applied Sciences, Augsburg, Germany
| | - Sabine Valenta
- Institute of Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Basel, Switzerland
- Department of Theragnostic, Hematology, University Hospital of Basel, Basel, Switzerland
- Correspondence: Sabine Valenta Institute of Nursing Science, Department Public Health, Faculty of Medicine, University of Basel, Bernoullistrasse 28, Basel, CH-4056, SwitzerlandTel +41 61 32 85275 Email
| | | |
Collapse
|
|
18
|
Baumgartner SL, Buffkin DE, Rukavina E, Jones J, Weiler E, Carnes TC. A Novel Digital Pill System for Medication Adherence Measurement and Reporting: Usability Validation Study. JMIR Hum Factors 2021; 8:e30786. [PMID: 34747709 PMCID: PMC8663639 DOI: 10.2196/30786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/07/2021] [Accepted: 07/10/2021] [Indexed: 11/13/2022] Open
Abstract
Background Medication nonadherence is a costly problem that is common in clinical use and clinical trials alike, with significant adverse consequences. Digital pill systems have proved to be effective and safe solutions to the challenges of nonadherence, with documented success in improving adherence and health outcomes. Objective The aim of this human factors validation study is to evaluate a novel digital pill system, the ID-Cap System from etectRx, for usability among patient users in a simulated real-world use environment. Methods A total of 17 patients with diverse backgrounds who regularly take oral prescription medications were recruited. After training and a period of training decay, the participants were asked to complete 12 patient-use scenarios during which errors or difficulties were logged. The participants were also interviewed about their experiences with the ID-Cap System. Results The participants ranged in age from 27 to 74 years (mean 51 years, SD 13.8 years), and they were heterogeneous in other demographic factors as well, such as education level, handedness, and sex. In this human factors validation study, the patient users completed 97.5% (196/201) of the total use scenarios successfully; 75.1% (151/201) were completed without any failures or errors. The participants found the ID-Cap System easy to use, and they were able to accurately and proficiently record ingestion events using the device. Conclusions The participants demonstrated the ability to safely and effectively use the ID-Cap System for its intended use. The ID-Cap System has great potential as a useful tool for encouraging medication adherence and can be easily implemented by patient users.
Collapse
Affiliation(s)
| | | | | | - Jason Jones
- Tensentric, Inc., Boulder, CO, United States
| | | | | |
Collapse
|
|
19
|
Ammann AM, Delman AM, Shah SA. Using Technology to Facilitate Monitoring of Transplant Patients. CURRENT TRANSPLANTATION REPORTS 2021. [DOI: 10.1007/s40472-021-00332-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
|
|
20
|
Miley D, Machado LB, Condo C, Jergens AE, Yoon KJ, Pandey S. Video Capsule Endoscopy and Ingestible Electronics: Emerging Trends in Sensors, Circuits, Materials, Telemetry, Optics, and Rapid Reading Software. ADVANCED DEVICES & INSTRUMENTATION 2021; 2021. [DOI: 10.34133/2021/9854040] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Real-time monitoring of the gastrointestinal tract in a safe and comfortable manner is valuable for the diagnosis and therapy of many diseases. Within this realm, our review captures the trends in ingestible capsule systems with a focus on hardware and software technologies used for capsule endoscopy and remote patient monitoring. We introduce the structure and functions of the gastrointestinal tract, and the FDA guidelines for ingestible wireless telemetric medical devices. We survey the advanced features incorporated in ingestible capsule systems, such as microrobotics, closed-loop feedback, physiological sensing, nerve stimulation, sampling and delivery, panoramic imaging with adaptive frame rates, and rapid reading software. Examples of experimental and commercialized capsule systems are presented with descriptions of their sensors, devices, and circuits for gastrointestinal health monitoring. We also show the recent research in biocompatible materials and batteries, edible electronics, and alternative energy sources for ingestible capsule systems. The results from clinical studies are discussed for the assessment of key performance indicators related to the safety and effectiveness of ingestible capsule procedures. Lastly, the present challenges and outlook are summarized with respect to the risks to health, clinical testing and approval process, and technology adoption by patients and clinicians.
Collapse
Affiliation(s)
- Dylan Miley
- Department of Electrical and Computer Engineering, Iowa State University, Ames, Iowa, USA
| | | | - Calvin Condo
- Department of Electrical and Computer Engineering, Iowa State University, Ames, Iowa, USA
| | - Albert E. Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
| | - Kyoung-Jin Yoon
- Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
| | - Santosh Pandey
- Department of Electrical and Computer Engineering, Iowa State University, Ames, Iowa, USA
| |
Collapse
|
|
21
|
Design and conduct of confirmatory chronic pain clinical trials. Pain Rep 2020; 6:e845. [PMID: 33511323 PMCID: PMC7837951 DOI: 10.1097/pr9.0000000000000854] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 08/07/2020] [Accepted: 08/19/2020] [Indexed: 12/30/2022] Open
Abstract
The purpose of this article is to provide readers with a basis for understanding the emerging science of clinical trials and to provide a set of practical, evidence-based suggestions for designing and executing confirmatory clinical trials in a manner that minimizes measurement error. The most important step in creating a mindset of quality clinical research is to abandon the antiquated concept that clinical trials are a method for capturing data from clinical practice and shifting to a concept of the clinical trial as a measurement system, consisting of an interconnected set of processes, each of which must be in calibration for the trial to generate an accurate and reliable estimate of the efficacy (and safety) of a given treatment. The status quo of inaccurate, unreliable, and protracted clinical trials is unacceptable and unsustainable. This article gathers aspects of study design and conduct under a single broad umbrella of techniques available to improve the accuracy and reliability of confirmatory clinical trials across traditional domain boundaries.
Collapse
|
|
22
|
Duettmann W, Naik MG, Zukunft B, Osmonodja B, Bachmann F, Choi M, Roller R, Mayrdorfer M, Halleck F, Schmidt D, Budde K. eHealth in transplantation. Transpl Int 2020; 34:16-26. [DOI: 10.1111/tri.13778] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 08/17/2020] [Accepted: 10/23/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Wiebke Duettmann
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Marcel G. Naik
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Bianca Zukunft
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Bilgin Osmonodja
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Friederike Bachmann
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Mira Choi
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Roland Roller
- German Research Center for Artificial Intelligence Berlin Germany
| | - Manuel Mayrdorfer
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| | - Danilo Schmidt
- Business Division IT Department of Research and Teaching Charité—Universitätsmedizin Berlin Berlin Germany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany
| |
Collapse
|
|
23
|
Bunova SS, Zhernakova NI, Fedorin MM, Skirdenko YP, Osipova OA. Effective antihypertensive therapy: focus on adherence management. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2020. [DOI: 10.15829/1728-8800-2020-2663] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
High medical adherence is a prerequisite for achieving goals in the treatment of hypertension (HTN). The majority of patients with HTN showed low adherence to treatment, which requires finding ways to solve this problem. This review describes the factors influencing adherence, ways of its assessment, and analyzes methods of increasing medical adherence in hypertensive patients. Noteworthy is the lack of publications describing the effectiveness of methods for increasing long-term (>2 years) adherence in hypertensive patients. The review also describes a not fully clear individualized approach, which consists in choosing a therapy regimen based on levels of medical adherence, medical follow-up and lifestyle modification.
Collapse
Affiliation(s)
- S. S. Bunova
- National Research University Belgorod State University (BelSU))
| | | | | | | | - O. A. Osipova
- National Research University Belgorod State University (BelSU))
| |
Collapse
|
|
24
|
Abstract
Medication nonadherence (MNA) after solid organ transplantation is highly prevalent and associated with (late) (sub)clinical acute rejection, graft dysfunction and graft loss, development of donor-specific anti-HLA antibodies, and antibody-mediated rejection. MNA is predominantly unintentional and originates from barriers to adherence that are often multifactorial and complex. Tools to establish an early diagnosis of MNA include incorporation of MNA as a vital sign in daily clinical practice, self-reporting using validated questionnaires, calculating intrapatient variability in drug exposure and applying electronic monitoring, and recent audio and video technologies such as in home telemonitoring. MNA is a modifiable risk factor after organ transplantation, and treatment is most effective if a multimodal approach is used. Management of MNA comprises education (cognitive) and counseling (behavioral) that require the involvement of a trained multidisciplinary team [ideally physician, nurse (specialist), social worker, transplant coordinator, psychologist, clinical pharmacist], electronic reminder and support systems (eg, Medication Event Monitoring System, smartphone), and different types of novel mobile health applications as well as simplification of the medication dosing regimen. Future studies that evaluate novel therapeutic approaches for MNA should assure the use of reliable MNA measures, focus on multimodal individualized therapy for enriched nonadherent target populations (eg, adolescents), and incorporate clinically relevant endpoints. Costs, time, and personnel investments should be taken into account when assessing scalability and cost-effectiveness of novel therapeutic strategies. This review provides suggestions how different types of transplant centers can set up a dedicated MNA program according to available resources to define and achieve realistic clinical goals in managing MNA.
Collapse
|
|
25
|
Lukina YV, Kutishenko NP, Martsevich SY, Drapkina OM. Questionnaires and scores for assessing medication adherence — advantages and disadvantages of the diagnostic method in research and actual clinical practice. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2020. [DOI: 10.15829/1728-8800-2020-2562] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
The problem of medication adherence is still relevant, and the search for a reliable method for its diagnosis continues. One of the most convenient and promising ways to assess medication adherence, both in research and actual clinical practice, is the use of various questionnaires and scores. Currently, several dozen different questionnaires and scores are presented in Russia and other countries. All of them are indirect methods of adherence assessment and are characterized by subjectivity. The article presents data on the most famous and widely used foreign adherence scales (the 4- and 8-item Morisky Medication Adherence Scale (MMAS-4 and MMAS-8), Hill-Bone, SEAMS, BMQ, MARS, etc.) and several questionnaires proposed by Russian authors (the National Society of Evidence-based Pharmacotherapy Adherence Scale, the Quantitative Adherence Questionnaire and the National Questionnaire of Treatment Compliance). The main characteristics of the described scales, their advantages, disadvantages and prospects for use in studies and clinical practice are considered. There are following conclusions: 1) none of the current questionnaires is devoid of subjectivity; 2) almost all questionnaires overestimate medication adherence, do not fully diagnose nonadherence, and often determine only specific type of adherence; 3) even validated questionnaires, which used in patients with different diseases in various countries, can have different values of sensitivity, specificity and reliability — from excellent to very poor; 4) in this regard, the results should be skeptically and cautiously interpreted; 5) in actual clinical practice, preference should be given to concise scales that include no more than 10 questions, with a simple scoring system, preferably validated with using well-known criteria from large clinical trials; 6) to improve the diagnosis accuracy, usage of several available methods for assessing medication adherence is recommended.
Collapse
Affiliation(s)
- Yu. V. Lukina
- National Medical Research Center for Therapy and Preventive Medicine
| | - N. P. Kutishenko
- National Medical Research Center for Therapy and Preventive Medicine
| | - S. Yu. Martsevich
- National Medical Research Center for Therapy and Preventive Medicine
| | - O. M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine
| |
Collapse
|
|
26
|
Alipour A, Gabrielson S, Patel PB. Ingestible Sensors and Medication Adherence: Focus on Use in Serious Mental Illness. PHARMACY 2020; 8:pharmacy8020103. [PMID: 32560178 PMCID: PMC7355811 DOI: 10.3390/pharmacy8020103] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 06/09/2020] [Accepted: 06/11/2020] [Indexed: 12/16/2022] Open
Abstract
Background: Poor medication adherence is a major public health concern. Patients living with a serious mental illness (SMI) commonly present with non-adherence to their medication regimen, which can lead to relapse and hospitalizations. The high rates of antipsychotic non-adherence continue to persist despite several interventions and medication advances. This review evaluates the possible role of the ingestible sensor technology for medication adherence in different conditions, with a focus on use in the SMI schizophrenia. Methods: Literature searches were conducted in July 2019 in the PubMed database. Results: In small studies of ingestible sensor use, the average adherence ranged from 73.9% to 88.6% for SMI and ≥ 80% for cardiac and transplant (99.4%) patients. In SMI studies, patients were clinically stable, and the majority had a clinical global impression severity of “mild disease”. Patients generally experienced relatively minor dermatological adverse effects related to wearable sensor use. Conclusions: A medication with an ingestible sensor may help provide real-time objective medication-taking adherence information for clinicians. However, further studies are needed to understand the impact of use on adherence and improvement on treatment outcomes with the ingestible sensor technology.
Collapse
Affiliation(s)
- Azita Alipour
- College of Pharmacy, Marshall B. Ketchum University, Fullerton, CA 92831, USA;
| | - Stephen Gabrielson
- Health Sciences Library System, University of Pittsburgh, Pittsburgh, PA 15261, USA;
| | - Puja Baldev Patel
- College of Pharmacy, Marshall B. Ketchum University, Fullerton, CA 92831, USA;
- Correspondence:
| |
Collapse
|
|
27
|
Kamal S, Rosen MI, Lazar C, Siqueiros L, Wang Y, Daar ES, Liu H. Perceptions of People Living with HIV and HIV Healthcare Providers on Real-Time Measuring and Monitoring of Antiretroviral Adherence Using Ingestible Sensors: A Qualitative Study. AIDS Res Treat 2020; 2020:1098109. [PMID: 32566285 PMCID: PMC7296466 DOI: 10.1155/2020/1098109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/25/2020] [Accepted: 05/08/2020] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE To describe and analyze the perception and attitudes of people living with HIV (PLWH) and HIV HCPs towards medication adherence with a focus on a digital medicine program (DMP) with ingestible sensors (ISs). METHODS This is a qualitative analysis pilot study of PLWH who were using DMP recruited by purposive sampling. A convenience sample of HCPs was interviewed. Semistructured interviews were conducted, and thematic analysis was performed. RESULTS Fifteen PLWH were interviewed, and thematic analysis resulted in three main themes: self-identified medication adherence patterns, experiences with the DMP, and recommending the DMP to others. Six health care providers (HCPs) described barriers and facilitators to adherence, as well as advantages and disadvantages of using or recommending the DMP to PLWH. CONCLUSION This study evaluated participant and provider responses to DMP, which is a novel technology for real-time measuring and monitoring adherence with the IS. Participant and provider responses were mixed, highlighting both the advantages and limitations of the technology. Practice Implications. Taking PLWH experiences into consideration will enhance the development of this and other useful tools that clinicians and researchers can use for enhanced patient care.
Collapse
Affiliation(s)
- Susan Kamal
- University of California, Los Angeles, School of Dentistry, Division of Public Health and Community Dentistry, Los Angeles, CA, USA
| | - Marc I. Rosen
- Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA
| | - Christina Lazar
- Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA
| | - Lisa Siqueiros
- The Lundquist Institute at Harbor-UCLA Medical Center, Los Angeles, CA, USA
| | - Yan Wang
- University of California, Los Angeles, School of Dentistry, Division of Public Health and Community Dentistry, Los Angeles, CA, USA
- University of California, Los Angeles, Fielding School of Public Health, Department of Biostatistics, Los Angeles, CA, USA
| | - Eric S. Daar
- The Lundquist Institute at Harbor-UCLA Medical Center, Los Angeles, CA, USA
| | - Honghu Liu
- University of California, Los Angeles, School of Dentistry, Division of Public Health and Community Dentistry, Los Angeles, CA, USA
- University of California, Los Angeles, Fielding School of Public Health, Department of Biostatistics, Los Angeles, CA, USA
- University of California, Los Angeles, David Geffen School of Medicine, Department of Medicine, Los Angeles, CA, USA
| |
Collapse
|
|
28
|
Beyond Survival in Solid Organ Transplantation: A Summary of Expert Presentations from the Sandoz 6th Standalone Transplantation Meeting, 2018. Transplantation 2020; 103:S1-S13. [PMID: 31449167 DOI: 10.1097/tp.0000000000002846] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
|
29
|
Haga SB. Toward digital-based interventions for medication adherence and safety. Expert Opin Drug Saf 2020; 19:735-746. [DOI: 10.1080/14740338.2020.1764935] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Susanne B Haga
- Duke School of Medicine, Center for Applied Genomics and Precision Medicine, Durham, NC, USA
| |
Collapse
|
|
30
|
Martani A, Geneviève LD, Poppe C, Casonato C, Wangmo T. Digital pills: a scoping review of the empirical literature and analysis of the ethical aspects. BMC Med Ethics 2020; 21:3. [PMID: 31914995 PMCID: PMC6950823 DOI: 10.1186/s12910-019-0443-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 12/27/2019] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Digital Pills (DP) are an innovative drug-device technology that permits to combine traditional medications with a monitoring system that automatically records data about medication adherence as well as patients' physiological data. Although DP are a promising innovation in the field of digital medicine, their use has also raised a number of ethical concerns. These ethical concerns, however, have been expressed principally from a theoretical perspective, whereas an ethical analysis with a more empirically oriented approach is lacking. There is also a lack of clarity about the empirical evidence available concerning the application of this innovative digital medicine. METHODS To map the studies where DP have been tested on patients and discuss the ethically relevant issues evident therein, we performed a scoping review of the empirical literature concerning DP. RESULTS Our search allowed us to identify 18 papers reporting on studies where DP were tested on patients. These included studies with different designs and involving patients with a variety of conditions. In the empirical literature, a number of issues with ethical relevance were evident. At the patient level, the ethical issues include users' interaction with DP, personal sphere, health-related risks and patients' benefits. At the provider level, ethically relevant issues touch upon the doctor-patient relationship and the question of data access. At the societal level, they concern the benefits to society, the quality of evidence and the dichotomy device-medicine. CONCLUSIONS We conclude that evidence concerning DP is not robust and that more research should be performed and study results made available to evaluate this digital medicine. Moreover, our analysis of the ethically relevant aspects within empirical literature underscores that there are concrete and specific open questions that should be tackled in the ethical discussion about this new technological solution.
Collapse
Affiliation(s)
- Andrea Martani
- Institute for Biomedical Ethics, University of Basel, Bernoullistrasse 28, Basel, Switzerland
| | - Lester Darryl Geneviève
- Institute for Biomedical Ethics, University of Basel, Bernoullistrasse 28, Basel, Switzerland
| | - Christopher Poppe
- Institute for Biomedical Ethics, University of Basel, Bernoullistrasse 28, Basel, Switzerland
| | | | - Tenzin Wangmo
- Institute for Biomedical Ethics, University of Basel, Bernoullistrasse 28, Basel, Switzerland
| |
Collapse
|
|
31
|
Daar ES, Rosen MI, Wang Y, Siqueiros L, Shen J, Guerrero M, Xiong D, Dao J, Young T, Corado K, Fletcher CV, Liu H. Real-Time and Wireless Assessment of Adherence to Antiretroviral Therapy With Co-Encapsulated Ingestion Sensor in HIV-Infected Patients: A Pilot Study. Clin Transl Sci 2020; 13:189-194. [PMID: 31536156 PMCID: PMC6951462 DOI: 10.1111/cts.12701] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Accepted: 07/23/2019] [Indexed: 11/28/2022] Open
Abstract
Adherence with antiretroviral therapy is important for preventing disease progression and HIV transmission. The co-encapsulated pill sensor system sends a signal through a cutaneous patch and allows real-time monitoring of pill ingestion. A 16-week pilot study used a sensor system in 15 HIV-infected individuals with real-time monitoring of pill-taking with a personalized short message system text. System acceptability was assessed by survey at weeks 4, 8, 12, and 16. Follow-up occurred in 80% of subjects through 8 weeks. The system effectively collected measures of pill ingestion, which triggered text message reminders. Only 2 of 14 participants stated that co-encapsulated pills were "unable to take" or "poorly tolerated." At least 75% of respondents stated at each visit that the patch was very or somewhat comfortable. With regard to text message reminders, only 10-15% of the participants at any visit did not find the messages to be helpful. Larger studies will define the utility of this system to assess antiretroviral adherence relative to standard measures.
Collapse
Affiliation(s)
- Eric S. Daar
- Los Angeles Biomedical Research Institute at Harbor‐University of CaliforniaLos Angeles (UCLA) Medical CenterTorranceCaliforniaUSA
| | - Marc I. Rosen
- School of MedicineYale UniversityNew HavenConnecticutUSA
| | - Yan Wang
- Fielding School of Public HealthUCLALos AngelesCaliforniaUSA
| | - Lisa Siqueiros
- Los Angeles Biomedical Research Institute at Harbor‐University of CaliforniaLos Angeles (UCLA) Medical CenterTorranceCaliforniaUSA
| | - Jie Shen
- School of DentistryUniversity of California, Los Angeles (UCLA)Los AngelesCaliforniaUSA
| | - Mario Guerrero
- Los Angeles Biomedical Research Institute at Harbor‐University of CaliforniaLos Angeles (UCLA) Medical CenterTorranceCaliforniaUSA
| | - Di Xiong
- Fielding School of Public HealthUCLALos AngelesCaliforniaUSA
| | - John Dao
- Proteus Digital HealthRedwood CityCaliforniaUSA
| | - Todd Young
- Proteus Digital HealthRedwood CityCaliforniaUSA
| | - Katya Corado
- Los Angeles Biomedical Research Institute at Harbor‐University of CaliforniaLos Angeles (UCLA) Medical CenterTorranceCaliforniaUSA
| | | | - Honghu Liu
- School of DentistryUniversity of California, Los Angeles (UCLA)Los AngelesCaliforniaUSA
| |
Collapse
|
|
32
|
Liu H, Daar E, Wang Y, Siqueiros L, Campbell K, Shen J, Guerrero M, Ko MW, Xiong D, Dao J, Young T, Rosen M, Fletcher CV. Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors. AIDS Res Hum Retroviruses 2020; 36:65-74. [PMID: 31516025 PMCID: PMC6944136 DOI: 10.1089/aid.2019.0202] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) coencapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were determined from plasma concentrations measured at predose, 1, 2, 4, and 6 h postdose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significantly different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [CI] 66.6-107.4) for AUC and 77.5% (60.1-99.9) for Cmax. For tenofovir (TFV), the GMR was 96.2% (90% CI 89.2-103.8) for AUC and 87.3% (64.2-118.7) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5-113.5) for AUC and 89.9% (84.5-95.7) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of coencapsulated ARVs for future HIV treatment-adherence research.
Collapse
Affiliation(s)
- Honghu Liu
- Division of Public Health and Community Dentistry, University of California, Los Angeles (UCLA), Los Angeles, California
- Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California
- Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, California
| | - Eric Daar
- Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California
| | - Yan Wang
- Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, California
- Urban Health Collaborative, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania
| | - Lisa Siqueiros
- Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California
| | - Kayla Campbell
- Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska
| | - Jie Shen
- Division of Public Health and Community Dentistry, University of California, Los Angeles (UCLA), Los Angeles, California
| | - Mario Guerrero
- Department of Medicine, Division of HIV Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California
| | - Meng-Wei Ko
- Division of Oral Biology and Medicine, School of Dentistry, UCLA, Los Angeles, California
| | - Di Xiong
- Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, California
| | - John Dao
- Proteus Digital Health, Redwood City, California
| | - Todd Young
- Proteus Digital Health, Redwood City, California
| | - Marc Rosen
- School of Medicine, Yale University, New Haven, Connecticut
| | - Courtney V. Fletcher
- Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska
| |
Collapse
|
|
33
|
Browne SH, Umlauf A, Tucker AJ, Low J, Moser K, Gonzalez Garcia J, Peloquin CA, Blaschke T, Vaida F, Benson CA. Wirelessly observed therapy compared to directly observed therapy to confirm and support tuberculosis treatment adherence: A randomized controlled trial. PLoS Med 2019; 16:e1002891. [PMID: 31584944 PMCID: PMC6777756 DOI: 10.1371/journal.pmed.1002891] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Accepted: 08/27/2019] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Excellent adherence to tuberculosis (TB) treatment is critical to cure TB and avoid the emergence of resistance. Wirelessly observed therapy (WOT) is a novel patient self-management system consisting of an edible ingestion sensor (IS), external wearable patch, and paired mobile device that can detect and digitally record medication ingestions. Our study determined the accuracy of ingestion detection in clinical and home settings using WOT and subsequently compared, in a randomized control trial (RCT), confirmed daily adherence to medication in persons using WOT or directly observed therapy (DOT) during TB treatment. METHODS AND FINDINGS We evaluated WOT in persons with active Mycobacterium tuberculosis complex disease using IS-enabled combination isoniazid 150 mg/rifampin 300 mg (IS-Rifamate). Seventy-seven participants with drug-susceptible TB in the continuation phase of treatment, prescribed daily isoniazid 300 mg and rifampin 600 mg, used IS-Rifamate. The primary endpoints of the trial were determination of the positive detection accuracy (PDA) of WOT, defined as the percentage of ingestions detected by WOT administered under direct observation, and subsequently the proportion of prescribed doses confirmed by WOT compared to DOT. Initially participants received DOT and WOT simultaneously for 2-3 weeks to allow calculation of WOT PDA, and the 95% confidence interval (CI) was estimated using the bootstrap method with 10,000 samples. Sixty-one participants subsequently participated in an RCT to compare the proportion of prescribed doses confirmed by WOT and DOT. Participants were randomized 2:1 to receive WOT or maximal in-person DOT. In the WOT arm, if ingestions were not remotely confirmed, the participant was contacted within 24 hours by text or cell phone to provide support. The number of doses confirmed was collected, and nonparametric methods were used for group and individual comparisons to estimate the proportions of confirmed doses in each randomized arm with 95% CIs. Sensitivity analyses, not prespecified in the trial registration, were also performed, removing all nonworking (weekend and public holiday) and held-dose days. Participants, recruited from San Diego (SD) and Orange County (OC) Divisions of TB Control and Refugee Health, were 43.1 (range 18-80) years old, 57% male, 42% Asian, and 39% white with 49% Hispanic ethnicity. The PDA of WOT was 99.3% (CI 98.1; 100). Intent-to-treat (ITT) analysis within the RCT showed WOT confirmed 93% versus 63% DOT (p < 0.001) of daily doses prescribed. Secondary analysis removing all nonworking days (weekends and public holidays) and held doses from each arm showed WOT confirmed 95.6% versus 92.7% (p = 0.31); WOT was non-inferior to DOT (difference 2.8% CI [-1.8%, 9.1%]). One hundred percent of participants preferred using WOT. WOT associated adverse events were <10%, consisting of minor skin rash and pruritus associated with the patch. WOT provided longitudinal digital reporting in near real time, supporting patient self-management and allowing rapid remote identification of those who needed more support to maintain adherence. This study was conducted during the continuation phase of TB treatment, limiting its generalizability to the entire TB treatment course. CONCLUSIONS In terms of accuracy, WOT was equivalent to DOT. WOT was superior to DOT in supporting confirmed daily adherence to TB medications during the continuation phase of TB treatment and was overwhelmingly preferred by participants. WOT should be tested in high-burden TB settings, where it may substantially support low- and middle-income country (LMIC) TB programs. TRIAL REGISTRATION ClinicalTrials.gov NCT01960257.
Collapse
Affiliation(s)
- Sara H. Browne
- University of California San Diego, La Jolla, California, United States of America
- * E-mail:
| | - Anya Umlauf
- University of California San Diego, La Jolla, California, United States of America
| | - Amanda J. Tucker
- University of California San Diego, La Jolla, California, United States of America
| | - Julie Low
- Orange County Health Care Agency, Santa Ana, California, United States of America
| | - Kathleen Moser
- Health and Human Services Agency, San Diego, California, United States of America
| | | | | | | | - Florin Vaida
- University of California San Diego, La Jolla, California, United States of America
| | - Constance A. Benson
- University of California San Diego, La Jolla, California, United States of America
| |
Collapse
|
|
34
|
Gokoel SRM, Gombert-Handoko KB, Zwart TC, van der Boog PJM, Moes DJAR, de Fijter JW. Medication non-adherence after kidney transplantation: A critical appraisal and systematic review. Transplant Rev (Orlando) 2019; 34:100511. [PMID: 31627978 DOI: 10.1016/j.trre.2019.100511] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Revised: 08/27/2019] [Accepted: 08/28/2019] [Indexed: 10/26/2022]
Abstract
Medication non-adherence is one of the most important causes for shortened graft survival subsequently leading to a reduction in kidney graft survival results. Our aim was to provide an overview of its prevalence, risk factors, diagnostic methods and interventions to improve adherence in kidney transplant recipients. Therefore, we systematically searched the databases PubMed, COCHRANE Library, Web of Science and EMBASE for studies addressing "medication adherence", "compliance", "adherence", "kidney transplantation" and "life style factors". We identified 96 studies that satisfied our inclusion criteria. A problematic lack of a uniformly accepted definition for non-adherence was found, consequently leading to a wide range in non-adherence prevalence (36-55%). Using one uniformly accepted non-adherence definition should therefore be encouraged. A wide range in diagnostic methods makes it difficult to accurately detect non-adherence. Heterogeneous results of intervention studies make it difficult to select the best adherence enhancing method, challenging the battle against medication non-adherence. Literature suggests a combination of personalized interventions, based on patient-specific non-adherent behavior, to be most successful in improvement of adherence. High quality diagnostic methods and multidisciplinary, personalized interventions with focus on relevant clinical outcome are essential in overcoming medication non-adherence in kidney transplant recipients.
Collapse
Affiliation(s)
- Sumit R M Gokoel
- Division of Nephrology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands.
| | - Kim B Gombert-Handoko
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Tom C Zwart
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Paul J M van der Boog
- Division of Nephrology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Dirk Jan A R Moes
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, the Netherlands
| | - Johan W de Fijter
- Division of Nephrology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands
| |
Collapse
|
|
35
|
de Mendoza AH, Cabling M, Dilawari A, Turner JW, Fernández N, Henderson A, Zhu Q, Gómez S, Sheppard VB. Providers' Perspectives on Adherence to Hormonal Therapy in Breast Cancer Survivors. Is there a Role for the Digital Health Feedback System? HEALTH AND TECHNOLOGY 2019; 9:175-184. [PMID: 31448187 DOI: 10.1007/s12553-018-0267-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Objective Despite the benefits of hormonal therapy (HT) adherence remains suboptimal in ER positive breast cancer patients. Medication adherence is challenging to assess and tends to be overestimated. The Digital Health Feedback System (DHFS) consists of an ingestible sensor attached to a pill that sends intake date and time to a smart phone or computer. Patients can share this information with health care providers and other persons. The DHFS can also send reminders. This mixed methods study examined providers' perceptions of HT medication adherence. The potential role of the DHFS in enhancing medication tracking and adherence was also explored. Methods We conducted semi-structured interviews with key informants (N=10). Questions examined perceptions about adherence barriers and facilitators, challenges tracking adherence, and views on the DHFS. Findings informed the development of a survey that was administered online (N=19). Results Providers emphasized the importance of fostering open and trustful communication around adherence. The most mentioned challenges to assessing adherence were the patient not disclosing discontinuation immediately (78.9%) and over-reporting adherence (57.9%). The perceived potential benefits of DHFS were the ability to track adherence better (94.7%) and reminders to take the medication (68.4%). Safety to ingest a sensor was as a major perceived barrier (8 4.2%). Conclusion Interventions that target providers and doctor-patient communication are warranted to enhance adherence and reduce communication delays around HT discontinuation. Practice Implications DHFS has the potential to enhance HT adherence by directly targeting barriers. Future studies should also examine the feasibility of adopting the DHFS with cancer patients.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Qi Zhu
- Georgetown University Medical Center
| | | | | |
Collapse
|
|
36
|
Steiger C, Abramson A, Nadeau P, Chandrakasan AP, Langer R, Traverso G. Ingestible electronics for diagnostics and therapy. NATURE REVIEWS MATERIALS 2018; 4:83-98. [DOI: 10.1038/s41578-018-0070-3] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
37
|
Advancing Transplantation: New Questions, New Possibilities in Kidney and Liver Transplantation. Transplantation 2018; 101 Suppl 2S:S1-S41. [PMID: 28125449 DOI: 10.1097/tp.0000000000001563] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
38
|
Richards VL, Johnson CK, Blosser CD, Sibulesky L. Strategies to Improve Patient Engagement in Young Kidney Transplant Recipients: A Review. Ann Transplant 2018; 23:654-658. [PMID: 30224627 PMCID: PMC6248007 DOI: 10.12659/aot.910698] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Young adult and adolescent kidney transplant recipients have shorter graft survival than older and younger recipients. Although multifactorial, the tendency toward premature graft loss in young kidney transplant recipients has often been attributed to medication nonadherence and the transition from pediatric to adult care. Multiple interventions for medication nonadherence in kidney transplant recipients have been studied. Potential preventative interventions include pre-transplant screening, transition and young adult clinics, technologies such as reminders or mobile applications, and simplification of the post-transplant medication regimen. There are also recent advances in monitoring interventions for nonadherence in transplant recipients, including electronic monitoring devices such as wireless pill bottles and the Ingestible Sensor System, which incorporates ingestible microsensors into medications. Treatment interventions for medication nonadherence include cognitive behavioral programs, behavioral contracts, and screening and treatment for depression. Several of the interventions reviewed are currently available to providers caring for young kidney transplant recipients, without any complex programmatic changes. Further research in all of these areas would be of great value.
Collapse
Affiliation(s)
- Vanessa L Richards
- Division of Nephrology, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA
| | - Christopher K Johnson
- Division of Nephrology, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA
| | - Christopher D Blosser
- Division of Nephrology, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA
| | - Lena Sibulesky
- Division of Transplant Surgery, Department of Surgery, University of Washington Medical Center, Seattle, WA, USA
| |
Collapse
|
|
39
|
Maldonado AQ, West-Thielke P, Dew MA, Peipert JD, Heldenbrand S, Kaiser TE, Chisholm-Burns M, Potter LM. Meeting report: Consensus recommendations for a research agenda to address immunosuppressant nonadherence in organ transplantation. Clin Transplant 2018; 32:e13362. [DOI: 10.1111/ctr.13362] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 07/13/2018] [Accepted: 07/24/2018] [Indexed: 11/26/2022]
Affiliation(s)
| | | | - Mary Amanda Dew
- University of Pittsburgh; School of Medicine and Medical Center; Pittsburgh Pennsylvania
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Steinberg EA, Moss M, Buchanan CL, Goebel J. Adherence in pediatric kidney transplant recipients: solutions for the system. Pediatr Nephrol 2018; 33:361-372. [PMID: 28349215 DOI: 10.1007/s00467-017-3637-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 02/24/2017] [Accepted: 02/27/2017] [Indexed: 12/13/2022]
Abstract
Non-adherence remains a significant problem among pediatric (and adult) renal transplant recipients. Non-adherence among solid organ transplant recipients results in US$15-100 million annual costs. Estimates of non-adherence range from 30 to 70% among pediatric patients. Research demonstrates that a 10% decrement in adherence is associated with 8% higher hazard of graft failure and mortality. Focus has begun to shift from patient factors that impact adherence to the contributing healthcare and systems factors. The purpose of this review is to describe problems within the systems implicated in non-adherence and potential solutions that may be related to positive adherence outcomes. Systems issues include insurance and legal regulations, provider and care team barriers to optimal care, and difficulties with transitioning to adult care. Potential solutions include recognition of how systems can work together to improve patient outcomes through improvements in insurance programs, a multi-disciplinary care team approach, evidence-based medical management, pharmacy-based applications and interventions to simplify medication regimens, improved transition protocols, and telehealth/technology-based multi-component interventions. However, there remains a significant lack of reliability in the application of these potential solutions to systems issues that impact patient adherence. Future efforts should accordingly focus on these efforts, likely by leveraging quality improvement and related principles, and on the investigation of the efficacy of these interventions to improve adherence and graft outcomes.
Collapse
Affiliation(s)
- Elizabeth A Steinberg
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA.
| | - Mary Moss
- Department of Pharmacy, Children's Hospital Colorado, Aurora, CO, USA
| | - Cindy L Buchanan
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA.,Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Jens Goebel
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
| |
Collapse
|
|
41
|
Browne SH, Peloquin C, Santillo F, Haubrich R, Muttera L, Moser K, Savage GM, Benson CA, Blaschke TF. Digitizing Medicines for Remote Capture of Oral Medication Adherence Using Co-encapsulation. Clin Pharmacol Ther 2017; 103:502-510. [PMID: 28597911 PMCID: PMC5836848 DOI: 10.1002/cpt.760] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 05/08/2017] [Accepted: 05/29/2017] [Indexed: 11/14/2022]
Abstract
High‐resolution measurement of medication adherence is essential to personalized drug therapy. A US Food and Drug Administration (FDA)‐cleared device, using an edible ingestion sensor (IS), external wearable patch, and paired mobile device can detect and record ingestion events. Oral medications must be combined with an IS to generate precise “digitized‐medication” ingestion records. We developed a Good Manufacturing Practice protocol to repackage oral medications with the IS within certified Capsugel capsules, termed co‐encapsulation (CoE). A randomized bioequivalence study of CoE‐IS‐Rifamate (Isoniazid/Rifampin 150/300 mg) vs. native‐Rifamate was conducted in 12 patients with active Mycobacterium tuberculosis and demonstrated bioequivalence using the population method ratio test (95% confidence interval). Subsequently, CoE‐IS‐medications across all biopharmaceutical classes underwent in vitro dissolution testing utilizing USP and FDA guidelines. CoE‐IS medications tested met USP dissolution specifications and were equivalent to their native formulations. CoE combines oral medications with the IS without altering the quality of the native formulation, generating “digitized” medications for remote capture of dosing histories.
Collapse
Affiliation(s)
- S H Browne
- University of California, San Diego School of Medicine, Division of Infectious Diseases, San Diego, California, USA
| | - C Peloquin
- University of Florida, College of Pharmacy and Emerging Pathogens Institute, Gainesville, Florida, USA
| | - F Santillo
- Research and Analytic Services, Sharp Clinical Services, Pennsylvania, USA
| | - R Haubrich
- University of California, San Diego School of Medicine, Division of Infectious Diseases, San Diego, California, USA.,Gilead Sciences, Gilead Sciences, Inc., Foster City, California, USA
| | - L Muttera
- University of California, San Diego Department of Medicine, Research Pharmacy, San Diego, California, USA
| | - K Moser
- San Diego County Health and Human Services Agency, San Diego, California, USA.,Centers for Disease Control, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, Georgia, USA
| | - G M Savage
- Proteus Digital Health, Inc., Redwood City, California, USA
| | - C A Benson
- University of California, San Diego School of Medicine, Division of Infectious Diseases, San Diego, California, USA
| | | |
Collapse
|
|
42
|
Fleming JN, Taber DJ, McElligott J, McGillicuddy JW, Treiber F. Mobile Health in Solid Organ Transplant: The Time Is Now. Am J Transplant 2017; 17:2263-2276. [PMID: 28188681 DOI: 10.1111/ajt.14225] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 01/24/2017] [Accepted: 02/04/2017] [Indexed: 01/25/2023]
Abstract
Despite being in existence for >40 years, the application of telemedicine has lagged significantly in comparison to its generated interest. Detractors include the immobile design of most historic telemedicine interventions and the relative lack of smartphones among the general populace. Recently, the exponential increase in smartphone ownership and familiarity have provided the potential for the development of mobile health (mHealth) interventions that can be mirrored realistically in clinical applications. Existing studies have demonstrated some potential clinical benefits of mHealth in the various phases of solid organ transplantation (SOT). Furthermore, studies in nontransplant chronic diseases may be used to guide future studies in SOT. Nevertheless, substantially more must be accomplished before mHealth becomes mainstream. Further evidence of clinical benefits and a critical need for cost-effectiveness analysis must prove its utility to patients, clinicians, hospitals, insurers, and the federal government. The SOT population is an ideal one in which to demonstrate the benefits of mHealth. In this review, the current evidence and status of mHealth in SOT is discussed, and a general path forward is presented that will allow buy-in from the health care community, insurers, and the federal government to move mHealth from research to standard care.
Collapse
Affiliation(s)
- J N Fleming
- Department of Pharmacy Services, Medical University of South Carolina, Charleston, SC
| | - D J Taber
- Department of Surgery, Medical University of South Carolina, Charleston, SC.,Department of Pharmacy, Ralph H Johnson VAMC, Charleston, SC
| | - J McElligott
- Center for Telehealth, Medical University of South Carolina, Charleston, SC
| | - J W McGillicuddy
- Department of Surgery, Medical University of South Carolina, Charleston, SC
| | - F Treiber
- Technology Center to Advance Healthful Lifestyles, College of Nursing, Medical University of South Carolina, Charleston, SC
| |
Collapse
|
|
43
|
Vallejos X, Wu C. Digital Medicine: Innovative Drug-Device Combination as New Measure of Medication Adherence. J Pharm Technol 2017; 33:137-139. [PMID: 34860983 DOI: 10.1177/8755122517704212] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
In September 2015, the Food and Drug Administration accepted the first digital medicine new drug application for a drug-device combination of Otsuka's Abilify® (aripiprazole) and an ingestible sensor embedded in the tablet that digitally records ingestion. When this digital medicine is taken, it sends a signal to a patch worn by the patient. The information is recorded, time-stamped, and relayed to any Bluetooth-enabled device and, with patients' consent, to their physicians and/or their caregivers. An encapsulation model in which a tablet is co-encapsulated with the ingestible sensor has been successfully used in the setting of renal transplant, diabetes, hypertension, and hypercholesterolemia.
Collapse
|
|
44
|
Frias J, Virdi N, Raja P, Kim Y, Savage G, Osterberg L. Effectiveness of Digital Medicines to Improve Clinical Outcomes in Patients with Uncontrolled Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster-Randomized Pilot Clinical Trial. J Med Internet Res 2017; 19:e246. [PMID: 28698169 PMCID: PMC5527253 DOI: 10.2196/jmir.7833] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 05/24/2017] [Accepted: 06/10/2017] [Indexed: 12/16/2022] Open
Abstract
Background Hypertension and type 2 diabetes mellitus are major modifiable risk factors for cardiac, cerebrovascular, and kidney diseases. Reasons for poor disease control include nonadherence, lack of patient engagement, and therapeutic inertia. Objective The aim of this study was to assess the impact on clinic-measured blood pressure (BP) and glycated hemoglobin (HbA1c) using a digital medicine offering (DMO) that measures medication ingestion adherence, physical activity, and rest using digital medicines (medication taken with ingestible sensor), wearable sensor patches, and a mobile device app. Methods Participants with elevated systolic BP (SBP ≥140 mm Hg) and HbA1c (≥7%) failing antihypertensive (≥2 medications) and oral diabetes therapy were enrolled in this three-arm, 12-week, cluster-randomized study. Participants used DMO (includes digital medicines, the wearable sensor patch, and the mobile device app) for 4 or 12 weeks or received usual care based on site randomization. Providers in the DMO arms could review the DMO data via a Web portal. In all three arms, providers were instructed to make medical decisions (medication titration, adherence counseling, education, and lifestyle coaching) on all available clinical information at each visit. Primary outcome was change in SBP at week 4. Other outcomes included change in SBP and HbA1c at week 12, and low-density lipoprotein cholesterol (LDL-C) and diastolic blood pressure (DBP) at weeks 4 and 12, as well as proportion of patients at BP goal (<140/90 mm Hg) at weeks 4 and 12, medical decisions, and medication adherence patterns. Results Final analysis included 109 participants (12 sites; age: mean 58.7, SD years; female: 49.5%, 54/109; Hispanic: 45.9%, 50/109; income ≤ US $20,000: 56.9%, 62/109; and ≤ high school education: 52.3%, 57/109). The DMO groups had 80 participants (7 sites) and usual care had 29 participants (5 sites). At week 4, DMO resulted in a statistically greater SBP reduction than usual care (mean –21.8, SE 1.5 mm Hg vs mean –12.7, SE 2.8 mmHg; mean difference –9.1, 95% CI –14.0 to –3.3 mm Hg) and maintained a greater reduction at week 12. The DMO groups had greater reductions in HbA1c, DBP, and LDL-C, and a greater proportion of participants at BP goal at weeks 4 and 12 compared with usual care. The DMO groups also received more therapeutic interventions than usual care. Medication adherence was ≥80% while using the DMO. The most common adverse event was a self-limited rash at the wearable sensor site (12%, 10/82). Conclusions For patients failing hypertension and diabetes oral therapy, this DMO, which provides dose-by-dose feedback on medication ingestion adherence, can help lower BP, HbA1c, and LDL-C, and promote patient engagement and provider decision making. Trial Registration Clinicaltrials.gov NCT02827630; https://clinicaltrials.gov/show/NCT02827630 (Archived by WebCite at http://www.webcitation.org/6rL8dW2VF)
Collapse
Affiliation(s)
- Juan Frias
- National Research Institute, Los Angeles, CA, United States
| | | | - Praveen Raja
- Proteus Digital Health, Redwood City, CA, United States
| | - Yoona Kim
- Proteus Digital Health, Redwood City, CA, United States
| | - George Savage
- Proteus Digital Health, Redwood City, CA, United States
| | - Lars Osterberg
- Stanford University, School of Medicine, Stanford, CA, United States
| |
Collapse
|
|
45
|
Gupta C, Moudgil A. Renal transplantation in children: Current status and challenges. APOLLO MEDICINE 2017. [DOI: 10.1016/j.apme.2017.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
|
|
46
|
Belaiche S, Décaudin B, Dharancy S, Noel C, Odou P, Hazzan M. Factors relevant to medication non-adherence in kidney transplant: a systematic review. Int J Clin Pharm 2017; 39:582-593. [PMID: 28374343 DOI: 10.1007/s11096-017-0436-4] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Accepted: 02/06/2017] [Indexed: 01/14/2023]
Abstract
Background Medication non-adherence is a major issue after transplant that can lead to misdiagnosis, rejection, poor health affecting quality of life, graft loss or death. Several estimations of adherence and related factors have previously been described but conclusions leave doubt as to the most accurate assessment method. Aim of the review To identify the factors most relevant to medication non-adherence in kidney transplant in current clinical practice. Method This systematic review is registered in the PROSPERO data base and follows the Prisma checklist. Articles in English in three databases from January 2009 to December 2014 were analysed. A synthesis was made to target adherence assessment methods, their prevalence and significance. Results Thirty-seven studies were analysed rates of non-adherence fluctuating from 1.6 to 96%. Assessment methods varied from one study to another, although self-reports were mainly used. It appears that youth (≤50 years old), male, low social support, unemployment, low education, ≥3 months post graft, living donor, ≥6 comorbidities, ≥5 drugs/d, ≥2 intakes/d, negative beliefs, negative behavior, depression and anxiety were the factors significantly related to non-adherence. Conclusion As there are no established guidelines, consideration should be given to more than one approach to identify medication non-adherence although self-reports should remain the cornerstone of adherence assessment.
Collapse
Affiliation(s)
- Stephanie Belaiche
- Institut de pharmacie, CHU Lille, 59000, Lille, France. .,EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Univ. Lille, 59000, Lille, France.
| | - Bertrand Décaudin
- Institut de pharmacie, CHU Lille, 59000, Lille, France.,EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Univ. Lille, 59000, Lille, France
| | - Sébastien Dharancy
- Service des Maladies de l'appareil digestif et de la Nutrition, CHU Lille, 59000, Lille, France.,Inserm U995 - LIRIC - Lille Inflammation Research International Center, Univ. Lille, 59000, Lille, France
| | - Christian Noel
- Service de Néphrologie, CHU Lille, 59000, Lille, France.,Inserm U995 - LIRIC - Lille Inflammation Research International Center, Univ. Lille, 59000, Lille, France
| | - Pascal Odou
- Institut de pharmacie, CHU Lille, 59000, Lille, France.,EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Univ. Lille, 59000, Lille, France
| | - Marc Hazzan
- Service de Néphrologie, CHU Lille, 59000, Lille, France.,Inserm U995 - LIRIC - Lille Inflammation Research International Center, Univ. Lille, 59000, Lille, France
| |
Collapse
|
|
47
|
Bain EE, Shafner L, Walling DP, Othman AA, Chuang-Stein C, Hinkle J, Hanina A. Use of a Novel Artificial Intelligence Platform on Mobile Devices to Assess Dosing Compliance in a Phase 2 Clinical Trial in Subjects With Schizophrenia. JMIR Mhealth Uhealth 2017; 5:e18. [PMID: 28223265 PMCID: PMC5340925 DOI: 10.2196/mhealth.7030] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 01/06/2017] [Accepted: 02/02/2017] [Indexed: 12/16/2022] Open
Abstract
Background Accurately monitoring and collecting drug adherence data can allow for better understanding and interpretation of the outcomes of clinical trials. Most clinical trials use a combination of pill counts and self-reported data to measure drug adherence, despite the drawbacks of relying on these types of indirect measures. It is assumed that doses are taken, but the exact timing of these events is often incomplete and imprecise. Objective The objective of this pilot study was to evaluate the use of a novel artificial intelligence (AI) platform (AiCure) on mobile devices for measuring medication adherence, compared with modified directly observed therapy (mDOT) in a substudy of a Phase 2 trial of the α7 nicotinic receptor agonist (ABT-126) in subjects with schizophrenia. Methods AI platform generated adherence measures were compared with adherence inferred from drug concentration measurements. Results The mean cumulative pharmacokinetic adherence over 24 weeks was 89.7% (standard deviation [SD] 24.92) for subjects receiving ABT-126 who were monitored using the AI platform, compared with 71.9% (SD 39.81) for subjects receiving ABT-126 who were monitored by mDOT. The difference was 17.9% (95% CI -2 to 37.7; P=.08). Conclusions Using drug levels, this substudy demonstrates the potential of AI platforms to increase adherence, rapidly detect nonadherence, and predict future nonadherence. Subjects monitored using the AI platform demonstrated a percentage change in adherence of 25% over the mDOT group. Subjects were able to use the technology successfully for up to 6 months in an ambulatory setting with early termination rates that are comparable to subjects outside of the substudy. Trial Registration ClinicalTrials.gov NCT01655680 https://clinicaltrials.gov/ct2/show/NCT01655680?term=NCT01655680
Collapse
Affiliation(s)
| | | | | | | | | | - John Hinkle
- EarlyPhase Sciences, Inc., Cary, NC, United States
| | | |
Collapse
|
|
48
|
Pizzo HP, Ettenger RB, Gjertson DW, Reed EF, Zhang J, Gritsch HA, Tsai EW. Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and nonadherence. Pediatr Nephrol 2016; 31:2345-2352. [PMID: 27286686 DOI: 10.1007/s00467-016-3422-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Revised: 05/12/2016] [Accepted: 05/13/2016] [Indexed: 01/06/2023]
Abstract
BACKGROUND Immunosuppression medication nonadherence has been associated with donor-specific antibodies and treatment-refractory rejection. Drug-level monitoring is a practical direct marker for nonadherence, as variations indicate erratic ingestion of medication. We previously reported that high variability in tacrolimus trough levels determined by the percent coefficient of variation (CV %) and standard deviation (SD) were associated with biopsy-proven rejection. We hypothesized that the CV % and SD in patients on a sirolimus/low-dose tacrolimus regimen may associate with self-reported medication nonadherence, rejection and donor-specific antibodies. METHODS In this pilot feasibility study, we studied 37 biopsies in 23 pediatric renal transplant patients on both sirolimus and tacrolimus immunosuppression; CV %, SD, de novo donor-specific antibodies, rejection, and self-reported adherence were examined. RESULTS A cut-off sirolimus CV % of 25 maximized the percentage of biopsies correctly classified as rejection (32 of 37, or 86 %, p = 0.001). A cut-off tacrolimus CV % of 31 maximized the percentage of correctly classified biopsies (25 of 37, or 68 %, p = 0.09). Among patients with both high sirolimus and tacrolimus CV %, 67 % developed de novo donor-specific antibodies (p = 0.002) with a DQ predominance and 71 % reported nonadherence (p = 0.05). CONCLUSIONS In pediatric renal transplantation, sirolimus and tacrolimus CV % is a potential tool for monitoring patients at risk for allograft rejection and donor-specific antibodies secondary to medication nonadherence.
Collapse
Affiliation(s)
- Helen P Pizzo
- Division of Pediatric Nephrology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
| | - Robert B Ettenger
- Division of Pediatric Nephrology, Mattel Children's Hospital UCLA, Los Angeles, CA, USA
| | - David W Gjertson
- UCLA Department of Pathology and Laboratory Medicine, Los Angeles, CA, USA
| | - Elaine F Reed
- UCLA Department of Pathology and Laboratory Medicine, Los Angeles, CA, USA
| | - Jennifer Zhang
- UCLA Department of Pathology and Laboratory Medicine, Los Angeles, CA, USA
| | | | - Eileen W Tsai
- Division of Pediatric Nephrology, Mattel Children's Hospital UCLA, Los Angeles, CA, USA
| |
Collapse
|
|
49
|
Flores GP, Peace B, Carnes TC, Baumgartner SL, Buffkin DE, Euliano NR, Smith LN. Performance, Reliability, Usability, and Safety of the ID-Cap System for Ingestion Event Monitoring in Healthy Volunteers: A Pilot Study. INNOVATIONS IN CLINICAL NEUROSCIENCE 2016; 13:12-19. [PMID: 27974996 PMCID: PMC5141592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Background: Nonadherence to prescribed medications is an important consideration in the clinical management of patients and in clinical research and drug development. The ID-Cap System is a novel technology that provides an objective measure of medication ingestion and enables real-time reporting of verified medication adherence data at the dose level. The ID-Cap System consists of an ingestible microsensor that is embedded in an oral dosage form and, once activated by stomach fluid, communicates digital messages to an external wearable reader to confirm ingestion. Objective: The objective of this exploratory study was to evaluate the performance, reliability, usability, and safety of the ID-Cap System for remote monitoring of 20 ingestion events over four weeks in 20 healthy volunteers. Design: This study was an open-label, single-arm, exploratory study of the ID-Cap System. The study design included the following three phases: 1) screening phase, 2) treatment phase consisting of 20 daily capsule ingestion events over a four-week period, and 3) follow-up phase consisting of a follow-up study visit that included an abdominal X-ray and a follow-up phone call. The initial use of the ID-Cap Reader and ingestion of the first study capsule were directly observed by the investigator during the first study visit. Subsequent study capsule ingestions were completed outside the research facility at the study participant's home or other location of his or her choice with ingestion assessed using the ID-Cap System. Setting: The study was conducted at a single clinical research site in Gainesville, Florida. Participants: Twenty healthy volunteers were enrolled in this four-week pilot study that was conducted between September and November 2014. Measurements: Study measurements included ID-Tag detection indicating capsule ingestion, utilization of the ID-Cap System consistent with instructions for use, adverse event reports, discontinuations of the System during the study, and safety assessments related to excretion of the ID-Tags through abdominal X-ray evaluations. Results: Positive detection accuracy was 100 percent for the 20 directly observed ingestions of study capsules that occurred during the initial study visits. Of the 384 ingestion events that were self-administered by the study participants without direct observation, 371 were accurately detected using the ID-Cap System. Overall adherence to the prescribed study capsules as measured by the ID-Cap System was 97.75 percent (391 detections/400 expected ingestion events). Significant intra-individual and inter-individual variability in the timing of self-administered doses was observed in this study. No adverse events were reported, and no study participants discontinued use of the ID-Cap System for any reason during the study. There was no evidence indicating retention of ID-Tags based on abdominal X-ray evaluations. Conclusion: The ID-Cap System enables accurate measurement of medication adherence for oral drug therapy at the dose level. This study supports the clinical validation of the technology and feasibility in using the system for the collection and real-time reporting of medication adherence in the clinical management of patients and in clinical research and drug development.
Collapse
Affiliation(s)
- Glen P Flores
- Drs. Flores, Carnes, Euliano, Mr. Peace, and Mr. Buffkin are with etectRx, Inc. in Newberry, Florida; and Drs. Baumgartner and Smith are from Gainesville, Florida
| | - Brian Peace
- Drs. Flores, Carnes, Euliano, Mr. Peace, and Mr. Buffkin are with etectRx, Inc. in Newberry, Florida; and Drs. Baumgartner and Smith are from Gainesville, Florida
| | - Tony C Carnes
- Drs. Flores, Carnes, Euliano, Mr. Peace, and Mr. Buffkin are with etectRx, Inc. in Newberry, Florida; and Drs. Baumgartner and Smith are from Gainesville, Florida
| | - Susan L Baumgartner
- Drs. Flores, Carnes, Euliano, Mr. Peace, and Mr. Buffkin are with etectRx, Inc. in Newberry, Florida; and Drs. Baumgartner and Smith are from Gainesville, Florida
| | - D Eric Buffkin
- Drs. Flores, Carnes, Euliano, Mr. Peace, and Mr. Buffkin are with etectRx, Inc. in Newberry, Florida; and Drs. Baumgartner and Smith are from Gainesville, Florida
| | - Neil R Euliano
- Drs. Flores, Carnes, Euliano, Mr. Peace, and Mr. Buffkin are with etectRx, Inc. in Newberry, Florida; and Drs. Baumgartner and Smith are from Gainesville, Florida
| | - Larry N Smith
- Drs. Flores, Carnes, Euliano, Mr. Peace, and Mr. Buffkin are with etectRx, Inc. in Newberry, Florida; and Drs. Baumgartner and Smith are from Gainesville, Florida
| |
Collapse
|
|
50
|
Doyle IC, Maldonado AQ, Heldenbrand S, Tichy EM, Trofe-Clark J. Nonadherence to therapy after adult solid organ transplantation: A focus on risks and mitigation strategies. Am J Health Syst Pharm 2016; 73:909-20. [PMID: 27189855 DOI: 10.2146/ajhp150650] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Affiliation(s)
- Ian C Doyle
- School of Pharmacy, Pacific University, Hillsboro, OR.
| | | | - Seth Heldenbrand
- Office of Experiential Education, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR
| | - Eric M Tichy
- Department of Pharmacy, Yale-New Haven Hospital, New Haven, CT
| | - Jennifer Trofe-Clark
- Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PARenal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| |
Collapse
|