HCI-modelling for improving the clinical usability of digital health technologies.

INTRODUCTION: Digital Health Technologies (DHTs) have been shown to have variable usability as measured by efficiency, effectiveness and user satisfaction despite large-scale government projects to regulate and standardise user interface (UI) design. We hypothesised that Human-Computer Interaction (HCI) modelling could improve the methodology for DHT design and regulation, and support the creation of future evidence-based UI standards and guidelines for DHTs. METHODOLOGY: Using a Design Science Research (DSR) framework, we developed novel UI components that adhered to existing standards and guidelines (combining the NHS Common User Interface (CUI) standard and the NHS Design System). We firstly evaluated the Patient Banner UI component for compliance with the two guidelines and then used HCI-modelling to evaluate the "Add New Patient" workflow to measure time to task completion and cognitive load. RESULTS: Combining the two guidelines to produce new UI elements is technically feasible for the Patient Banner and the Patient Name Input components. There are some inconsistencies between the NHS Design System and the NHS CUI when implementing the Patient Banner. HCI-modelling successfully quantified challenges adhering to the NHS CUI and the NHS Design system for the "Add New Patient" workflow. DISCUSSION: We successfully developed new design artefacts combing two major design guidelines for DHTs. By quantifying usability issues using HCI-modelling, we have demonstrated the feasibility of a methodology that combines HCI-modelling into a human-centred design (HCD) process could enable the development of standardised UI elements for DHTs that is more scientifically robust than HCD alone. CONCLUSION: Combining HCI-modelling and Human-Centred Design could improve scientific progress towards developing safer and more user-friendly DHTs.

The Diaspora Human Genomics Institute Launches the Together for Change Initiative: A Transformative, Historic Partnership to Ensure Health Equity in a Time of Unprecedented Technological Advancements.

Human subjects research and drug and device development currently base their findings largely on the genetic data of the non-Hispanic White population, excluding People of Color. This practice puts People of Color at a distinct and potentially deadly disadvantage in being treated for sickness, disability, and disease, as seen during the COVID-19 pandemic. Major disparities exist in all chronic health conditions, including cancer. Data show that less than 2% of genetic information being studied today originates from people of African ancestry. If genomic datasets do not adequately represent People of Color, new drugs and genetic therapies may not work as well as for people of European descent. Addressing the urgent concern that historically marginalized people may again be excluded from the next technological leap affecting human health and the benefits it will bring will requires a paradigm shift. Thus, on behalf of underserved and marginalized people, we developed the Together for CHANGE (T4C) initiative as a unique collaborative public-private partnership to address the concern. The comprehensive programs designed in the T4C initiative, governed by the Diaspora Human Genomics Institute founded by Meharry Medical College, will transform the landscape of education and health care and positively affect global Black communities for decades to come.

Exploring the approach to parameter uncertainty in early economic evaluations of surgical technology - a systematic review.

INTRODUCTION: The role of early economic evaluation (EEE) in the development of medical technology has been increasingly recognized; however, data on the use of EEE in surgical technology are sparse. The objective of this review was to explore the use of EEE in the development of surgical technologies, with emphasis on how uncertainty has been addressed. AREAS COVERED: A systematic review was conducted, and original articles employing any form of EEE of surgical technology were selected for review, with 10 studies included in the analysis. These studies demonstrated significant variation in the approach to managing parameter uncertainty, specifically regarding the type of analysis used and the inclusion of effectiveness parameters in sensitivity analysis. The conclusions drawn did not appear to factor in uncertainty in the models. EXPERT OPINION: Approaches to handling parameter uncertainty in previous EEEs of surgical technology have been limited, with some studies failing to address parameter uncertainty. In addition, EEEs do not appear to follow established guidelines with respect to the use of sensitivity analyses. It is important that EEEs of surgical technology address parameter uncertainty in order to draw more robust conclusions from the analysis and allow investors to consider this uncertainty when making investment decisions.

Effects of Healthcare Technologies on the Promotion of Physical Activities in Older Persons: A Systematic Review.

This study aimed to explore the effects of health technologies on the promotion of health through physical activities of older persons. Following PRISMA guidelines, a systematic review of relevant articles published prior to 2020 was conducted from selected indices such as COCHRANE, PubMed, Science Direct, Proquest, including the use of hand search procedure. Twenty-seven articles were analyzed with significant findings influential to older people nursing: types of health technologies used for promoting physical activity; effects of technology use in promoting physical activity of older person care; and aspects that need to be considered in technology use among older persons. Characteristics of technologies were accuracy, usefulness, reliability, comfort, safety, and relevancy. Most technologies promoting physical activities for older people were wearable technologies that use artificial intelligence. Altogether, these technologies influenced overall healthcare behaviors of older persons. With healthcare technology efficiencies, proficiencies, and dependencies, technology-based healthcare have served older people well. Most technologies for older people care, such as wearables, reliably produce characteristics enhancing dependency and accuracy of bio-behavioral information influencing physical activities of older persons. Health technologies foster the values of physical activities among older persons thereby promoting healthy living.

Las normas técnicas para la formación en ingeniería biomédica, tecnología y administración en salud / Technical standards for the training in biomedical engineering, health technology and health management

Introducción: Los documentos normativos establecen el estado del arte relacionado con determinado campo del conocimiento. Existe una gran cantidad de normas relacionadas con los servicios de salud y su gestión, cuya aplicación es relevante en este sector. Objetivo: Exponer la importancia de las normas técnicas en la formación de los profesionales en ingeniería biomédica, tecnología y administración en salud. Desarrollo: Diferentes aspectos relacionados con el desempeño y las funciones de los profesionales en ingeniería biomédica, tecnología de la salud y administración en salud están recogidos en normas técnicas internacionales y en otras de carácter nacional, que resultan pertinentes y de gran utilidad para su formación en el nivel de grado y el posgrado. Conclusiones: Las profesiones abordadas requieren emplear los documentos normativos relacionados con sus funciones para contribuir con la calidad de los servicios de salud; de ahí la pertinencia de su incorporación en los planes de estudio de estas carreras(AU)

Introduction: Normative documents establish the state of the art related to a certain field of knowledge. There is a large number of standards related to health services and their management, whose application is relevant in this sector. Objective: To show the importance of technical standards in the training of professionals from the fields of biomedical engineering, health technology and health management. Development: Different aspects related to the performance and functions of professionals from the fields of biomedical engineering, health technology and health management are gathered in international and other national technical standards, relevant and useful for their training at the undergraduate and postgraduate levels. Conclusions: The addressed professions require the use of normative documents related to their functions in order to contribute to the quality of health services, hence the relevance of their incorporation into the curriculums of these major(AU)

Do Health Technology Safety Issues Vary by Vendor?

There is a need to determine the relative similarity and differences in safety issues across specific types of software and medical devices in order to develop standardized solutions that can be used across these technologies. Over the past several years, health informatics researchers have identified differing types of technology-induced errors or safety issues. This work has led to a literature that has been effective in identifying varying technology-induced errors. Less effort has been made in attempting to understand if there are common types of safety issues and outcomes across vendors for specific types of technology such as electronic health records (EHRs). Our findings demonstrate that some safety issues are common across the same type of software. The findings suggest there is a need to develop standardized approaches to managing technology-induced errors.

Digital Technology Application for Improved Responses to Health Care Challenges: Lessons Learned From COVID-19.

While COVID-19 is still ongoing and associated with more than 5 million deaths, the scope and speed of advances over the past year in terms of scientific discovery, data dissemination, and technology have been staggering. It is not a matter of "if" but "when" we will face the next pandemic, and how we leverage technology and data management effectively to create flexible ecosystems that facilitate collaboration, equitable care, and innovation will determine its severity and scale. The aim of this review is to address emerging challenges that came to light during the pandemic in health care and innovations that enabled us to adapt and continue to care for patients. The pandemic highlighted the need for seismic shifts in care paradigms and technology with considerations related to the digital divide and health literacy for digital health interventions to reach full potential and improve health outcomes. We discuss advances in telemedicine, remote patient monitoring, and emerging wearable technologies. Despite the promise of digital health, we emphasise the importance of addressing its limitations, including interpretation challenges, accuracy of findings, and artificial intelligence-driven algorithms. We summarise the most recent recommendation of the Virtual Care Task Force to scaling virtual medical services in Canada. Finally, we propose a model for optimal implementation of health digital innovations with 5 tenets including data management, data security, digital biomarkers, useful artificial intelligence, and clinical integration.

Health data poverty: an assailable barrier to equitable digital health care.

Data-driven digital health technologies have the power to transform health care. If these tools could be sustainably delivered at scale, they might have the potential to provide everyone, everywhere, with equitable access to expert-level care, narrowing the global health and wellbeing gap. Conversely, it is highly possible that these transformative technologies could exacerbate existing health-care inequalities instead. In this Viewpoint, we describe the problem of health data poverty: the inability for individuals, groups, or populations to benefit from a discovery or innovation due to a scarcity of data that are adequately representative. We assert that health data poverty is a threat to global health that could prevent the benefits of data-driven digital health technologies from being more widely realised and might even lead to them causing harm. We argue that the time to act is now to avoid creating a digital health divide that exacerbates existing health-care inequalities and to ensure that no one is left behind in the digital era.

The Isolation and Manufacture of GMP-Grade Bone Marrow Stromal Cells from Bone Specimens.

Bone marrow stromal cells (BMSCs, also known as bone marrow mesenchymal stem cells) are a plastic-adherent heterogeneous cell population that contain inherent skeletal progenitors and a subset of multipotential skeletal stem cells (SSCs). Application of BMSCs in therapeutic protocols implies its isolation and expansion under good manufacturing practices (GMP). Here we describe the procedures we have found to successfully generate practical BMSCs numbers, with preserved biological potency.

Quality Management Systems (QMSs) of Human-Based Tissue and Cell Product Manufacturing Facilities.

In the broadest sense, a quality management system (QMS) runs by continuous interaction of elements based on processes, procedures, policies, guidelines, and resources that are compiled to guide an organization under the scope of its operational mission, vision, and objectives. QMSs in the biopharmaceutical sector defines a written and applied set of rules which aids in improvement of the quality of biopharmaceutical process engineering, while primarily assuring human tissue- and cell-based starting material and end product safety and minimizing the risk of human medicinal product recall, in the most cost-effective ways possible. This chapter aims to outline the crucial position of a QMS under the scope of good practices (GxPs) in the biopharmaceutical industry, as regards human tissue- and cell-based products.

Addressing Manufacturing Challenges for Commercialization of iPSC-Based Therapies.

The development of reprogramming technology to generate human induced pluripotent stem cells (iPSCs) has tremendously influenced the field of regenerative medicine and clinical therapeutics where curative cell replacement therapies can be used in the treatment of devastating diseases such as Parkinson's disease (PD) and diabetes. In order to commercialize these therapies to treat a large number of individuals, it is important to demonstrate the safety and efficacy of these therapies and ensure that the manufacturing process for iPSC-derived functional cells can be industrialized at an affordable cost. However, there are a number of manufacturing obstacles that need to be addressed in order to meet this vision. It is important to note that the manufacturing process for generation of iPSC-derived specialized cells is relatively long and fairly complex and requires differentiation of high-quality iPSCs into specialized cells in a controlled manner. In this chapter, we have summarized our efforts to address the main challenges present in the industrialization of iPSC-derived cell therapy products with focus on the development of a current Good Manufacturing Practice (cGMP)-compliant iPSC manufacturing process, a comprehensive iPSC characterization platform, long-term stability of cGMP compliant iPSCs, and innovative technologies to address some of the scale-up challenges in establishment of iPSC processing in 3D computer-controlled bioreactors.

Swiss Fetal Transplantation Program and Non-enzymatically Isolated Primary Progenitor Cell Types for Regenerative Medicine.

Primary progenitor cell types adequately isolated from fetal tissue samples present considerable therapeutic potential for a wide range of applications within allogeneic musculoskeletal regenerative medicine. Progenitor cells are inherently differentiated and extremely stable in standard bioprocessing conditions and can be culture-expanded to establish extensive and robust cryopreserved cell banks. Stringent processing conditions and exhaustive traceability are prerequisites for establishing a cell source admissible for further cGMP biobanking and clinical-grade production lot manufacture. Transplantation programs are ideal platforms for the establishment of primary progenitor cell sources to be used for manufacture of cell therapies or cell-based products. Well-defined and regulated procurement and processing of fetal biopsies after voluntary pregnancy interruptions ensure traceability and safety of progeny materials and therapeutic products derived therefrom. We describe herein the workflows and specifications devised under the Swiss Fetal Progenitor Cell Transplantation Program in order to traceably isolate primary progenitor cell types in vitro and to constitute Parental Cell Banks fit for subsequent industrial-scale cGMP processing. When properly devised, derived, and maintained, such cell sources established after a single organ donation can furnish sufficient progeny materials for years of development in translational musculoskeletal regenerative medicine.

Scalable Manufacturing of Human Hematopoietic Stem/Progenitor Cells Exploiting a Co-culture Platform with Mesenchymal Stromal Cells.

In the context of hematopoietic cell transplantation, hematopoietic stem/progenitor cells (HSPC) from the umbilical cord blood (UCB) present several advantages compared to adult sources including higher proliferative capacity, abundant availability and ease of collection, non-risk and painless harvesting procedure, and lower risk of graft-versus-host disease. However, the therapeutic utility of UCB HSPC has been limited to pediatric patients due to the low cell frequency per unit of UCB. The development of efficient and cost-effective strategies to generate large numbers of functional UCB HSPC ex vivo would boost all current and future medical uses of these cells. Herein, we describe a scalable serum-free co-culture system for the expansion of UCB-derived CD34+-enriched cells using microcarrier-immobilized human bone marrow-derived mesenchymal stromal cells as feeder cells.

GMP-Compliant Adenoviral Vectors for Gene Therapy.

Recently, gene therapy as one of the most promising treatments can apply genes for incurable diseases treatment. In this context, vectors as gene delivery systems play a pivotal role in gene therapy procedure. Hereupon, viral vectors have been increasingly introduced as a hyper-efficient tools for gene therapy. Adenoviral vectors as one of the most common groups which are used in gene therapy have a high ability for humans. Indeed, they are not integrated into host genome. In other words, they can be adapted for direct transduction of recombinant proteins into targeted cells. Moreover, they have large packaging capacity and high levels of efficiency and expression. In accordance with translational pathways from the basic to the clinic, recombinant adenoviral vectors packaging must be managed under good manufacturing practice (GMP) principles before applying in clinical trials. Therein, in this chapter standard methods for manufacturing of GMP-compliant Adenoviral vectors for gene therapy have been introduced.

Validation of the Media Fill Method for Solid Tissue Processing in Good Manufacturing Practice-Compliant Cell Production.

Over the past few years, a large number of clinical studies for advanced therapy medicinal products have been registered and/or conducted for treating various diseases around the world and many have generated very exciting outcomes. Media fill, the validation of the aseptic manufacturing process, is the simulation of medicinal product manufacturing using nutrient media. The purpose of this study is to explain the media fill procedure stepwise in the context of cellular therapy medicinal products. The aseptic preparation of patient individual cellular product is simulated by using tryptic soy broth as the growth medium, and sterile vials as primary packaging materials.

Isolation, Culture, Cryopreservation, and Preparation of Umbilical Cord-Derived Mesenchymal Stem Cells as a Final Cellular Product Under Good Manufacturing Practices-Compliant Conditions.

Mesenchymal stem cells have gained popularity in cell-based therapies due to their regenerative capabilities, immunomodulation properties, and paracrine activity through trophic factors. It is of utmost importance to establish clinical-grade procedures for the preparation of the mesenchymal stem cells for clinical applications. Here, we describe detailed procedures for isolation, culture, cryopreservation, and preparation of mesenchymal stem cells derived from umbilical cord as a final product under good manufacturing practices-compliant conditions.

Isolation, Culture, Cryopreservation, and Preparation of Skin-Derived Fibroblasts as a Final Cellular Product Under Good Manufacturing Practice-Compliant Conditions.

Cell-based therapies have become a popular approach in the field of regenerative medicine. Human fibroblast cells, one of the cell types widely used in clinical applications, have been used for skin regeneration and wound healing procedures. Furthermore, they are utilized for aesthetic purposes since fibroblasts lose their abilities such as collagen synthesis with age. Here, we describe detailed procedures for isolation, culture, cryopreservation, and preparation of fibroblasts derived from adult human skin as a final product under good manufacturing practice-compliant conditions.

GMP-Compatible, Xeno-Free Culture of Human Induced Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have been used in therapies owing to their regenerative potential, paracrine regulatory effects, and immunomodulatory activity. To foster commercialization and implementation of stem cells treatments, researchers have recently derived MSCs from human induced pluripotent stem cells (iMSCs). For therapeutic applications, human iMSCs must be produced in xeno-free culture conditions and following procedures that are compatible with the principles of Good Manufacturing Practice.

GMP-Grade Methods for Cardiac Progenitor Cells: Cell Bank Production and Quality Control.

Cardiac explant-derived cells (cEDC), also referred as cardiac progenitors cells (CPC) (Barile et al., Cardiovasc Res 103(4):530-541, 2014; Barile et al., Cardiovasc Res 114(7):992-1005, 2018), represent promising candidates for the development of cell-based therapies, a novel and interesting treatment for cardioprotective strategy in heart failure (Kreke et al., Expert Rev Cardiovasc Ther 10(9):1185-1194, 2012). CPC have been tested in a preclinical setting for direct cell transplantation and tissue engineering or as a source for production of extracellular vesicles (EV) (Oh et al., J Cardiol 68(5):361-367, 2016; Barile et al., Eur Heart J 38(18):1372-1379, 2017; Rosen et al., J Am Coll Cardiol 64(9):922-937, 2014). CPC cultured as cardiospheres derived cells went through favorable Phase 1 and 2 studies demonstrating safety and possible efficacy (Makkar et al., Lancet 379(9819):895-904, 2012; Ishigami et al., Circ Res 120(7):1162-1173, 2017; Ishigami et al., Circ Res 116 (4):653-664, 2015; Tarui et al., J Thorac Cardiovasc Surg 150(5):1198-1207, 1208 e1191-1192, 2015). In this context and in view of clinical applications, cells have to be prepared and released according to Good Manufacturing Practices (GMP) (EudraLex-volume 4-good manufacturing practice (GMP) guidelines-Part I-basic requirements for medicinal products. http://ec.europa.eu/health/documents/eudralex/vol-4 ; EudraLex-volume 4-good manufacturing practice (GMP) guidelines-Part IV-guidelines on good manufacturing practices specific to advanced therapy medicinal products. http://ec.europa.eu/health/documents/eudralex/vol-4 ). This chapter describes GMP-grade methods for production and testing of a CPC Master Cell Bank (MCB), consisting of frozen aliquots of cells that may be used either as a therapeutic product or as source for the manufacturing of Exo for clinical trials.The MCB production method has been designed to isolate and expand CPC from human cardiac tissue in xeno-free conditions (Andriolo et al., Front Physiol 9:1169, 2018). The quality control (QC) methods have been implemented to assess the safety (sterility, endotoxin, mycoplasma, cell senescence, tumorigenicity) and identity/potency/purity (cell count and viability, RT-PCR, immunophenotype) of the cells (Andriolo et al., Front Physiol 9:1169, 2018).