Challenges In Delivery Research Articles

Polymer nanotherapeutics: A promising approach toward microglial inhibition in neurodegenerative diseases.

Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve therapeutic transport and efficacy across the blood-brain barrier (BBB). CNS nanotherapeutics mostly target neurons and endothelial cells, however, microglial immune cells are the first line of defense against neuronal damage and brain infections. Through triggering release of inflammatory cytokines, chemokines and proteases, microglia can however precipitate neurological damage-a significant factor in neurodegenerative diseases. Thus, microglial inhibitory agents are attracting much attention among those researching and developing novel treatments for neurodegenerative disorders. The most established inhibitors of microglia investigated to date are resveratrol, curcumin, quercetin, and minocycline. Thus, there is great interest in developing novel agents that can bypass or easily cross the BBB. One such approach is the use of modified-nanocarriers as, or for, delivery of, therapeutic agents to the brain and wider CNS. For microglial inhibition, polymeric NPs are the preferred vehicles for choice. Here, we summarize the immunologic and neuroinflammatory role of microglia, established microglia inhibitor agents, challenges of CNS drug delivery, and the nanotherapeutics explored for microglia inhibition to date. We also discuss applications of the currently considered "most useful" polymeric NPs for microglial-inhibitor drug delivery in CNS-related diseases.

Recent advances in nanogels for drug delivery and biomedical applications.

Nanotechnology has shown great promise for researchers to develop efficient nanocarriers for better therapy, imaging, and sustained release of drugs. The existing treatments are accompanied by serious toxicity limitations, leading to severe side effects, multiple drug resistance, and off-target activity. In this regard, nanogels have garnered significant attention for their multi-functional role combining advanced therapeutics with imaging in a single platform. Nanogels can be functionalized to target specific tissues which can improve the efficiency of drug delivery and other challenges associated with the existing nanocarriers. Translation of nanogel technology requires more exploration towards stability and enhanced efficiency. In this review, we present the advances and challenges related to nanogels for cancer therapy, ophthalmology, neurological disorders, tuberculosis, wound healing, and anti-viral applications. A perspective on recent research trends of nanogels for translation to clinics is also discussed.

Advancements in nanotheranostics for glioma therapy.

Gliomas are brain tumors mainly derived from glial cells that are difficult to treat and cause high mortality. Radiation, chemotherapy, and surgical excision are the conventionaltreatments for gliomas. Patients who have surgery or have undergone chemotherapy for glioma treatment have poor prognosis with tumor recurrence. In particular, for glioblastoma,the 5-year averagesurvival rateis 4-7%, and the median survival is 12-18months. Anumber of issues hinder effective treatmentsuch as, poor surgical resection, tumor heterogeneity, insufficient drug penetration across the blood-brain barrier, multidrug resistance, and difficulties with drug specificity. Nanotheranostic-mediated drug delivery is becoming a well-researched consideration, and an efficient non-invasive method for delivering chemotherapeutic drugs to the target area. Theranostic nanomedicines, which incorporate therapeutic drugs and imaging agents forpersonalized therapies, can be used for preventing overdose of non-responders. Through the identification of massive and complicated information from next-generation sequencing, machine learning enables for precise prediction of therapeutic outcomes and post-treatment management for patients with cancer. This article gives a thorough overview of nanocarrier-mediated drug delivery with a brief introduction to drug delivery challenges. In addition, this assessment offers a current summary of preclinical and clinical research on nanomedicines for gliomas. In the future, nanotheranostics will provide personalized treatment for gliomas and other treatable cancers.

Development of bioconjugate-based delivery systems for nucleic acids.

Nucleic acids are a class of drugs that can modulate gene and protein expression by various mechanisms, namely, RNAi, mRNA degradation by RNase H cleavage, splice modulation, and steric blocking of protein binding or mRNA translation, thus exhibiting immense potential to treat various genetic and rare diseases. Unlike protein-targeted therapeutics, the clinical use of nucleic acids relies on Watson-Crick sequence recognition to regulate aberrant gene expression and impede protein translation. Though promising, targeted delivery remains a bottleneck for the clinical adoption of nucleic acid-based therapeutics. To overcome the delivery challenges associated with nucleic acids, various chemical modifications and bioconjugation-based delivery strategies have been explored. Currently, liver targeting by N-acetyl galactosamine (GalNAc) conjugation has been at the forefront for the treatment of rare and various metabolic diseases, which has led to FDA approval of four nucleic acid drugs. In addition, various other bioconjugation strategies have been explored to facilitate active organ and cell-enriched targeting. This review briefly covers the different classes of nucleic acids, their mechanisms of action, and their challenges. We also elaborate on recent advances in bioconjugation strategies in developing a diverse set of ligands for targeted delivery of nucleic acid drugs.

Virtual Hospitals and Patient Experience: Protocol for a Mixed Methods Observational Study.

Virtual care is increasingly incorporated within routine health care settings to improve patient experience and access to care. A patient's experience encompasses all the interactions an individual has with the health care system. This includes a greater emphasis on actively involving carers in the decisions and activities surrounding a patient's health care. This study aimed to investigate the variety of health care delivery challenges encountered in a virtual hospital and explore potential ways to improve the patient experience. Focusing on acute respiratory, this protocol outlines a mixed methods study exploring the patient experience of a virtual hospital in Australia, Royal Prince Alfred Virtual Hospital (rpavirtual). We will use an exploratory mixed methods approach comprising of secondary data analysis, observations, interviews, and co-design focus groups. Participants will include patients, their carers, and health care workers who are involved in the acute respiratory virtual hospital model of care. Together, the data will be triangulated to explore views and experiences of using this model of care, as well as co-designing recommendations for further improvement. Findings from this study will identify current barriers and facilitators to implementing virtual care, such as work-as-done versus work-as-imagined, equity of care, the role of carers, and patient safety during virtual care. As of August 2024, a total of 25 participants have been interviewed. This protocol outlines a mixed methods case study on the acute respiratory model of care from Australia's first virtual hospital, rpavirtual. This study will collect the experiences of patients, carers, and health care workers to co-design a series of recommendations to improve the patient experience. DERR1-10.2196/58683.

Factors influencing protective gear use in crisis-affected Afghanistan during COVID-19

Abstract Background Afghanistan has faced considerable challenges in healthcare delivery during the COVID-19 pandemic. These challenges were compounded by limited health literacy, shortages of skilled health workers, and fragile health infrastructure, which increased the country’s double burden of disease. The World Health Organization (WHO) recommended the use of masks as part of a comprehensive strategy to mitigate the spread of SARS-CoV-2. Nevertheless, research on mask-wearing practices in Afghanistan is limited. This study aims to investigate the factors influencing the wearing of protective gear, including masks, during the COVID-19 pandemic in Afghanistan. Methods This study analyzed 16,058 households from the 2020 Afghanistan Multi-Sector Needs Assessment (MSNA) survey data. This survey was conducted between August and September 2020 by the Racial and Ethnic Approaches to Community Health (REACH) Initiative. Sampling weighted multivariable binary logistic regression analysis was performed. Results Recent internally displaced persons (IDPs) and returnees in Afghanistan were more likely to wear protective gear to prevent COVID-19 compared to non-recent IDPs. Factors such as household sizes, household income, knowledge of humanitarian support, and the distance to healthcare facilities were significantly associated with the likelihood of wearing protective gear. Conclusions The study suggests that certain factors place crisis-affected populations in Afghanistan at high risk in COVID-19 preventive behaviors, especially in wearing protective gear. The findings in this study indicate that public health interventions should focus on improving healthcare accessibility and enhancing information dissemination while considering socioeconomic factors. Additionally, this study highlights the need for access to personal protective gear during outbreaks of infectious disease, such as the COVID-19 pandemic. Key messages • Socioeconomic factors and accessibility on health services and information can affect COVID-19 preventive behaviors in crisis-affected populations. • This study can inform public health professionals to develop adequate interventions during infectious disease outbreaks.

Evidencing the challenges of care delivery for people with intellectual disability and epilepsy in England by using the Step Together toolkit.

People with intellectual disability (PwID) and epilepsy have increased premature and potentially preventable mortality. This is related to a lack of equitable access to appropriate care. The Step Together guidance and toolkit, developed with patient, clinical, charity and commissioning stakeholders, allows evaluation and benchmarking of essential epilepsy service provision for PwID in eight key domains, at a care system level. To evaluate care provisions for adult PwID and epilepsy at a system level in the 11 integrated care systems (ICSs) of the Midlands, the largest NHS England region (population: approximately 11 million), using the Step Together toolkit. Post training, each ICS undertook its benchmarking with the toolkit and submitted their scores to Epilepsy Action, a national UK epilepsy charity, who oversaw the process. The outcomes were analysed descriptively to provide results, individual and cumulative, at care domain and system levels. The toolkit was completed fully by nine of the 11 ICSs. Across all eight domains, overall score was 44.2% (mean 44.2%, median 43.3%, range 52.4%, interquartile range 23.8-76.2%). The domains of local planning (mean 31.1%, median 27.5%) and care planning (mean 31.4%, median 35.4%) scored the lowest, and sharing information scored the highest (mean 55.2%, median 62.5%). There was significant variability across each domain between the nine ICS. The user/carer participation domain had the widest variation across ICSs (0-100%). The results demonstrate a significant variance in service provision for PwID and epilepsy across the nine ICSs. The toolkit identifies specific areas for improvement within each ICS and region.

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

Comprehensive insights into glioblastoma multiforme: drug delivery challenges and multimodal treatment strategies.

Glioblastoma multiforme (GBM) is one of the most common and malignant brain tumors, with a high prevalence in elderly population. Most chemotherapeutic agents fail to reach the tumor site due to various challenges. However, smart nanocarriers have demonstrated excellent drug-loading capabilities, enabling them to cross the blood brain tumor barrier for the GBM treatment. Surface modification of nanocarriers has significantly enhanced their potential for targeting therapeutics. Moreover, recent innovations in drug therapies, such as the incorporation of theranostic agents in nanocarriers and antibody-drug conjugates, have offered newer insights for both diagnosis and treatment. This review focuses on recent advances in new therapeutic interventions for GBM, with an emphasis on the nanotheranostics systems to maximize therapeutic and diagnostic outcomes.

Вопросы обеспечения запасных магазинов в Якутской области в 40-х гг. XIX в.

The article examines the organization and provisioning of spare stores in the Yakutsk region during the 1840s, which played a crucial role in ensuring the region’s food security. These stores were part of a broader state system aimed at accumulating food supplies for public use during periods of crisis. The author investigates historical documents that describe contracts, supply logistics, and storage conditions, shedding light on critical issues such as delivery challenges, food spoilage, and supplier reliability. The analysis focuses on the measures implemented by authorities to address these challenges, emphasizing the significance of centralized management, quality control, and timely delivery. This study contributes to an understanding of the complex logistics of managing food reserves in the harsh and remote regions of the country, such as Yakutia.

Integrated development plan strategies for service delivery in Nelson Mandela Metropolitan Municipality

Background: Following the end of apartheid in 1994, the democratic government recognised the importance of local government as a key vehicle for service delivery.Aim: This article examined the effectiveness of the integrated development plan (IDP) strategies of the Nelson Mandela Metropolitan Municipality (NMMM) as a public service delivery tool.Setting: In South Africa, poor service delivery has remained a challenge. This has been attributed to the challenge of transparency and accountability. Thus, the lack of access to basic needs is more profound at the local government level. While urban centres have access to certain basic facilities, rural communities such as Walmer and Motherwell townships remain underdeveloped.Methods: The study used a qualitative research design for data collection and analysis. Thirty participants were purposively selected among municipal officials, ward councillors and community members for semi-structured interviews. Thematic data analysis was used for the analysis of data.Results: Despite the IDP’s well-structured strategic framework, various challenges, such as insufficient community participation, inadequate resource allocation and a lack of essential planning skills among officials hindered its effective implementation.Conclusion: The study concluded that for the IDP to achieve its aims, its implementation should be evidence-based and responsive to community needs. Effective service delivery requires a fundamental transformation in municipal leadership and public participation.Contribution: The article presents the challenge of public service delivery within the context of the IDP strategies in a specific municipality. It serves as a signpost for understanding the implementation of the IDP as a public service delivery strategy.

A Non-Invasive and DNA-free Approach to Upregulate Mammalian Voltage-Gated Calcium Channels and Neuronal Calcium Signaling via Terahertz Stimulation.

Mammalian voltage-gated calcium channels (CaV) play critical roles in cardiac excitability, synaptic transmission, and gene transcription. Dysfunctions in CaV are implicated in a variety of cardiac and neurodevelopmental disorders. Current pharmacological approaches to enhance CaV activity are limited by off-target effects, drug metabolism issues, cytotoxicity, and imprecise modulation. Additionally, genetically-encoded channel activators and optogenetic tools are restricted by gene delivery challenges and biosafety concerns. Here a novel terahertz (THz) wave-based method to upregulate CaV1.2, a key subtype of CaV, and boost CaV1-mediated Ca2+ signaling in neurons without introducing exogenous DNA is presented. Using molecular dynamics simulations, it is shown that 42.5 THz (7.05µm, 1418cm-1) waves enhance Ca2+ conductance in CaV1.2 by resonating with the stretching mode of the -COO- group in the selectivity filter. Electrophysiological recordings and Ca2+ imaging confirm that these waves rapidly, reversibly, and non-thermally increase calcium influx of CaV1.2 in HEK293 cells and induce acute Ca2+ signals in neurons. Furthermore, this irradiation upregulates critical CaV1 signals, including CREB phosphorylation and c-Fos expression, in vitro and in vivo, without raising significant biosafety risks. This DNA-free, non-invasive approach offers a promising approach for modulating CaV gating and Ca2+ signaling and treating diseases characterized by deficits in CaV functions.

Physical-Matched Nanoplatelets Boost Heterogeneous Thrombi Targeting Through Self-Adaptive Deformation for Thrombolysis and Endothelial Repairing.

The heterogeneity of thrombi in terms of composition, structure, and blood rheology parameters presents a challenge for effective thrombus-targeting drug delivery. To address this, a self-adaptive nano-delivery system, termed D-PLT, is developed. It consists of platelet membrane-cloaked deformable mesoporous organic silicon dioxide nanocomposite, enabling it to respond to the challenge of the heterogeneity of thrombi in arteries and veins. The system exhibits progressive targeting, with the ability to target arterial and venous thrombosis and damaged blood vessels. D-PLT physically matches the pore structure of the thrombus by undergoing varied deformation, leading to advanced targeting and enrichment of arterial and venous thrombus. When co-loaded with the thrombolytic drug urokinase (UK) and the endothelium-protecting agent atorvastatin calcium (AT), the system improves rapid vascular opening of arterial and venous thrombosis in 90 min and provides up to 7 days of durable thrombolysis and recovery from endothelial dysfunction in vivo. This self-adaptive delivery system offers a promising strategy to overcome thrombus heterogeneity.

Proteins-Based Nanoparticles for Benznidazole Enteric Delivery.

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects millions worldwide, particularly in Latin America. Despite its prevalence, treatment options remain limited. Current drugs, such as benznidazole, cause adverse effects possibly due to ineffective administration. In this context, nanoparticles offer a promising solution to target and control drug delivery by leading the effector site and minimizing side effects. This article focuses on zein-casein-based nanoparticles (Bioparticles, BP) coated with Eudragit L100-55 (BP:EU) for enteric delivery of benznidazole. BP:EU structures are synthesized to minimize premature drug release in the stomach, promoting release in the small intestine. Physical characterization confirmed the successful synthesis of BP:EU and their pH-responsive trigger for drug release. These findings suggest that this material can be a promising approach for Chagas disease treatment, addressing challenges in benznidazole delivery that can lead to improved therapeutic responses.

Single-Dose Physically Cross-Linked Hyaluronic Acid and Lipid Hybrid Nanoparticles Containing Cyclic Guanosine Monophosphate-Adenosine Monophosphate Eliminate Established Tumors.

Activating the STING pathway in the cytosol of tumor-infiltrating antigen-presenting cells (APCs) represents a promising strategy to elicit potent antitumor immune responses for cancer therapy. However, STING agonists are mostly small hydrophilic molecules that suffer from rapid clearance and poor cytosolic delivery following systemic administration. While various nanoparticles have been developed to promote cytosolic delivery, they often exhibit premature drug release during circulation. Alternatively, stable nanoparticles with sustained release during circulation have poor cytosolic delivery. In this study, we have developed physically cross-linked hyaluronic acid (HA) and lipid hybrid nanoparticles containing cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), denoted as HLHC, to address these challenges. The HLH delivery system has sustained drug release due to multiple lipid layers physically cross-linked by HA. HLHC efficiently delivers cGAMP to the cytosol of APCs, inducing more IFNβ than cGAMP and liposomal cGAMP. HLH also improves the drug circulation time and biodistribution to the tumor compared with the liposomal formulation and free drug. Strikingly, a single dose of HLHC, but not liposomal cGAMP or free cGAMP, elicits potent antitumor immunity and regresses established MC38 tumors. A single dose of HLHC even regresses established B16F10 tumors upon combination with αPD-L1. Moreover, cured animals were protected from rechallenge with the same tumor cells. HLHC represents an efficient strategy to address delivery challenges associated with STING agonists and may have broad applications for the delivery of drugs acting in the cytosol.

Applications of radionuclide-carrying liposomes for diagnosis and treatment of cancer

Using nanocapsules to deliver diagnostic and therapeutic agents to targeted biological sites enhances the safety and effectiveness of healthcare by decreasing toxicity and increasing the accumulation of medicinal agents at targeted sites. Liposomes, nanocapsules made of naturally occurring lipids, boast many advantages for the delivery of therapeutic agents. This article reviews both the advantages and challenges associated with liposomal drug delivery for the treatment of cancerous tumors and infectious diseases. These minute spherical sacs of phospholipid molecules are flexible carriers that can be modified in various ways to optimize their use. Examples of this include alteration of the size of liposomes to selectively accumulate in tumor microenvironments and “PEGylation” of their surface to reduce uptake of liposomes by the mononuclear phagocytic system (MPS). While one of the main challenges of liposomal drug delivery is the heightened uptake of liposomes by the MPS, this unique property can be used to target diseased areas with a significant MPS presence. Furthermore, the liposomal structure can be manipulated to allow for the triggered release of internal contents with externally controlled factors. Liposomes carrying therapeutic radionuclides can be injected directly into solid tumors and dispersed throughout the tumor by convection-enhanced delivery. The flexibility and pliability of liposomes allow them to move through tight spaces within a tumor with much greater dispersion and penetration when compared to more rigid nanoparticles. Due to the benefits of radionuclide-carrying liposomes in disease diagnosis and delivery of chemotherapeutic agents, their utilization is expected to be expanded.

Immunological dynamics in MASH: from landscape analysis to therapeutic intervention.

Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is a multifaceted liver disease characterized by inflammation and fibrosis that develops from simple steatosis. Immune and inflammatory pathways have a central role in the pathogenesis of MASH, yet, how to target immune pathways to treat MASH remains perplexed. This review emphasizes the intricate role that immune cells play in the etiology and pathophysiology of MASH and highlights their significance as targets for therapeutic approaches. It discusses both current strategies and novel therapies aimed at modulating the immune response in MASH. It also highlights challenges in liver-specific drug delivery, potential off-target effects, and difficulties in targeting diverse immune cell populations within the liver. This review is a comprehensive resource that integrates current knowledge with future perspectives in the evolving field of MASH, with the goal of driving forward progress in medical therapies designed to treat this complex liver disease.

The Importance of Honoring Family Caregiver Burden: Challenges in Mental Health Care Delivery.

There is growing recognition of the profound mental health challenges faced by the 53 million U.S.family caregivers, and the need for increased access to psychosocial care for this vulnerable population. Family caregivers are increasingly seeking support from hospital-based counseling centers. This trend-combined with a public policy landscape that promotes the delivery of caregiver-specific supports and services-highlights challenges faced by mental health professionals to provide and bill for psychosocial care to family caregivers. In this paper, we discuss three interrelated challenges that mental health professionals face in providing care to family caregivers and which our field needs to confront as healthcare transfers more responsibilities onto the shoulders of family caregivers: (1) caregiver burden is not recognized as a formal diagnosis; (2) current documentation for caregivers is typically linked to patient encounters; and (3) support for family caregivers occurs within larger systematic barriers to mental health integration. By accurately describing and documenting caregiver burden and advocating for increased parity in mental health coverage, we hope that the field can bridge the gap between emerging research, momentum in policy, and available psychosocial services for this vulnerable population.

Lipid-Based Nanoparticles as Drug Delivery System for Modern Therapeutics.

The emergence of lipid-based nanoparticulate systems has significantly reshaped the landscape of drug delivery. This review aims to encapsulate the advancements, challenges, and potential of lipid-based nanoparticulate drug delivery in modern therapeutics. Lipid-based nanoparticles, including liposomes, lipid nanoparticles, and solid lipid nanoparticles, harness the biocompatibility and biodegradability of lipids to encapsulate and deliver a diverse range of therapeutic agents. This platform offers solutions to various drug delivery challenges, such as enhancing drug solubility and bio- availability, achieving controlled and sustained release, targeted delivery, and co-delivery of multi-agents. These nanoparticles have demonstrated potential in overcoming biological barriers, including the blood-brain barrier, mucosal barriers, and cellular barriers, enabling the delivery of drugs to previously inaccessible sites. Biocompatibility and reduced toxicity are intrinsic attributes of lipid-based nanoparticles, minimizing immune responses and systemic toxicity while promoting personalized medicine possibilities. However, challenges in formulation, stability, and regulatory approval underscore the need for ongoing research and innovation in this field.

Taking a Team Approach: Keep up with the EHR with a Training and Optimization Program.

This study aimed to describe the current landscape of electronic health record (EHR) training and optimization programs (ETOPs) and their impact on healthcare workers' (HCWs) experience with the EHR. A 72-question electronic survey was developed and distributed to healthcare organization (HCO) leaders in clinical informatics through various channels such as national informatics conferences, social media, and email distribution lists of vendors and informatics associations. The survey collected data on the characteristics, resourcing, approach, and outcomes of ETOPs. Descriptive statistics were applied to analyze the data. There were 193 responses from 147 distinct HCOs. Of these, 69% offer ongoing EHR training, and 52% offer some version of an ETOP. Offered ETOPs vary in their timing, modality, audience, team composition, duration, and EHR build strategy. The most commonly measured outcomes were EHR satisfaction, efficiency, and provider burnout, and most ETOPs reported improvement in these areas. The findings suggest that ETOPs are inconsistently implemented across HCOs, and while there are some commonalities, there is a wide variety of design and methods of evaluation for the programs. Though the problems to solve for (EHR efficiency, proficiency, and satisfaction) are the same, the organizational structure and culture of HCOs varies widely, which may partially explain the variability seen in reported ETOPs. When considering the measured outcomes, ETOPs may have direct and indirect effects on HCW burnout by improving EHR efficiency and satisfaction, as well as driving organizational culture towards teamwork and flexible problem solving. For this reason, ETOPs may also serve as a model for addressing other challenges in healthcare delivery. ETOPs are a promising intervention to enhance HCW experience with the EHR and reduce burnout. More research is needed to identify the optimal features, methods, and outcomes of ETOPs, and to disseminate them across HCOs.