Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice.

OBJECTIVE: There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling. We hypothesized that rectal administration of Tac would effectively mitigate PEP by ensuring systemic and pancreatic bioavailability of Tac. We have tested the efficacy of rectal Tac in a preclinical PEP model and in cerulein-induced experimental pancreatitis. METHODS: C57BL/6 mice underwent ductal cannulation with saline infusion to simulate pressure-induced PEP or were given seven, hourly, cerulein injections to induce pancreatitis. To test the efficacy of rectal Tac in pancreatitis prevention, a rectal Tac suppository (1 mg/kg) was administered 10 min prior to cannulation or first cerulein injection. Histological and biochemical indicators of pancreatitis were evaluated post-treatment. Pharmacokinetic parameters of Tac in the blood after rectal delivery compared to intravenous and intragastric administration was evaluated. RESULTS: Rectal Tac was effective in reducing pancreatic injury and inflammation in both PEP and cerulein models. Pharmacokinetic studies revealed that the rectal administration of Tac helped achieve optimal blood levels of Tac over an extended time compared to intravenous or intragastric delivery. CONCLUSION: Our results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.

Preclinical safety evaluation of calcineurin inhibitors delivered through an intraductal route to prevent post-ERCP pancreatitis demonstrates endocrine and systemic safety.

OBJECTIVE: There is an urgent need for safe and targeted interventions to mitigate post-ERCP pancreatitis (PEP). Calcineurin inhibitors (CnIs) offer therapeutic promise as calcineurin signaling within acinar cells is a key initiating event in PEP. In previous proof-of-concept studies using experimental models, we showed that concurrent intra-pancreatic ductal administration of the CnIs, tacrolimus (Tac) or cyclosporine A (CsA) with the ERCP radiocontrast agent (RC) prevented PEP. To translate this finding clinically, we investigated potential toxic effects of intraductal delivery of a single-dose RC-CnI formulation on endocrine pancreas function and systemic toxicities in a preclinical PEP model. METHODS: C57BL/6J mice underwent ductal cannulation and received a single, intra-pancreatic ductal infusion of RC or RC with Tac or CsA (treatment groups) or underwent ductal cannulation without infusion ('sham' group). To assess endocrine function, intraperitoneal glucose tolerance test (IPGTT) was performed at two days before infusion and on day 2 and 14 post-surgery. To evaluate off-target tissue toxicities, renal and hepatic function-related parameters including blood urea nitrogen, plasma creatinine, potassium, aspartate aminotransferase, alanine aminotransferase, and total bilirubin were measured at the same time-points as IPGTT. Histological and biochemical indicators of pancreas injury and inflammation were also evaluated. RESULTS: No abnormalities in glucose metabolism, hepatic or renal function were observed on day 2 or 14 in mice administered with intraductal RC or RC with Tac or CsA. CONCLUSION: Intraductal delivery of RC-CnI formulation was safe and well-tolerated with no significant acute or subacute endocrine or systemic toxicities, underscoring its clinical utility to prevent PEP.

Artificial Intelligence in Health: Enhancing a Return to Patient-Centered Communication.

The medical environment is on the verge of a dramatic transformation as artificial intelligence (AI) evolves. With the inevitable shift toward AI in health care delivery, there are concerns around its implementation, including ethics, privacy, data representation, and the potential for eliminating physicians. However, AI cannot replicate a physician's knowledge and understanding of the patient as a person and the conditions in which he or she lives. Therefore, provider-patient communication will be paramount in providing safe and effective health care. This piece describes the importance of patient-centered communication and the unintentional move away from this in recent times. We argue that patient-provider communication is vital in the age of AI as it will integrate into the way medicine is practiced, thus leading to more time with the patient to build rapport, trust, and empathy. This will ultimately lead to optimal health-related outcomes.

A review of the rationale for the testing of the calcineurin inhibitor tacrolimus for post-ERCP pancreatitis prevention.

Endoscopic retrograde cholangiopancreatography (ERCP) is commonly performed for the management of pancreaticobiliary disorders. The most troublesome ERCP-associated adverse event is post-ERCP pancreatitis (PEP), which occurs in up to 15% of all patients undergoing ERCP. A substantial body of preclinical data support a mechanistic rationale for calcineurin inhibitors in preventing PEP. The findings are coupled with recent clinical data suggesting lower rates of PEP in patients who concurrently use the calcineurin inhibitor tacrolimus (e.g., solid organ transplant recipients). In this review, we will firstly summarize data in support of testing the use of tacrolimus for PEP prophylaxis, either in combination with rectal indomethacin or by itself. Secondly, we propose that administering tacrolimus through the rectal route could be favorable for PEP prophylaxis over other routes of administration.

Development and Validation of Telemedicine for Disaster Response: The North Atlantic Treaty Organization Multinational System.

BACKGROUND: Disasters, whether natural or manmade, are unpredictable. While there may be some forewarning as in natural disasters like a hurricane, response is often suboptimal. There is a need for an integrated and structured action for all three well defined phases of disaster management (pre-, during, and postdisaster) that must be addressed to ameliorate the impact on life and the necessary steps for recovery. Over the past several decades, telemedicine has been integrated in some form of disaster response. This adoption and integration has been shown to be effective. Since 2013, North Atlantic Treaty Organization (NATO), under the auspices of the Science for Peace and Security Programme, has worked on developing a Multinational Telemedicine System (MnTS) for disaster response. METHODS: A group of subject matter experts from Europe and the United States developed the MnTS by establishing the network and a concept of operations, to be used in disaster management between countries. RESULTS: An integrated system, including personnel, hardware, communication protocols, portable power generation, medical kits, and Web-based tools, was developed and successfully tested in the Euro-Atlantic Disaster Response Coordination Centre's Exercises Ukraine 2015. The field exercise tested and validated the MnTS and identified areas of improvement. The system and its evaluation provide additional information for establishing deployment capabilities. CONCLUSIONS: A MnTS approach to telemedicine in disaster response and management is possible and should be further advanced.

mCare: using secure mobile technology to support soldier reintegration and rehabilitation.

BACKGROUND: The U.S. Army Medical Department conducted a pilot mobile health project to determine the requirements for coordination of care for "Wounded Warriors" using mobile messaging. The primary objective was to determine if a secure mobile health (mhealth) intervention provided to geographically dispersed patients would improve contact rates and positively impact the military healthcare system. METHODS AND MATERIALS: Over 21 months, volunteers enrolled in a Health Insurance Portability and Accountability Act-compliant, secure mobile messaging initiative called mCare. The study included males and females, 18-61 years old, with a minimum of 60 days of outpatient recovery. Volunteers were required to have a compatible phone. The mhealth intervention included appointment reminders, health and wellness tips, announcements, and other relevant information to this population exchanged between care teams and patients. RESULTS: Provider respondents reported that 85% would refer patients to mCare, and 56% noted improvement in appointment attendance (n=90). Patient responses also revealed high acceptability of mCare and refined the frequency and delivery times (n=114). The pilot project resulted in over 84,000 outbound messages and improved contact rates by 176%. CONCLUSIONS: The mCare pilot project demonstrated the feasibility and administrative effectiveness of a scalable mhealth application using secure mobile messaging and information exchanges, including personalized patient education.

The empirical foundations of telemedicine interventions for chronic disease management.

The telemedicine intervention in chronic disease management promises to involve patients in their own care, provides continuous monitoring by their healthcare providers, identifies early symptoms, and responds promptly to exacerbations in their illnesses. This review set out to establish the evidence from the available literature on the impact of telemedicine for the management of three chronic diseases: congestive heart failure, stroke, and chronic obstructive pulmonary disease. By design, the review focuses on a limited set of representative chronic diseases because of their current and increasing importance relative to their prevalence, associated morbidity, mortality, and cost. Furthermore, these three diseases are amenable to timely interventions and secondary prevention through telemonitoring. The preponderance of evidence from studies using rigorous research methods points to beneficial results from telemonitoring in its various manifestations, albeit with a few exceptions. Generally, the benefits include reductions in use of service: hospital admissions/re-admissions, length of hospital stay, and emergency department visits typically declined. It is important that there often were reductions in mortality. Few studies reported neutral or mixed findings.

Autonomous precision resuscitation during ground and air transport of an animal hemorrhagic shock model.

We tested the ability of a physiologically driven minimally invasive closed-loop algorithm, called Resuscitation based on Functional Hemodynamic Monitoring (ReFit), to stabilize for up to 3 h a porcine model of noncompressible hemorrhage induced by severe liver injury and do so during both ground and air transport. Twelve animals were resuscitated using ReFit to drive fluid and vasopressor infusion to a mean arterial pressure (MAP) > 60 mmHg and heart rate < 110 min-1 30 min after MAP < 40 mmHg following liver injury. ReFit was initially validated in 8 animals in the laboratory, then in 4 animals during air (23nm and 35nm) and ground (9 mi) to air (9.5nm and 83m) transport returning to the laboratory. The ReFit algorithm kept all animals stable for ~ 3 h. Thus, ReFit algorithm can diagnose and treat ongoing hemorrhagic shock independent to the site of care or during transport. These results have implications for treatment of critically ill patients in remote, austere and contested environments and during transport to a higher level of care.

The U.S. Army Telemedicine and m-Health Program: making a difference at home and abroad.

This article highlights the deployment of telemedicine by the U.S. Army through the various echelons of care and in overseas locations, including range and scope of health services provided by telemedicine in a challenging environment. This is followed by a discussion of technological developments advances in mobile communications likely to change the practice of telemedicine in the military from limited fixed-point access to a highly mobile individual with handheld communication devices.

Telehealth in the Military Health System: Impact, Obstacles, and Opportunities.

BACKGROUND: The U.S. Military Health System (MHS) pioneered the use of telehealth in deployed environments in the early 1990s. However, its use in non-deployed environments historically lagged behind that of the Veterans Health Administration (VHA) and comparable large civilian health systems, due to administrative, policy, and other obstacles that slowed or blocked its expansion in the MHS. A report was prepared in December 2016, which summarized past and then-present telehealth initiatives in the MHS; described the obstacles, opportunities, and policy environment; and provided three possible courses of action for expansion of telehealth in deployed and non-deployed settings. METHODS: Gray literature, peer-reviewed literature, presentations, and direct input were aggregated under the guidance of subject matter experts. RESULTS: Past and then-current efforts demonstrated significant telehealth capability in use and in development for the MHS, mainly in deployed or operational settings. Policy from 2011 to 2017 demonstrated an environment favorable for MHS expansion, while the review of comparable civilian and veterans' healthcare systems showed significant benefits including increased access and lower cost from use of telehealth in non-deployed settings. The 2017 National Defense Authorization Act charged the Secretary of Defense with promoting telehealth usage for the Department of Defense, including provisions for removing obstacles and reporting progress within 3 years. The MHS has the ability to reduce burdensome interstate licensing and privileging requirements, but still requires an increased level of cybersecurity, compared to civilian systems. DISCUSSION: The benefits of telehealth fit with the MHS Quadruple Aim of improving cost, quality, access, and readiness. Readiness is particularly served by the use of "physician extenders," which allows nurses, physician assistants, medics, and corpsmen to provide hands-on care under remote oversight and to practice at the top of their licenses. Based on this review, three courses of action were recommended: to focus largely on developing telehealth in deployed environments; to maintain focus in deployed environments and increase telehealth development in non-deployed environments to keep pace with the VHA and private sector; or to use lessons learned from military and civilian telehealth initiatives to leapfrog the private sector. CONCLUSION: This review serves as a snapshot in time of the steps leading to telehealth expansion before 2017, which helped to set the stage for later use of telehealth in behavioral health initiatives and as a response to coronavirus disease 2019. The lessons learned are ongoing and further research is expected to inform additional development of telehealth capability for the MHS.

Adopting and expanding ethical principles for generative artificial intelligence from military to healthcare.

In 2020, the U.S. Department of Defense officially disclosed a set of ethical principles to guide the use of Artificial Intelligence (AI) technologies on future battlefields. Despite stark differences, there are core similarities between the military and medical service. Warriors on battlefields often face life-altering circumstances that require quick decision-making. Medical providers experience similar challenges in a rapidly changing healthcare environment, such as in the emergency department or during surgery treating a life-threatening condition. Generative AI, an emerging technology designed to efficiently generate valuable information, holds great promise. As computing power becomes more accessible and the abundance of health data, such as electronic health records, electrocardiograms, and medical images, increases, it is inevitable that healthcare will be revolutionized by this technology. Recently, generative AI has garnered a lot of attention in the medical research community, leading to debates about its application in the healthcare sector, mainly due to concerns about transparency and related issues. Meanwhile, questions around the potential exacerbation of health disparities due to modeling biases have raised notable ethical concerns regarding the use of this technology in healthcare. However, the ethical principles for generative AI in healthcare have been understudied. As a result, there are no clear solutions to address ethical concerns, and decision-makers often neglect to consider the significance of ethical principles before implementing generative AI in clinical practice. In an attempt to address these issues, we explore ethical principles from the military perspective and propose the "GREAT PLEA" ethical principles, namely Governability, Reliability, Equity, Accountability, Traceability, Privacy, Lawfulness, Empathy, and Eutonomy, for generative AI in healthcare. Furthermore, we introduce a framework for adopting and expanding these ethical principles in a practical way that has been useful in the military and can be applied to healthcare for generative AI, based on contrasting their ethical concerns and risks. Ultimately, we aim to proactively address the ethical dilemmas and challenges posed by the integration of generative AI into healthcare practice.

Mobile health evaluation methods: the Text4baby case study.

Mobile phones have been shown effective in several public health domains. However, there are few evaluations of the effectiveness of mobile health in health promotion. Also, although many studies have referenced behavioral theory, none appears to have explicitly tested theoretical assumptions or demonstrated mechanisms of change. More robust evaluation models that incorporate theory and measurement of behavioral mediators are needed. As in all public health programs, mobile health operates within a social ecological context. For example, organizational- and individual-level programs seek to influence health and health care practices and individual health behaviors. New programs such as Text4baby demonstrate how theory and explicit testing of mediators can be incorporated in evaluations. There are challenges and opportunities facing mHealth evaluations given the nature of the mobile channel. Mobile communication is ubiquitous, available at all times and places, and thus experimental control is often difficult. Natural experiments using variation in dosage of mHealth and place- or location-based designs may increase experimental control. Text4baby is a text messaging program that provides prenatal care messages to pregnant women and new mothers. It uses a partnership model with health care facilities often serving as local implementation partners. The authors review a case example of the evaluation of Text4baby at Madigan Army Medical Center. Participants were randomized to usual prenatal care plus text messaging or usual care alone. The evaluation has a theoretical model of behavior change and measures mediators as well as behavioral outcomes. Results will inform how behavioral theory works within mobile health programs.

Challenges, solutions, and best practices in telemental health service delivery across the pacific rim-a summary.

The Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, in conjunction with the American Telemedicine Association's Annual Mid-Year Meeting, conducted a 1-day workshop on how maturing and emerging processes and applications in the field of telemental health (TMH) can be expanded to enhance access to behavioral health services in the Pacific Rim. The purpose of the workshop was to bring together experts in the field of TMH from the military, federal agencies, academia, and regional healthcare organizations serving populations in the Pacific Rim. The workshop reviewed current technologies and systems to better understand their current and potential applications to regional challenges, including the Department of Defense and other federal organizations. The meeting was attended by approximately 100 participants, representing military, government, academia, healthcare centers, and tribal organizations. It was organized into four sessions focusing on the following topic areas: (1) Remote Screening and Assessment; (2) Post-Deployment Adjustment Mental Health Treatment; (3) Suicide Prevention and Management; and (4) Delivery of Training, Education, and Mental Health Work Force Development. The meeting's goal was to discuss challenges, gaps, and collaborative opportunities in this area to enhance existing or create new opportunities for collaborations in the delivery of TMH services to the populations of the Pacific Rim. A set of recommendations for collaboration are presented.

A standard telemental health evaluation model: the time is now.

The telehealth field has advanced historic promises to improve access, cost, and quality of care. However, the extent to which it is delivering on its promises is unclear as the scientific evidence needed to justify success is still emerging. Many have identified the need to advance the scientific knowledge base to better quantify success. One method for advancing that knowledge base is a standard telemental health evaluation model. Telemental health is defined here as the provision of mental health services using live, interactive video-teleconferencing technology. Evaluation in the telemental health field largely consists of descriptive and small pilot studies, is often defined by the individual goals of the specific programs, and is typically focused on only one outcome. The field should adopt new evaluation methods that consider the co-adaptive interaction between users (patients and providers), healthcare costs and savings, and the rapid evolution in communication technologies. Acceptance of a standard evaluation model will improve perceptions of telemental health as an established field, promote development of a sounder empirical base, promote interagency collaboration, and provide a framework for more multidisciplinary research that integrates measuring the impact of the technology and the overall healthcare aspect. We suggest that consideration of a standard model is timely given where telemental health is at in terms of its stage of scientific progress. We will broadly recommend some elements of what such a standard evaluation model might include for telemental health and suggest a way forward for adopting such a model.

Defining core issues in utilizing information technology to improve access: evaluation and research agenda.

The Department of Veterans Affairs (VA) has been at the vanguard of information technology (IT) and use of comprehensive electronic health records. Despite the widespread use of health IT in the VA, there are still a variety of key questions that need to be answered in order to maximize the utility of IT to improve patient access to quality services. This paper summarizes the potential of IT to enhance healthcare access, key gaps in current evidence linking IT and access, and methodologic challenges for related research. We also highlight four key issues to be addressed when implementing and evaluating the impact of IT interventions on improving access to quality care: 1) Understanding broader needs/perceptions of the Veteran population and their caregivers regarding use of IT to access healthcare services and related information. 2) Understanding individual provider/clinician needs/perceptions regarding use of IT for patient access to healthcare. 3) System/Organizational issues within the VA and other organizations related to the use of IT to improve access. 4) IT integration and information flow with non-VA entities. While the VA is used as an example, the issues are salient for healthcare systems that are beginning to take advantage of IT solutions.

Application of health technology in humanitarian response: U.S. Military deployed health technology summit--a summary.

Disasters are unpredictable, occurring without notice. They have a devastating effect and forever change the people they affect. We have witnessed the devastation from several significant events in 2010 and 2011, including the horrendous earthquakes in Haiti, Chili, New Zealand, and Japan. In the Japanese earthquake, a tsunami caused significant destruction to property and, of special concern, nuclear power plants along the Pacific Ocean, which will likely have a lasting impact worldwide. In a number of these events, the U.S. Military is often called upon to provide some level of support to help in the immediate aftermath. In early 2010, a massive earthquake struck the island nation of Haiti. In the days that followed, there was a significant influx of help from both military and nongovernmental organizations (NGOs). Although the response was not coordinated in any significant way, there was, nevertheless, wide application of various technologies as never before. Aside for the need to respond rapidly and efficiently, the U.S. Military is especially interested in how to utilize technology in a better way both internally and with NGOs. In the fall of 2010, the U.S. Army's Telemedicine and Advanced Technology Research Center partnered with the American Telemedicine Association to bring together a group of experts from industry, government, and academia to assess the challenges and opportunities for applying technologies not only in combat missions but for humanitarian response as well. This article summarizes the "U.S. Military Deployed Health Technology Summit" held on September 29, 2010, in Baltimore, Maryland, highlighting significant points. It presents a balance of capabilities across a broad spectrum of technologies and will help the U.S. Military in defining a roadmap for research and development to strengthen its ability to respond in future disasters and humanitarian events.

Innovative new technologies to identify and treat traumatic brain injuries: crossover technologies and approaches between military and civilian applications.

Traumatic brain injury (TBI) has become the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom. The use of improvised explosive devices has seen an exponential increase in both Iraq and Afghanistan. In previous conflicts prior to Iraq, survivability of such an injury was far less. Today, technological improvements in trauma care have increased an injured warfighter's chance of survival. A reduction in severe TBI has been achieved but an increase in mild or moderate TBI has been observed. The consequences of this kind of injury can be both physical and mental and can often be hidden or even misdiagnosed. The U.S. Army is interested in pursuing technological solutions for early detection and treatment of TBI to reduce its lasting impact on the warfighter. Such technological breakthroughs have benefit beyond the military, as TBI is a high probable event in nonmilitary settings as well. To gauge what technologies or methods are currently available, the U.S. Army's Telemedicine and Advanced Technology Research Center partnered with the American Telemedicine Association to organize and conduct a discipline-specific symposium entitled "Innovative New Technologies to Identify and Treat Traumatic Brain Injuries: Crossover Technologies and Approaches Between Military and Civilian Applications." This symposium was held in Palm Springs, CA, in September 2009. The purpose of the meeting was to provide a unique opportunity for leaders from disparate organizations involved in telemedicine and related other activities to meet and explore opportunities to collaborate in new partnership models. The meeting was designed to help Telemedicine and Advanced Technology Research Center identify opportunities to expand strategic operations and form new alliances. This report summarizes this symposium while raising awareness for collaboration into better ways of adapting and adopting technologies to address this growing health issue.

Developing next-generation telehealth tools and technologies: patients, systems, and data perspectives.

The major goals of telemedicine today are to develop next-generation telehealth tools and technologies to enhance healthcare delivery to medically underserved populations using telecommunication technology, to increase access to medical specialty services while decreasing healthcare costs, and to provide training of healthcare providers, clinical trainees, and students in health-related fields. Key drivers for these tools and technologies are the need and interest to collaborate among telehealth stakeholders, including patients, patient communities, research funders, researchers, healthcare services providers, professional societies, industry, healthcare management/economists, and healthcare policy makers. In the development, marketing, adoption, and implementation of these tools and technologies, communication, training, cultural sensitivity, and end-user customization are critical pieces to the process. Next-generation tools and technologies are vehicles toward personalized medicine, extending the telemedicine model to include cell phones and Internet-based telecommunications tools for remote and home health management with video assessment, remote bedside monitoring, and patient-specific care tools with event logs, patient electronic profile, and physician note-writing capability. Telehealth is ultimately a system of systems in scale and complexity. To cover the full spectrum of dynamic and evolving needs of end-users, we must appreciate system complexity as telehealth moves toward increasing functionality, integration, interoperability, outreach, and quality of service. Toward that end, our group addressed three overarching questions: (1) What are the high-impact topics? (2) What are the barriers to progress? and (3) What roles can the National Institutes of Health and its various institutes and centers play in fostering the future development of telehealth?

Use of mobile phones as a tool for United States health diplomacy abroad.

Rapidly emerging mobile communications platforms, such as mobile phones, in countries across Africa, Iraq, and Afghanistan offer new opportunities for direct public engagement in health systems, placing tools and timely information into the hands of those who need it most. Early results from pioneering work suggest real benefits of mobile devices in addressing access to care, monitoring and treating diseases, and providing continuous medical education and training. The Military Health System, a $43-billion global healthcare system within the U.S. Department of Defense, in partnership with other U.S. government agencies and nongovernmental organizations and the international health sector, can make valuable contributions to creating a sustainable global m-health infrastructure.