J. Sanders

Telemedicine: Where It Is and Where It's Going

Telemedicine has proliferated throughout much of the industrialized world, reflecting the convergence of scientific, technological, economic, and social factors. During the past 20 years, high-capacity digital networks and improved switching technologies have been deployed in many regions of North America. Computer hardware and software have become fast, powerful, easy to use, and affordable. Compressible, high-resolution digital images can be enhanced and manipulated. The availability of and access to health-related information has improved substantially. Telemedicine has begun to take hold, almost 40 years after the first experiments in providing medical care at a distance demonstrated its feasibility. Telemedicine Defined Telemedicine uses technology to deliver medical services to the point of need. In its report on the evaluation of clinical applications of telemedicine, a committee of the Institute of Medicine defined telemedicine as the use of electronic information and communications technologies to provide and support health care when distance separates the participants [1]. The committee settled on this expansive definition after considering at least 10 others [2-6]. Probably the most inclusive definition cited in the Institute of Medicine report was that telemedicine encompasses all of the health care, education, information and administrative services that can be transmitted over distances by telecommunications technologies [7]. Broad definitions of telemedicine have complicated the discussion of telemedicine policy. Telemedicine covers a range of technologies, including telephone, radio, facsimile, modem, and video. It may be conducted in real time, as with interactive video, or asynchronously, for the transmission of text or graphic data, auditory verbal information, still images, short video clips, and full-motion video. Robotics and virtual reality interfaces have been introduced into some experimental applications [8]. These technologies may be applied in various ways (management of chronic conditions, routine consultation, preventive medicine, public health, and patient education, for example). Some definitions of telemedicine even encompass meetings of hospital administrators, access to MEDLINE, and continuing medical education. Because the term telemedicine can be defined in so many ways, discussions of such issues as the cost-effectiveness of telemedicine become meaningless. Hence, we have limited the scope of this paper to a somewhat narrower definition of telemedicine: the use of telecommunications and information technology to provide health care services to persons at a distance from the provider. The Range of Transmission Media Telemedicine has used various terrestrial and space-based (satellite) transmission media. The medium that is used is important in part because its bandwidth or bit rate (the amount of information sent per unit of time) limits the type of technology that may be used. Narrow-bandwidth systems, such as ordinary telephone lines, are inexpensive but lack the capacity for full-motion video. They may be adequate, however, for transmitting still images, voice, text, or data. No single technology or bandwidth is best for all telemedicine purposes; rather, each systems capacities and capabilities must be determined by the needs of the users. Broad-bandwidth networks have transmission rates that permit interactive, full-motion video. For example, T1 lines have a relatively high bit rate of 1.544 megabits per second. They are not, however, available in many rural and frontier areas. Interactive video may be used with narrower bandwidths if data compression algorithms are also used, but the images are sometimes too jerky to permit resolution of detail or subtle movement. Broad-bandwidth networks are costly because transmission charges are directly related to bandwidth. This problem was partly addressed by rules that were developed by the U.S. Federal Communications Commission for the implementation of changes in the universal service program under the Telecommunications Act of 1996. These rules provide subsidies for telecommunications services, for which certain rural health care providers are eligible. Clinical Uses of Telemedicine Most of the early telemedicine programs used interactive video to bring patients, referring providers, and consultants together. From 1959 until the 1970s, telemedicine was tested in medical schools, state psychiatric hospitals, municipal airports, jails, nursing homes, Native American reservations, and other settings [9-16]. Most of these early programs proved too costly to be self-sustaining and were terminated when external funding ran out. The clinical applications of telemedicine are even more varied than the technologies, although considerable attention has been focused on the use of interactive video for specialty and subspecialty consultation in rural areas. The generic interactive video telemedicine system typically uses fixed, studio-type video equipment to link a rural facility with an urban tertiary care center. Consultants communicate with patients and, often, with their primary care providers in an interactive situation. The precise configuration of these networks varies, ranging from a single source of referrals (for example, a rural community hospital) and a single source of consultants (such as an academic medical center) to complex hub-and-spoke networks involving many referring and consulting facilities. Almost every clinical specialty has used telemedicine in some way, although some have used it more than others. Radiologists, for example, have embraced the technology on a large scale. Cardiologists, dermatologists, and psychiatrists have been the clinical specialists most actively involved in telemedicine. The reasons for this are unclear, but this distribution may represent a kind of founders effect because physicians practicing these specialties were among the clinicians to first become involved with telemedicine. Nevertheless, the fact that these specialists choose to see patients through telemedicine suggests that the medium is suited to many of their consultative tasks. A 1996 survey of almost 2400 nonfederal rural hospitals [17] found that about 17% were participating in a telemedicine network of some kind (including services as limited as facsimile) and that another 13% had definite plans to begin using telemedicine. The number of clinics and outpatient facilities participating in such networks is unknown. Despite widespread interest in telemedicine, the actual number of patients per telemedicine program who receive telemedicine services remains relatively low [18]. One recent survey of 80 programs (1032 sites on hub-and-spoke networks) estimated that about 21 000 consultations occurred in 1996 (mean, 37.4 consultations per site per year) [19]. Telemedicine has proven its feasibility in several challenging environments, including peacekeeping missions and the space shuttle (Pool SL, Stonesifer JC, Belasco N. Application of telemedicine systems in future manned space flight [Presented paper]. Second Telemedicine Workshop, 1975, Tucson, Arizona; [20-22]), and in the more prosaic settings of the home, clinic, hospital, and long-term care facility. It has been used for many years in Canadas maritime provinces ([23]; House AM, Keough EM. Distance health systems-collaboration brings success: the past, present, and future of telemedicine in Newfoundland [Presented paper]. Conference on Information Technology in Community Health, 1992, Victoria, Canada) and in Norway above the Arctic Circle [24]. The program at Memorial University of Newfoundland in Canada has used many technologies, from facsimile (transmission of electroencephalograms) to interactive video. In addition to gaining improved access to care for patients, referring physicians may benefit from increased contact with their colleagues and greater opportunities for continuing medical education. One observer described telemedicine as a means by which medical schools can provide an extended warranty on medical education. Trends in Telemedicine Technology Although the early 1990s saw the proliferation of telemedicine systems that provided real-time, broad-bandwidth, synchronous consultations, the focus has shifted toward more personal computer-based store-and-forward telemedicine. Desktop systems are a convenient and probably cost-effective means of providing services. Store-and-forward technology can be used to forward medical records, laboratory results, and radiographs and other diagnostic images to a consultant. By using a multimedia e-mail format, consultants can conduct an increasing number of telemedical consultations across a readily available, accessible, and inexpensive Internet platform. The consultant has convenient access to e-mailed consultative requests that accommodate his or her schedule. The data can be reviewed, and a report of diagnostic impressions can be e-mailed to the referring physician. Government Telemedicine Policy Since the 1960s, the federal government has supported the development of telemedicine through grants, contracts, and National Aeronautics and Space Administration and Department of Defense budget line items that total several hundred million dollars. Several agencies currently provide such support, and their representatives have been actively involved in discussions that shape both policy and directions of growth in telemedicine. Although a comprehensive discussion of those policy issues is beyond the scope of this paper, we address one especially important and problematic matter: coverage and payment for telemedical services. With a few exceptions (teleradiology, some telepathology, and some cardiologic data and facsimile transmission applications), Medicare reimbursement of fee-for-service telemedicine is generally not available. The reasons for this are complex, but the most immediate impediment to the coverage of telemedici

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.

National telemedicine initiatives: essential to healthcare reform.

Contributing authors: Elizabeth A. Krupinski, Ph.D.,3 Jim Grigsby, Ph.D.,4 Joseph C. Kvedar, M.D.,5 Ronald S. Weinstein, M.D.,3 Jay H. Sanders, M.D.,6 Karen S. Rheuban, M.D.,7 Thomas S. Nesbitt, M.D.,8 Dale C. Alverson, M.D.,9 Ronald C. Merrell, M.D.,10 Jonathan D. Linkous,11 A. Stewart Ferguson, Ph.D.,12 Robert J. Waters, J.D.,13 Max E. Stachura, M.D.,14 David G. Ellis, M.D.,15 Nina M. Antoniotti, Ph.D.,16 Barbara Johnston, M.S.N.,17 Charles R. Doarn, M.B.A.,18 Peter Yellowlees, M.D.,19 Steven Normandin,20 and Joseph Tracy 21

Characteristics of a human monoclonal autoantibody to the thyrotropin receptor: sequence structure and function.

The properties of a human monoclonal antibody to the thyrotropin receptor (TSHR) (M22) with the characteristics of patient sera thyroid stimulating autoantibodies is described. Similar concentrations (pmol/L) of M22 Fab and porcine TSH had similar stimulating effects on cyclic adenosine monophosphate (cAMP) production in TSHR-transfected Chinese hamster ovary cells whereas higher doses of intact M22 immunoglobulin G (IgG) were required to cause the same level of stimulation. Patient sera containing TSHR autoantibodies with TSH antagonist (blocking) activity inhibited M22 Fab and IgG stimulation in a similar way to their ability to block TSH stimulation. Thyroid-stimulating monoclonal antibodies (TSmAbs) produced in mice inhibited 125I-TSH binding and 125I-M22 Fab binding to the TSHR but the mouse TSmAbs were less effective inhibitors than M22. These competition studies emphasized the close relationship between the binding sites on the TSHR for TSH, TSHR autoantibodies with TSH agonist activity, and TSHR autoantibodies with TSH antagonist activity. Recombinant M22 Fab could be produced in Escherichia coli and the recombinant and hybridoma produced Fabs were similarly active in terms of inhibition of TSH binding and cAMP stimulation. The crystal structure of M22 Fab was determined to 1.65 A resolution and is that of a standard Fab although the hypervariable region of the heavy chain protrudes further from the framework than the hypervariable region of the light chain. The M22 antigen binding site is rich in aromatic residues and its surface is dominated by acidic patches on one side and basic patches on the other in agreement with an important role for charge-charge interactions in the TSHR-autoantibody interaction.

Telehealth: the promise of new care delivery models.

Telehealth possesses a significant potential to revolutionize healthcare delivery processes by challenging some of the long-held assumptions about healthcare delivery and by creating innovative alternative models. Those assumptions relate to the location-linked nature of healthcare and its episodic nature. Telehealth can challenge the assumption that healthcare is inextricably linked to the providers location. Numerous models involving such approaches as interactive videoconferencing and store-and-forward technologies already exist. Telehealth also challenges the episodic nature of care. One example is provided by the models evolving from the convergence of three technologies: remote monitoring, electronic health records, and clinical decision support systems. Telehealth-based models of care can also lead to a reduced demand for services and greater efficiencies in the care process. These telehealth-enabled care delivery models have the potential to reduce the costs of care, improve quality, and mitigate provider shortages. However, the achievement of these goals is not straightforward. The current healthcare financing system is not designed to support such new models, and the existing healthcare culture is deeply ingrained within workflow processes and provider attitudes. A great deal of work remains to be done before the benefits of telehealth-based care delivery models are fully realized. Change is inherently risky but we must have the courage to assume the risk in order to create telehealth-driven innovations that lead to better and more cost-effective medical care for all.

Thyroid stimulating autoantibody M22 mimics TSH binding to the TSH receptor leucine rich domain: a comparative structural study of protein-protein interactions

The TSH receptor (TSHR) ligands M22 (a thyroid stimulating human monoclonal antibody) and TSH, bind to the concave surface of the leucine rich repeats domain (LRD) of the TSHR and here, we show that M22 mimics closely the binding of TSH. We compared interactions produced by M22 with the TSHR in the M22-TSHR crystal structure (2.55 A resolution) and produced by TSH with the TSHR in a TSH-TSHR comparative model. The crystal structure of the TSHR and a comparative model of TSH based on the crystal structure of FSH were used as components to build the TSH-TSHR model. This model was built based on the FSH-FSH receptor structure (2.9 A) and then the structure of the TSHR in the model was replaced by the TSHR crystal structure. The analysis shows that M22 light chain mimics the TSHbeta chain in its interaction with TSHR LRD, while M22 heavy chain mimics the interactions of the TSHalpha chain. The M22-TSHR complex contains a greater number of hydrogen bonds and salt bridges and fewer hydrophobic interactions than the TSH-TSHR complex, consistent with a higher M22 binding affinity. Furthermore, the surface area formed by TSHR residues N208, Q235, R255, and N256 has been identified as a candidate target region for small molecules which might selectively block binding of autoantibodies to the TSHR.

FSH and TSH binding to their respective receptors: similarities, differences and implication for glycoprotein hormone specificity

The crystal structures of the leucine-rich repeat domain (LRD) of the FSH receptor (FSHR) in complex with FSH and the TSH receptor (TSHR) LRD in complex with the thyroid-stimulating autoantibody (M22) provide opportunities to assess the molecular basis of the specificity of glycoprotein hormone-receptor binding. A comparative model of the TSH-TSHR complex was built using the two solved crystal structures and verified using studies on receptor affinity and activation. Analysis of the FSH-FSHR and TSH-TSHR complexes allowed identification of receptor residues that may be important in hormone-binding specificity. These residues are in leucine-rich repeats at the two ends of the FSHR and the TSHR LRD structures but not in their central repeats. Interactions in the interfaces are consistent with a higher FSH-binding affinity for the FSHR compared with the binding affinity of TSH for the TSHR. The higher binding affinity of porcine (p)TSH and bovine (b)TSH for human (h)TSHR compared with hTSH appears not to be dependent on interactions with the TSHR LRD as none of the residues that differ among hTSH, pTSH or bTSH interact with the LRD. This suggests that TSHs are likely to interact with other parts of the receptors in addition to the LRD with these non-LRD interactions being responsible for affinity differences. Analysis of interactions in the FSH-FSHR and TSH-TSHR complexes suggests that the alpha-chains of both hormones tend to be involved in the receptor activation process while the beta-chains are more involved in defining binding specificity.

Teleconsultation practice guidelines: report from G8 Global Health Applications Subproject 4.

This report presents a series of recommendations derived from deliberations of the G8 countries Subproject 4 Group (SP4 Group) of the Global Health Care Applications Project entitled, A Teleconsultation Practice Guideline. The recommendations provide an initial step toward developing a general guideline platform for the practice of telemedicine/teleconsultation.

International Concerted Action on Collaboration in Telemedicine: Recommendations of the G-8 Global Healthcare Applications Subproject-4

The main objectives of the G-8 Global Healthcare Applications Subproject-4 (G-8 GHAP-SP-4) were to establish an international concerted action on collaboration in telemedicine, telehealth, and health telematics (hereafter referred in this paper as telemedicine). In order to promote and facilitate the implementation of telemedicine or health telematics networks around the world, it was considered necessary to address certain key issues. Five thematic solution-seeking forums were held between May 1998 and December 1999. Each addressed a key issue, including interoperability of telemedicine and telehealth systems, impact of telemedicine on health care management, evaluation and cost effectiveness of telemedicine, clinical and technical quality and standards, and medico-legal aspects of national and international applications. The main objectives of these forums were to establish best practices and a thorough review of the issues and discussions among experts to determine the best solutions for the facilitation of global international telemedicine networks. More than 650 invited participants from 16 countries attended the five forums, which were of 2-3 days in duration. These forums provided a foundation for the exchange of ideas resulting in the initiation of collaborative activities. Based on these deliberations, a series of 21 recommendations were prepared by the national representatives of the G-8 GHAP SP-4. These recommendations propose to political leaders and health care managers of the G-8 and other countries roadmaps to follow in order to accelerate the achievement of a Global Society of Healthcare via Telemedicine, Telehealth, and Health Telematics. The 21 recommendations are presented in this report.

Reactivity of Thyrotropin Receptor Autoantibodies with the Thyrotropin Receptor on Western Blots

Affinity purified recombinant human thyrotropin receptor (TSHR) was run on sodium dodecyl sulfate (SDS) gels and subjected to a renaturing and blotting procedure. Twenty sera from thyrotropin receptor autoantibodies (TRAb)-positive patients with a history of hyperthyroidism and 20 sera with high levels of TSH blocking activity were analyzed. Four of 20 sera with blocking-type of TRAb (i.e., TSH antagonist activity) were able to recognize the mature, fully glycosylated 120-kd form of the receptor on blots of gels run under reducing conditions. No sera recognized the 100-kd high mannose precursor form of the TSHR. Three of the four recognized a 74-kd band and 2 of the 4 recognized a 50-kd band. These bands are probably proteolytic cleavage fragments of the mature 120-kd TSHR. In the absence of reducing agent the same 4 of 20 sera described above together with a further serum sample (i.e., 5/20 in total) reacted with the 120-kd form of the receptor. No specific reaction with the TSHR was observed on Western blots with the remaining 15 sera with TSH blocking activity, nor with 20 sera from patients with a history of hyperthyroidism, nor with sera from 10 healthy blood donors, 10 Hashimoto sera (negative for TRAb) and 10 systemic lupus erythematosus sera. No clear differences were observed in the TRAb positive sera that were reactive and nonreactive on Western blots in terms of their ability to inhibit TSH binding or to immunoprecipitate 125I-labeled TSHR. Overall, our results indicate that the mature 120-kd form of the TSHR that is principally responsible for binding TSH is also responsible for binding TRAb (when this binding can be detected). These observations together with immunoprecipitation and TSH binding inhibition studies, emphasize the close relationship between the receptors binding sites for TSH and TRAb.