A Knowledge-based Clinical Toxicology Consultant for Diagnosing Multiple Exposures

Objective: This paper presents continued research toward the development of a knowledge-based system for the diagnosis of human toxic exposures. In particular, this research focuses on the challenging task of diagnosing exposures to multiple toxins. Although only 10% of toxic exposures in the United States involve multiple toxins, multiple exposures account for more than half of all toxin-related fatalities. Using simple medical mathematics, we seek to produce a practical decision support system capable of supplying useful information to aid in the diagnosis of complex cases involving multiple unknown substances. Methods: The system is automatically trained using data mining techniques to extract prior probabilities and likelihood ratios from a database managed by the Florida Poison Information Center (FPIC). When supplied with observed clinical effects, the system produces a ranked list of the most plausible toxic exposures. During testing, the system diagnosed toxins at three levels: identifying the substance, identifying the toxin’s major and minor categories, and identifying the toxin’s major category alone. To enable comparison between these three levels, accuracy was calculated as the percentage of exposures correctly identified in top 10% of trained diagnoses. Results: System evaluation utilized a dataset of 8,901 multiple exposure cases and 37,617 single exposure cases. Initial system testing using only multiple exposure cases yielded poor results, with diagnosis accuracies ranging from 18.5-50.1%. Further investigation revealed that the system’s inability to diagnose multiple disorders resulted from insufficient data and that the clinical effects observed in multiple exposures are dominated by a single substance. Including single exposures when training, the system achieved accuracies as high as 83.5% when 2 diagnosing the primary contributors in multiple exposure cases by substance, 86.9% when diagnosing by major and minor categories, and 79.9% when diagnosing by major category alone. Conclusions: Although the system failed to completely diagnose exposures to multiple toxins, the ability to identify the primary contributor in such cases may prove valuable in aiding medical personnel as they seek to diagnose and treat patients. As time passes and more cases are added to the FPIC database, we believe system accuracy will continue to improve, producing a viable decision support system for clinical toxicology

A Knowledge-based Clinical Toxicology Consultant for Diagnosing Single Exposures

Objective: Every year, toxic exposures kill twelve hundred Americans. To aid in the timely diagnosis and treatment of such exposures, this research investigates the feasibility of a knowledge-based system capable of generating differential diagnoses for human exposures involving unknown toxins. Methods: Data mining techniques automatically extract prior probabilities and likelihood ratios from a database managed by the Florida Poison Information Center. Using observed clinical effects, the trained system produces a ranked list of plausible toxic exposures. The resulting system was evaluated using 30,152 single exposure cases. In addition, the effects of two filters for refining diagnosis based on a minimum number of exposure cases and a minimum number of clinical effects were also explored. Results: The system achieved accuracies (calculated as the percentage of exposures correctly identified in top 10% of trained diagnoses) as high as 79.8% when diagnosing by substance and 78.9% when diagnosing by the major and minor categories of toxins. Conclusions: The results of this research are modest, yet promising. At this time, no similar systems are currently in use in the United States and it is hoped that these studies will yield an effective medical decision support system for clinical toxicology

Lessons from Toxicology: Developing a 21st‑Century Paradigm for Medical Research

Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual framework that repurposes the 21st-century transition underway in toxicology. Human disease should be conceived as resulting from integrated extrinsic and intrinsic causes, with research focused on modern human-specific models to understand disease pathways at multiple biological levels that are analogous to adverse outcome pathways in toxicology. Systems biology tools should be used to integrate and interpret data about disease causation and pathophysiology. Such an approach promises progress in overcoming the current roadblocks to understanding human disease and successful drug discovery and translation. A discourse should begin now to identify and consider the many challenges and questions that need to be solved

2012-13 Report of the Department of Veterans Affairs Gulf War Veterans? Illnesses Task Force to the Secretary of Veterans Affairs

The Gulf War Veterans' Illnesses Task Force (GWVI-TF) was formed to ensure that the Department of Veterans Affairs (VA) maintains a focus on the unique health issues faced by Veterans of the 1990-1991 Gulf War (Operations Desert Shield and Desert Storm). The Persian Gulf War is legally defined in title 38 United States Code (U.S.C.) § 101(33) as beginning on August 2, 1990, and ending on the date thereafter prescribed by Presidential proclamation or by law. Although the term "Gulf War Veterans" could refer to all Veterans of conflicts during this period, including Veterans of Operation Iraqi Freedom, and subsequent conflicts, the GWVI-TF target population is Veterans who were deployed on the Operation Desert Shield and/or Operation Desert Storm components of the 1990-1991 Gulf War, hereafter referred to as Gulf War Veterans. In August 2009, the Secretary of VA directed a comprehensive review of VA's programs to support this population of Veterans with the goal of developing an overarching action plan to advance their services, and ultimately improving their satisfaction with the quality of services and support that VA provides. This is GWVI-TF's third annual report and is intended to document VA's roadmap for achieving these goals and the concrete actions that VA has taken to improve care and services to Gulf War Veterans. The work of GWVI-TF continues to be based on a premise that the efforts are part of the core VA mission "to care for him who shall have borne the battle and for his widow, and his orphan.

Textbook of Adult Emergency Medicine

Now fully revised and updated, Textbook of Adult Emergency Medicine provides clear and consistent coverage of this rapidly evolving specialty. Building on the success of previous editions, it covers all the major topics that present to the trainee doctor in the emergency department. It will also prove invaluable to the range of other professionals working in this setting - including nurse specialists and paramedics - who require concise, highly practical guidance, incorporating latest best practice and current guidelines. For the first time this edition now comes with a complete and enhanced electronic version, providing a richer learning experience and making rapid reference easier than ever before, anytime, anywhere

The Health impact of chemical exposures during the Gulf War: a research planning conference

On February 28 through March 2, 1999, the Centers for Disease Control and Prevention (CDC) and other agencies of the Department of Health and Human Services (HHS) brought together scientists, clinicians, veterans, veterans\ue2\u20ac\u2122 service organizations, Congressional staff, and other interested parties to discuss and make recommendations regarding the direction of future research on undiagnosed illnesses among Gulf War veterans and their links with multiple chemical and environmental exposures. The format for the conference included plenary sessions, concurrent workgroups, and a veterans\ue2\u20ac\u2122 forum. The plenary sessions were meant to provide background information and to stimulate dialog on research questions. The plenary sessions included an overview of research findings regarding the health impact of the Gulf War, a panel discussion of the experience of Gulf War veterans, a series of presentations on the possible health outcomes of low-level chemical exposures focusing on nervous system, immune system, and pulmonary system outcomes, a series of panel discussions on research and clinical findings regarding multiple chemical sensitivity among Gulf War veterans and civilian populations, a series of presentations on possible mechanisms of action of chemical exposures, and a panel discussion on methodological considerations in studying the health impact of chemical exposures during the Gulf War. The concurrent workgroups were asked to develop research recommendations in four areas: pathophysiology, etiology, and mechanisms of action; assessment and diagnosis of illnesses; treatment; and prevention of illnesses in future deployments. Each workgroup was asked to develop research recommendations that addressed specific issues. For the pathophysiology workgroup, these issues included synergistic and subclinical effects of chemicals, genetic susceptibility, biomarkers of susceptibility and exposure, and appropriate study methods. The assessment and diagnosis workgroup was asked to focus on case definition, overlap of conditions, the role of chronic multi-system conditions, biomarkers of illness, optimal methods for assessment and diagnosis, and validation of assessment approaches. The treatment workgroup was asked to focus on appropriate treatment paradigms, rehabilitation approaches, health care opportunities, education of physicians, and appropriate study methods. The prevention workgroup was asked to focus on health education and risk communication, approaches to environmental assessment, biomonitoring, and health preparedness. The workgroups were free to use whatever approach they found useful for developing research recommendations. In some cases there was considerable disagreement among workgroup members on the direction of the recommendations. Thus, the final recommendations of the workgroups were not necessarily endorsed by all workgroup members. This report summarizes the outcome of each of the four workgroup sessions. Chapters 2 - 5 present the recommendations as developed by the workgroups. Although the workgroups were asked to focus on research recommendations, some recommendations reflect clinical care, administrative, or policy issues. No attempt was made to filter non-research recommendations from this report. Chapter 6 provides a discussion of the workgroup deliberations and attempts to place the recommendations in the context of current Gulf War research activities. The recommendations developed at this conference represent the deliberations of the workgroup participants and do not necessarily imply endorsement by the veteran or scientific community as a whole or by the federal government. While some of the recommendations could be implemented in the short-term, many of the recommendations reflect long-term goals requiring significant restructuring of current systems and are unlikely to be easily implemented, especially in the time frame requested by Gulf War veterans. Some of the recommendations may not be feasible, given current federal regulations. Other recommendations reflect initiatives that have already been instituted by federal agencies responsible for the care of veterans.sponsored by Centers for Disease Control and Prevention (CDC) in coordination with other offices and agencies of the U.S. Department of Health and Human Services (DHHS), Office of Public Health and Science, DHHS ; National Institutes of Health (NIH) and Agency for Toxic Substances and Disease Registry (ATSDR).Title from title screen (viewed Apr. 27, 2001).Mode of access: Internet.Includes bibliographical references (p. 34-42)

Trichloroethane

"Prepared by DeLima Associates ... under contract no. 205-90-0817"--p. 2 of cover.1993205-90-081