Dr. Dart is a physician specializing in emergency medicine and toxicology. His research interests include the epidemiology of substance abuse, snake and spider envenomation and the toxicity of many drugs like cough and cold products, acetaminophen and laundry pods. He is Executive Director of Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System. He has published more than 300 publications and has been recognized with numerous awards. He also serves as a Deputy Editor of the medical journal Annals of Emergency Medicine.
Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated t... more Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated the need new analytical strategies and techniques to understand the medications involved, user characteristics and other factors needed to address the epidemic.
3403 Introduction: In 2008, five emergency department patients with unexplained neutropenia and t... more 3403 Introduction: In 2008, five emergency department patients with unexplained neutropenia and thrombovasculitis were reported from Vancouver, Canada. Similar reports have appeared from San Francisco, Denver, Providence, Chicago, New York, and Los Angeles. Methods: 156 case reports of patients of unexplained thrombovasculopathy were identified from the published literature or by SONAR. Results: The average patient age was 44 years old (SD, 11 years); 65% were female. The earliest time to symptom onset was 12 hours following last cocaine use. Dermatologic findings included retiform purpura, purpuric rash, hemorrhagic bullae, or skin necrosis (59% of cases), and lesions on the ears (35% of cases), upper extremities (33% of cases), torso (22% of cases), and the nose (10% of cases). Of 79 patients with available data, 72% presented with severe neutropenia (<1500cells/μl). Among 80 persons who had serologic studies, 95% demonstrated anti-neutrophil cytoplasmic antibodies, 31% were po...
The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of pres... more The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics. The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency. Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME). There were 19,480 c...
Pharmacoepidemiology and drug safety, Jan 15, 2018
Diverted prescription opioids are significant contributors to drug overdose mortality. Street pri... more Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07...
It is the current policy of the US Food and Drug Administration (FDA) to convene expert Advisory ... more It is the current policy of the US Food and Drug Administration (FDA) to convene expert Advisory Committees to provide input on key regulatory decisions regarding opioid products, including approval and labeling of opioid abuse-deterrent formulations (ADFs). Advisory Committee meetings on ADF opioids consider whether the laboratory and clinical data submitted by the sponsor are sufficient to support marketing approval and labeling of the product with properties expected to deter abuse by specific routes of abuse (ie, oral, intranasal, intravenous). The FDA has typically followed the approval and labeling recommendations for ADFs reviewed by its Advisory Committees, highlighting the importance of these meetings in the regulatory approval process. This review describes common issues considered by Advisory Committees for ADF opioids as well as insights on how to prepare for these meetings based on recent relevant experience and regulatory decisions.
To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain... more To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from v...
Pharmacoepidemiology and drug safety, Jan 10, 2017
Recent limited epidemiologic and case reports suggest that gabapentin is being misused, especiall... more Recent limited epidemiologic and case reports suggest that gabapentin is being misused, especially among prescription opioid misusers. However, no apparent studies have reported data from law enforcement on the diversion and misuse of gabapentin. Case report data are drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies who engage in drug diversion investigations. Rates of gabapentin diversion per 100 000 population were calculated for each quarter from 2002 through 2015. Qualitative data are drawn from a brief questionnaire completed by a subsample of survey respondents and were organized and presented by theme. In total, 407 new cases of diverted gabapentin were reported during the time period, with diversion rates steadily increasing from zero cases in the first 2 quarters of 2002 to a high of 0.027 cases per 100 000 population in the fourth quarter of 2015. Qualitative data suggest that gabapentin i...
The journal of pain : official journal of the American Pain Society, Jan 4, 2017
Accurate assessment of inappropriate medication use events (i.e., misuse, abuse, and related even... more Accurate assessment of inappropriate medication use events (i.e., misuse, abuse, and related events [MAREs]) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions [27]. Only 2 approaches have been reported that are specifically designed to identify and classify MAREs occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion [SR-MAD] instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System [MADDERS]. The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively in order to determine the underlying in...
Clinical pharmacology and therapeutics, Jan 12, 2016
An extended-release opioid analgesic (OxyContin, abbreviated as OC) was reformulated with abuse-d... more An extended-release opioid analgesic (OxyContin, abbreviated as OC) was reformulated with abuse-deterrent properties to deter abuse. This report examines changes in abuse through oral and non-oral routes, doctor-shopping, and fatalities in ten studies 3.5 years after reformulation. Changes in OC abuse from one year before to three years after OC reformulation were calculated, adjusted for prescription changes. Abuse of OC decreased 48% in national poison center surveillance systems, decreased 32% in a national drug treatment system, and decreased 27% among individuals prescribed OC in claims databases. Doctor-shopping for OC decreased 50%. Overdose fatalities reported to the manufacturer decreased 65%. Abuse of other opioids without abuse-deterrent properties decreased 2 years later than OC and with less magnitude, suggesting OC decreases were not due to broader opioid interventions. Consistent with the formulation, decreases were larger for non-oral than oral abuse. Abuse-deterrent...
Pharmacoepidemiology and drug safety, Jan 13, 2015
A high prevalence of chronic pain and high rates of polypharmacy among older adults suggest that ... more A high prevalence of chronic pain and high rates of polypharmacy among older adults suggest that this age group may be particularly susceptible to unintentional misuse of prescription opioids. We examined recent trends in misuse of prescription opioids and associated medical outcomes among older-aged adults (60+ years) and compared the patterns with trends among younger-aged adults (20-59 years). Linear regression trend analysis was used to analyze 57 681 misuse cases reported to participating US poison centers during 2006-2014. Population rates of misuse of prescription opioids were higher for older adults than for younger adults, and this disparity increased over time. Rates among the older ages increased each year, although the rate of increase slowed over time (p < 0.0001 for negative quadratic trend). In contrast, among the younger adults, there was a significant negative quadratic trend in population rates (p < 0.0001) with a rise in rates during 2006-2010 followed by a ...
Analgesic consumption poses special risks for regular users of alcohol. Among the numerous advers... more Analgesic consumption poses special risks for regular users of alcohol. Among the numerous adverse health effects are acetaminophen toxicity and gastrointestinal (GI) bleeding associated with nonsteroidal anti-inflammatory drug (NSAID) use. An alcohol-acetaminophen hypothesis contends that alcohol enhances acetaminophen toxicity. Because 22% of adults use acetaminophen each week and 5% to 10% of the population is alcoholic, the healthcare implications of serious adverse interactions are considerable. However, such interactions are rare when NSAID doses remain in the therapeutic range. Although clinical studies fail to support anecdotal case reports of liver damage associated with consumption of therapeutic doses of acetaminophen by alcohol users, such reports are probably inaccurate because of the uncritical acceptance of patient history by the clinician and a lack of well-designed prospective trials. Over-the-counter (OTC) NSAIDs, such as aspirin, naproxen, and ketoprofen, are othe...
... Richard C. Dart, MD 1 , E. Campagna, MS 2 , J. Elise Bailey, MSPH 3 , Meredith Kirtland, BA 2... more ... Richard C. Dart, MD 1 , E. Campagna, MS 2 , J. Elise Bailey, MSPH 3 , Meredith Kirtland, BA 2 , and Henry A. Spiller, MS RN DABAT 4 . (1) Rocky Mountain Poison & Drug Center, 777 Bannock Street, Mail Code 0180, Denver, CO 80204, (2) Reseach and Consulting, Rocky ...
Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated t... more Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated the need new analytical strategies and techniques to understand the medications involved, user characteristics and other factors needed to address the epidemic.
3403 Introduction: In 2008, five emergency department patients with unexplained neutropenia and t... more 3403 Introduction: In 2008, five emergency department patients with unexplained neutropenia and thrombovasculitis were reported from Vancouver, Canada. Similar reports have appeared from San Francisco, Denver, Providence, Chicago, New York, and Los Angeles. Methods: 156 case reports of patients of unexplained thrombovasculopathy were identified from the published literature or by SONAR. Results: The average patient age was 44 years old (SD, 11 years); 65% were female. The earliest time to symptom onset was 12 hours following last cocaine use. Dermatologic findings included retiform purpura, purpuric rash, hemorrhagic bullae, or skin necrosis (59% of cases), and lesions on the ears (35% of cases), upper extremities (33% of cases), torso (22% of cases), and the nose (10% of cases). Of 79 patients with available data, 72% presented with severe neutropenia (<1500cells/μl). Among 80 persons who had serologic studies, 95% demonstrated anti-neutrophil cytoplasmic antibodies, 31% were po...
The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of pres... more The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics. The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency. Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME). There were 19,480 c...
Pharmacoepidemiology and drug safety, Jan 15, 2018
Diverted prescription opioids are significant contributors to drug overdose mortality. Street pri... more Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07...
It is the current policy of the US Food and Drug Administration (FDA) to convene expert Advisory ... more It is the current policy of the US Food and Drug Administration (FDA) to convene expert Advisory Committees to provide input on key regulatory decisions regarding opioid products, including approval and labeling of opioid abuse-deterrent formulations (ADFs). Advisory Committee meetings on ADF opioids consider whether the laboratory and clinical data submitted by the sponsor are sufficient to support marketing approval and labeling of the product with properties expected to deter abuse by specific routes of abuse (ie, oral, intranasal, intravenous). The FDA has typically followed the approval and labeling recommendations for ADFs reviewed by its Advisory Committees, highlighting the importance of these meetings in the regulatory approval process. This review describes common issues considered by Advisory Committees for ADF opioids as well as insights on how to prepare for these meetings based on recent relevant experience and regulatory decisions.
To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain... more To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from v...
Pharmacoepidemiology and drug safety, Jan 10, 2017
Recent limited epidemiologic and case reports suggest that gabapentin is being misused, especiall... more Recent limited epidemiologic and case reports suggest that gabapentin is being misused, especially among prescription opioid misusers. However, no apparent studies have reported data from law enforcement on the diversion and misuse of gabapentin. Case report data are drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies who engage in drug diversion investigations. Rates of gabapentin diversion per 100 000 population were calculated for each quarter from 2002 through 2015. Qualitative data are drawn from a brief questionnaire completed by a subsample of survey respondents and were organized and presented by theme. In total, 407 new cases of diverted gabapentin were reported during the time period, with diversion rates steadily increasing from zero cases in the first 2 quarters of 2002 to a high of 0.027 cases per 100 000 population in the fourth quarter of 2015. Qualitative data suggest that gabapentin i...
The journal of pain : official journal of the American Pain Society, Jan 4, 2017
Accurate assessment of inappropriate medication use events (i.e., misuse, abuse, and related even... more Accurate assessment of inappropriate medication use events (i.e., misuse, abuse, and related events [MAREs]) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions [27]. Only 2 approaches have been reported that are specifically designed to identify and classify MAREs occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion [SR-MAD] instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System [MADDERS]. The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively in order to determine the underlying in...
Clinical pharmacology and therapeutics, Jan 12, 2016
An extended-release opioid analgesic (OxyContin, abbreviated as OC) was reformulated with abuse-d... more An extended-release opioid analgesic (OxyContin, abbreviated as OC) was reformulated with abuse-deterrent properties to deter abuse. This report examines changes in abuse through oral and non-oral routes, doctor-shopping, and fatalities in ten studies 3.5 years after reformulation. Changes in OC abuse from one year before to three years after OC reformulation were calculated, adjusted for prescription changes. Abuse of OC decreased 48% in national poison center surveillance systems, decreased 32% in a national drug treatment system, and decreased 27% among individuals prescribed OC in claims databases. Doctor-shopping for OC decreased 50%. Overdose fatalities reported to the manufacturer decreased 65%. Abuse of other opioids without abuse-deterrent properties decreased 2 years later than OC and with less magnitude, suggesting OC decreases were not due to broader opioid interventions. Consistent with the formulation, decreases were larger for non-oral than oral abuse. Abuse-deterrent...
Pharmacoepidemiology and drug safety, Jan 13, 2015
A high prevalence of chronic pain and high rates of polypharmacy among older adults suggest that ... more A high prevalence of chronic pain and high rates of polypharmacy among older adults suggest that this age group may be particularly susceptible to unintentional misuse of prescription opioids. We examined recent trends in misuse of prescription opioids and associated medical outcomes among older-aged adults (60+ years) and compared the patterns with trends among younger-aged adults (20-59 years). Linear regression trend analysis was used to analyze 57 681 misuse cases reported to participating US poison centers during 2006-2014. Population rates of misuse of prescription opioids were higher for older adults than for younger adults, and this disparity increased over time. Rates among the older ages increased each year, although the rate of increase slowed over time (p < 0.0001 for negative quadratic trend). In contrast, among the younger adults, there was a significant negative quadratic trend in population rates (p < 0.0001) with a rise in rates during 2006-2010 followed by a ...
Analgesic consumption poses special risks for regular users of alcohol. Among the numerous advers... more Analgesic consumption poses special risks for regular users of alcohol. Among the numerous adverse health effects are acetaminophen toxicity and gastrointestinal (GI) bleeding associated with nonsteroidal anti-inflammatory drug (NSAID) use. An alcohol-acetaminophen hypothesis contends that alcohol enhances acetaminophen toxicity. Because 22% of adults use acetaminophen each week and 5% to 10% of the population is alcoholic, the healthcare implications of serious adverse interactions are considerable. However, such interactions are rare when NSAID doses remain in the therapeutic range. Although clinical studies fail to support anecdotal case reports of liver damage associated with consumption of therapeutic doses of acetaminophen by alcohol users, such reports are probably inaccurate because of the uncritical acceptance of patient history by the clinician and a lack of well-designed prospective trials. Over-the-counter (OTC) NSAIDs, such as aspirin, naproxen, and ketoprofen, are othe...
... Richard C. Dart, MD 1 , E. Campagna, MS 2 , J. Elise Bailey, MSPH 3 , Meredith Kirtland, BA 2... more ... Richard C. Dart, MD 1 , E. Campagna, MS 2 , J. Elise Bailey, MSPH 3 , Meredith Kirtland, BA 2 , and Henry A. Spiller, MS RN DABAT 4 . (1) Rocky Mountain Poison & Drug Center, 777 Bannock Street, Mail Code 0180, Denver, CO 80204, (2) Reseach and Consulting, Rocky ...
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