Jody L. Green

2007 ANNUAL REPORT OF THE AMERICAN ASSOCIATION OF POISON CONTROL CENTERS' NATIONAL POISON DATA SYSTEM (NPDS): 25TH ANNUAL REPORT

Background: This report is the 25th Annual Report of the American Association of Poison Control Centers (AAPCC; http://www.aapcc.org) National Poison Data System (NPDS). During 2007, 60 of the nations 61 U.S. Poison Centers upload case data automatically. The median upload time is 14 [5.3, 55] (median [25%, 75%]) min creating a real-time national exposure database and surveillance system. Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Fatalities were reviewed by a team of 29 medical and clinical toxicologists and assigned to 1 of 6 categories according to Relative Contribution to Fatality. Results: Over 4.2 million calls were captured by NPDS in 2007: 2,482,041 human exposure calls, 1,602,489 information requests, and 131,744 nonhuman exposure calls. Substances involved most frequently in all human exposures were analgesics (12.5% of all exposures). The most common exposures in children less than age 6 were cosmetics/personal care products (10.7% of pediatric exposures). Drug identification requests comprised 66.8% of all information calls. NPDS documented 1,597 human fatalities. Conclusions: Poisoning continues to be a significant cause of morbidity and mortality in the United States NPDS represents a valuable national resource to collect and monitor U.S. poisoning exposure cases. It offers one of the few real-time surveillance systems in existence, provides useful data, and is a model for public health surveillance.

Trends in Opioid Analgesic Abuse and Mortality in the United States

BACKGROUND The use of prescription opioid medications has increased greatly in the United States during the past two decades; in 2010, there were 16,651 opioid-related deaths. In response, hundreds of federal, state, and local interventions have been implemented. We describe trends in the diversion and abuse of prescription opioid analgesics using data through 2013. METHODS We used five programs from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System to describe trends between 2002 and 2013 in the diversion and abuse of all products and formulations of six prescription opioid analgesics: oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol. The programs gather data from drug-diversion investigators, poison centers, substance-abuse treatment centers, and college students. RESULTS Prescriptions for opioid analgesics increased substantially from 2002 through 2010 in the United States but then decreased slightly from 2011 through 2013. In general, RADARS System programs reported large increases in the rates of opioid diversion and abuse from 2002 to 2010, but then the rates flattened or decreased from 2011 through 2013. The rate of opioid-related deaths rose and fell in a similar pattern. Reported nonmedical use did not change significantly among college students. CONCLUSIONS Postmarketing surveillance indicates that the diversion and abuse of prescription opioid medications increased between 2002 and 2010 and plateaued or decreased between 2011 and 2013. These findings suggest that the United States may be making progress in controlling the abuse of opioid analgesics. (Funded by the Denver Health and Hospital Authority.).

2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report

Background: This is the 26th Annual Report of the American Association of Poison Control Centers (AAPCC; http://www. aapcc.org) National Poison Data System (NPDS). During 2008, 60 of the nations 61 US poison centers uploaded case data automatically. The median upload time was 24 [7.2, 112] (median [25%, 75%]) minutes creating a real-time national exposure and information database and surveillance system. Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 28 medical and clinical toxicologist reviewers using an ordinal scale of 1–6 to determine Relative Contribution to Fatality (RCF) from the exposure to the death. Results: In 2008, 4,333,012 calls were captured by NPDS: 2,491,049 closed human exposure cases, 130,495 animal exposures, 1,703,762 information calls, 7,336 human confirmed nonexposures, and 370 animal confirmed nonexposures. The top five substances most frequently involved in all human exposures were analgesics (13.3%), cosmetics/personal care products (9.0%), household cleaning substances (8.6%), sedatives/hypnotics/antipsychotics (6.6%), and foreign bodies/toys/miscellaneous (5.2%). The top five most common exposures in children age 5 or less were cosmetics/personal care products (13.5%), analgesics (9.7%), household cleaning substances (9.7%), foreign bodies/toys/miscellaneous (7.5%), and topical preparations (6.9%). Drug identification requests comprised 66.8% of all information calls. NPDS documented 1,756 human exposures resulting in death with 1,315 human fatalities deemed related with an RCF of at least contributory (1, 2, or 3). Conclusions: Poisoning continues to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national resource to collect and monitor US poisoning exposure cases and information calls. NPDS continues its mission as one of the few real-time national surveillance systems in existence, providing a model public health surveillance system for all types of exposures, public health event identification, resilience response and situational awareness tracking.

2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS).

Abstract Background: The American Association of Poison Control Centers (AAPCC; http://www.aapcc.org ) maintains the National Poison Data System (NPDS). Today, 60 of the nations 61 US poison centers upload case data automatically. Most upload every 1- 60 minutes (median 11 minutes) to NPDS creating a real-time national exposure database and surveillance system. Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Fatalities were reviewed by a team of 27 medical and clinical toxicologists and assigned to 1 of 6 categories according to Relative Contribution to Fatality (RCF). Results: Over 4 million calls were captured by NPDS in 2006: 2,403,539 human exposure calls, 1,488,993 information requests, and 128,353 nonhuman exposure calls Substances involved most frequently in all human exposures were analgesics. The most common exposures in children less than age 6 were cosmetics/personal care products. NPDS documented 1,229 human fatalities. Conclusions: Poisoning continues to be a significant cause of morbidity and mortality in the US. NPDS represents a valuable national resource to collect and monitor US poisoning exposure cases. It offers one of the few real-time surveillance systems in existence, provides useful data and is a model for public health surveillance.

Pediatric Fatalities Associated With Over the Counter (Nonprescription) Cough and Cold Medications

STUDY OBJECTIVE The use of nonprescription cough and cold medicines is widespread, but their use has been sporadically associated with severe toxicity and death. We evaluate the role of these medications in pediatric fatalities and identified factors that contributed to the death. METHODS Fatalities that involved a child younger than 12 years and mentioned a cough and cold ingredient were obtained from 5 sources. An independent panel of 8 experts (pediatrics, pediatric critical care, pediatric toxicology, clinical toxicology, forensic toxicology, forensic pathology) used explicit definitions to assess the causal relationship between medication ingestion and death. Contributing factors were identified. RESULTS Of 189 cases included, 118 were judged possibly, likely, or definitely related to a cough and cold ingredient. Of these 118 cases, 103 involved a nonprescription drug, whereas 15 cases involved a prescription medication alone. Of 103 cases associated with nonprescription drugs, the evidence indicated that 88 involved an overdosage. A dosage could not be assessed in the remaining 15 cases. Several contributing factors were identified: age younger than 2 years, use of the medication for sedation, use in a daycare setting, use of 2 medicines with the same ingredient, failure to use a measuring device, product misidentification, and use of a nonprescription product intended for adult use. All cases that occurred in a daycare setting involved a child younger than 2 years. CONCLUSION In our sample, pediatric fatalities caused by nonprescription cough and cold medications were uncommon, involved overdose, and primarily affected children younger than 2 years. The intent of caregivers appears to be therapeutic to relieve symptoms in some cases and nontherapeutic to induce sedation or to facilitate child maltreatment in other cases.

Trends in abuse and misuse of prescription opioids among older adults

BACKGROUND Dramatic increases in the prescriptive use of opioid analgesics during the past two decades have been paralleled by alarming increases in rates of the abuse and intentional misuse of these drugs. We examined recent trends in the abuse and misuse and associated fatal outcomes among older adults (60+ years) and compared these to trends among younger adults (20-59 years). METHODS Trend analysis using linear regression models was used to analyze 184,136 cases and 1149 deaths associated with abuse and misuse of the prescription opioids oxycodone, fentanyl, hydrocodone, morphine, oxymorphone, hydromorphone, methadone, buprenorphine, tramadol, and tapentadol that were reported to participating U.S. Poison Centers of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(®)) System between 2006-Q1 and 2013-Q4. RESULTS Rates of abuse and misuse of prescription opioids were lower for older adults than for younger adults; however, mortality rates among the older ages followed an increasing linear trend (P < 0.0001) and surpassed rates for younger adults in 2012 and 2013. In contrast, mortality rates among younger adults rose and fell during the period, with recent rates trending downward (P = 0.0003 for quadratic trend). Sub-analysis revealed an increasing linear trend among older adults specifically for suicidal intent (P < 0.0001), whereas these rates increased and then decreased among younger adults (P < 0.0001 for quadratic trend). CONCLUSION Recent linear increases in rates of death and use of prescription opioids with suicidal intent among older adults have important implications as the U.S. undergoes a rapid expansion of its elderly population.

The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients – a multicenter randomized study

BackgroundHepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects.MethodsAdult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT.ResultsA total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 ± 45 IU/L and 55 ± 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group.ConclusionAlcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.

Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis

Introduction: There are few reports summarizing the effectiveness of oral and intravenous (IV) acetylcysteine. We determined the proportion of acetaminophen poisoned patients who develop hepatotoxicity (serum transaminase > 1000 IU/L) when treated with oral and IV acetylcysteine. Methods: Studies were double abstracted by trained researchers. We determined the proportions of patients who developed hepatotoxicity for each route using a random effects model. Studies were further stratified by early and late treatment. Results: We screened 4,416 abstracts; 16 articles, including 5,164 patients, were included in the meta-analysis. The overall rate of hepatotoxicity for the oral and IV routes were 12.6% and 13.2%, respectively. Treatment delays are associated with a higher rate of hepatotoxicity. Conclusion: Studies report similar rates of hepatotoxicity for oral and IV acetylcysteine, but direct comparisons are lacking. While it is difficult to disentangle the effects of dose and duration from route, our findings suggest that the rates of hepatotoxicity are similar for oral and IV administration.

Crowdsourcing Black Market Prices For Prescription Opioids

Background Prescription opioid diversion and abuse are major public health issues in the United States and internationally. Street prices of diverted prescription opioids can provide an indicator of drug availability, demand, and abuse potential, but these data can be difficult to collect. Crowdsourcing is a rapid and cost-effective way to gather information about sales transactions. We sought to determine whether crowdsourcing can provide accurate measurements of the street price of diverted prescription opioid medications. Objective To assess the possibility of crowdsourcing black market drug price data by cross-validation with law enforcement officer reports. Methods Using a crowdsourcing research website (StreetRx), we solicited data about the price that site visitors paid for diverted prescription opioid analgesics during the first half of 2012. These results were compared with a survey of law enforcement officers in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System, and actual transaction prices on a “dark Internet” marketplace (Silk Road). Geometric means and 95% confidence intervals were calculated for comparing prices per milligram of drug in US dollars. In a secondary analysis, we compared prices per milligram of morphine equivalent using standard equianalgesic dosing conversions. Results A total of 954 price reports were obtained from crowdsourcing, 737 from law enforcement, and 147 from the online marketplace. Correlations between the 3 data sources were highly linear, with Spearman rho of 0.93 (P<.001) between crowdsourced and law enforcement, and 0.98 (P<.001) between crowdsourced and online marketplace. On StreetRx, the mean prices per milligram were US

Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone

3.29 hydromorphone, US