Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015.

IMPORTANCE: As of 2015, almost half of US states allow medical marijuana, and 4 states allow recreational marijuana. To our knowledge, the effect of recreational marijuana on the pediatric population has not been evaluated. OBJECTIVE: To compare the incidence of pediatric marijuana exposures evaluated at a children's hospital and regional poison center (RPC) in Colorado before and after recreational marijuana legalization and to compare population rate trends of RPC cases for marijuana exposures with the rest of the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of hospital admissions and RPC cases between January 1, 2009, and December 31, 2015, at Children's Hospital Colorado, Aurora, a tertiary care children's hospital. Participants included patients 0 to 9 years of age evaluated at the hospital's emergency department, urgent care centers, or inpatient unit and RPC cases from Colorado for single-substance marijuana exposures. EXPOSURE: Marijuana. MAIN OUTCOMES AND MEASURES: Marijuana exposure visits and RPC cases, marijuana source and type, clinical effects, scenarios, disposition, and length of stay. RESULTS: Eighty-one patients were evaluated at the children's hospital, and Colorado's RPC received 163 marijuana exposure cases between January 1, 2009, and December 31, 2015, for children younger than 10 years of age. The median age of children's hospital visits was 2.4 years (IQR, 1.4-3.4); 25 were girls (40%) . The median age of RPC marijuana exposures was 2 years (IQR, 1.3-4.0), and 85 patients were girls (52%). The mean rate of marijuana-related visits to the children's hospital increased from 1.2 per 100 000 population 2 years prior to legalization to 2.3 per 100,000 population 2 years after legalization (P = .02). Known marijuana products involved in the exposure included 30 infused edibles (48%). Median length of stay was 11 hours (interquartile range [IQR], 6-19) and 26 hours (IQR, 19-38) for admitted patients. Annual RPC pediatric marijuana cases increased more than 5-fold from 2009 (9) to 2015 (47). Colorado had an average increase in RPC cases of 34% (P < .001) per year while the remainder of the United States had an increase of 19% (P < .001). For 10 exposure scenarios (9%), the product was not in a child-resistant container; for an additional 40 scenarios (34%), poor child supervision or product storage was reported. Edible products were responsible for 51 exposures (52%). CONCLUSIONS AND RELEVANCE: Colorado RPC cases for pediatric marijuana increased significantly and at a higher rate than the rest of the United States. The number of children's hospital visits and RPC case rates for marijuana exposures increased between the 2 years prior to and the 2 years after legalization. Almost half of the patients seen in the children's hospital in the 2 years after legalization had exposures from recreational marijuana, suggesting that legalization did affect the incidence of exposures.

Analysis of the Abuse and Diversion of the Buprenorphine Transdermal Delivery System.

UNLABELLED: Prescription opioid abuse and diversion are major causes of morbidity and mortality in the United States. The buprenorphine transdermal delivery system (BTDS) is indicated for the treatment of moderate to severe chronic pain and provides a continuous dose of 5, 7.5, 10, 15, or 20 µg/h buprenorphine for 7 days. Quarterly rates of abuse and diversion of BTDS were compared with 4 comparator groups: 1) other buprenorphine products, 2) fentanyl patches, 3) extended-release (ER) opioid tablets/capsules, and 4) ER tramadol. Data were obtained from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Treatment Programs Combined (Opioid Treatment and Survey of Key Informants' Patients Programs), and College Survey Programs. Rates were calculated using case counts per population and mentions per prescriptions filled. Poisson regression analysis was used to compare mean rates over time across drug groups after allowing for drug group-specific dispersion parameters. Population adjusted abuse rates were low for BTDS in all of the RADARS System programs compared with the other comparator groups. Findings were similar for the prescription adjusted rates, with BTDS reported at the lowest rates in all programs. Route of abuse differed slightly for BTDS and the comparator groups depending on the program. BTDS was abused and diverted at low rates compared with the other opioid groups in 5 programs of the RADARS System using either population-based rates or prescription dispensed rates. PERSPECTIVE: Data from the RADARS System show the BTDS is abused and diverted at low rates compared with other opioid groups including other forms of buprenorphine, fentanyl patches, ER opioid formulations, and ER tramadol.

Diversion and Illicit Sale of Extended Release Tapentadol in the United States.

OBJECTIVE: Prescription opioid analgesics are commonly prescribed for moderate to severe pain. An unintended consequence of prescribing opioid analgesics is the abuse and diversion of these medications. Tapentadol ER is a recently approved centrally acting analgesic with synergistic mechanisms of action: µ-opioid receptor agonism and inhibition of norepinephrine reuptake. We assessed the amount of diversion and related cost of obtaining tapentadol IR (Nucynta®) and tapentadol ER (Nucynta ER®) as well as other Schedule II opioid medications in street transactions in the United States using the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System. METHODS: The Drug Diversion Program measures the number of cases opened by 260 drug diversion investigators in 49 states. StreetRx(TM) uses a crowd-sourcing Website to collect the prices paid for licit or illicit drugs. RESULTS: The population-based rates of diversion were 0.003 (tapentadol IR), 0.001 (tapentadol ER), and 1.495 (other Schedule II opioid tablets) reports per 100,000 population. The tapentadol ER rate was lower than the other Schedule II opioid tablets (P < 0.001) and tapentadol IR (P= 0.004). Diversion rates based on drug availability were 0.03 (tapentadol IR), 0.016 (tapentadol ER), and 0.172 (other Schedule II opioid tablets) per 1,000 prescriptions dispensed. The median street price per milligram was $0.18 (tapentadol IR), $0.10 (tapentadol ER), and $1.00 (other Schedule II opioid tablets). DISCUSSION: Our results indicate that tapentadol ER is rarely sold illicitly in the United States. When sold illicitly, tapentadol ER costs less than other Schedule II opioid products.

Assessment of prescription opioid intentional exposures across the rural-urban continuum in the United States using both population and drug availability rates.

PURPOSE: Prescription opioid abuse and misuse are a serious problem in the U.S. today. Several studies have shown that the epidemic disproportionately affects rural areas. This paper uses three different rates to gain a more complete picture of opioid abuse in rural areas. METHODS: This study examines prescription opioid intentional exposures using opioid classes tracked in the RADARS(®) System Poison Center Program. Intentional exposure rates were calculated adjusting for population and unique recipients of dispensed drug (URDD). These rates were analyzed using time (quarter) and the proportion of a three-digit zip code residing in a rural area as covariates. Additionally, the URDD per population rate was calculated to examine the proportion of the population filling prescriptions for opioids. RESULTS: After adjusting for population, intentional exposure cases significantly increased as the proportion of the population residing in a rural area increased. However, when adjusting for URDD, intentional exposure cases decreased with increasing rural population. The URDD per population increased as the proportion of people residing in a rural area increased. CONCLUSIONS: Using both population and URDD adjusted intentional exposure rates gives a more complete picture of opioid abuse in rural areas. Considering product availability can be used to develop opioid abuse prevention strategies and further the education of physicians serving rural areas about this epidemic.

Abuse and diversion of buprenorphine sublingual tablets and film.

Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants' Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ("unique recipients of a dispensed drug," URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned.

Association of unintentional pediatric exposures with decriminalization of marijuana in the United States.

STUDY OBJECTIVE: We compare state trends in unintentional pediatric marijuana exposures, as measured by call volume to US poison centers, by state marijuana legislation status. METHODS: A retrospective review of the American Association of Poison Control Centers National Poison Data System was performed from January 1, 2005, to December 31, 2011. States were classified as nonlegal if they have not passed legislation, transitional if they enacted legislation between 2005 and 2011, and decriminalized if laws passed before 2005. Our hypotheses were that decriminalized and transitional states would experience a significant increase in call volume, with more symptomatic exposures and more health care admissions than nonlegal states. RESULTS: There were 985 unintentional marijuana exposures reported from 2005 through 2011 in children aged 9 years and younger: 496 in nonlegal states, 93 in transitional states, and 396 in decriminalized states. There was a slight male predominance, and the median age ranged from 1.5 to 2.0 years. Clinical effects varied, with neurologic effects the most frequent. More exposures in decriminalized states required health care evaluation and had moderate to major clinical effects and critical care admissions compared with exposures from nonlegal states. The call rate in nonlegal states to poison centers did not change from 2005 to 2011. The call rate in decriminalized states increased by 30.3% calls per year, and transitional states had a trend toward an increase of 11.5% per year. CONCLUSION: Although the number of pediatric exposures to marijuana reported to the National Poison Data System was low, the rate of exposure increased from 2005 to 2011 in states that had passed marijuana legislation.

The effect of a statewide smoking ordinance on acute myocardial infarction rates.

BACKGROUND: Public smoking ordinances may reduce acute myocardial infarction events. Most studies assessed small communities with reported reductions as high as 40%. No reduction or smaller reductions were found in countrywide studies; less is known about the impact of statewide ordinances. We previously demonstrated identical 27% reductions in acute myocardial infarction hospitalizations in 2 Colorado communities after enactment of strict smoking ordinances. Subsequently, on July 1, 2006, a statewide ordinance went into effect. We sought to determine the impact of this legislation on acute myocardial infarction hospitalization rates. METHODS: Hospital admissions for a primary acute myocardial infarction diagnosis were examined from 2000 to 2008. Poisson regression models were fit to the monthly events from January 1, 2000, to March 31, 2008. The final model included a quadratic trend over time, harmonic terms, and a post-ordinance effect. The model was adjusted temporally for population changes, using population estimates as an offset variable. RESULTS: A total of 58,399 unique acute myocardial infarctions were recorded during the study period. No significant reduction in acute myocardial infarction rates was observed post-ordinance (relative risk, 1.059; 95% confidence interval, 0.993-1.131). However, a steep decline in acute myocardial infarction rates was noted from 2000 to 2005 just before enactment. There were 11 strict, local smoking ordinances in effect within Colorado before enactment of the statewide ordinance. After excluding these communities, the findings were similar (relative risk, 1.038; 95% confidence interval, 0.971-1.11). CONCLUSIONS: Although local smoking ordinances in Colorado previously suggested a reduction in acute myocardial infarction hospitalizations, no significant impact of smoke-free legislation was demonstrated at the state level, even after accounting for preexisting ordinances.

Unintentional pediatric exposures to central alpha-2 agonists reported to the National Poison Data System.

OBJECTIVE: To investigate national trends in unintentional pediatric exposures to 3 common alpha-2 agonists: clonidine, guanfacine, and tizanidine. Secondary objectives were to describe outcomes, symptoms, treatments, and death. STUDY DESIGN: Retrospective chart review from the American Association of Poison Control Centers National Poison Data System from January 2000 to December 2011 for unintentional exposure to clonidine, guanfacine, and tizanidine in children ≤ 12 years of age. RESULTS: From 2000-2011, there was a significant increase (5.9% per year, CI 3.6, 8.2) in unintentional pediatric exposures to National Poison Data System for central alpha-2 agonists. There were 27,825 clonidine exposures (67.3% male, median age: 4 years), 6143 guanfacine exposures (69.8% male, median age: 6 years), and 856 tizanidine exposures (51.9% male, median age: 2 years). Guanfacine had the greatest proportional increase among the medications. Clonidine was associated with the most respiratory (799, 2.9%) and central nervous system symptoms (12,612, 45.3%), as well as the most episodes of bradycardia (2847, 10.2%) and hypotension (2365, 8.5%). Seven-hundred twenty-eight (2.0%) patients were intubated, and 141 patients (0.5%) were administered vasopressors. There were 7 cardiac arrests and 3 deaths from clonidine. CONCLUSIONS: The number of unintentional pediatric exposures to alpha-2 agonists increased from 2000-2011. Clonidine exposures were the most commonly reported, more symptomatic, and associated with 3 deaths. Despite central nervous system depression, bradycardia, and hypotension being common, the need for intubation and vasopressors was rare.