Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

Purpose: An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse.

Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration.

Background: Prescription opioid abuse and misuse is a serious and growing public health issue. While the most common form of abuse is swallowing intact tablets/capsules, some abusers manipulate, or tamper with, these medications by altering the dosage form to allow for non-oral routes of administration (e.g.

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

Background: The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism.

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.

Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.

Background: Paracetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity.

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.

A randomized, placebo-controlled trial to determine the course of aminotransferase elevation during prolonged acetaminophen administration.

Background: Acetaminophen administration for more than 4 days causes aminotransferase elevation in some subjects. The objective of this randomized, placebo-controlled trial is to describe the course of alanine aminotransferase (ALT) elevation in subjects administered 4 g/day of acetaminophen for at least 16 days.

Methods: A randomized, placebo controlled trial of acetaminophen (4 g/day) vs placebo.

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.

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.

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.

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.

Using poison center exposure calls to predict prescription opioid abuse and misuse-related emergency department visits.

Background: Prescription drug abuse is a critical problem in the USA and has been linked to more deaths than automobile accidents. Despite this growing epidemic, the USA lacks a timely early warning system. Poison centers (PCs) have the potential to act as sentinel reporting entities for prescription drug abuse and misuse due to near-real-time data reporting and abundant coverage in the USA.

Root causes, clinical effects, and outcomes of unintentional exposures to buprenorphine by young children.

Objective: To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations.

Study Design: Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates.

QTc interval screening in an opioid treatment program.

Methadone is highly effective for opioid dependency, but it is associated with Torsade de pointes. Although electrocardiography (ECG) has been proposed, its utility is uncertain, because an ECG-based intervention has not been described. An ECG-based cardiac safety program in methadone maintenance patients was evaluated in a single opioid treatment program from September 1, 2009, to August 31, 2011, in the United States.

Reduced abuse, therapeutic errors, and diversion following reformulation of extended-release oxycodone in 2010.

Unlabelled: This study evaluated changes in abuse exposures, therapeutic error exposures, and diversion into illegal markets associated with brand extended-release oxycodone (ERO) following introduction of reformulated ERO. Original ERO and reformulated ERO street prices also were compared. Data from the Poison Center and Drug Diversion programs of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System were used.

Trends in reporting methadone-associated cardiac arrhythmia, 1997-2011: an analysis of registry data.

Background: Long-acting opioids are a leading cause of accidental death in the United States, and methadone is associated with greater mortality rates. Whether this increase is related to the proarrhythmic properties of methadone is unclear.

Objective: To describe methadone-associated arrhythmia events reported in the U.

Medically significant late bleeding after treated crotaline envenomation: a systematic review.

Study Objective: We estimate the proportion of patients with crotaline snake envenomation who are treated with Crotalidae polyvalent immune Fab (ovine) antivenom and who develop medically significant late bleeding.

Methods: We performed a systematic review of all published cohort studies of North American crotaline snake envenomation patients treated with Fab antivenom. We searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to April 30, 2012.

A randomized, double-blind, placebo-controlled trial of a highly purified equine F(ab)2 antibody black widow spider antivenom.

Study Objective: Black widow spider antivenom has never been tested in a randomized clinical trial, to our knowledge. We explore various efficacy measures for a novel F(ab)2 antivenom in patients with moderate to severe pain caused by black widow spider envenomation.

Methods: A randomized, placebo-controlled, double-blind, clinical trial was conducted in 12 academic emergency departments.

Characterization of adolescent prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-related Surveillance (RADARS(®)) System.

Objective: To describe the characteristics and health effects of adolescent (age 13-19 years) prescription drug abuse and misuse using the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS(®)) System.

Method: Secondary analysis of data collected from RADARS System participating poison centers was performed. Data for all intentional exposures from 2007 through 2009 were used to describe adolescent prescription opioid (oxycodone, fentanyl, hydrocodone, hydromorphone, morphine, methadone, buprenorphine, and tramadol) and stimulant (methylphenidate and amphetamines) exposures.

Assessment of the abuse of tapentadol immediate release: the first 24 months.

Objective: Prescription opioid analgesics play an important role in the management of moderate to severe pain. An unintended consequence of prescribing opioid analgesics is the abuse and diversion of these medications. The authors estimated abuse and diversion rates for tapentadol immediate release (IR) compared with oxycodone, hydrocodone, and tramadol during the first 24 months of tapentadol IR availability.

Effect of therapeutic doses of acetaminophen (up to 4 g/day) on serum alanine aminotransferase levels in subjects consuming ethanol: systematic review and meta-analysis of randomized controlled trials.

Study Objective: To quantify the effect of therapeutic doses of acetaminophen on serum alanine aminotransferase (ALT) levels in subjects who consumed ethanol.

Design: Systematic review of six randomized placebo-controlled trials, of which five were included in a meta-analysis.

Subjects: Subjects included in the meta-analysis were those who consumed ethanol and received acetaminophen in doses up to 4 g/day (551 subjects) or placebo (350 subjects).

A US perspective of symptomatic Latrodectus spp. envenomation and treatment: a National Poison Data System review.

Background: Black widow spider (Latrodectus spp.) envenomation remains the most clinically significant spider envenomation in the US. The syndrome is characterized by painful muscle rigidity and autonomic disturbances.