The Association between Direct Oral Anticoagulants Prescribing Behavior and Non-Valvular Atrial Fibrillation Outcomes: An Instrumental Variable Analysis of Real-World Data.

Several observational studies have compared apixaban with rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), but these analyses may be confounded by unmeasured characteristics. This study used provider prescribing preference (PPP) as an instrumental variable (IV) to assess the association between prescriber choice of rivaroxaban vs. apixaban and the study outcomes of stroke/systemic embolism (SE), major bleeding, and death in a retrospective cohort of NVAF patients in the US. Initiators of either medication were linked to their prescribers and followed until the first of the study outcome, the end of rivaroxaban/apixaban use, or 365 days after initiation. PPP for each patient was the percent of rivaroxaban initiations issued by the provider for the prior 10 NVAF patients. Cox regression models tested associations between quintiles of PPP and each outcome. A total of 61,155 patients and 1726 providers were included. The IV was a strong predictor of rivaroxaban prescription (OR = 17.9; 95% CI: 16.6, 19.3). There were statistically significant associations between increasing preference for rivaroxaban and rates of major bleeding (ptrend = 0.041) and death (ptrend = 0.031), but not stroke/SE (ptrend = 0.398). This analysis provides evidence of the relative safety of apixaban over rivaroxaban for the risk of major bleeding and death.

Differences in severity of poison centers exposures involving XTAMPZA® ER versus other opioid analgesics.

Aims: Xtampza® ER (Collegium Pharmaceutical, MA, USA) is an abuse-deterrent formulation (ADF) of oxycodone intended to deter tampering for use by unintended routes of administration. We assessed whether Xtampza ER exposures were less likely to result in severe medical outcomes relative to other opioid analgesic exposures. Materials & methods: Exposures reported to participating poison centers between 2016 and 2021 inclusive that were followed to a known medical outcome were analyzed. Xtampza ER was compared with other ADF opioids, non-ADF extended-release opioids, single-entity oxycodone immediate-release, unspecified oxycodone and unspecified morphine. Results & conclusion: No Xtampza ER exposures involved unintended routes of administration. Xtampza ER exposures were less likely to be abuse, misuse or suspected suicidal, and medical outcomes were less severe than comparators.

Trends in characteristics of fentanyl-related poisonings in the United States, 2015-2021.

Background: Fentanyl-related deaths continue to increase in the United States; however, most national studies focus on fatal overdose. More research, including data on nonfatal overdose, is needed.Objective: We examined trends in characteristics of fatal and nonfatal fentanyl-related poisonings ("exposures") in the US.Methods: National Poison Control data were examined to estimate trends in characteristics of reported exposures between 2015 and 2021 (N = 15,391; 38.7% female). We also delineated correlates of experiencing a major adverse effect or death.Results: The proportion of exposures increased among all age groups between ages 13 and 39 (ps < .05) with the largest increase among those age 13-19 (a 127.8% increase). With respect to reasons for use, the proportion of cases involving fentanyl "abuse" increased by 63.8% (p < .001). The proportion involving fentanyl inhalation increased 427.6% from 5.7% to 29.9% and injection increased from 6.7% to 9.6%, a 42.3% increase (ps < .01). The proportion also increased for co-use of methamphetamine (by 669.0%), cocaine (by 374.0%), and heroin (by 159.5%). The proportion of major adverse effects increased from 15.5% to 39.6% (p < .001). In the multivariable model, "abuse", suspected suicide attempts, and use via inhalation were risk factors for experiencing a major effect or death, and misuse, ingestion, dermal use, and co-use of methamphetamine were associated with lower risk.Conclusion: Poison Control data suggest that characteristics of individuals exposed to fentanyl continue to shift, with use via inhalation increasing and medical outcomes of nonfatal poisonings becoming more severe. These results complement mortality data and inform prevention and harm reduction efforts.

Increasing rates of buprenorphine diversion in the United States, 2002 to 2019.

PURPOSE: Recent reports suggest that buprenorphine is being diverted and used non-medically. However, no apparent studies have reported national-level data on buprenorphine diversion. METHODS: Case report data were 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. Quarterly rates of buprenorphine diversion per 100 000 population and 100 000 prescriptions dispensed were calculated for the period 2002 through 2019. Population-based diversion rates were also calculated by U.S. region. RESULTS: In total, 9670 cases of diverted buprenorphine were reported across all 50 states and the District of Columbia during the study period. Buprenorphine diversion rates, per 100 000 population, were characterized by an accelerating increase over time; increases in diversion rates from 1st quarter 2002 through 4th quarter 2006 were not statistically significant, yet from 1st quarter 2007 through 4th quarter 2019, the rate of diversion cases increased by 0.0067 cases per 100 000 per quarter (p < 0.001). Buprenorphine diversion rates per 100 000 prescriptions dispensed indicated a gradual increase over time; from 3rd quarter 2010 through 4th quarter 2019, diversion rates showed a statistically significant increase of 0.28 cases (p = 0.037) per quarter on average. The Northeast was the only region that did not observe an increase in the average quarterly change in buprenorphine diversion rates after 2006. CONCLUSIONS: Findings from this study illustrate longitudinal national trends of increasing buprenorphine diversion. Continued systematic surveillance of this phenomenon is needed.

Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

PURPOSE: 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. METHODS: 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. RESULTS: 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 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. CONCLUSION: Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price.

Understanding abuse of buprenorphine/naloxone film versus tablet products using data from ASI-MV® substance use disorder treatment centers and RADARS® System Poison Centers.

OBJECTIVES: The objectives were to examine the abuse prevalence and route-of-administration (ROA) profiles of sublingual buprenorphine/naloxone combination (BNX) film in comparison with the BNX tablet and to identify clinically-relevant subgroups of patients or geographic patterns. METHODS: Between Q1 2015 through Q3 2015, data were collected from two major surveillance systems: (1) assessment of individuals in substance use disorder (SUD) treatment collected from the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO®) ASI-MV® system and (2) intentional abuse/misuse exposures in the RADARS® System Poison Center Program. Poisson regression models were tailored to each system's data characteristics by population (all SUD treatment patients, US census) and adjusted for prescription volume. Effects of gender, race, age and US region as well as ROA profile were examined. RESULTS: For the ASI-MV study, 45,695 assessments of unique adults evaluated for substance use problems were collected. The abuse rate unadjusted for prescription volume of BNX tablet formulation was 2.64 cases/100 ASI-MV respondents versus 7.01 cases for the film formulation (RR=0.390, p<0.001). Prescription-adjusted abuse, however, was greater for the tablet version (0.47 abuse cases/100 ASI-MV respondents/100,000 dosage units compared with 0.38 for the film) (RR=1.25, p<0.001). Results among the US population from the RADARS System Poison Center Program data revealed a similar pattern; population rates for film abuse (0.0364) were greater than for tablet (0.0161), while prescription-adjusted rates were greater for tablet (0.2114) than for film (0.1703) per 100,000 prescriptions. ASI-MV ROA analyses indicated less abuse of the film by any alternate route, insufflation or injection than the tablet. Poison center data found more injection of tablets than film, although insufflation was not significantly different. CONCLUSIONS: On a prescription-adjusted basis, overall abuse of the BNX tablet is greater than that of the sublingual film formulation. For those who continue to abuse BNX, use by alternate ROAs was, in general, lower for the film.

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. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. METHODS: Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. RESULTS: OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. DISCUSSION: Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years.

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. Quarterly rates 2 years prior to introduction of reformulated ERO (October 2008 through September 2010) were compared to quarterly rates after introduction (October 2010 through March 2012) using negative binomial regression. Street prices were compared using a mixed effects linear regression model. Following reformulated ERO introduction, poison center ERO abuse exposures declined 38% (95% confidence interval [CI]: 31-45) per population and 32% (95% CI: 24-39) per unique recipients of dispensed drug. Therapeutic error exposures declined 24% (95% CI: 15-31) per population and 15% (95% CI: 6-24) per unique recipients of dispensed drug. Diversion reports declined 53% (95% CI: 41-63) per population and 50% (95% CI: 39-59) per unique recipients of dispensed drug. Declines exceeded those observed for other prescription opioids in aggregate. After its introduction, the street price of reformulated ERO was significantly lower than original ERO. PERSPECTIVE: This article indicates that the abuse, therapeutic errors, and diversion of ERO declined following the introduction of a tamper-resistant reformulation of the product. Reformulating abused prescription opioids to include tamper-resistant properties may be an effective approach to reduce abuse of such products.

Neighborhood & Family Effects on Learning Motivation among Urban African American Middle School Youth.

Motivational theorists in psychology have moved away from individual-based approaches to socio-cognitive and socio-ecological models to explain student engagement and motivation for learning. Such approaches consider, for example, the influence of family and neighborhood environments as important constructs in youth behavior. In this study, links between neighborhood condition (e.g. external appearance of the blocks nearest to the respondents' home), family dysfunction, and motivation for learning are investigated. Data were obtained from two hundred and sixteen (216) urban African American middle school children enrolled in a substance use prevention intervention. Analytic models show associations between poor neighborhood condition and both family dysfunction and lower learning motivation. Family dysfunction was also found to mediate the effect of neighborhood condition on motivated learning. Neighborhood and family characteristics are important determinants of urban schoolchildren's motivation for learning.

The association between executive functioning and motivation to enter treatment among regular users of heroin and/or cocaine in Baltimore, MD.

This study explored the association between readiness to enter treatment and performance on the Wisconsin Card Sorting Test (WCST), a measure of problem solving ability and executive functioning. Data for this analysis was collected on 258 current regular users of heroin and/or cocaine as part of an epidemiologic study on executive function and drug use. A structural equation model was used to test the hypotheses that poorer performance on the WCST would predict lower scores on two latent constructs measuring motivation to change drug use. Specifically, poorer performance on the WCST was associated with lower recognition of problem use. Associations between treatment enrollment within the past six months and regular use of more than one drug were also observed. Findings highlight the importance of considering cognitive impairment in programs targeting active drug users and promoting treatment participation.

The relationship between performance on the Shipley Institute of Living Scale (SILS) and hepatitis C infection among active injection drug users in Baltimore, Maryland.

BACKGROUND: Hepatitis C represents a significant public health problem, particularly among injection drug users. Other than injection drug practices, little is understood about individual level characteristics that may place some injection drug users at particularly high risk. OBJECTIVES: The current study sought to examine two associations among active, regular heroin injection drug users. The first was to determine whether there was an association between two scales from the Shipley Institute of Living Scale (SILS: a neuropsychological measure used to estimate cognitive impairment/intellectual functioning) and self-reported preexisting conditions independent of years of drug use. The second was to examine whether performance on the scales was associated with hepatitis C infection. METHODS: Data from 260 HIV negative injection drug users from the Baltimore metropolitan region were used. Participants completed a risk behavior interview, brief neuropsychological battery, and were tested for Hepatitis C. RESULTS: Findings indicated that scale performances varied by self-reported learning disabilities and attention deficit disorder. Poorer performance on one scale was statistically significantly associated with greater hepatitis C prevalence on the vocabulary scale, the discrepancy scale showed a statistical trend. CONCLUSIONS: Cognitive impairment measured among this sample of injection drug use was related to pre-existing conditions and hepatitis C independent of years of drug use. Such impairment may exist prior to initiation of use and increase vulnerability to poor health outcomes among injection drug users. SCIENTIFIC SIGNIFICANCE: This study highlights the need for interventions targeting a possible high risk subpopulation of injection drug users.

Factors related to correctional facility incarceration among active injection drug users in Baltimore, MD.

AIM: We investigated the moderating effect of impulse control on the association between drug use and incarceration among active injection drug users (IDU). METHODS: The study sample consisted of 282 IDUs aged 15-50 years from the Baltimore metropolitan region who reported injection drug use within the past 6 months and indicated that heroin or speedball was their drug of choice. Impulse control was measured using commission error standardized scores from the Test of Variables of Attention (TOVA). Incarceration was obtained using self-reported lifetime history of incarceration in correctional facilities. RESULTS: Findings indicated that impulse control moderated the association between years of injection drug use and incarceration in correctional facilities adjusting for ethnicity, gender, estimated pre-morbid intelligence, and age of first injection use. Specifically, among individuals who were intact in impulse control, four or more years of injection drug use was associated with incarceration (AOR=4.97, 95% CI: 2.02-12.23). This finding was not observed among individuals with impaired impulse control (AOR=0.57, 95% CI: 0.10-3.23). Furthermore, impulse control moderated the association between regular cocaine use and incarceration. Among individuals who had a history of cocaine use, individuals with low impulse control but not impaired were more likely to have reported time in a correctional facility (AOR=6.28, 95% CI: 1.68-23.60). There was no association among individuals with impaired or intact impulse control. CONCLUSION: Results highlight the importance of considering cognitive measures of impulse control in addressing negative outcomes associated with drug use.