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Opioid Deaths: Trends, Biomarkers, and Potential Drug Interactions Revealed by Decision Tree Analyses.

ABSTRACT: Opioid abuse is now the primary cause of accidental deaths in the United States. Studies over several decades established the cyclical nature of abused drugs of choice, with a current resurgence of heroin abuse and, more recently, fentanyl's emergence as a major precipitant of drug-related deaths. To better understand abuse trends and to explore the potential lethality of specific drug-drug interactions, we conducted statistical analyses of forensic toxicological data from the Wayne County Medical Examiner's Office from 2012-2016. We observed clear changes in opioid abuse over this period, including the rapid emergence of fentanyl and its analogs as highly significant causes of lethality starting in 2014. We then used Chi-square Automatic Interaction Detector (CHAID)-based decision tree analyses to obtain insights regarding specific drugs, drug combinations, and biomarkers in blood most predictive of cause of death or circumstances surrounding death. The presence of the non-opioid drug acetaminophen was highly predictive of drug-related deaths, likely reflecting the abuse of various combined acetaminophen-opioid formulations. The short-lived cocaine adulterant levamisole was highly predictive of a short post-cocaine survival time preceding sudden non-drug-related death. The combination of the opioid methadone and the antidepressant citalopram was uniformly linked to drug death, suggesting a potential drug-drug interaction at the level of a pathophysiological effect on the heart and/or drug metabolism. The presence of fentanyl plus the benzodiazepine midazolam was diagnostic for in-hospital deaths following serious medical illness and interventions that included these drugs. These data highlight the power of decision tree analyses not only in the determination of cause of death, but also as a key surveillance tool to inform drug abuse treatment and public health policies for combating the opioid crisis.

SUBMITTER: Saad MH

PROVIDER: S-EPMC6206231 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Opioid Deaths: Trends, Biomarkers, and Potential Drug Interactions Revealed by Decision Tree Analyses.

Saad Manal H MH Savonen Candace L CL Rumschlag Matthew M Todi Sokol V SV Schmidt Carl J CJ Bannon Michael J MJ

Frontiers in neuroscience 20181023

Opioid abuse is now the primary cause of accidental deaths in the United States. Studies over several decades established the cyclical nature of abused drugs of choice, with a current resurgence of heroin abuse and, more recently, fentanyl's emergence as a major precipitant of drug-related deaths. To better understand abuse trends and to explore the potential lethality of specific drug-drug interactions, we conducted statistical analyses of forensic toxicological data from the Wayne County Medic ...[more]

PMID: 30405330

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Project description:BACKGROUND:As several regulatory and environmental changes have occurred in North America, trends in overdose deaths were examined in the United States (US), Ontario and British Columbia (BC), including changes in consumption levels of prescription opioids (PO) and overdose deaths, changes in correlations between consumption levels of PO and overdose deaths and modeled differences between observed and predicted overdose deaths if no changes had occurred. METHODS:Consumption levels of PO included defined daily doses for statistical purposes per million inhabitants per day for the US and Canada (2001-2015). Overdose deaths included opioid overdose deaths for the US (2001-2017) and Ontario (2003-2017) and illicit drug overdose deaths for BC (2001-2017). The analytic techniques included structural break point analyses, Pearson product-moment correlations and multivariate Gaussian state space modeling. RESULTS:Consumption levels of PO changed in the US in 2010 and in Canada in 2012. Overdose deaths changed in the US in 2014 and in Ontario and BC in 2015. Prior to the observed changes in consumption levels of PO, there were positive correlations between consumption levels of PO and overdose deaths in the US (r?=?0.99, p?<?0.001) and Ontario (r?=?0.92, p?=?0.003). After the observed changes in consumption levels of PO, there was a negative correlation between consumption levels of PO and overdose deaths in the US (r?=?-?0.99, p?=?0.002). Observed overdose deaths exceeded predicted overdose deaths by 5.7 (95% Confidence Interval [CI]: 4.8-6.6), 3.5 (95% CI: 3.2-3.8) and 21.8 (95% CI: 18.6-24.9) deaths per 100,000 people in the US, Ontario and BC, respectively in 2017. These excess deaths corresponded to 37.7% (95% CI: 31.9-43.6), 39.2% (95% CI: 36.3-42.1) and 72.2% (95% CI: 61.8-82.6) of observed overdose deaths in the US, Ontario and BC, respectively in 2017. CONCLUSIONS:The opioid crisis has evolved in North America, as a sizeable proportion of overdose deaths are now attributable to the several regulatory and environmental changes. These findings necessitate substance use policies to be conceptualized more broadly as well as the continued expansion of harm reduction services and types of pharmacotherapy interventions.

Project description:ImportanceData suggest that the opioid crisis in North America has recently been reflected in opioid-related mortality among youths. Despite recommendation for its use, youths encounter barriers to accessing OAT, including stigma, burden of witnessed dosing, and lack of availability of youth-oriented services and prescribers comfortable treating this population.ObjectiveTo compare rates of opioid agonist treatment (OAT) and opioid-related mortality between youths aged 15 to 24 years and adults aged 25 to 44 years in Ontario, Canada, over time.Design, setting, and participantsThis cross-sectional analysis of rates of OAT and opioid-related deaths between 2013 and 2021 used data obtained from the Ontario Drug Policy Research Network, Public Health Ontario, and Statistics Canada. Individuals included in the analysis were aged 15 to 44 years and residing in Ontario, the most populous province in Canada.ExposuresYouths aged 15 to 24 years compared with adults aged 25 to 44 years.Main outcomes and measuresOAT (methadone, buprenorphine, and slow-release oral morphine) per 1000 population and opioid-related deaths per 100 000 population.ResultsBetween 2013 and 2021, 1021 youths aged 15 to 24 years died from opioid toxicity; 710 were male (69.5%). In the final year of the study period, 225 youths (146 male [64.9%]) died from opioid toxicity, and 2717 (1494 male [55.0%]) were dispensed OAT. Over the study period, the rate of opioid-related deaths among youths in Ontario increased 369.2% from 2.6 to 12.2 per 100 000 population (48 to 225 total deaths) and the rate of OAT use decreased 55.9% from 3.4 to 1.5 per 1000 (6236 to 2717 individuals). For adults aged 25 to 44 years, the rate of opioid-related deaths increased 371.8% from 7.8 to 36.8 per 100 000 (283 to 1502 deaths), and the rate of OAT increased 27.8% from 7.9 to 10.1 per 1000 population (28 667 to 41 200 individuals). Trends for youths and adults persisted across both sexes.Conclusions and relevanceThe findings of this study suggest that opioid-related deaths are increasing among youths while OAT use is paradoxically declining. The reasons for these observed trends require further investigation, including a consideration of changing trends in opioid use and opioid use disorder among youths, barriers to OAT, and opportunities to optimize care and reduce harms for youths who use substances.

Project description:BackgroundWarnings about drug-drug interactions (DDIs) between warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) within electronic health records indicate potential harm but fail to account for contextual factors and preferences. We developed a tool called DDInteract to enhance and support shared decision-making (SDM) between patients and physicians when both warfarin and NSAIDs are used concurrently. DDInteract was designed to be integrated into electronic health records using interoperability standards.ObjectiveThe purpose of this study was to conduct a formative evaluation of a DDInteract that incorporates patient and product contextual factors to estimate the risk of bleeding.MethodsA randomized formative evaluation was conducted to compare DDInteract to usual care (UC) using physician-patient dyads. Using case vignettes, physicians and patients on warfarin participated in simulated virtual clinical encounters where they discussed the use of taking ibuprofen and warfarin concurrently and determined an appropriate therapeutic plan based on the patient's individualized risk. Dyads were randomized to either DDInteract or UC. Participants completed a postsession interview and survey of the SDM process. This included the 9-item Shared Decision-Making Questionnaire (SDM-Q-9), tool usability and workload National Aeronautics and Space Administration (NASA) Task Load Index, Unified Theory of Acceptance and Use of Technology (UTAUT), Perceived Behavioral Control (PBC) scale, System Usability Scale (SUS), and Decision Conflict Scale (DCS). They also were interviewed after the session to obtain perceptions on DDInteract and UC resources for DDIs.ResultsTwelve dyad encounters were performed using virtual software. Most (n=11, 91.7%) patients were over 50 years of age, and 9 (75%) had been taking warfarin for more than 2 years (75%). Regarding scores on the SDM-Q-9, participants rated DDInteract higher than UC for questions pertaining to helping patients clarify the decision (P=.03), involving patients in the decision (P=.01), displaying treatment options (P<.001), identifying advantages and disadvantages (P=.01), and facilitating patient understanding (P=.01) and discussion of preferences (P=.01). Five of the 8 UTAUT constructs showed differences between the 2 groups, favoring DDInteract (P<.05). Usability ratings from the SUS were significantly higher (P<.05) for physicians using DDInteract compared to those in the UC group but showed no differences from the patient's perspective. No differences in patient responses were observed between groups using the DCS. During the session debrief, physicians indicated little concern for the additional time or workload entailed by DDInteract use. Both clinicians and patients indicated that the tool was beneficial in simulated encounters to understand and mitigate the risk of harm from this DDI.ConclusionsOverall, DDInteract may improve encounters where there is a risk of bleeding due to a potential drug-drug interaction involving anticoagulants. Participants rated DDInteract as logical and useful for enhancing SDM. They reported that they would be willing to use the tool for an interaction involving warfarin and NSAIDs.

Dataset Information

Opioid Deaths: Trends, Biomarkers, and Potential Drug Interactions Revealed by Decision Tree Analyses.

Publications

Opioid Deaths: Trends, Biomarkers, and Potential Drug Interactions Revealed by Decision Tree Analyses.

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