The recent opioid prescribing guideline cautions about the concomitant prescribing of opioids and skeletal muscle relaxants (SMRs) given the additive central nervous system depressant effect. ...However, the clinical relevance remains unclear. In this retrospective cohort study, we compared the risk of opioid overdose associated with concomitant use of opioids and SMRs vs. opioid use alone. Adjusted hazard ratios were 1.09 (95% confidence interval (CI), 0.74–1.62) and 1.26 (95% CI, 1.00–1.58) in the incident and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21 (95% CI, 1.00–1.48). This risk seemed to increase with treatment duration (≤ 14 days: 0.91 and 95% CI, 0.67–1.22; 15–60 days: 1.37 and 95% CI, 0.81–2.37; >60 days: 1.80 and 95% CI, 1.30–2.48) and for baclofen (1.83 and 95% CI, 1.11–3.04) and carisoprodol (1.84 and 95% CI, 1.34–2.54). Concomitant users with daily opioid dose ≥50 mg (1.50 and 95% CI, 1.18–1.92) and benzodiazepine use (1.39 and 95% CI, 1.08–1.79) also had elevated risk. Clinicians should be cautious about these potentially unsafe practices to optimize pain care and improve patient safety.
Abstract
Consumption of poppy seed-containing food products can result in opiate-positive urine drug test results and may pose challenges in distinguishing poppy seed consumption from opiate ...administration. In this context, guidance has suggested that codeine concentrations exceeding 300 ng/mL coupled with morphine-to-codeine ratios <2 are indicative of codeine consumption and, therefore, exclude poppy seed consumption as a legitimate explanation for the test result. In recent years, we performed independent medical examinations of three individuals who produced codeine-positive/morphine-negative (300 ng/mL) forensic urine drug test results but denied codeine administration, attributing their test results to the consumption of specific poppy seed-containing food products. In the present study, 11 participants consumed one of the 10 unique poppy seed-containing food products, including the three implicated food products. Six of 33 non-baseline urine samples (18%)—representing three food products—were positive for codeine and negative for morphine at 300 ng/mL cut-offs (and therefore featured morphine-to-codeine ratios <2). This study adds to a small literature indicating that consumption of poppy seed-containing food products cannot reliably be distinguished from codeine administration based on previously published urinary opiate concentrations and ratios. An important caveat is that in none of these cases did maximum urinary codeine concentrations exceed 1,300 µg/g creatinine.
•In 2017, approximately 17,000 patients in Florida were concurrently dispensed opioids, benzodiazepines, and carisoprodol.•“Holy Trinity” recipients were associated with top 1% prescribers in ...multiple drug classes and more multiple provider episodes.•In 2017, approximately one-half of the triple drug combinations were written by single, as opposed to multiple, prescribers.
High-risk combinations of controlled medications, such as those involving opioid analgesics, are under increased scrutiny because of their contribution to the opioid epidemic in the United States. Responsible prescribing guidelines indicate that the triple drug combination--opioids, benzodiazepines and skeletal muscle relaxants, especially carisoprodol--should not be concurrently prescribed.
This pharmacoepidemiologic study was designed to primarily examine the characteristics of patients receiving this triple combination compared to the group receiving only opioids and benzodiazepines.
Results show that, while the number of exposed patients has declined since 2012, approximately 17,000 Floridians were prescribed this combination in 2017 alone. Demographically, recipients of these prescriptions were younger, more likely to be female, and geographically-localized. Furthermore, these patients were more frequently associated with a prescriber in the top 1% of opioid and/or benzodiazepine prescribing, have more multiple provider episodes (“doctor shopping”), and receive higher mean daily opioid dosages.
These findings raise important questions as to how frequently prescribers are checking prescription drug monitoring programs, following US Centers for Disease Control and Prevention opioid prescribing guidelines, and/or handling the clinical challenges associated with pharmaceutical management of patients with complex, painful health conditions.
Abstract Abuse of the psychoactive “designer drug” methylenedioxypyrovalerone (MDPV) has become a serious international public health concern because of the severity of its physical and behavioral ...toxicities. MDPV is the primary ingredient in so-called “bath salts,” labeled as such to avoid criminal prosecution and has only been classified recently as a controlled substance in the United States and some other countries. However, it remains a danger because of illegal sources, including the Internet. MDPV is a synthetic, cathinone-derivative, central nervous system stimulant and is taken to produce a cocaine- or methamphetamine-like high. Administered via oral ingestion, nasal insufflation, smoking, intravenous or intramuscular methods, or the rectum, the intoxication lasts 6 to 8 hours and has high addictive potential. Overdoses are characterized by profound toxicities, causing increased attention by emergency department and law enforcement personnel. Physical manifestations range from tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, and seizures to those as severe as stroke, cerebral edema, cardiorespiratory collapse, myocardial infarction, and death. Behavioral effects include panic attacks, anxiety, agitation, severe paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, and behavior that is aggressive, violent, and self-destructive. Treatment is principally supportive and focuses on counteracting the sympathetic overstimulation, including sedation with intravenous benzodiazepines, seizure-prevention measures, intravenous fluids, close (eg, intensive care unit) monitoring, and restraints to prevent harm to self or others. Clinical presentation is often complicated by coingestion of other psychoactive substances that may alter the treatment approach. Clinicians need to be especially vigilant in that MDPV is not detected by routine drug screens and overdoses can be life-threatening.
Abstract Blood phosphatidylethanol (PEth), a metabolite of ethanol, is emerging as a direct biomarker of choice for characterizing ethanol consumption in clinical, research, and forensic contexts. An ...accumulating body of evidence, and a recent international consensus conference, supports a cutoff of 20 μg/L of PEth (16:0/18:1) to distinguish abstinence from beverage ethanol consumption. There is a dearth of research, however, on whether exposures to nonbeverage ethanol sources are sufficient to produce PEth concentrations that exceed this cutoff. To explore this possibility, we recruited 30 participants, who indicated past‐90‐day abstinence from beverage alcohol, to characterize their past‐30‐day nonbeverage ethanol exposures (including source, frequency, and intensity of exposures) and to undergo PEth testing. Two of the 30 participants (6.7%) produced PEth concentrations ≥20 μg/L. One of these participants (PEth = 26 μg/L) reported multiple ethanol exposure sources, including near‐daily intensive exposures to ethanol vapor. The other participant (PEth = 49 μg/L) reported only once‐daily use of an ethanol‐containing mouthwash; the veracity of his abstinence claim is refuted. The results of this study support a rebuttable presumption that PEth ≥20 μg/L is indicative of beverage ethanol consumption. They suggest, however, that intensive, incidental alcohol exposures have the potential, under unusual circumstances, to result in PEth concentrations that modestly exceed this threshold.
Abstract
This study examined the urine and hair opiate profiles associated with the daily consumption of presumptive codeine-predominant poppy seed food products. Ten participants consumed one of ...five food products at breakfast for 10 consecutive days. Baseline urine and hair samples were collected on Day 1. The urine samples were collected 4, 8 and 12 h following poppy seed consumption on Days 1 and 10, and the first morning void urine samples were collected on Days 2–10. A second hair specimen was collected on Day 20 ± 2. Urine drug test results: Three of the food products were associated with opiate-negative urine drug test results at all time points at a 300 ng/mL cut-off. Two of the food products were associated with opiate-positive drug test results at all non-baseline time points at a 300 ng/mL cut-off. Of these, all samples (n = 60) were codeine-positive, and 27 (45%) were morphine-positive. Codeine concentrations exceeded morphine concentrations in every sample and always by multiples. Thirty-nine of the 60 samples (65%) were codeine-positive at a 2,000 ng/mL cut-off, while none of these samples were morphine-positive at this cut-off. None of the 60 samples reached an opiate threshold of 15,000 ng/mL, although one participant produced a maximum codeine concentration of 13,161 ng/mL (13,854 ng/mg creatinine). There was no clear trend toward increasing urinary opiate concentrations over the course of the study. Hair drug test results: The hair samples of two participants produced quantifiable codeine (41 pg/mg and 51 pg/mg), but no sample reached a common reporting threshold of 200 pg/mg for codeine or morphine.
Alcohol use disorders are prevalent in the USA and throughout the world. Monitoring for alcohol abstinence is useful in several clinical and forensic contexts. The direct alcohol biomarkers have the ...requisite sensitivity and specificity for abstinence monitoring. The relatively new direct biomarker phosphatidylethanol (PEth), measured in blood, is gaining increasing acceptance in monitoring abstinence from beverage alcohol consumption, but there remains little research addressing the potential for PEth formation consequent to incidental alcohol exposures. In the midst of the coronavirus disease 2019 pandemic, high-alcohol content hand sanitizer is a particularly important source of nonbeverage alcohol exposure. To assess the extent of alcohol absorption and subsequent formation of blood PEth related to intensive use of high alcohol content hand sanitizer, we recruited 15 participants to use a 70% ethyl alcohol-based hand sanitizer 24-100 times daily, for 12-13 consecutive days. Blood was analyzed for PEth 16:0/18:1 by liquid chromatography--tandem mass spectrometry. Our hypothesis that blood PEth concentrations would fail to reach a 20 ng/mL threshold was confirmed. This work adds to the nascent literature on the effects of incidental alcohol exposures on blood PEth formation.
Background and aims
Little is known about opioid and gabapentinoid (OPI‐GABA) use duration and dose patterns’ associations with adverse outcome risks. We examined associations between OPI‐GABA dose ...and duration trajectories and subsequent drug overdose.
Design
Retrospective cohort study.
Setting
US Medicare.
Participants
Using a 5% sample (2011–16), we identified 71 005 fee‐for‐service Medicare beneficiaries with fibromyalgia, low back pain, neuropathy and/or osteoarthritis initiating OPIs and/or GABAs mean age ± standard deviation (SD) = 65.5 ± 14.5 years, female = 68.1%, white = 76.8%.
Measurements
Group‐based multi‐trajectory models identified distinct OPI‐GABA use patterns during the year of OPI and/or GABA initiation, based on weekly average standardized daily dose (i.e. OPIs = morphine milligram equivalent, GABAs = minimum effective daily dose). We estimated models with three to 12 trajectories and selected the best model based on Bayesian information criterion (BIC) and Nagin's criteria. We estimated risk of time to first drug overdose diagnosis within 12 months following the index year, adjusting for socio‐demographic and health factors using inverse probability of treatment weighted multivariable Cox proportional hazards models.
Findings
We identified 10 distinct trajectories (BIC = –1 176 954; OPI‐only = 3, GABA‐only = 3, OPI‐GABA = 4). Compared with OPI‐only early discontinuers (40.6% of the cohort), 1‐year drug overdose risk varied by trajectory group: consistent low‐dose OPI‐only users 16.6%; hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.19–1.82, consistent high‐dose OPI‐only users (1.8%; HR = 4.57, 95% CI = 2.99–6.98), GABA‐only early discontinuers (12.5%; HR = 1.39, 95% CI = 1.09–1.77), consistent low‐dose GABA‐only users (11.0%; HR = 1.44, 95% CI = 1.12–1.85), consistent high‐dose GABA‐only users (3.1%; HR = 1.43, 95% CI = 0.94–2.17), early discontinuation of OPIs and consistent low‐dose GABA users (6.9%; HR = 1.24, 95% CI = 0.90–1.69), consistent low‐dose OPI‐GABA users (3.4%; HR = 2.49, 95% CI = 1.76–3.52), consistent low‐dose OPI and high‐dose GABA users (3.2%; HR = 2.46, 95% CI = 1.71–3.53) and consistent high‐dose OPI and moderate‐dose GABA users (0.9%; HR = 7.22, 95% CI = 4.46–11.69).
Conclusions
Risk of drug overdose varied substantially among US Medicare beneficiaries on different use trajectories of opioids and gabapentinoids. High‐dose opioid‐only users and all consistent opioid and gabapentinoid users (regardless of doses) had more than double the risk of subsequent drug overdose compared with opioid‐only early discontinuers.
Abstract
Direct biomarkers of ethanol are used to monitor individuals who are required to abstain from ethanol consumption. In recent years, blood phosphatidylethanol (PEth) has gained acceptance in ...clinical and forensic contexts as an abstinence marker. Its elimination half-life of several days provides a window of detection of days to weeks. However, there is no research addressing the extent of PEth formation related to extraneous ethanol exposures. To assess the degree of ethanol absorption and subsequent formation of blood PEth related a common extraneous exposure, regular use of an ethanol-containing mouthwash, we recruited 16 participants to gargle with an alcohol-based mouthwash (21.6% ethanol) 4 times daily, for 12 consecutive days. Blood was analyzed for PEth 16:0/18:1 by liquid chromatography–tandem mass spectrometry. Our hypothesis that blood PEth concentrations would not equal or exceed 20 ng/mL was confirmed. Although the data suggest that regular use of mouthwash is unlikely to result in suprathreshold PEth concentrations, this work highlights the importance of considering extraneous ethanol exposures in clinical decision-making and in future research.
According to the Centers for Disease Control and Prevention (CDC), approximately 46 people died each day in 2016 from prescription opioid related poisoning. Opioid prescribing volume per capita, ...which directly correlates with mortality, has declined but remains three times higher than in the late 1990s. The lifesaving drug naloxone is being rapidly deployed as a stopgap measure to prevent deaths. However, multifaceted strategies for preventing and treating opioid use disorders, such as increased access to evidence-based treatment such as medication-assisted treatment, are urgently needed. Here, Delcher et al focus on the national implications on the rapid expansion of the opioid ecosystem among prescribers and pharmacists.
