The effect of incidental ethanol exposures on the formation of blood phosphatidylethanol.

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.

Association between Opioid-Benzodiazepine Trajectories and Injurious Fall Risk among US Medicare Beneficiaries.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate injurious fall risk (e.g., falls and fractures) compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious fall risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated the time to first injurious falls within the 3-month post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age ≥ 65 = 84.6%, female = 58.1%, White = 82.7%; having injurious falls = 0.45%), we identified 13 distinct OPI-BZD trajectories: Group (A): Very-low OPI-only (early discontinuation) (44.9% of the cohort); (B): Low OPI-only (rapid decline) (15.1%); (C): Very-low OPI-only (late discontinuation) (7.7%); (D): Low OPI-only (gradual decline) (4.0%); (E): Moderate OPI-only (rapid decline) (2.3%); (F): Very-low BZD-only (late discontinuation) (11.5%); (G): Low BZD-only (rapid decline) (4.5%); (H): Low BZD-only (stable) (3.1%); (I): Moderate BZD-only (gradual decline) (2.1%); (J): Very-low OPI (rapid decline)/Very-low BZD (late discontinuation) (2.9%); (K): Very-low OPI (rapid decline)/Very-low BZD (increasing) (0.9%); (L): Very-low OPI (stable)/Low BZD (stable) (0.6%); and (M): Low OPI (gradual decline)/Low BZD (gradual decline) (0.6%). Compared with Group (A), six trajectories had an increased 3-month injurious falls risk: (C): HR = 1.78, 95% CI = 1.58-2.01; (D): HR = 2.24, 95% CI = 1.93-2.59; (E): HR = 2.60, 95% CI = 2.18-3.09; (H): HR = 2.02, 95% CI = 1.70-2.40; (L): HR = 2.73, 95% CI = 1.98-3.76; and (M): HR = 1.96, 95% CI = 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing injurious fall risk of OPI-BZD use among older adults.

Urine and hair drug test results associated with daily consumption of codeine-predominant poppy seed food products.

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.

Poppy Seed Consumption May Be Associated with Codeine-Only Urine Drug Test Results.

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.

Blood Phosphatidylethanol (PEth) Concentrations following Intensive Use of an Alcohol-based Hand Sanitizer.

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.

Dosing profiles of concurrent opioid and benzodiazepine use associated with overdose risk among US Medicare beneficiaries: group-based multi-trajectory models.

BACKGROUND AND AIMS: One-third of opioid (OPI) overdose deaths involve concurrent benzodiazepine (BZD) use. Little is known about concurrent opioid and benzodiazepine use (OPI-BZD) most associated with overdose risk. We aimed to examine associations between OPI-BZD dose and duration trajectories, and subsequent OPI or BZD overdose in US Medicare. DESIGN: Retrospective cohort study. SETTING: US Medicare. PARTICIPANTS: Using a 5% national Medicare data sample (2013-16) of fee-for-service beneficiaries without cancer initiating OPI prescriptions, we identified 37 879 beneficiaries (age ≥ 65 = 59.3%, female = 71.9%, white = 87.6%, having OPI overdose = 0.3%). MEASUREMENTS: During the 6 months following OPI initiation (i.e. trajectory period), we identified OPI-BZD dose and duration patterns using group-based multi-trajectory models, based on average daily morphine milligram equivalents (MME) for OPIs and diazepam milligram equivalents (DME) for BZDs. To label dose levels in each trajectory, we defined OPI use as very low (< 25 MME), low (25-50 MME), moderate (51-90 MME), high (91-150 MME) and very high (>150 MME) dose. Similarly, we defined BZD use as very low (< 10 DME), low (10-20 DME), moderate (21-40 DME), high (41-60 DME) and very high (> 60 DME) dose. Our primary analysis was to estimate the risk of time to first hospital or emergency department visit for OPI overdose within 6 months following the trajectory period using inverse probability of treatment-weighted Cox proportional hazards models. FINDINGS: We identified nine distinct OPI-BZD trajectories: group A: very low OPI (early discontinuation)-very low declining BZD (n = 10 598; 28.0% of the cohort); B: very low OPI (early discontinuation)-very low stable BZD (n = 4923; 13.0%); C: very low OPI (early discontinuation)-medium BZD (n = 4997; 13.2%); D: low OPI-low BZD (n = 5083; 13.4%); E: low OPI-high BZD (n = 3906; 10.3%); F: medium OPI-low BZD (n = 3948; 10.4%); G: very high OPI-high BZD (n = 1371; 3.6%); H: very high OPI-very high BZD (n = 957; 2.5%); and I: very high OPI-low BZD (n = 2096; 5.5%). Compared with group A, five trajectories (32.3% of the study cohort) were associated with increased 6-month OPI overdose risks: E: low OPI-high BZD [hazard ratio (HR) = 3.27, 95% confidence interval (CI) = 1.61-6.63]; F: medium OPI-low BZD (HR = 4.04, 95% CI = 2.06-7.95); G: very high OPI-high BZD (HR = 6.98, 95% CI = 3.11-15.64); H: very high OPI-very high BZD (HR = 4.41, 95% CI = 1.51-12.85); and I: very high OPI-low BZD (HR = 6.50, 95% CI = 3.15-13.42). CONCLUSIONS: Patterns of concurrent opioid and benzodiazepine use most associated with overdose risk among fee-for-service US Medicare beneficiaries initiating opioid prescriptions include very high-dose opioid use (MME > 150), high-dose benzodiazepine use (DME > 40) or medium-dose opioid with low-dose benzodiazepine use.

Utilization Patterns of Skeletal Muscle Relaxants Among Commercially Insured Adults in the United States from 2006 to 2018.

OBJECTIVE: To examine the prevalence and duration of skeletal muscle relaxant (SMR) treatment among commercially insured adults in the United States. METHODS: We used the MarketScan Research Database to identify a cohort of adults 18 to 64 years who had ≥2-year continuous enrollment between 2005 and 2018. We estimated the prevalence of SMR treatment using a repeated cross-sectional design and derived treatment duration using the Kaplan-Meier method. Analyses were stratified by age group, sex, geographic region, individual SMR agent, and musculoskeletal disorder. RESULTS: 48.7 million individuals were included. Treatment prevalence ranged from 61.5 to 68.3 per 1,000. About one-third of users did not have a preceding musculoskeletal disorder diagnosis. Cyclobenzaprine was the dominant agent accounting for >50% of prescriptions. The considerable growth in the use of baclofen, tizanidine, and methocarbamol paralleled with a decline in carisoprodol and metaxalone use. The prevalence was highest in the South while lowest in the Northeast. The median treatment duration was 14 days with 4.0%, 1.9%, and 1.0% of individuals using SMRs for more than 90, 180, and 365 days, respectively. Compared with cyclobenzaprine, patients initiating baclofen, tizanidine, and carisoprodol had longer treatment duration. CONCLUSIONS: SMRs are widely used in the United States. Their use slightly increased in recent years, but trends varied among individual agents, patient groups, and geographic regions. Despite limited evidence to support efficacy, a sizable number of U.S. adults used SMRs for long-term and off-label conditions. Further study is needed to understand determinants of treatment as well as outcomes associated with such use.

Association Between Dual Trajectories of Opioid and Gabapentinoid Use and Healthcare Expenditures Among US Medicare Beneficiaries.

OBJECTIVES: Little is known about relationships between opioid- and gabapentinoid-use patterns and healthcare expenditures that may be affected by pain management and risk of adverse outcomes. This study examined the association between patients' opioid and gabapentinoid prescription filling/refilling trajectories and direct medical expenditures in US Medicare. METHODS: This cross-sectional study included a 5% national sample (2011-2016) of fee-for-service beneficiaries with fibromyalgia, low back pain, neuropathy, or osteoarthritis newly initiating opioids or gabapentinoids. Using group-based multitrajectory modeling, this study identified patients' distinct opioid and gabapentinoid (OPI-GABA) dose and duration patterns, based on standardized daily doses, within a year of initiating opioids and/or gabapentinoids. Concurrent direct medical expenditures within the same year were estimated using inverse probability of treatment weighted multivariable generalized linear regression, adjusting for sociodemographic and health status factors. RESULTS: Among 67 827 eligible beneficiaries (mean age ± SD = 63.6 ± 14.8 years, female = 65.8%, white = 77.1%), 11 distinct trajectories were identified (3 opioid-only, 4 gabapentinoid-only, and 4 concurrent OPI-GABA trajectories). Compared with opioid-only early discontinuers ($13 830, 95% confidence interval = $13 643-14 019), gabapentinoid-only early discontinuers and consistent low-dose and moderate-dose gabapentinoid-only users were associated with 11% to 23% lower health expenditures (adjusted mean expenditure = $10 607-$11 713). Consistent low-dose opioid-only users, consistent high-dose opioid-only users, consistent low-dose OPI-GABA users, consistent low-dose opioid and high-dose gabapentinoid users, and consistent high-dose opioid and moderate-dose gabapentinoid users were associated with 14% to 106% higher healthcare expenditures (adjusted mean expenditure = $15 721-$28 464). CONCLUSIONS: Dose and duration patterns of concurrent OPI-GABA varied substantially among fee-for-service Medicare beneficiaries. Consistent opioid-only users and all concurrent OPI-GABA users were associated with higher healthcare expenditures compared to opioid-only discontinuers.

Blood Phosphatidylethanol Concentrations Following Regular Exposure to an Alcohol-Based Mouthwash.

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.

Dual-trajectories of opioid and gabapentinoid use and risk of subsequent drug overdose among Medicare beneficiaries in the United States: a retrospective cohort study.

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.

The roles of phosphatidylethanol, ethyl glucuronide, and ethyl sulfate in identifying alcohol consumption among participants in professionals health programs.

Direct alcohol biomarkers, including urinary ethyl glucuronide (EtG), urinary ethyl sulfate (EtS), and blood phosphatidylethanol (PEth), are used to monitor alcohol abstinence in individuals who are mandated to abstain. In this consecutive case series study, we examined 1000 forensic reports of participants enrolled in a professionals health program who were contractually obligated to abstain from alcohol and who underwent recovery status evaluations. We identified 52 evaluations in which urinary EtG, EtS, and blood PEth were measured and which produced a positive result for at least one of these analytes. PEth, at a cutoff concentration of 20 ng/mL, revealed alcohol use more frequently than EtG or EtS at our laboratory's cutoff concentrations of 100 and 25 ng/mL, respectively. This was true, as well, at alternative EtG/EtS cutoff concentrations of 200/50, 300/75, and 400/100 ng/mL. PEth was more likely than EtG/EtS to be positive in participants previously diagnosed with alcohol use disorders (AUD), whereas EtG/EtS was more likely than PEth to be positive in participants without AUD. In this study, blood PEth was the most sensitive biomarker for evidencing alcohol use.

Persistent Urinary Ethyl Sulfate in the Absence of Urinary Ethyl Glucuronide in a Patient with Alcohol Use Disorder Who Claimed Abstinence.

A 48-year-old nurse with an alcohol use disorder history was being monitored in a professional health program. She consistently produced low-to-moderate urinary ethyl sulfate (EtS) concentrations in the absence of detectable urinary ethyl glucuronide (EtG), blood phosphatidylethanol and breath alcohol. She denied intentional ethanol consumption. After prolonged monitoring in a drug treatment program, including a period in a controlled environment, we concluded that this individual's urinary EtS likely resulted from anatomical and microbial factors related to Roux-en-Y gastric bypass surgery, with possible contributions from hidden dietary sources of ethanol. We have no definitive explanation for the lack of urinary EtG.

Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population-Based Cohort Study.

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.

Overlapping prescriptions of opioids, benzodiazepines, and carisoprodol: "Holy Trinity" prescribing in the state of Florida.

BACKGROUND: 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. METHODS: 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: 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. CONCLUSIONS: 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.

Impact of Schedule IV controlled substance classification on carisoprodol utilization in the United States: An interrupted time series analysis.

BACKGROUND: In January 2012, the Drug Enforcement Agency (DEA) classified carisoprodol as a Schedule IV controlled substance at the US federal level. We aimed to examine the effect of this policy on the use of carisoprodol in a commercially-insured population. METHODS: This interrupted time series study included individuals with musculoskeletal disorders in the IBM MarketScan Commercial Database between December 2009 and February 2014. We used comparative segmented linear regression to assess changes in the proportions of patients who filled/newly filled carisoprodol each month. RESULTS: A total of 13.3 million patients were included. 29 states with no scheduling prior to the DEA classification had lower baseline prevalence of carisoprodol use compared to 17 states that had scheduled carisoprodol individually before 2010 (11.0 vs. 21.1 patients with fills per 1000 patients). The federal scheduling was associated with an immediate decline (-1.12 per 1000 patients, p < 0.01) and decreasing trend in prevalence (-0.07 per 1000 patients per month, p = 0.02). This effect was not modified by existing state-level scheduling status. During the first, second, third, and fourth 6-month periods after federal scheduling, the relative difference between observed and predicted prevalence was 7.8%, 10.5%, 13.4%, and 19.8%. Similar patterns were observed for carisoprodol initiation. Overall, declining use was more pronounced among younger age groups and patients with injury. CONCLUSIONS: Schedule IV controlled substance classification at the federal level was associated with a moderate reduction in the dispensing of carisoprodol regardless of whether scheduling was already present at the state level.

Trends in Florida's Prescription Drug Monitoring Program registration and utilization: Implications for increasing voluntary use.

OBJECTIVE: Effective use of state prescription drug monitoring programs (PDMPs) to track controlled substance prescribing and dispensing may help mitigate the current opioid crisis. Our objective was to examine trends in registration for and use of Florida's PDMP by physicians and pharmacists, from 2013 to 2016. We discuss implications for PDMP uptake and policy. DESIGN: Key measures, such as cumulative number of registrants per license type and monthly utilization intensity, are presented. A time series forecasting approach was used to (1) model the monthly count of new PDMP registrants and users from January 2013 to December 2016 and (2) estimate cumulative registration totals after 1 year. SETTING: Florida. RESULTS: As of November 2016, there were 16,498 physicians (representing 31 percent of Drug Enforcement Administration licensees) and 17,241 pharmacists registered with the PDMP, representing 21 and 57 percent of professional licensees, respectively. Of note, the PDMP's designation as a "specialized registry" for electronic medical record "meaningful use" criteria led to a nearly sevenfold increase in physician registrations in a single month. In November 2016, pharmacists displayed a higher past-month PDMP utilization rate (52.2 percent vs 30.1 percent), while physicians displayed a higher past-month PDMP utilization intensity (58.1 vs. 36.1 queries per user). Approximately 25,000 physicians and 31,000 pharmacists must register by the end of 2017 to meet national policy goals. CONCLUSION: PDMP registration among physicians and pharmacists is limited, and the use of the PDMP among registrants is more limited still. Our findings suggest that Florida will not meet national policy goals for registrants by the end of 2017, although new initiatives may alter this trend. Allowing the PDMP to help prescribers meet other professional needs, such as "meaningful use" or similar efforts, may be effective in increasing PDMP use.

Opioid Use Disorders, Medication-Assisted Treatment, and the Role of the Laboratory.

Urine drug testing is an essential component in the evaluation and management of individuals with opioid use disorders, including those on buprenorphine or methadone maintenance therapies. Notwithstanding its centrality in adherence monitoring, studies have shown that clinicians have important knowledge deficiencies regarding the ordering and interpretation of drug tests. In this review, we discuss the scope and frequency of testing, the advantages and disadvantages of immunoassay- (presumptive) and liquid chromatograph-mass spectrometry- (definitive) based techniques, indications for definitive testing, medical necessity, and other considerations. Optimal use of urine drug testing depends on collaboration between clinicians and laboratory scientists.