Medical Cannabis Legalization: No Contribution to Rising Stimulant Rates in the USA.

INTRODUCTION: There has been a pronounced increase in the use of Schedule II stimulants to treat attention-deficit hyperactivity disorder (ADHD) in the United States over the last two decades. Interestingly, chronic medical cannabis (MC) use can present with cognitive impairments that resemble ADHD symptoms. This study aimed to determine if MC legalization increased prescription stimulant distribution. METHODS: Information on the distribution of methylphenidate, amphetamine, and lisdexamfetamine for 2006 to 2021 was extracted from the Drug Enforcement Administration's comprehensive database and the three-year population-corrected slopes of stimulant distribution before and after MC program implementation were compared. RESULTS: We found a significant main effect of time (p<0.001); however, contrary to the hypothesis, the sales status of states' MC, did not influence slopes of distribution (p=0.391). There was a significantly large interaction effect of time and MC sales status on slopes of distribution (p<0.001). Slopes of distribution rates of stimulants were significantly lower in states that proceeded to legalize MC prior to MC program implementation than those states that did not (p=0.022). After MC program implementation, however, the distribution rates of the Schedule II stimulants were not significantly different when comparing states with MC sales to those without (p=0.355). DISCUSSION: These findings suggest that MC program legalization did not contribute to certain states having rapid increases in Schedule II stimulant distribution rates over time. Other factors, including the liberalization of the adult ADHD diagnostic criteria in the DSM-5 and the introduction of Binge Eating Disorder, also likely contributed to elevations in stimulant distribution.

High Prescribing and State-Level Variation in Z-Drug Use Among Medicare Patients.

BACKGROUND: Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences. This study also aimed to determine prescribing patterns of Z-drugs to Medicare patients. METHODS: Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions per provider within each specialty was also determined. RESULTS: Zolpidem was the most prescribed Z-drug (95.0%). Prescriptions per 100 enrollees were significantly high in Utah (28.2) and Arkansas (26.7) and significantly low in Hawaii (9.3) relative to the national average (17.5). Family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly high among psychiatrists. DISCUSSION: Contrary to the Beers criteria, Z-drugs are prescribed to older adults at high rates.

Pronounced Regional Disparities in United States Methadone Distribution.

BACKGROUND: Methadone is an evidence-based treatment for opioid use disorder (OUD) and pain management. Methadone for OUD may be difficult for some patients to access, particularly those in rural areas. OBJECTIVE: The purpose of this study was to characterize methadone distribution patterns between 2017 and 2019 across the United States. METHODS: The US Drug Enforcement Administration's Automated Reports and Consolidated Ordering System was used to acquire the number of opioid treatment programs (OTPs) per state and methadone distribution weight in grams. Methadone distributions by weight, corrected for state population and number of OTPs, were compared from 2017 to 2019 between states, within regions, and nationally. RESULTS: The national distribution of methadone increased +12.3% for OTPs but decreased -34.6% for pain. Whereas all states saw a decrease in pain distribution, the Northeast showed a significantly smaller decrease than all other regions. Additionally, the majority of states experienced an increase in distribution for OTPs, and most states demonstrated a relatively stable or increasing number of OTPs, with an +11.5% increase nationally. The number of OTPs per 100K state population ranged from 2.1 in Rhode Island to 0.0 in Wyoming. CONCLUSION AND RELEVANCE: Although methadone distribution for OUD was increasing in the United States, the pronounced regional disparities identified warrant further consideration to improve patient access to this evidence-based pharmacotherapy, particularly in the Midwest and West regions. Greater implementation of telehealth and involvement of primary care into opioid treatment practice offer possible solutions to eliminating geographical treatment barriers.

Analysis of naloxone access and primary medication nonadherence in a community pharmacy setting.

BACKGROUND: Access to naloxone is a primary public health strategy to prevent opioid overdose death. Factors associated with primary medication nonadherence (PMN) to naloxone are underreported in the literature. OBJECTIVE: The objective of this study was to evaluate naloxone dispensing trends and PMN in a community pharmacy setting. METHODS: This retrospective analysis included patients of a community pharmacy chain in Maine and New Hampshire (57 and 29 pharmacy locations, respectively) for whom a claim for a naloxone prescription was billed between January 1, 2019, and July 31, 2020. RESULTS: A total of 2152 patients associated with 2606 naloxone claims were identified for analysis. A majority of the subjects were women (52.7%) and the mean age of all the subjects was 46.4 ± 16.0 years. Of the 2606 naloxone claims, 565 prescriptions were returned to stock and never dispensed to the patient for a PMN rate of 21.7%. Gender and age were not associated with naloxone PMN. Factors associated with naloxone PMN were urban location [x2(1) = 12.49, P = 0.0004], concomitant opioid analgesic [x2(1) = 4.56, P = 0.0328], and payment method [x2(4) = 251.07, P < 0.0001]. Regarding payment method, nonadherence was higher among cash (138 of 386, 35.8%) and private insurance (191 of 455, 42.0%) transactions whereas lower among Medicare (132 of 681, 19.4%) and Medicaid (89 of 899, 9.9%) transactions. Concomitant buprenorphine [x2(1) = 44.57, P < 0.0001] and the use of a naloxone standing order [x2(1) = 4.79, P = 0.0162] were associated with primary adherence to take-home naloxone. CONCLUSION: A notable portion of naloxone prescribed and filled in the community pharmacy setting was never obtained by the patient. Factors associated with PMN in this study included geographic location, use of a standing order, concomitant prescriptions for buprenorphine or opioid analgesic medications, and payment method. Underlying causes of PMN must be addressed (e.g., removing financial barriers and optimizing the use of standing orders) to increase naloxone access for persons at risk of opioid overdose.

Examination of multiple drug arrests reported to the Maine Diversion Alert Program.

PURPOSE: Much of the responsibility for the increasing drug overdoses in the US has been attributed to opioids but most opioid overdoses also involve another drug. The objective of this study was to identify the drugs involved in polysubstance arrests. The substances that were more likely to be found in conjunction with other substances, using the drug arrests reported to Maine's Diversion Alert Program (DAP) were examined. METHODS: Single and multiple drug arrests were quantified (N = 9,216). Multiple drug arrest percentages were compared to single drug arrest percentages to create a Multiple-to-Single Ratio (MSR) specific to each drug family and each drug to identify over (MSR > 1) and under-representation (MSR < 1). RESULTS: Over three-fifths (63.8%) of all arrests involved a single drug. Opioids accounted for over-half (53.5%) of single arrests, followed by stimulants (27.7%) and hallucinogens (7.7%). Similarly, nearly two-fifths (39.6%) of multiple arrests were for opioids, followed by stimulants (30.8%) and miscellaneous (13.0%). Miscellaneous psychoactive prescription substances (e.g. clonidine, gabapentin, cyclobenzaprine, hydroxyzine) had the highest (1.51) MSR of any drug family. Conversely, stimulants (0.63), opioids (0.42), and hallucinogens (0.35) were significantly underrepresented in polysubstance arrests. Carisoprodol (8.80), amitriptyline (6.34), and quetiapine (4.69) had the highest MSR. Bath-salts (0.34), methamphetamine (0.44), and oxycodone (0.54) had the lowest MSR. CONCLUSION: The misuse of opioids, both alone and in conjunction with another drug, deserves continued surveillance. In addition, common prescription drugs with less appreciated misuse potential, especially carisoprodol, amitriptyline, and quetiapine, require greater attention for their ability to enhance the effects of other drugs.

Opioid Mortality Following Implementation of Medical Cannabis Programs in the United States.

INTRODUCTION: The United States is in the midst of an opioid overdose epidemic. Emerging evidence suggests that medical cannabis (MC) may reduce use of opioids for pain in some individuals, with potential impacts on opioid-related overdose. However, there may be other important differences between states that did, and did not, adopt MC. METHODS: This study evaluated differences following legal MC sales on US opioid-related overdose deaths, corrected for population, from 1999 to 2017 using an interrupted time series. Comparisons by MC status were also made for Medicaid expansion and the Centers for Disease Control death certificate reporting quality (0:

Decline and Pronounced Regional Disparities in Medical Cocaine Usage in the United States.

Background: Cocaine is a stimulant and Schedule II drug used as a local anesthetic and vasoconstrictor. Objective: This descriptive study characterized medical cocaine use in the United States. Methods: Retail drug distribution data from 2002 to 2017 were extracted for each state from the Drug Enforcement Administration, which reports on medical, research, and analytical chemistry use. The percentage of buyers (pharmacies, hospitals, and providers) was obtained. Use per state, corrected for population, was determined. Available cross-sectional data on cocaine use as reported by the Medicare and Medicaid programs for 2013-2017 and electronic medical records were examined. Results: Medical cocaine use decreased by -62.5% from 2002 to 2017. Hospitals accounted for 84.9% and practitioners for 9.9% of cocaine distribution in 2017. The number of pharmacies carrying cocaine dropped by -69.4%. The percentages of hospitals, practitioners, and pharmacies that carried cocaine in 2017 were 38.4%, 2.3%, and 0.3%, respectively. There was a 7-fold difference in 2002 (South Dakota, 76.1 mg/100 persons; Delaware, 10.1 mg/100 persons). Relative to the average state in 2017, those reporting the highest values (Montana, 20.1; North Dakota, 24.1 mg/100 persons) were significantly elevated. Cocaine use within the Medicare and Medicaid programs was negligible. Cocaine use within the Geisinger system was rare from 2002 to 2007 (<4 orders/100 000 patients per year) but increased to 48.7 in 2018. Conclusion and Relevance: If these pharmacoepidemiological patterns continue, licit cocaine may soon become a historical relic. The pharmacology and pharmacotherapeutics education of health care providers may need to be adjusted accordingly.

Rise and regional disparities in buprenorphine utilization in the United States.

PURPOSE: Buprenorphine is an opioid partial agonist used to treat opioid use disorder. While several policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution of the medication. METHODS: The amount of buprenorphine distributed from 2007 to 2017 was obtained from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System. Data were expressed as the percent change and milligrams per person in each state. The formulations and cost for prescriptions covered by Medicaid (2008 to 2018) were also examined. RESULTS: Buprenorphine distributed to pharmacies increased about 7-fold (476.8 to 3179.9 kg) while the quantities distributed to hospitals grew 5-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of physicians authorized to prescribe buprenorphine and distribution per state (r[49] = +0.94, P < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but accounted for less than three-fifth (57.3% of 6.56 million prescriptions) in 2018. CONCLUSIONS: Although buprenorphine availability has substantially increased over the last decade, distribution was very nonhomogeneous across the United States.

Opioid Prescribing Laws Are Not Associated with Short-term Declines in Prescription Opioid Distribution.

OBJECTIVE: To determine whether the adoption of laws that limit opioid prescribing or dispensing is associated with changes in the volume of opioids distributed in states. METHODS: State-level data on total prescription opioid distribution for 2015-2017 were obtained from the US Drug Enforcement Administration. We included in our analysis states that enacted an opioid prescribing law in either 2016 or 2017. We used as control states those that did not have an opioid prescribing law during the study period. To avoid confounding, we excluded from our analysis states that enacted or modified mandates to use prescription drug monitoring programs (PDMPs) during the study period. To estimate the effect of opioid prescription laws on opioid distribution, we ran ordinary least squares models with indicators for whether an opioid prescription law was in effect in a state-quarter. We included state and quarter fixed effects to control for time trends and time-invariant differences between states. RESULTS: With the exception of methadone and buprenorphine, the amount of opioids distributed in states fell during the study period. The adoption of opioid prescribing laws was not associated with additional decreases in opioids distributed. CONCLUSIONS: We did not detect an association between adoption of opioid prescribing laws and opioids distributed. States may instead wish to pursue evidence-based efforts to reduce opioid-related harm, with a particular focus on treatment access and harm reduction interventions.

Quantification of Conflicts of Interest in an Online Point-of-Care Clinical Support Website.

Online medical reference websites are utilized by health care providers to enhance their education and decision making. However, these resources may not adequately reveal pharmaceutical-author interactions and their potential conflicts of interest (CoIs). This investigation: (1) evaluates the correspondence of two well-utilized CoI databases: the Centers for Medicare and Medicaid Services Open Payments (CMSOP) and ProPublica's Dollars for Docs (PDD) and (2) quantifies CoIs among authors of a publicly available point of care clinical support website which is used to inform evidence-based medicine decisions. Two data sources were used: the hundred most common drugs and the top fifty causes of death. These topics were entered into a freely available database. The authors (N = 139) were then input into CMSOP and PDD and compensation and number of payments were determined for 2013-2015. The subset of highly compensated authors that also reported "Nothing to disclose" were further examined. There was a high degree of similarity between CMSOP and PDD for compensation (R2 ≥ 0.998) and payment number (R2 ≥ 0.992). The amount received was 1.4% higher in CMSOP ($4,059,194) than in PDD ($4,002,891). The articles where the authors had received the greatest compensation were in neurology (Parkinson's Disease = $1,810,032), oncology (Acute Lymphoblastic Leukemia = $616,727), and endocrinology (Type I Diabetes = $377,388). Two authors reporting "Nothing to disclose" received appreciable and potentially relevant compensation. CMSOP and PDD produced almost identical results. CoIs were common among authors but self-reporting may be an inadequate reporting mechanism. Recommendations are offered for improving the CoI transparency of pharmaceutical-author interactions in point-of-care electronic resources.

Trends in the medical supply of fentanyl and fentanyl analogues: United States, 2006 to 2017.

Fentanyl is an important opioid for pain management, but also has exceptional potential for misuse. Seven states have implemented opioid prescribing laws. The objectives of this study were to: 1) characterize the temporal pattern of fentanyl, fentanyl analogue, and other opioid use over the past decade, and 2) determine whether opioid prescribing laws impacted fentanyl use in the US. Drug weights were obtained from the US Automated Reports of Consolidated Orders System (June 2018), a comprehensive publically available resource, from 2006 to 2017 for fentanyl, sufentanil, remifentanil, alfentanil, other prescription opioids, and analyzed by presence of a state opioid prescribing law. Fentanyl, corrected for population, was reduced from 2016 to 2017 (-17.9%) and these decreases significantly exceeded the changes in hydrocodone (-12.3%), oxycodone (-10.1%), morphine (-13.3%), or codeine (-8.8%). Fentanyl showed a particularly large decline in Maine, a state with a strong opioid prescribing law. There was a 3.5 fold difference in fentanyl (µg per capita) in Alaska (488.2) relative to Oregon (1718.4). Hospital use of remifentanil and sufentanil tripled from 2006 to 2017. Although all states experienced a 2016 to 2017 decline in fentanyl, and this reduction was larger than many other prescription opioids, the rate of decline varied over three-fold between states. Strong state laws may account for a portion of the variance in fentanyl and other opioid reductions. The population health risks of fentanyl and fentanyl analogues warrants ongoing vigilance.

Sex, but not Apolipoprotein E Polymorphism, Differences in Spatial Performance in Young Adults.

The purpose of this study was to examine how sex and apolipoprotein E (APOE) genotype contribute to individual differences in spatial learning and memory. The associations of APOE genotype with neurocognitive function have been well studied among the elderly but less is known at earlier ages. Young adults (n = 169, 88 females) completed three neurocognitive tasks: mental rotation, spatial span, and Memory Island, a spatial navigation test. Males outperformed females on all three tasks: finding the hidden targets more quickly on Memory Island (Cohen's d = 0.62) and obtaining higher scores on mental rotation (d = 0.54) and spatial span (d = 0.37). In contrast, no significant effects of APOE were observed. The identified sex differences elaborate upon past literature documenting sexually dimorphic performance on specific neurobehavioral tasks.

Functional polymorphisms in BDNF and COMT genes are associated with objective differences in arithmetical functioning in a sample of young adults.

BACKGROUND: Understanding the molecular genetics of complex human behaviors and functions remains a substantial challenge for the neurosciences. Previous studies have shown a genetic basis for individual differences in mathematical functioning; however, the specific genes remain to be completely identified. In the present study, we explored the possibility that 2 functional polymorphisms in candidate genes could be associated with differences in arithmetical performance. METHODS: A computerized test to analyze performance in basic arithmetical calculations (additions and subtractions) was applied to 168 healthy young Colombian participants using the PEBL (Psychology Experiment Building Language) battery. DNA samples were genotyped for 2 functional SNPs in candidate genes: brain-derived neurotrophic factor (BDNF)-Val66Met and catechol-O-methyltransferase (COMT)-Val158Met. RESULTS: We found significant differences for arithmetical processing scores between genotypes. For BDNF, Val/Val subjects had a worse performance (p value: 0.025) and for COMT, Val/Val carriers had a better performance (p value: 0.006). A multivariate model, including both BDNF and COMT genes, accounted for 7.1% of the variance in math processing scores. DISCUSSION: To our knowledge, this is the first study finding associations of polymorphisms in BDNF and COMT genes with quantitative measures of numerical aptitude in healthy young participants. A future study of other genes involved in neural plasticity could be helpful to identify genetic correlates of arithmetical functioning, which will be important for the understanding of normal human behaviors and related neuropsychiatric disorders.

Adolescent MDMA exposure diminishes the physiological and neurotoxic consequences of an MDMA binge in female rats.

Intermittent MDMA pretreatment blocked the reductions in serotonin transporter (SERT) binding induced by an MDMA binge in a prior study in adolescent male rats. The objective of this investigation was to determine if the physiological, behavioral, and neurochemical responses to MDMA are sexually dimorphic. Female Sprague-Dawley rats received MDMA (10 mg/kg × 2) or Saline on every fifth day from postnatal day (PD) 35-60 and an MDMA binge (5 mg/kg × 4) on PD 67. The MDMA binge induced a pronounced temperature dysregulation in MDMA-naïve, but not MDMA-pretreated, groups. Similarly, MDMA-pretreated animals were resistant to the binge-induced SERT reductions, especially in the hippocampus. Motor activity at PD 68 was not reduced by the binge, unlike the responses found in males. These results show that female rats differ from males in their responses to an MDMA binge but are similar with respect to preconditioning from prior MDMA exposure.

Reliability and validity of Brief Problem Monitor, an abbreviated form of the Child Behavior Checklist.

AIM: The parent form of the 113-item Child Behavior Checklist (CBCL) is widely utilized by child psychiatrists and psychologists. This report examines the reliability and validity of a recently developed abbreviated version of the CBCL, the Brief Problem Monitor (BPM). METHODS: Caregivers (n = 567) completed the CBCL online and the 19 BPM items were examined separately. RESULTS: Internal consistency of the BPM was high (Cronbach's alpha = 0.91) and satisfactory for the Internalizing (0.78), Externalizing (0.86), and Attention (0.87) scales. High correlations between the CBCL and BPM were identified for the total score (r = 0.95) as well as the Internalizing (0.86), Externalizing (0.93), and Attention (0.97) scales. The BPM and scales were sensitive and identified significantly higher behavioral and emotional problems among children whose caregiver reported a psychiatric diagnosis of attention-deficit hyperactivity disorder, bipolar disorder, depression, anxiety, developmental disabilities, or autism spectrum disorders relative to a comparison group that had not been diagnosed with these disorders. BPM ratings also differed by the socioeconomic status and education of the caregiver. Mothers with higher annual incomes rated their children as having 38.8% fewer total problems (Cohen's d = 0.62) as well as 42.8% lower Internalizing (d = 0.53), 44.1% less Externalizing (d = 0.62), and 30.9% decreased Attention (d = 0.39). A similar pattern was evident for maternal education (d = 0.30-0.65). CONCLUSION: Overall, these findings provide strong psychometric support for the BPM, although the differences based on the characteristics of the parent indicate that additional information from other sources (e.g., teachers) should be obtained to complement parental reports.

Pronounced State-Level Disparities in Medicaid Prescribing of Buprenorphine for Opioid Use Disorder (2019-2020).

OBJECTIVE: The purpose of this study was to analyze buprenorphine prescribing across states in Medicaid patients during 2019-2020. METHOD: Buprenorphine prescriptions per Medicaid enrollee per state were calculated for 2019 and 2020. Data analysis was conducted with buprenorphine formulations that are approved by the U.S. Food & Drug Administration for opioid use disorder (OUD; including generic and brand name formulations of buprenorphine mono product and buprenorphine/naloxone combination products) using Microsoft Excel. The totals of mono product buprenorphine were divided over the total of combination buprenorphine/naloxone in 2019 and 2020 to obtain the ratio of mono/combo. Formulations of buprenorphine indicated for pain were excluded. States outside 95% confidence intervals (1.96 standard deviations above and below the mean) were considered statistically significant. RESULTS: The overall change in buprenorphine prescribing between 2019 and 2020 was modest (+3.6%) but highly variable, with more than a 10% increase in 17 states (Iowa = +100.5%, p < .05) but more than a 10% decrease in 9 states (Alabama = -68.5%, p < .05). Total amount reimbursed in 2019 increased (+9.9%) to $1.42 billion in 2020. Branded formulations accounted for two fifths (39.5%) of prescribing but more than two thirds (66.8%) of spending in 2020. CONCLUSIONS: The COVID-19 pandemic exacerbated state-level disparities in buprenorphine prescribing for OUD among Medicaid patients. Legislation expanding buprenorphine-waivered providers and Medicaid expansion may have contributed to the statistically significant changes in state buprenorphine prescriptions.

First generation antipsychotic-associated serious adverse events in women: a retrospective analysis of a pharmacovigilance database.

BACKGROUND: Women have been under-represented in trials of antipsychotic medications. AIM: Our primary objective was to evaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to men through an analysis of the FDA Adverse Event Reporting System (FAERS). METHOD: We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360). Cases of neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), Torsades de Pointes (TdP), agranulocytosis (AG), and cerebrovascular adverse events (CVAE) were identified. Reporting odds ratios (ROR) and associated 95% confidence intervals (CI) were calculated with logistic regression for each AE among women relative to men. RESULTS: A total of 2,857 serious AEs were evaluated in the study cohort (NMS = 1810, TD = 434, TdP = 260, AG = 149, CVAE = 204). The ROR for women compared to men was 0.79 (95% CI, 0.71-0.87) for NMS, 0.83 (0.68-1.01) for TD, 1.21 (0.94-1.53) for TdP, 0.71 (0.51-0.98) for AG, and 0.91 (0.68-1.19) for CVAE. A secondary analysis revealed a higher odds in women compared to men of hospitalization associated with reports of TD (ROR = 1.95, 1.29-2.94) and death associated with reports of AG (ROR = 2.46, 1.15-5.24). A subgroup analysis of haloperidol revealed an ROR = 1.67 (1.26-2.21) for women relative to men for TdP. CONCLUSION: The subgroup analysis of haloperidol AEs revealed a significantly higher reporting odds ratio for TdP. Additionally, the secondary study findings suggest that women were more vulnerable to worse outcomes associated with certain AEs of FGAs.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

Decreases and Pronounced Geographic Variability in Antibiotic Prescribing in Medicaid.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1000 Medicaid enrollees for two years, 2018 and 2019, for four broad-spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow-spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim-sulfamethoxazole) antibiotics. Antibiotic prescriptions in MEPS decreased from 2013 to 2020 by 38.7%, with a larger decline for the broad (-53.7%) than narrow (-23.5%) spectrum antibiotics. Antibiotic prescriptions in Medicaid decreased by 6.7%. Amoxicillin was the predominant antibiotic, followed by azithromycin, cephalexin, trimethoprim-sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in prescribing existed, with a 2.8-fold difference between the highest (Kentucky = 855/1000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1000) than the West (381/1000). There were significant correlations across states (r = 0.81 for azithromycin and amoxicillin). This study identified sizable disparities by geography in the prescribing rates of eight antibiotics with over three-fold state-level differences. Areas with high prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.