Pharmacology Research & Perspectives

ObjectiveThe primary objective of this study was to explore fentanyl and fentanyl derivative distribution patterns from 2010 and 2019 across the United States (US). This study builds upon previous literature that has analyzed the trends in opioid distribution and assesses changes in opioid prescription preferences. MethodsThe amount of fentanyl base distributed in the US from 2010-2019 was obtained from the Drug Enforcement Administrations Automated Reports and Consolidated Ordering System (ARCOS). Fentanyl derivatives (sufentanil, alfentanil, remifentanil) were also analyzed using ARCOS from 2010-2017, the most recent date reported. Census data from the American Community Survey was used to correct for population. Prescriptions, units, and reimbursement of fentanyl and fentanyl citrate formulations for 2010 and 2019 were obtained from Medicaid and prescriber specialty in Medicare Part D. ResultsTotal grams of fentanyl distributed in the US from 2010 to 2019 decreased by 63%. Correspondingly, there was a 65% decrease in the milligrams per person distributed when correcting for population. From a regional perspective, Ohio had the greatest decrease (-79.3%) while Mississippi saw the smallest (-44.5%). Medicaid reimbursement in 2019 was $165 million for over eight hundred-thousand prescriptions with the majority to generic (99.7%) and injectable (77.6%) formulations. Interventional pain management and anesthesia were over-represented, and hematology/oncology under-represented for fentanyl in Medicare. ConclusionThe production and distribution of fentanyl-based substances has decreased, although not uniformly, in the US over the last decade. Additionally, the most prescribed formulations of fentanyl have transitioned away from transdermal, potentially in an effort to regulate its availability. Although impactful, the overdose deaths attributed to synthetic opioid deaths continue to increase highlighting the need for public health interventions beyond the pharmaceutical and medical communities.

PurposeThe purpose of our study was to investigate dronabinol prescribing in Medicare from 2014 to 2019 by provider specialty and state. MethodsData was collected and analyzed from the Centers for Medicare & Medicaid Services databases from 2014 to 2019. The mean number of prescriptions for each area of practice, each individual year, and for 2014 to 2019 overall for the 50 United States and District of Columbia was determined. The prescriptions were separated by state and the state totals were determined. Individual states with dronabinol prescriptions [&ge;]1.96 standard deviations (SD) from the mean were identified as significant. ResultsThe total number of dronabinol prescriptions decreased 9.1% from 2014 to 2019. Dronabinol prescriptions were more concentrated in the eastern United States in 2019 than compared to 2014 [Tennessee (107.2), Kentucky (94.2), and West Virginia (87.6) (>1.96 SD)]. The largest portion of dronabinol prescriptions originated from primary care (1,736) compared to specialty areas of practice (1,233). Internal medicine (789.5), family medicine (608.8), hematology-oncology (343.3), nurse practitioners (337.3), and infectious disease (271.0) had the highest average number of dronabinol prescriptions per year (p<0.05). The areas of practice with the highest ratio of percent dronabinol prescriptions to percent Medicare utilization were infectious disease (15.8), hematology-oncology (12.2), and medical oncology (12.1). ConclusionDronabinol usage declined among Medicare patients and became more concentrated in the eastern United States. Most prescriptions originated from primary care, although after accounting for Medicare patient utilization, the highest ratios originated from infectious disease, hematology-oncology, and medical oncology.

ObjectiveTo evaluate the changing pattern of the distribution of Schedule II and III opioids, stimulants, and barbiturates by advanced practice providers (APP; i.e., physician assistants and nurse practitioners) in the United States (US). DesignRetrospective study. SampleAdvanced practice providers from every US state (and DC) that directly dispense Schedule II/III drugs to patients. ProceduresControlled substances distributed by APP was obtained from the Drug Enforcement Administrations Automated Reports and Consolidated Orders System (DEAs ARCOS) for opioids (e.g., hydrocodone, fentanyl, buprenorphine), barbiturates (pentobarbital, butalbital), and stimulants (amphetamine, methylphenidate, lisdexamfetamine) from 2006-2023. Opioids were converted to their morphine milligram equivalents (MME), stimulants converted to daily doses, and barbiturates to kilograms. Opioid use by state in three selected years (2013, 2020, 2023) was further analyzed. ResultsThe total weight of controlled substances as distributed exhibited both overall and drug-specific changes since 2006. Buprenorphine accounted for only a modest amount (0.6%) in 2013 but the preponderance (94.6%) of opioids distributed by MME in 2023 nationally. Examination of the opioid MME per state and corrected for population revealed the states with the highest reported use for 2013 (Nevada), 2020 (North Dakota), and 2023 (Maine). There has been an overall modest decline in stimulant (-97.9%) and barbiturate (-64.1%) since 2010. Conclusions and Clinical RelevanceThe use of Schedule II/III drugs as distributed to APP has fluctuated yet overall increased in the past decades. Opioids by total MME have had rather small changes throughout the years, except for buprenorphine. APP direct distribution has transitioned from treating pain to Opioid Use Disorder. Future research should discover the causes underlying the yearly and state level disparities for opioid, stimulant, and barbiturate use.

ObjectivesMeperidine, once viewed as relatively safe, is now discouraged in clinical settings due to its associated risks. Previous studies have identified a significant decrease in meperidine distribution across the US from 2000 to 2021. Regional disparities accompanied this decline. The goal of this study was to investigate if the decrease in meperidine distribution has continued in recent years: 2019 to 2023; and if regional variations persist. This investigation also aimed to identify correlates of meperidine distribution, including adult obesity prevalence and annual income, to provide insight into the regional variation. DesignRetrospective observational study utilizing data from the Automation of Reports and Consolidated Orders System (ARCOS) Drug Retail Summary Reports by the Drug Enforcement Administration (DEA), the CDC, and the US Census Bureau. SettingUSA, including Puerto Rico ParticipantsUS population Primary and secondary outcome measuresThe primary outcome was the meperidine distribution across the US between 2019 and 2023. Secondary outcomes included associations between meperidine distribution and adult obesity prevalence and median household income. ResultsTotal meperidine distribution across the US dropped by 57.8% from 2019 to 2023. A substantial geographic variation was found with southern states accounting for the 2nd, 3rd, and 4th highest in meperidine use capita in 2023, only behind Puerto Rico. In contrast, northeastern states accounted for four of the five lowest states. A significant relationship was found between annual income and meperidine distribution in 2022 (r(49) = -.38, p < .005). A trend was observed between adult obesity prevalence and meperidine distribution (r(52) = +.24, p = .078). ConclusionOur study revealed a continued decrease in meperidine distribution and continued presence of geographical variation from 2019 to 2023. Furthermore, a novel relationship was identified between meperidine distribution and annual income. Strengths and WeaknessesStrengths O_LIThe ARCOS database is comprehensive for meperidine distribution in every year/location used in this study. C_LIO_LIThis study reports on the pronounced state level differences in meperidine use and the association with other variables which include annual income and adult obesity prevalence by location. C_LI Weaknesses O_LIThe Automation of Reports and Consolidated Orders System database lacks information on formulations and the number of prescriptions. C_LIO_LIFurther study should examine spending on meperidine by Medicaid, Medicare, or private insurance agencies. C_LI

BackgroundOpioid overdoses in the US have increased to unprecedented levels. Administration of the opioid antagonist naloxone can prevent overdoses. This study was conducted to reveal the pharmacoepidemiologic patterns in naloxone prescribing to Medicaid patients from 2018-2021 as well as Medicare in 2019. MethodsThe Medicaid State Drug Utilization Data File was utilized to extract information on number of prescriptions and amount prescribed of naloxone at a national and state level. States with naloxone prescription rates differing from the mean by [&ge;] 1.96 standard deviations were considered statistically significant. The Medicare Provider Utilization and Payment was also utilized to analyze prescription data from 2019. ResultsThe number of generic naloxone prescriptions per 100,000 Medicaid enrollees decreased 5.15% whereas brand naloxone prescriptions increased 245.00% from 2018-2021. There was a 33.14-fold difference in prescriptions between the highest (New Mexico = 1809.55) and lowest (South Dakota = 54.61) states in 2019. Medicare saw a 30.32-fold difference in prescriptions between the highest (New Mexico) and lowest states (also South Dakota) after correcting per 100,000 enrollees. ConclusionsThis pronounced increase in the number of naloxone prescriptions to Medicaid patients from 2018-2021 indicates a national response to this widespread public health emergency. Further research into the origins of the pronounced state-level disparities is warranted.

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. We previously demonstrated that four nucleotide analogues (specifically, the active triphosphate forms of Sofosbuvir, Alovudine, AZT and Tenofovir alafenamide) inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Tenofovir and emtricitabine are the two components in DESCOVY and TRUVADA, the two FDA-approved medications for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection. This is a preventative method in which individuals who are HIV negative (but at high-risk of contracting the virus) take the combination drug daily to reduce the chance of becoming infected with HIV. PrEP can stop HIV from replicating and spreading throughout the body. We report here that the triphosphates of tenofovir and emtricitabine, the two components in DESCOVY and TRUVADA, act as terminators for the SARS-CoV-2 RdRp catalyzed reaction. These results provide a molecular basis to evaluate the potential of DESCOVY and TRUVADA as PrEP for COVID-19.

BackgroundOpioid-related overdoses are a major concern in the United States (US) stemming from the high rates of Opioid Use Disorder (OUD). The rates of US overdoses continue to exceed one-hundred thousand per year. Methadone, a medication used as a treatment for OUD, is effective in reducing cravings and withdrawal symptoms which improves the quality of life for OUD. This study analyzed the distribution of methadone to Opioid Treatment Programs (OTP) across the US including the District of Columbia and Puerto Rico. MethodsThe weight of methadone (in grams) was gathered from the Drug Enforcement Administrations Automated Reports and Consolidated Ordering System (ARCOS) database and population data from the US Census Bureau. The number of OTPs per state from the ARCOS Database was obtained. GraphPad Prism Version10.2.3 was used to make figures and perform data analysis. A paired t-test compared distribution in 2019 to 2023. Datawrapper was used to create heat maps. ResultsAnalyzing the population-adjusted percent change by state from 2019 to 2023 showed 32 states had a positive percent change (61.5%), 19 states had a negative one (36.5%), and one state had no change (1.9%). The percent change between 2019 and 2023 (+6.2%) was statistically significant (p=0.047). When looking at the number of OTPs (population-adjusted), there was a twenty-fold state-level difference in 2023. DiscussionAlthough there was a modest increase overall, there were pronounced state-level differences in methadone distribution across the nation. An emphasis on establishing policies to make a positive change widespread over the nation is crucial. New policies are urgently needed to increase the availability of OUD treatments more widely by initiating more OTPs and a more treatment retention focused program to reverse the escalation in overdose deaths.

BackgroundCompounded versions of tirzepatide are widely available in the U.S. in the form of fixed-dose combinations of tirzepatide and various analogs of vitamin B12. These combinations are mass marketed in the U.S. and other countries as comparable to FDA-approved tirzepatide products even though they undergo no evaluation of their potency or impurity profiles. Research Design and MethodsSamples of compounded tirzepatide combined with B12 obtained from various sources in the U.S. market were tested using various analytical methods. Samples were assessed for unacceptable levels of peptide-related impurities. ResultsOur testing identified a widespread and previously unidentified impurity in compounded tirzepatide-B12 products resulting from a chemical reaction between tirzepatide and certain analogs of B12. ConclusionDespite the presence of this impurity, these products continue to be mass marketed as "personalized" treatments. Our findings underscore the importance of testing and FDA approval before new drugs are marketed and highlights potential risks for patients associated with untested combinations. A novel impurity, present at substantial levels in compounded tirzepatide/B12 products, highlights risks inherent in marketing complex therapies outside the drug-approval framework. Although clinical effects of this impurity are unknown, the identification of a widespread impurity adds to the existing quality concerns presented by compounded tirzepatide.

ObjectiveTo compare the 2017 National Academies of Sciences, Engineering, and Medicine (NAS) report to state medical cannabis (MC) laws defining approved qualifying conditions (QC) from 2017 to 2024 and to determine if there exist gaps in evidence-based decision making. MethodsThe 2017 NAS report assessed therapeutic evidence for over twenty medical conditions treated with MC. We identified the QCs of 38 states (including Washington, D.C.) where MC was legal in 2024. We also identified the QCs that these states used in 2017. QCs were then categorized based on NAS-established level of evidence: substantial/conclusive evidence of effectiveness, moderate evidence of effectiveness, limited evidence of effectiveness, limited evidence of ineffectiveness, and no/insufficient evidence to support or refute effectiveness. This study was completed between January 31, 2023 through May 20, 2024. ResultsMost states listed at least one QC with substantial evidence--80.0% of states in 2017 and 97.0% in 2024. However, in 2024 only 8.3% of the QCs on states QC lists met the standard of substantial evidence. Of the 20 most popular QCs in the country in 2017 and 2024, one only (chronic pain) was categorized by the NAS as having substantial evidence for effectiveness. However, seven (ALS, Alzheimers disease, epilepsy, glaucoma, Huntingtons disease, Parkinsons disease, spastic spinal cord damage) were rated as either ineffective or insufficient evidence. ConclusionMost QCs lack evidence for use based on the 2017 NAS report. Many states recommend QCs with little evidence, such as amyotrophic lateral sclerosis (ALS), or even those for which MC is ineffective, like depression. There have been insufficient updates to QCs since the NAS report. These findings highlight a disparity between state-level MC recommendations and the evidence to support them.

BackgroundHealth care inequity includes the lack of adequate representation of various populations in clinical trials. Government, academic and industry organizations have highlighted these issues and committed to actions to improve. In order to assess the current status and future success of these initiatives a quantitative objective measure to assess the state of clinical trial diversity is needed. MethodsFDA review documents for all novel drug approvals from January 2022 through February 16, 2023 were assessed using a scorecard that considers diversity across different demographic subgroups including age (>65 yo), sex (female), race (Black and Asian) and ethnicity (Hispanic/Latino). The scorecard assigns each drug a letter grade, between A and F, for each subgroup (and overall) based on 1) the percent of each sub-population included in the trials and grades relative to the percent of the US population, 2) the number of participants from each subpopulation that received the novel new drug in the trials, 3) the incidence or prevalence of the disease/condition in each of the sub-populations. ResultsThe FDA approved 43 novel new drugs for 44 indications (one drug was simultaneously approved for two indications). The three drugs with A Grades reflecting the best diversity in their registration trials were tapinarof (Vtama from Dermavant), daprodustat (Jesduvroq from GlaxoSmithKline) and eflapegrastim (Rolvedon from Spectrum Pharmaceuticals.) There was good representation of elderly and females with only two drugs receiving a D grade in either of these sub-populations. In contrast, Black and Hispanic representation was often inadequate with 4 drugs receiving F grades. There were 9 drugs (20%) where there were no Black participants receiving the novel new drug and an additional 14 approvals where there were <10 Black participants receiving the novel drug. The median number of Black participants receiving the investigational drug was 9. In the Hispanic/Latino population there were 2 approvals with no Hispanic participants receiving the novel drug and 14 approvals where there were < 10 Hispanic participants receiving the drug. The median number of Hispanic participants receiving the novel drug was 12.5. ConclusionsThis newly developed scorecard provides an objective quantitative approach to assess the current state of diversity in clinical trials supporting new drug approvals. Substantial improvement in racial and ethnic representation is needed. Meaningful change will require actions and cooperation amongst all stakeholders to address this multifaceted issue and will take commitment, perseverance, and appropriate incentives.

PurposeWe investigated if the use of peripheral nerve blockade (PNB) was associated with a lower incidence of prescription opioid fill within 30 days post-surgery and persistent postoperative opioid use (PPOU) in patients undergoing foot and ankle surgery. MethodsWe identified adults who had undergone foot or ankle surgery between 2012 and 2018 and did or did not receive PNB in an Optums de-identified Integrated Claims-Clinical dataset (n=12,643). Pharmacy data was used to track opioid prescription fill date and supply. PPOU was defined as >90 days of continuous opioid use. Entropy balancing was used to control differences in the distribution of covariates. Log-binomial models in unweighted and weighted data estimated crude and adjusted relative risk (RR) with 95% confidence intervals (CI) for the outcomes. ResultsOne-third of the sample filled an opioid within 30 days of surgery, and among these patients, 57.3% continued use for > 90 days. Performance of PNB was associated with an increased risk for filling opioid prescriptions within 30 days post-surgery before (RR=1.40; 95%CI:1.32-1.49) and after (RR=1.31; 95%CI:1.22-1.41; p<0.0001) controlling for confounding. However, the group that received a PNB showed significantly lower risk of PPOU before (0.91; 95%CI:0.85-0.98; p=0.016) and after controlling for confounding (RR=0.92; 95%CI:0.85-0.99; p=0.029). ConclusionPerformance of PNB for patients undergoing foot and ankle surgery was associated with a 31% increased risk of any opioid prescription fill within 30 days after surgery. However, among the patients that initially filled their prescriptions, patients that received PNB had a significantly (8%) lower risk for PPOU.

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/25332171v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@8d02e8org.highwire.dtl.DTLVardef@1b9e538org.highwire.dtl.DTLVardef@177d5f5org.highwire.dtl.DTLVardef@7fe54c_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOVisual AbstractC_FLOATNO C_FIG BackgroundSemaglutide is a glucagon-like peptide 1 receptor agonist that has been used to treat type 2 diabetes and for weight management since its approval in 2018 and 2021, respectively. Our research aimed to examine the geographic distribution of semaglutide prescriptions across the United States Medicaid program and determine the accessibility of this efficacious but costly to those on Medicaid. MethodsMedicaid data on state drug utilization was collected to identify the number of semaglutide prescriptions distributed in each state per quarter from 2018 to 2022 and standardized them per 10,000 Medicaid enrollees. States whose rates fell outside the 95% confidence interval were considered significant outliers. Preferred drug lists for 2019-2022 were retrieved from state Medicaid website archives to explore coverage policies. ResultsNational semaglutide prescribing in Medicaid rose steadily from 2018 to 2022. Notably, states in the Midwest, West, and Northeast regions showed the largest increases. After adjusted for enrollment, Indiana led usage of semaglutide from 2018 to 2020 at 185.6 prescriptions/10,000 enrollees. A notable surge in semaglutide prescriptions was observed in West Virginia in 2021. Conversely, states within the South and lower Midwest regions recorded the lowest prescription rates, with Arkansas (0.1 prescriptions/10,000 enrollees) ranking the lowest in 2020. Prescription volume did not correlate with obesity prevalence, per enrollee Medicaid spending, or the percentage of non-White population. ConclusionSemaglutide use within Medicaid climbed rapidly, but unevenly. Marked state-level variations highlight potential barriers to access despite the drugs growing clinical importance.

Due to the uncertainty of the health effects medical marijuana poses, states differ in their medical marijuana laws (MML). Long-term effects of marijuana are found to be like attention-deficit-hyperactive disorder (ADHD). With amphetamines being prescribed to treat ADHD symptoms we hypothesized that amphetamine prescriptions would increase in states implementing MML. The number of amphetamine prescriptions filled quarterly for each state from 2006 to 2021 were calculated. States with MML and dispensaries opened before 2020 were examined and states with no MML laws were the control. Prism was utilized to visualize the data and conduct four t-tests between the pre and post of MML+ versus MML-states. Three MML+ states were excluded due to limited post-MML data. Among the remaining states, 31 were MML+ and 17 were MML-. No significant differences were found in amphetamine prescribing (p > 0.30). Medical marijuana legalization did not have a statistically significant impact on amphetamine prescribing in Medicaid patients during the analyzed period. Contrary to the hypothesis, the results revealed a non-significant decrease in prescriptions in MML+ states. Further research with recreational cannabis laws or with electronic health records is warranted.

In this paper, we investigate what conditions need to be in place to make progress in combating a disease using a case-control design: we compare cases (diseases with a successful therapy) to controls (diseases without a successful therapy). We find five conditions ("hurdles") must typically be cleared for success: (A) understanding of biological drivers, (B) ability to modulate biology, (C) availability of translational models, (D1) ability to identify patients, and (D2) ability to measure clinical response. This framework is similar to ones deployed to evaluate individual drug candidates but is employed here to make inferences about entire diseases. It can be used to identify diseases most ready for progress, where efforts should be focused to make progress in diseases that are currently intractable, and where the industry could benefit from development of tools to address the hurdle that is most commonly the last to be cleared across diseases--namely, (C) translational models.

BackgroundHydromorphone is a semi-synthetic opioid agonist and a hydro-genated ketone of morphine. This study observed hydromorphone use in the United States (US) using three databases. Methods: The distribution of hydromorphone in the US (in grams) was provided by US Drug Enforcement Administrations Automated Reports and Consolidated Orders System (ARCOS) by state, zip code, and by business types (pharmacies, hospitals, providers, etc.). Hydromorphone prescriptions claims were also examined using the Medicaid and Medicare Part D programs from 2010 to 2023. Results: Hydromorphone increased by +30.6% by 2013, followed by a decrease of -55.9% by 2023 in ARCOS. Medicaid hydromorphone prescriptions increased +39.6% by 2015 and de-creased -48.9% by 2023. Medicare Part D hydromorphone claims increased +8.5% by 2015 and decreased -31.9% by 2023. There were also pronounced regional disparities in hydro-morphone use identified in ARCOS (158.7 fold), Medicaid (17.5 fold), and Medicare Part D (13.7 fold). Conclusions: Hydromorphone use in the US has decreased substantially from 2010 to 2023. Additionally, these findings highlight regional disparities in hydro-morphone use, which may inform targeted opioid stewardship initiatives and guide policymakers to ensure safe and equitable opioid prescribing practices.

BackgroundZ-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance that have been shown to increase the risk of fall-related injuries in patients aged 65 and older. The American Geriatrics Society Beers criteria classifies them as a high-risk medication and strongly recommends avoiding prescribing z-drugs to the elderly due to adverse effects. The objective of this study was to determine the prevalence of Z-drug prescribing among Medicare patients. MethodsZ-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data (CMS SDUD) 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 prescribed by providers within each specialty was also determined. ResultsZolpidem was the most prescribed z-drug, making up 95.0% of all z-drug prescriptions. Prescriptions per 100 enrollees were significantly elevated in Utah (28.2) and Arkansas (26.7) and significantly lower in Hawaii (9.3) relative to the national average (17.5). The specialties 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 elevated for psychiatry relative to other specialties. ConclusionsContrary to the Beers criteria, z-drugs are being prescribed to Medicare enrollees over age 65 at high rates. While sleep disturbances in the elderly should not be ignored, alternative therapies must be considered to avoid the serious adverse effects of z-drugs. Key PointsMore than one-half million Medicare patients received z-drug prescriptions in 2018 that were inconsistent with the Beers criteria. Z-drug prescriptions per 100,000 Medicare patients were significantly elevated in Utah and Arkansas. Family Medicine had the highest number of prescriptions out of all medical specialties. Psychiatry had a significantly higher number of prescriptions per provider compared to all other specialties.

BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, are widely prescribed to treat type 2 diabetes mellitus and obesity. Recent anecdotal reports have suggested these agents might be associated with allodynia, a neuropathic pain syndrome, but large-scale epidemiologic evidence is lacking. MethodsTo investigate this potential link, a retrospective cohort study was conducted using the IQVIA PharMetrics(R) Plus database. Adults aged 18 and older who initiated liraglutide, semaglutide, or bupropion-naltrexone between 2006 and 2020 were included, excluding those with prior diabetes or antihyperglycemic therapy. Incident allodynia was identified via ICD-9/10 codes as the primary outcome. ResultsAmong 20,504 new users, those on GLP-1 receptor agonists had an allodynia incidence of 35 per 1,000 person-years, compared to 15 per 1,000 person-years for bupropion-naltrexone users. Adjusted analyses demonstrated over a twofold increased risk of allodynia with GLP-1 receptor agonists (aHR 2.15, 95% CI 1.57-2.96). ConclusionThese findings emphasize the need for heightened clinical vigilance and further research into mechanisms and management.

BackgroundViruses such as Ebola, Marburg, influenza, mpox, MERS-CoV, SARS-CoV, and SARS-CoV-2 pose a significant risk for future pandemics. Developing novel antiviral medicines can be time-consuming and resource intensive. Repurposing existing medicines with antiviral activity offers a faster, cost-effective strategy to expand treatment options during public health emergencies. This scan aimed to identify and synthesise recent evidence on repurposed antiviral medicines under investigation for these viruses. MethodA horizon scanning approach was employed, starting with a targeted search in Embase, followed by a systematic search of ClinicalTrials.gov to capture the developmental stages of the technologies. Eligible technologies included UK- or EU-licensed medicines repurposed as antiviral therapies for the viruses of interest. Vaccines, unlicensed medicines, and already approved treatments for the targeted viruses were excluded. ResultsA total of 196 repurposed technologies targeting the viruses were identified from published literature, and the expanded search on the clinical trials registry yielded 58 technologies in active clinical development. Interventional clinical trial activity was limited to influenza and COVID-19, with 29 technologies for COVID-19 and two for influenza advancing to phase III evaluation. For other viruses, proposed antiviral candidates were identified in the literature but had not progressed into clinical development. Commonly investigated pharmacological classes included direct-acting antivirals, tyrosine kinase inhibitors, immunomodulators, and anti-inflammatory agents. ConclusionRepurposing antiviral medicines represents a pragmatic strategy for rapid therapeutic deployment against emerging viral threats. Collaboration among researchers, policymakers, research funders, and regulatory bodies will be essential to improve pandemic preparedness and support repurposing efforts in emergency situations.

Approximately 77,000 children 16 years or less suffered burn injuries in the United States in 2018. Treatment, reconstruction, and rehabilitation are painful experiences. For some, the experience triggers post-traumatic stress disorder (PTSD) and/or a chronic pain syndrome. Given the role pain plays as a major secondary disease, it must be addressed to achieve optimal healing. Regional anesthesia has been used extensively to manage postoperative pain and reduce the need for opioids following other surgical procedures in children. Nevertheless, regional anesthesia has not yet been widely used in pediatric burn care. We present a demonstration project utilizing regional anesthesia in 15 pediatric burn patients over an eight-month period. Our results indicate that the use of regional anesthesia reliably reduces perioperative pain and opioid requirements in the immediate peri-operative period. In this cohort, 93% of patients scored a 0/10 on a FLACC scale for pain by post-anesthesia care unit (PACU) discharge, with an average PACU stay of 70 minutes. Thirty-three percent of patients received no opioids, and the average opioid dose was only 0.06mg/kg morphine equivalents. We conclude that regional anesthesia can be used to improve patient comfort and decrease opioid requirement.

ObjectivesCharacterize oxycodones distribution in the US by state and its adverse effect profile from 2000-2021. DesignObservational SettingMore than 80,000 Americans died of an opioid overdose in 2021 as the United States (US) 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. MethodsThe Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System (ARCOS) 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 normalized for population. ResultsThere was a sharp 280.13% increase in total MME/person of oxycodone from 2000-2010, followed by a slower 54.34% decrease from 2010-2021. Florida (2007-11), Delaware (2003-20), and Tennessee (2012-21) displayed consistent and substantial elevations in combined MME/person compared to 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 (2000-01, 2008, 2010-21), Colorado (2008-21), and DC (2000-11) distributed substantially more MME/person over many years compared to other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006-2010. The percentage of consumer reports in the FDA Adverse Drugs Events Reporting System (FAERS) increased from 6.3% (2001) to 95% (2021). Adverse effects distribution remained constant by age and sex, with higher average proportions in males (55%) and the 18-65 age group (79%). ConclusionsOxycodone distribution across the US 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. Strengths and limitations of this studyO_LIARCOS is publicly accessible, comprehensive, and includes institutions that are unavailable in other commonly used databases (i.e. IQVIA). C_LIO_LIDiversion of oxycodone or whether the prescribed amounts were utilized cannot be determined from ARCOS data. C_LIO_LIFAERS data includes duplicates, incomplete results, and non-verifiable data which cannot be used to suggest causation between oxycodone and adverse events. C_LIO_LIThese complementary results from two databases may not generalize to other countries with more restrictive oxycodone policies. C_LI