Direct analysis in real time mass spectrometry (DART-MS/MS) for rapid urine opioid detection in a clinical setting.

BACKGROUND AND AIMS: Current laboratory methods for opioid detection involve an initial screening with immunoassays which offers efficient but non-specific results and a subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmation which offers accurate results but requires extensive sample preparation and turnaround time. Direct Analysis in Real Time (DART) tandem mass spectrometry is evaluated as an alternative approach for accurate opioid detection with efficient sample preparation and turnaround time. MATERIALS AND METHODS: DART-MS/MS was optimized by testing the method with varying temperatures, operation modes, extraction methods, hydrolysis times, and vortex times. The method was evaluated for 12 opioids by testing the analytical measurement range, percent carryover, precision studies, stability, and method-to-method comparison with LC-MS/MS. RESULTS: DART-MS/MS shows high sensitivity and specificity for the detection of 6-acetylmorphine, codeine, hydromorphone, oxymorphone, hydrocodone, naloxone, buprenorphine, norfentanyl, and fentanyl in urine samples. However, its performance was suboptimal for norbuprenorphine, morphine and oxycodone. CONCLUSION: In this proof-of-concept study, DART-MS/MS is evaluated for its rapid quantitative definitive testing of opioids drugs in urine. Further research is needed to expand its application to other areas of drug testing.

The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines.

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

The Cost of Opioid Use in High-Risk Hospitalized Infants.

INTRODUCTION: Hospitalizations of high-risk infants are among the most expensive in the United States, with many requiring surgery and months of intensive care. Healthcare costs and resource use associated with hospitalized infant opioid exposure are less well known. METHODS: A retrospective cohort of high-risk infants aged <1 y admitted from 47 children's hospitals from 2010 to 2020 was identified from Pediatric Healthcare Information System. High-risk infants were identified by International Classification of Diseases 9/10 codes for congenital heart disease procedures, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and gastrointestinal tract malformations. Healthcare resource utilization was estimated using standardized unit costs (SUCs). The impact of opioid use on SUC was examined using general linear models and an instrumental variable. RESULTS: Overall, 126,897 high-risk infants were identified. The cohort was majority White (57.1%), non-Hispanic (72.0%), and male (55.4%). Prematurity occurred in 26.4% and a majority underwent surgery (77.9%). Median SUC was $120,585 (interquartile range: $57,602-$276,562) per infant. On instrumental variable analysis, each day of opioid use was associated with an increase of $4406 in SUC. When adjusting for biologic sex, race, ethnicity, insurance type, diagnosis category, number of comorbidities, mechanical ventilation, and total parental nutrition use, each day of opioid use was associated with an increase of $2177 per infant. CONCLUSIONS: Prolonged opioid use is significantly associated with healthcare utilization and costs for high-risk infants, even when accounting for comorbidities, intensive care, ventilation, and total parental nutrition use. Future studies are needed to estimate the long-term complications and additional costs resulting from prolonged opioid exposures in high-risk infants.

Association Between Diabetes Mellitus and Postoperative Opioid use: A Meta-Analysis.

INTRODUCTION: Diabetes mellitus (DM) is a prevalent metabolic disorder associated with various postoperative complications. The association between DM and postoperative opioid use remains unclear, with conflicting evidence in the literature. This systematic review and meta-analysis comprehensively evaluated the association between DM and postoperative opioid consumption, pain sensation, and adverse effects in surgical patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of electronic databases identified studies investigating the relationship between DM and postoperative pain outcomes. Eligible studies, both prospective and retrospective, were included based on the predefined criteria. Data extraction and quality assessment were performed independently by the authors. Meta-analyses were performed using Review Manager 5. RESULTS: Among 100 initially identified articles, five studies met the inclusion criteria. In the meta-analysis, 473 participants were included. The results indicated that patients with DM had significantly higher postoperative opioid consumption (standardized mean difference, 0.79; 95% confidence interval, 0.26-1.31; P = 0.003) than those in the control group, with substantial heterogeneity (I2 = 83%). No significant differences in postoperative pain scale scores at rest or during movement were observed. Adverse effects, including nausea, vomiting, and pruritus, showed varied outcomes, whereas overall satisfaction did not differ between the two groups. CONCLUSIONS: This meta-analysis provides evidence that patients with DM undergoing surgery consume more opioids postoperatively. Understanding the association between DM and pain management is crucial for optimizing perioperative care in this patient population.

Barriers and facilitators to implementing CareConnect: A telehealth, low-barrier buprenorphine bridge clinic in Philadelphia.

INTRODUCTION: Rates of fatal overdose continue to rise in the United States, and most people with opioid use disorder (OUD) are not engaged in evidence-based treatment with medications. In Philadelphia, a city with one of the highest fatal overdose rates in the country, many residents face significant care access barriers. The COVID-19 pandemic - which destabilized the street drug supply and forced many clinics to limit services - worsened this crisis, but also led to regulatory changes that allowed for buprenorphine induction and maintenance visits via telehealth in the U.S. To increase access to buprenorphine across the Philadelphia area and reach individuals who struggle to access care, Penn Medicine developed the CareConnect Warmline in October 2021. CareConnect is embedded in an existing virtual urgent care practice. Staffed by advanced practice providers and substance use navigators (SUNs), CareConnect provides same-day buprenorphine bridge (i.e., short-term) prescriptions and linkage to longitudinal OUD care. OBJECTIVE: To examine barriers and facilitators to implementing CareConnect from the perspective of key stakeholders, including CareConnect leadership, clinicians, and staff, and attitudes and beliefs about providing care for patients with OUD via this model. METHODS: In this qualitative descriptive study, we interviewed 14 participants and used thematic analysis to analyze the data. The sample included CareConnect prescribing clinicians, SUNs, and administrative staff. RESULTS: Our analysis yielded four themes: 1/ CareConnect is a unique program that fills an important care gap; 2/ Benefits of leveraging existing infrastructure; 3/ Importance of an interdisciplinary team; and 4/ Necessity of relationships with outside stakeholders. Prescribing clinicians and administrative staff - most of whom had little experience with OUD care before CareConnect - stressed how embedding the model within an existing virtual clinic and involving experienced SUNs increased their comfort prescribing buprenorphine. However, all participants highlighted how the program's effectiveness is contingent upon buy-in from outside stakeholders, including pharmacists who fill the prescriptions and longitudinal care providers in the community. CONCLUSIONS: Innovative delivery models can help expand OUD care access to individuals who are poorly served by traditional treatment infrastructure. Our findings provide valuable insight to improve and sustain CareConnect and can guide the development and implementation of future programs nationally.

Examining the effect of prescription drug monitoring program integration and mandatory use policies on the distribution of methadone and buprenorphine for opioid use disorder, United States, 2009-2021.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have been shown to reduce opioid prescribing for pain, but it is not well understood whether PDMPs influence utilization of medications for opioid use disorder. PDMP integration and mandatory use policies are two approaches implemented by states to increase use of PDMPs by prescribers. This study examined the effect of these approaches on distribution of methadone and buprenorphine from 2009 to 2021 for 50 states and DC. METHODS: The effect of PDMP integration and mandatory use policies on four outcomes (distribution of buprenorphine to opioid treatment programs, distribution of buprenorphine to pharmacies, distribution of methadone to opioid treatment programs, and the total combined distribution of methadone and buprenorphine) was estimated using a Callaway and Sant'Anna difference-in-differences model, controlling for co-occurring opioid-related state policies. RESULTS: Distribution of buprenorphine to pharmacies decreased 8 % (95 % CI -14 %, -1 %) following implementation of mandatory use policies. Distribution of methadone to opioid treatment programs increased 17 % (95 % CI 4 %, 34 %) and the total combined distribution of methadone and buprenorphine increased 6 % (95 % CI -0 %, 14 %) following the joint implementation of both approaches. CONCLUSION: Distribution of methadone and buprenorphine has increased since 2009, but less than a quarter of people with opioid use disorder currently receive these medications. We observed a small net benefit of PDMP integration and mandatory use policies on distribution of methadone and buprenorphine. Policymakers should continue to assess the impact of PDMPs on access to medications for opioid use disorder and consider additional approaches to increase access to treatment.

Medications for opioid use disorder: Predictors of early discontinuation and reduction of overdose risk in US military veterans by medication type.

AIM: This study: (1) estimated the effect of early discontinuation of medication for opioid use disorder (MOUD) on overdose probability and (2) measured the relationship between patient characteristics and early discontinuation probability for each MOUD type. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort using electronic health record data from the US Veterans Healthcare Administration. Participants were veterans initiating MOUD with buprenorphine (BUP), methadone (MET) or extended-release naltrexone (XR-NTX) from fiscal years 2012-19. A total of 39 284 veterans met eligibility with 22 721 (57.8%) initiating BUP, 12 652 (32.2%) initiating MET and 3911 (10.0%) initiating XR-NTX. MEASUREMENTS: Measurements (1) determined whether the veteran experienced an overdose in the 365 days after MOUD initiation (primary) and (2) early discontinuation of MOUD, defined as discontinuation before 180 days (secondary). We assumed that unobserved patient characteristics would jointly influence the probability of discontinuation and overdose. and estimated the joint distribution with a bivariate probit model. FINDINGS: We found that 9.0% of BUP initiators who experienced an overdose above the predicted 3.9% had no veteran-discontinued BUP early; findings for XR-NTX were similar, with 12.2% of initiators overdosing above the predicted 4.5%, but this was statistically inconclusive. We found no relationship between early discontinuation and overdose for MET initiators, probably due to the high risk of both events. The patient characteristics included in our post-estimation exploratory analysis of early discontinuation varied by MOUD type, with between 14 (XR-NTX) and 25 (BUP) tested. The only characteristics with at least one level showing a statistically significant change in probability of early discontinuation for all three MOUD types were geography and prior-year exposure to psychotherapy, although direction and magnitude varied. CONCLUSION: Early discontinuation of buprenorphine, and probably extended-release naltrexone, appears to be associated with a greater probability of experiencing a fatal or non-fatal overdose among US veterans receiving medication for opioid use disorder (MOUD); methadone does not show the same association. There is no consistent set of characteristics among early discontinuers by MOUD type.

Community-Based Medications First for Opioid Use Disorder - Care Utilization and Mortality Outcomes.

Purpose: A large treatment gap exists for people who could benefit from medications for opioid use disorder (MOUD). People OUD accessing services in harm reduction and community-based organizations often have difficulty engaging in MOUD at opioid treatment programs and traditional health care settings. We conducted a study to test the impacts of a community-based medications first model of care in six Washington (WA) State communities that provided drop-in MOUD access. Participants and Methods: Participants included people newly prescribed MOUD. Settings included harm reduction and homeless services programs. A prospective cohort analysis tested the impacts of the intervention on MOUD and care utilization. Intervention impacts on mortality were tested via a synthetic comparison group analysis matching on demographics, MOUD history, and geography using WA State agency administrative data. Results: 825 people were enrolled in the study of whom 813 were matched to state records for care utilization and outcomes. Cohort analyses indicated significant increases for days' supply of buprenorphine, months with any MOUD, and months with any buprenorphine for people previously on buprenorphine (all results p<0.05). Months with an emergency department overdose did not change. Months with an inpatient hospital stay increased (p<0.05). The annual death rate in the first year for the intervention group was 0.45% (3 out of 664) versus 2.2% (222 out of 9893) in the comparison group in the 12 months; a relative risk of 0.323 (95% CI 0.11-0.94). Conclusion: Findings indicated a significant increase in MOUD for the intervention group and a lower mortality rate relative to the comparison group. The COVID-19 epidemic and rapid increase in non-pharmaceutical-fentanyl may have lessened the intervention impact as measured in the cohort analysis. Study findings support expanding access to a third model of low barrier MOUD care alongside opioid treatment programs and traditional health care settings.

An Indigenous-led buprenorphine-naloxone treatment program to address opioid use in remote Northern Canada.

Background/purpose: In response to the opioid use challenges exacerbated from the COVID-19 pandemic, Fort Albany First Nation (FAFN), a remote Cree First Nation community situated in subarctic Ontario, Canada, implemented a buprenorphine-naloxone program. The newly initiated program was collaboratively developed by First Nations' nurses and community leaders, driven by the community's strengths, resilience, and forward-thinking approach. Using the First Nations Information Governance Centre strengths-based model, this article examines discussions with four community leaders to identify key strengths and challenges that emerged during the implementation of this program. Methods: this qualitative study amplify the positive aspects and community strengths through the power of oral narratives. We conducted 20 semi-structured face-to-face interviews with community members who helped lead FAFN's COVID-19 pandemic response. Utilizing the Medicine Wheel framework, this work introduces a holistic model for the buprenorphine-naloxone program that addresses the cognitive, physical, spiritual, and emotional dimensions of well-being. Results: Recommendations to support this initiative included the need for culturally competent staff, customized education programs, and the expanding of the program. Additionally, there is a pressing need for increased funding to support these initiatives effectively and sustainably. The development of this program, despite challenges, underscores the vital role of community leadership and cultural sensitivity to address the opioid crisis in a positive and culturally safe manner. Conclusion: The study highlights the successes of the buprenorphine-naloxone program, which was developed in response to the needs arising from the pandemic, specifically addressing community members suffering from opioid addiction. The timely funding for this program came as the urgent needs of community members became apparent due to pandemic lockdowns and isolation. Holistic care, including mental health services and fostering community relations, is important. By centering conversations on community strengths and advocating for culturally sensitive mental health strategies that nurture well-being, resilience, and empowerment, these findings can be adapted and expanded to support other Indigenous communities contending with opioid addiction.

Addressing the barrier of transport costs in accessing headache care in Sub-Saharan Africa.

The article by Leone et al. (2024) highlights the significant barrier of transport costs in accessing headache care for HIV-positive patients in Malawi, a concern that resonates with challenges observed in opioid agonist therapy (OAT) in Taiwan. This letter draws parallels between the findings of Leone et al. and the Taiwanese experience, where distance to treatment centers has been shown to influence patients' choice of OAT. The discussion underscores the importance of expanding healthcare service availability and exploring telemedicine as potential solutions to mitigate geographical barriers. Integrating these approaches could improve patient retention and treatment outcomes in both regions. This commentary emphasizes the broader implications of transport-related barriers in healthcare access, advocating for strategic interventions to enhance healthcare delivery in resource-limited settings.

Development of pharmacy-based best practices to support safer use and management of prescription opioids based on an e-Delphi methodology.

BACKGROUND: Opioid utilization and related harm have increased in recent decades, notably in Australia, the United States, Canada, and some European countries. For people who are prescribed opioids, pharmacies offer an accessible, regular point-of-contact, providing a unique opportunity to address opioid prescription drugs risks. OBJECTIVE: This project aimed to develop consensus-based, best practice statements for improving the safer use of prescription opioids through community pharmacy settings. METHODS: The e-Delphi technique is used to obtain consensus from experts about issues where conclusive evidence is lacking, using multiple rounds of online participation. The investigator group identified an international group of potential participants with relevant expertise who were invited to the study, and asked to identify other experts for invitation. The e-Delphi process comprised three online rounds, involving (1) statement idea generation, (2) developing statement consensus, and (3) confirming and ranking statements. RESULTS: A diverse group of 42 experts (76 % female, 6 countries) participated, comprising pharmacists (n = 24, 57 %), medical doctors of differing specialties (n = 12, 29 %), and/or researchers (n = 28, 67 %), with a mean of 15 years' professional experience (SD = 8.08). Eighty-five statements were initially developed in Round 1, and 78 were supported with amendments, with suggestions to merge and remove items in Round 2, resulting in 72 final statements which were all endorsed in Round 3. Items spanned seven themes: education, monitoring outcomes and risk, deprescribing and pain management, overdose education and naloxone, opioid agonist treatment, staff education, and overarching practices. Preferred terminology was determined in Round 2 and confirmed in Round 3. CONCLUSIONS: Community pharmacies offer a unique opportunity to support the safer use of prescription opioids. These 72 best practice statements provide practical guidance on specific practices that pharmacists can undertake to support patients' safer use of prescription opioids and prevent or reduce harms from prescribed opioid use.

Factors Associated with Take Home Naloxone Refusal among Emergency Department Patients Participating in an Opioid Overdose Prevention Program.

BACKGROUND: Increasing the equitable distribution of take home naloxone (THN) may result in reduced deaths from opioid overdose (OD). OBJECTIVES: The primary study objective is to describe the demographic and clinical characteristics of emergency department (ED) patients who decline THN. The findings of this descriptive study may generate new hypotheses for successful THN distribution. METHODS: Retrospective chart review using prospectively collected program evaluation data from a single urban EDs Health Education THN database and electronic health record. Characteristics of participants who refused versus accepted THN were compared using Chi-square testing for categorical variables and t-tests for continuous variables. A multivariate model was built to assess associations of statistical and clinically relevant characteristics with THN refusal. RESULTS: A total of 711 ED patients were offered THN of which 334 (46%) declined. In unadjusted analysis, with the independent variable being refusal of the THN offer, being currently on medication for opioid use disorder (MOUD) was associated with a greater odds of refusal (OR 1.9, 95%CI 1.3-2.6) while any drug related overdose (OR 0.6, 95%CI 0.4-0.8) or being given a prescription for buprenorphine in the ED (OR 0.2, 95%CI 0.1-0.9) were both associated with a lower odds of refusal. CONCLUSIONS: Demographic characteristics did not differ between those who accept versus refuse THN. Patients already receiving MOUD were more likely to refuse THN while those starting MOUD in the ED were less likely to refuse THN. Further studies are needed to determine the root causes of patients' declination of THN and develop targeted interventions to address these causes.

The Odyssey of HOMER: Comparative Effectiveness Research on Medication for Opioid Use Disorder During the COVID-19 Pandemic.

The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous). The study aimed to enroll 1,000 participants from 100 diverse primary care practices associated with the State Networks of Colorado Ambulatory Practices and Partners and the American Academy of Family Physicians National Research Network. The research team faced unexpected challenges related to the COVID-19 pandemic and dramatic changes in the opioid epidemic. These challenges required changes to the study design, protocol, recruitment intensity, and funding conversations, as well as patience. As this is a participatory research study, we sought, documented, and responded to practice and patient requests for adaptations. Changes included adding a third study arm using telehealth induction (observed via telephone or video, synchronous) and switching to a comprehensive cohort design to answer meaningful patient-centered research questions. Using a narrative approach based on the Greek myth of Homer, we describe here the challenges and adaptations that have provided the opportunity for HOMER to thrive and find the way home. These clinical trial strategies may apply to other studies faced with similar cultural and extreme circumstances.

An economic analysis of the cost of mobile units for harm reduction, naloxone distribution, and medications for opioid use disorder.

BACKGROUND & OBJECTIVE: Mobile substance use treatment units are effective approaches to increase treatment access and reduce barriers to opioid use disorder (OUD) care. However, little is known about the economic costs of maintaining and operating these units. This study aimed to estimate the economic costs of starting and maintaining mobile units providing harm reduction, overdose education and naloxone distribution (OEND), and medication for opioid use disorder (MOUD). METHODS: As part of the HEALing Communities Study, four communities in Massachusetts (Bourne/Sandwich, Brockton, Gloucester, Salem) implemented mobile units offering OEND and MOUD (buprenorphine and naltrexone only); each selected different services tailored to their community. All provided MOUD linkage via telehealth, but only one offered in-person MOUD prescribing on the unit. We retrospectively collected detailed resource utilization data from invoices to estimate the direct economic costs from August 2020 through June 2022. Cost components were categorized into start-up and operating costs. We calculated total economic cost over the study period and the average monthly operating cost. RESULTS: Implementing a mobile unit offering OEND and MOUD required a one-time median start-up cost of $59,762 (range: $52,062-$113,671), with 80 % of those costs attributed to the vehicle purchase. The median monthly operating cost was $14,464. The largest cost category for all mobile units was personnel costs. The monthly ongoing costs varied by community settings and services: approximately $5000 for two urban communities offering OEND and MOUD linkage via telehealth (Gloucester, Salem), $28,000 for a rural community (Bourne/Sandwich), and $23,000 for an urban community also providing in-person MOUD prescribing on the unit (Brockton). CONCLUSION: The economic costs of mobile substance use treatment and harm reduction units are substantial but vary by community settings and services offered. Our results provide valuable community-level economic data to stakeholders and policymakers considering establishing and/or expanding mobile units with OEND and MOUD services. Further exploration of cost-effectiveness and efficiency should be considered across different settings.

Europe must continue to lead on harm reduction.

Europe has been at the forefront of harm reduction since its inception. These important early steps were in large part a response to the dramatically expanding HIV epidemic, and investing in these innovative interventions early and robustly had a transformative effect. This brought about not just pioneering services but also pioneering policy changes. However, while Western Europe and Member States in the European Union often have been at the vanguard of harm reduction innovation and vocal advocates for public health and human rights-based drug policy reform, the situation has been much different in the "wider" WHO European region, which also includes Eastern and Southeastern Europe as well as Central Asia. This is a result not just of limited budgets for health, but also of punitive laws and policies and persistent stigma and discrimination. Even as harm reduction has demonstrated huge successes in Europe, there is a need to move forward a wider array of services to respond to an evolving and increasingly complex drug situation in Europe. Instead, it is a lack of political will and of political courage that is holding back the establishment, expansion, and deepening of these essential, lifesaving interventions. Responding proactively and effectively to this changing drug situation will require redoubled investment in public health and harm reduction approaches.

Understanding the role of intraoperative hypothermia in perioperative opioid requirements in immediate implant-based breast reconstruction.

BACKGROUND: The relationship between perioperative temperatures and postoperative pain is unknown. The present study investigated the relationship of intraoperative hypothermia and perioperative opioid requirements after immediate implant-based breast reconstruction. METHODS: A retrospective chart review was conducted on patients undergoing immediate implant-based breast reconstruction from 2019-2023. Patients were classified into the hypothermic group (majority of procedure <36.0 °C) or normothermic group (majority of procedure ≥36.0 °C). Cumulative inpatient opioid requirements (morphine milli-equivalents [MMEs]) and frequency of patients requiring "high-dose opioids" (≥100 MMEs) were collected and compared between the groups. RESULTS: In total, 536 patients (835 breasts) were included, among whom 135 (25.1%) were hypothermic. The hypothermic group had lower mean intraoperative (88.4 vs. 99.1 MMEs, P = 0.007) and postoperative (45.6 vs. 56.8 MMEs, P = 0.006) than the normothermic group. Mean (B = 14.6, P = 0.004) and nadir (B = 10.4, P = 0.038) intraoperative temperatures directly predicted higher opioid requirements while higher percentages of the procedure time spent under 36 °C (B = -27.6, P = 0.004) predicted lower opioid requirements. The hypothermic group was associated with 66% decreased odds of requiring high-dose opioids after adjusting for differences in patient and operative characteristics (P = 0.007). CONCLUSION: Hypothermia is associated with decreased perioperative opioid requirements. Future studies should further investigate ideal temperature thresholds for warming protocols to minimize postoperative pain.

Present and Future of Pharmacological Management for Acute Moderate-to-Severe Postoperative, Traumatic, or Musculoskeletal Pain in Europe: A Narrative Review.

Acute moderate-to-severe pain is common after surgery, trauma, or musculoskeletal injury, but its management remains suboptimal. Current single-agent treatments are limited by safety concerns, narrow therapeutic windows, and abuse potential, leaving substantial unmet needs. Here, we aimed to review guidelines for the management of acute moderate-to-severe post-surgical, trauma-related, or musculoskeletal pain in adults and discuss existing and potential future analgesics in this setting. We searched PubMed to identify relevant guidelines and existing analgesics for acute pain. To identify compounds in development, we searched ClinicalTrials.gov and the European Union Clinical Trials Register. Guidelines universally recognize the limitations of single-agent analgesics (particularly those with a single mechanism of action [MoA]) and recommend a multimodal approach as an established standard for acute pain. The benefit-risk profiles of traditional treatments, including paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, and opioids, can be improved by combining agents targeting different pain pathways. In multimodal approaches, lower doses of constituent agents can be used to achieve the same or superior analgesic effects relative to the individual agents. In some cases, novel formulations and co-crystal technology offer enhanced physicochemical and pharmacokinetic properties over individual agents. Lastly, initiatives to increase patient awareness and education around pain management may improve treatment satisfaction and quality of life, and hasten recovery. In conclusion, management of acute moderate-to-severe pain remains inadequate. Multimodal analgesics may offer advantages over traditional single-agent treatments (that often have a single MoA) for acute moderate-to-severe post-surgical, trauma-related, or musculoskeletal pain in adults. Multimodal analgesics, combined with patient education initiatives and non-pharmacological measures, when necessary, offer promise in addressing unmet needs in this setting.

Adverse Events at 1 Month Following Medication Initiation for Opioid Use Disorder Among Adolescents and Young Adults.

BACKGROUND: We assess adverse events (AEs) following medication initiation for adolescents and young adults with opioid use disorder (OUD). METHODS: This is a secondary analysis of a clinical trial of long-acting injectable naltrexone (LAI-naltrexone) among youth with OUD aged 15 to 21 years. Participants were recruited from residential treatment and placed into 1 of 3 treatment groups based on medication receipt at time of discharge (no medication, sublingual buprenorphine-naloxone [buprenorphine], or LAI-naltrexone). Frequencies and percentages of AEs by body system were compared by medication group at the 1-month follow-up visit. Logistic regression was used to compare groups on their likelihood of reporting an AE, overall and excluding injection site reactions. RESULTS: Of 199 participants, 71 (36%) received no medication, 59 (30%) buprenorphine, and 69 (35%) LAI-naltrexone at discharge. Participants who received LAI-naltrexone experienced more AEs, primarily due to injection site reactions (62%, accounting for 43% of all AEs among participants who received LAI-naltrexone). There were 6 reports of nonlethal overdose, 5 in the no medication, 1 in the buprenorphine, and none in the LAI-naltrexone group. Participants receiving LAI-naltrexone were more likely to report an AE compared to the other groups (P = .04), but this difference was no longer significant when excluding injection site reactions (P = .82). CONCLUSIONS: Excluding injection site reactions, there were no significant differences in the likelihood of reporting an AE 1 month after receiving LAI-NTX, buprenorphine, and no medications. LAI-naltrexone should be among the medications offered for the treatment of OUD in youth.

Increasing Prevalence of Xylazine and Worsening Upper-Extremity Wounds in Injection Drug Use: A Local Phenomenon With National Implications.

The rising presence of xylazine in Philadelphia's fentanyl supply has led to various upper-extremity complications in individuals who inject drugs. Sociogeographic trends predict that our current local phenomenon will spread nationally. We aim to discuss the drug's impact on clinical presentation and patient care via a cohort of five patients with upper-extremity wounds related to drug use. Interventions included local wound care, revascularization, compartment release, free flap reconstruction, and amputation. Successful treatment of these patients, who are often in challenging psychosocial environments, requires an individualized and interdisciplinary approach including surgical services, infectious disease, wound care, addiction medicine, psychiatry, social services, and prosthetic services.