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Introduction: Coronavirus 2019 (COVID-19) has had a devastating impact on mental health and access to addiction treatment in the United States, including in California, which resulted in the highest rates of emergency department visits (ED) for opioid poisoning in 2020. As California slowly returns to pre-pandemic normalcy, it remains uncertain whether the rates of opioid-related events have slowed down over time. We hypothesized that the number of opioid-related ED visits were exacerbated after the period of the COVID-19 pandemic and continue at a high rate in the present.Methods: In this analysis we searched the University of California (UC) Health Data Warehouse—a database of electronic health records from six UC health centers—for opioid-related ED visits, identifiying using the following International Classification of Diseases, 10th Ed, Clinical Modification codes: F11 codes, and T40.0*, T40.1*, T40.2*, T40.3*, T40.4*, T40.6*. Opioid overdose-associated visits were classified by types of opioids involved: heroin (T40.1*); prescription opioids (T40.2* or T40.3*); and synthetic opioids (T40.4*). We performed interrupted time analysis to estimate the immediate (level) change and change-in-time trend (trend change), from before (January 2018–October 2019) and during the pandemic (April 2020–December 2022). Monthly visit rates were evaluated with negative binomial regression adjusted for first-order autoregression and using all-cause ED counts as the offset. We present effect sizes as rate ratios (RR) and 95% confidence intervals (CI), tested at α = .05.Results: Before COVID-19, a steadily increasing trend in ED visit rates was observed for all outcomes (P < 0.05) except synthetic opioids. Total opioid-related ED visit rates increased by 15% (RR 1.15, 95%CI 1.02–1.29, P = 0.20) immediately after March 2020 before decreasing by 0.5% every month, albeit without statistical significance (RR .995, 95% CI .991–1.00, P = 0.06). Similar trends were observed with prescription opioid overdoses, with a step increase of 44% (RR 1.44, 95% CI 1.10–1.89, P = .008) before plateauing after March 2020 (RR 1.01, 95% CI .998–1.02, P = 0.12). After March 2020, ED visit rates for synthetic opioid overdoses were increasing steadily by 4% every month (RR 1.04, 95% CI 1.02–1.06, P = .001), unlike with heroin, which was observed with an 8% monthly reduction (RR .92, 95% CI .90–.93, P < .001). No immediate increase in visit rates was observed for either opioid.Conclusion: While opioid-related ED admissions among the UC health centers showed an overall decrease, prescription and synthetic opioid overdoses remained significantly higher than pre-pandemic trends as of December 2022. A multilevel approach to improve awareness of new opioid health policies could ameliorate these alarming rises in the post-pandemic era.

Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.

BackgroundPostoperative nausea and vomiting occur frequently following thyroid and parathyroid surgery and are associated with worse patient outcomes. We hypothesised that opioid-free propofol anaesthesia would reduce the incidence of postoperative nausea and vomiting compared with opioid-inclusive propofol anaesthesia in patients undergoing these procedures.MethodsWe conducted a randomised, double-blinded controlled trial in adult patients scheduled to undergo thyroid and parathyroid surgery at two medical centres in mainland China. Patients were allocated randomly (1:1, stratified by sex and trial site) to an opioid-free anaesthesia group (esketamine, lidocaine, dexmedetomidine and propofol) or an opioid-inclusive group (sufentanil and propofol). Propofol infusions were titrated to bispectral index 45-55. Patients received prophylaxis for nausea and vomiting using dexamethasone and ondansetron and multimodal analgesia with paracetamol and flurbiprofen axetil. The primary outcome was the incidence of postoperative nausea and vomiting in the first 48 h after surgery.ResultsWe assessed 557 patients for eligibility and 394 completed this trial. The incidence of postoperative nausea and vomiting in the first postoperative 48 h was lower in the opioid-free anaesthesia group (10/197, 5%) compared with opioid-inclusive group (47/197, 24%) (OR (95%CI) 0.17 (0.08-0.35), p

The intensifying global opioid crisis, majorly attributed to fentanyl (FT) and its analogs, has necessitated the development of rapid and ultrasensitive remote/on-site FT sensing modalities. However, current approaches for tracking FT exposure through wastewater-based epidemiology (WBE) are unadaptable, time-consuming, and require trained professionals. Toward developing an extended in situ wastewater opioid monitoring system, we have developed a screen-printed electrochemical FT sensor and integrated it with a customized submersible remote sensing probe. The sensor composition and design have been optimized to address the challenges for extended in situ FT monitoring. Specifically, ZIF-8 metal-organic framework (MOF)-derived mesoporous carbon (MPC) nanoparticles (NPs) are incorporated in the screen-printed carbon electrode (SPCE) transducer to improve FT accumulation and its electrocatalytic oxidation. A rapid (10 s) and sensitive square wave voltammetric (SWV) FT detection down to 9.9 µgL-1 is thus achieved in aqueous buffer solution. A protective mixed-matrix membrane (MMM) has been optimized as the anti-fouling sensor coating to mitigate electrode passivation by FT oxidation products and enable long-term, intermittent FT monitoring. The unique MMM, comprising an insulating polyvinyl chloride (PVC) matrix and carboxyl-functionalized multi-walled carbon nanotubes (CNT-COOH) as semiconductive fillers, yielded highly stable FT sensor operation (> 95% normalized response) up to 10 h in domestic wastewater, and up to 4 h in untreated river water. This sensing platform enables wireless data acquisition on a smartphone via Bluetooth. Such effective remote operation of submersible opioid sensing probes could enable stricter surveillance of community water systems toward timely alerts, countermeasures, and legal enforcement.

BackgroundYoung adult (18-30 years) people who inject drugs (PWID) face high hepatitis C virus (HCV) prevalence. In San Francisco, where >60% of PWID lack stable housing, barriers hinder HCV treatment access. We assessed progress towards the World Health Organization's (WHO) HCV elimination goal of an 80% reduction in incidence over 2015-2030, focusing on young (YPWID) and unstably housed PWID in San Francisco.MethodsWe developed a dynamic HCV transmission model among PWID, parameterized and calibrated using bio-behavioural survey datasets from San Francisco. This included 2018 estimates for the antibody-prevalence among PWID (77%) and care cascade estimates for HCV for YPWID (72% aware of their status and 33% ever initiating treatment). Based on programmatic data, we assumed a 53.8% reduction in testing and 40.7% decrease in treatment from 2020 due to the COVID-19 pandemic, which partially rebounded from April 2021 with testing rates then being 31.1% lower than pre-pandemic rates and treatment numbers being 19.5% lower. We simulated different scenarios of how services changed after the pandemic to project whether elimination goals would be met.ResultsContinuing post-pandemic rates of testing and treatment, the model projects an 83.3% (95% credibility interval [95% CrI]:60.6-96.9%) decrease in incidence among PWID over 2015-2030 to 1.5/100pyrs (95% CrI:0.3-4.4) in 2030. The probability of achieving the elimination goal by 2030 is 62.0%. Among YPWID and unstably housed PWID, the probability of achieving the elimination goal by 2030 is 54.8 and 67.6%, respectively. Importantly, further increasing testing and treatment rates to pre-pandemic levels by 2025 only results in a small increase in the probability (67.5%) of the elimination goal being achieved among all PWID by 2030, while increased coverage of medication for opioid use disorder among YPWID and/or housing interventions results in the probability of achieving elimination increasing to over 75%.ConclusionThe COVID-19 pandemic impeded progress toward achieving HCV elimination. Our findings indicate that existing partial rebounds in HCV testing and treatment may achieve the elimination goal by 2030, with an additional scale-up of interventions aimed at YPWID or unstably housed PWID ensuring San Francisco is likely to achieve elimination by 2030.

INTRODUCTION: Across specialties, surgeons over-prescribe opioids to patients after surgery. We aimed to develop and implement an evidence-based calculator to inform post-discharge opioid prescription size for gynecologic oncology patients after laparotomy. METHODS: In 2021, open surgical gynecologic oncology patients were called 2-4 weeks after surgery to ask about their home opioid use. This data was used to develop a calculator for post-discharge opioid prescription size using two factors: 1) age of the patient, 2) oral morphine equivalents (OME) used by patients the day before hospital discharge. The calculator was implemented on the inpatient service from 8/21/22 and patients were contacted 2-4 weeks after surgery to again assess their opioid use at home. RESULTS: Data from 95 surveys were used to develop the opioid prescription size calculator and are compared to 95 post-intervention surveys. There was no difference pre- to post-intervention in demographic data, surgical procedure, or immediate postoperative recovery. The median opioid prescription size decreased from 150 to 37.5 OME (p

Introduction: People who use drugs in community settings are at risk of a fatal overdose, which can be mitigated by naloxone administered via bystanders. In this study we sought to investigate methods of estimating and tracking opioid overdose reversals by community members with take-home naloxone (THN) to coalesce possible ways of characterizing THN reach with a metric that is useful for guiding both distribution of naloxone and advocacy of its benefits.Methods: We conducted a scoping review of published literature on PubMed on August 15, 2022, using PRISMA-ScR protocol, for articles discussing methods to estimate THN reversals in the community. The following search terms were used: naloxone AND (“take home” OR kit OR “community distribution” OR “naloxone distribution”). We used backwards citation searching to potentially find additional studies. Overdose education and naloxone distribution program-based studies that analyzed only single programs were excluded.Results: The database search captured 614 studies, of which 14 studies were relevant. Backwards citation searching of 765 references did not reveal additional relevant studies. Of the 14 relevant studies, 11 were mathematical models. Ten used Markov models, and one used a system dynamics model. Of the remaining three articles, one was a meta-analysis, and two used spatial analysis. Studies ranged in year of publication from 2013–2022 with mathematical modeling increasing in use over time. Only spatial analysis was used with a focus on characterizing local naloxone use at the level of a specific city.Conclusion: Of existing methods to estimate bystander administration of THN, mathematical models are most common, particularly Markov models. System dynamics modeling, meta-analysis, and spatial analysis have also been used. All methods are heavily dependent upon overdose education and naloxone distribution program data published in the literature or available as ongoing surveillance data. Overall, there is a paucity of literature describing methods of estimation and even fewer with methods applied to a local focus that would allow for more targeted distribution of naloxone.

Introduction: The opioid epidemic is a major cause of morbidity and mortality in the United States. Prior work has shown that emergency department (ED) opioid prescribing can increase the incidence of opioid use disorder in a dose-dependent manner, and systemic changes that decrease default quantity of discharge opioid tablets in the electronic health record (EHR) can impact prescribing practices. However, ED leadership may be interested in the impact of communication around the intervention as well as whether the intervention may differentially impact different types of clinicians (physicians, physician assistants [PA], and nurse practitioners). We implemented and evaluated a quality improvement intervention of an announced decrease in EHR default quantities of commonly prescribed opioids at a large, academic, urban, tertiary-care ED.Methods: We gathered EHR data on all ED discharges with opioid prescriptions from January 1, 2019–December 6, 2021, including chief complaint, clinician, and opioid prescription details. Data was captured and analyzed on a monthly basis throughout this time period. On March 29, 2021, we implemented an announced decrease in EHR default dispense quantities from 20 tablets to 12 tablets for commonly prescribed opioids. We measured pre- and post-intervention quantities of opioid tablets prescribed per discharge receiving opioids, distribution by patient demographics, and inter-clinician variability in prescribing behavior.Results: The EHR change was associated with a 14% decrease in quantity of opioid tablets per discharge receiving opioids, from 14 to 12 tablets (P =

Opioid receptors are therapeutically important G protein-coupled receptors (GPCRs) with diverse neuromodulatory effects. The functional consequences of opioid receptor activation are known to depend on receptor location in the plasma membrane, but mechanisms mediating selective localization of receptors to any particular membrane domain remain elusive. Here, we demonstrate the targeting of the mu opioid receptor (MOR) to the primary cilium, a discrete microdomain of the somatic plasma membrane, both in vivo and in cultured cells. We further show that ciliary targeting is specific to MORs, requires a 17-residue sequence unique to the MOR cytoplasmic tail, and additionally requires the Tubby-like protein 3 (TULP3) ciliary adaptor protein. Our results reveal the potential for opioid receptors to undergo selective localization to the primary cilium. We propose that ciliary targeting is mediated through an elaboration of the recycling pathway, directed by a specific C-terminal recycling sequence in cis and requiring TULP3 in trans.

BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. METHODS: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. RESULTS: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. CONCLUSIONS: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients withdrawal experiences.

Introduction: Bystander provision of naloxone is a key modality to reduce opioid overdose-related death. Naloxone training courses are available, but no standardized program exists. As part of a bystander empowerment course, we created and evaluated a brief naloxone training module.Methods: This was a retrospective evaluation of a naloxone training course, which was paired with Stop the Bleed training for hemorrhage control and was offered to administrative staff in an office building. Participants worked in an organization related to healthcare, but none were clinicians. The curriculum included the following topics: 1) background about the opioid epidemic; 2) how to recognize the signs of an opioid overdose; 3) actions not to take when encountering an overdose victim; 4) the correct steps to take when encountering an overdose victim; 5) an overview of naloxone products; and 6) Good Samaritan protection laws. The 20-minute didactic section was followed by a hands-on session with nasal naloxone kits and a simulation mannequin. The course was evaluated with the Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales for take-home naloxone training evaluation. We used the paired Wilcoxon signed-rank test to compare scores pre- and post-course.Results: Twenty-eight participants completed the course. The OOKS, measuring objective knowledge about opioid overdose and naloxone, had improved scores from a median of 73.2% (interquartile range [IQR] 68.3%–79.9%) to 91.5% (IQR 85.4%–95.1%), P < 0.001. The three domains on the OOAS score also showed statistically significant results. Competency to manage an overdose improved on a five-point scale from a median of 2.5 (IQR 2.4–2.9) to a median of 3.7 (IQR 3.5–4.1), P < 0.001. Concerns about managing an overdose decreased (improved) from a median of 2.3 (IQR 1.9–2.6) to median 1.8 (IQR 1.5–2.1), P < 0.001. Readiness to intervene in an opioid overdose improved from a median of 4 (IQR 3.8–4.2) to a median of 4.2 (IQR 4–4.2), P < 0.001.Conclusion: A brief course designed to teach bystanders about opioid overdose and naloxone was feasible and effective. We encourage hospitals and other organizations to use and promulgate this model. Furthermore, we suggest the convening of a national consortium to achieve consensus on program content and delivery.

RationaleUse of electronic drug delivery systems (EDDS, "e-cigarettes") to ingest nicotine and Δ9-tetrahydrocannabinol (THC) has surged in adolescents in the USA; five times as many high-school seniors vape nicotine daily using tobacco. At the same time, 19.5% of seniors use cannabis at least monthly, with 12% using EDDS to deliver it.ObjectivesThis study was conducted to examine the impact of repeated adolescent vapor inhalation of nicotine and THC in rats.MethodsFemale Sprague-Dawley rats were exposed to 30-min sessions of vapor inhalation, twice daily, from post-natal day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle, nicotine (60 mg/mL in the PG), THC (100 mg/mL in the PG), or the combination of nicotine (60 mg/mL) and THC (100 mg/mL). Rats were assessed on wheel activity, heroin anti-nociception and nicotine and heroin vapor volitional exposure during adulthood.ResultsNicotine-exposed rats exhibited few differences as adults, but were less sensitive to anti-nociceptive effects of heroin (1 mg/kg, s.c.). THC- and THC + nicotine-exposed rats were less spontaneously active, and obtained fewer nicotine vapor deliveries as adults. In contrast, THC-exposed rats obtained volitional heroin vapor at rates indistinguishable from the non-THC-exposed groups. Repeated THC exposure also caused tolerance to temperature-disrupting effects of THC (5 mg/kg, i.p.).ConclusionsThese studies further confirm that the effects of repeated vapor exposure to THC in adolescence last into early to middle adulthood, including decreased volitional consumption of nicotine. Effects of repeated nicotine in adolescence were comparatively minor.

The harmful side effects of opioid drugs such as respiratory depression, tolerance, dependence, and abuse potential have limited the therapeutic utility of opioids for their entire clinical history. However, no previous attempt to develop effective pain drugs that substantially ameliorate these effects has succeeded, and the current opioid epidemic affirms that they are a greater hindrance to the field of pain management than ever. Recent attempts at new opioid development have sought to reduce these side effects by minimizing engagement of the regulatory protein arrestin-3 at the mu-opioid receptor, but there is significant controversy around this approach. Here, we discuss the ongoing effort to develop safer opioids and its relevant historical context. We propose a new model that reconciles results previously assumed to be in direct conflict to explain how different signaling profiles at the mu-opioid receptor contribute to opioid tolerance and dependence. Our goal is for this framework to inform the search for a new generation of lower liability opioid analgesics.

IntroductionDeaths from drug overdoses are rising dramatically in the United States. Treatment for opioid use disorders may include behavioral treatments as well as medications for opioid use disorders (MOUD). Buprenorphine can be prescribed by physicians, nurse practitioners (NPs), other advanced practice registered nurses (APRNs), and physician assistants (PAs) and required a training and a federal waiver until recently. The number of NP MOUD prescribers grew steadily over the past decade, but research has identified state-level scope of practice regulations as a barrier to NP MOUD prescribing. This article explores the contributions of, and remaining barriers faced by NP and other APRN MOUD prescribers. We describe qualitative findings from a study of NPs and other key stakeholders involved in MOUD treatment in four states with two differing levels of regulatory structure.MethodsIn this qualitative study, we conducted site visits and semi-structured interviews with NPs and other APRNs, physicians, clinic managers, and regulators in four states including New Mexico and West Virginia (full practice authority for NPs), and Ohio and Michigan (which require physician supervision). Interview notes were entered into a qualitative software package and coded and reviewed by two members of the research team. Data were grouped into key themes.ResultsA total of 76 participants participated in individual or small group interviews in the four states. We found key themes and several subthemes that describe NP practice in MOUD. Participants described key contributions of NP engagement in MOUD, including increasing access, serving rural areas, the unique role of psychiatric NPs, and the value of the nursing model of care in working with people with substance use disorders (SUD). Participants also identified barriers including scope of practice regulations, other regulatory barriers, stigma, and lack of supportive services to address psychosocial needs.ConclusionsThe waiver requirements were eliminated at the end of 2022 in federal budget legislation. Other barriers for NP and other APRN prescribers remain and should be addressed in practice, and in state and federal regulations. Research needs to explore the impact of the waiver elimination on MOUD prescribing and access to services.

BackgroundIncarceration is associated with drug-related harms among people who inject drugs (PWID). We trained >1800 police officers in Tijuana, Mexico on occupational safety and HIV/HCV, harm reduction, and decriminalization reforms (Proyecto Escudo). We evaluated its effect on incarceration, population impact and cost-effectiveness on HIV and fatal overdose among PWID.MethodsWe assessed self-reported recent incarceration in a longitudinal cohort of PWID before and after Escudo. Segmented regression was used to compare linear trends in log risk of incarceration among PWID pre-Escudo (2012-2015) and post-Escudo (2016-2018). We estimated population impact using a dynamic model of HIV transmission and fatal overdose among PWID, with incarceration associated with syringe sharing and fatal overdose. The model was calibrated to HIV and incarceration patterns in Tijuana. We compared a scenario with Escudo (observed incarceration declines for 2 years post-Escudo among PWID from the segmented regression) compared to a counterfactual of no Escudo (continuation of stable pre-Escudo trends), assessing cost-effectiveness from a societal perspective. Using a 2-year intervention effect and 50-year time horizon, we determined the incremental cost-effectiveness ratio (ICER, in 2022 USD per disability-adjusted life years [DALYs] averted).FindingsCompared to stable incarceration pre-Escudo, for every three-month interval in the post-Escudo period, recent incarceration among PWID declined by 21% (adjusted relative risk = 0.79, 95% CI: 0.68-0.91). Based on these declines, we estimated 1.7% [95% interval: 0.7%-3.5%] of new HIV cases and 12.2% [4.5%-26.6%] of fatal overdoses among PWID were averted in the 2 years post-Escudo, compared to a counterfactual without Escudo. Escudo was cost-effective (ICER USD 3746/DALY averted compared to a willingness-to-pay threshold of $4842-$13,557).InterpretationEscudo is a cost-effective structural intervention that aligned policing practices and human-rights-based public health practices, which could serve as a model for other settings where policing constitutes structural HIV and overdose risk among PWID.FundingNational Institute on Drug Abuse, UC MEXUS CONACyT, and the San Diego Center for AIDS Research (SD CFAR).

BACKGROUND: The overdose crisis driven by synthetic opioids continues to escalate in the USA. We evaluated the efficacy of multiple manufacturing lots of a fentanyl test strip (FTS) to detect fentanyl and fentanyl analogs and assessed cross-reactivity with possible interferences. METHODS: Drug standards were dissolved in water in a laboratory setting and serially diluted. Drug dilutions were tested using five different manufacturing lots of BTNX Rapid Response (20 ng/mL cutoff) lateral flow chromatographic immunoassay strips to assess lot-to-lot variability for FTS sensitivity and cross-reactivity for the analytes of interest. RESULTS: All five manufacturing lots cross-reacted with fentanyl and eleven fentanyl analogs. Diphenhydramine, lidocaine, MDMA, and methamphetamine were found to cause false positives with the strips. There was notable lot-to-lot variability in the sensitivity of the strips for fentanyl, fentanyl analogs, and known interferences. DISCUSSION: FTS remains an important overdose prevention tool, but lot-to-lot variability in performance complicates robust instructions that balance the prevention of false positives and false negatives. Continued lot-to-lot performance assessment is recommended to ensure health education for FTS remains accurate. More sophisticated drug checking technologies and services are needed in the community landscape to augment personal FTS use to facilitate informed consumption and overdose risk mitigation.

INTRODUCTION: The opioid overdose crisis in the United States has become a significant national emergency. Buprenorphine, a primary medication for individuals coping with opioid use disorder (OUD), presents promising pharmacokinetic properties for use in primary care settings, and is often delivered as a take-home therapy. The COVID-19 pandemic exacerbated the scarcity of access to buprenorphine, leading to dire consequences for those with OUD. Most existing studies, primarily focused on the immediate aftermath of the COVID-19 outbreak, highlight the challenges in accessing medications for opioid use disorder (MOUDs), particularly buprenorphine. However, these studies only cover a relatively short timeframe. METHODS: To bridge this research gap, in our study, we utilized 33 months of Californias prescription drug monitoring program (PDMP) data to provide insights into real-world buprenorphine dispensing trends since the onset of the pandemic from 2018 to 2021, focusing on outcomes such as patient counts, prescription volumes, prescriber involvement, days supply, and dosage. Statistical analysis employed interrupted time series analysis to measure changes in trends before and during the pandemic. RESULTS: We found no significant impact on patient counts or prescription volumes during the pandemic, although it impeded the upward trajectory of prescriber numbers that was evident prior to the onset of the pandemic. An immediate increase in days supply per prescription was observed post-pandemic. CONCLUSION: Our findings differ in comparison to previous data regarding the raw monthly count of patients and prescriptions. The analysis encompassed uninsured patients, offering a comprehensive perspective on buprenorphine prescribing in California. Our studys insights contribute to understanding the impact of COVID-19 on buprenorphine access, emphasizing the need for policy adjustments.

In 2020, three crises coalesced to transform the clinical care landscape of addiction medicine in the United States (US). The opioid overdose crisis (crisis #1), which had been contributing to excess US mortality for over two decades, worsened during the COVID-19 pandemic (crisis #2). The racial reckoning (crisis #3) spurred by the murder of George Floyd at the hands of police impacted clinical care, especially in safety net clinical settings where the majority of people targeted by police violence, and other forms of structural violence, receive healthcare to mend both physical and psychological wounds. Collectively, the three crises changed how providers and patients viewed their experiences of clinical surveillance and altered their relationships to the violence of US healthcare. Drawing from two different research studies conducted during the years preceding and during the COVID-19 pandemic (2017-2022) with low income, safety net patients at risk for opioid overdose and their care providers, I analyze the relationship between surveillance and violence in light of changes wrought by these three intersecting health and social crises. I suggest that shifting perceptions about surveillance and violence contributed to clinical care innovations that offer greater patient autonomy and transform critical components of addiction medicine care practice.

BackgroundThis study evaluated the real-world impact of acupuncture on analgesics and healthcare resource utilization among breast cancer survivors.MethodsFrom a United States (US) commercial claims database (25% random sample of IQVIA PharMetrics® Plus for Academics), we selected 18-63 years old malignant breast cancer survivors experiencing pain and ≥ 1 year removed from cancer diagnosis. Using the difference-in-difference technique, annualized changes in analgesics [prevalence, rates of short-term (

BackgroundXylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence.MethodsFrom June-July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes.ResultsFrom interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a "tranquilizer-like substance" that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers' experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation.ConclusionsXylazine's emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.

BACKGROUND: Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch. OBJECTIVE: This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses. STUDY DESIGN: This is a randomized experimental study with a Latin square design. METHODS: Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 μg h-1 matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (TailTDP), metacarpus region (MetacarpusTDP), or gaskin region (GaskinTDP). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables. RESULTS: Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses (p > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml-1 when applied to the ventral aspect of the tail base. In the TailTDP group, the mean plasma buprenorphine concentrations were >0.1 ng ml-1 from 2 to 32 h. The highest group mean was 0.25 ng ml-1 noted at 4 h. CONCLUSIONS: The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.

INTRODUCTION: An increased incidence of maternal opioid use disorder (OUD) and neonatal abstinence syndrome (NAS) has prompted recommendations supporting a dyadic approach to care for birthing persons and their infants. However, there are no consensus guidelines outlining how the dyad is clinically defined. METHODS: To examine how the opioid-exposed birthing person-infant dyad has been defined for purposes of data collection and research, a literature review applying the RAND/UCLA Appropriateness Method was conducted. RESULTS: The search yielded 320 abstracts, with 110 articles identified as having a dyadic focus. While no articles included a specific definition for the dyad, 33 (30%) contained a descriptive reference to the birthing person-infant dyad. Thematic analysis revealed eight recurring elements characteristic of the dyad: (1) engagement, (2) communication, (3) bonding, (4) attachment, (5) mutual responsiveness, (6) reciprocity, (7) synchrony, and (8) attunement. Integrating these elements revealed the interactional relationship between the opioid-exposed birthing person and infant as the foundational principle that defines the dyad. DISCUSSION: This definition shifts the focus of the opioid-exposed dyad from two individual patient populations to an interactional relationship that has broad applicability for clinical use, public health data collection, and research considerations.

ObjectiveMany persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood.Method and participantsStudy participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time.ResultsHPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14.ConclusionsWorsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

BackgroundMortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered.MethodsWe conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: "clients" (individuals who use drugs and receive harm reduction services) and "providers" (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis.ResultsWe found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels.ConclusionThis study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.

BACKGROUND: Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization. OBJECTIVE: Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 μg h-1 and 40 μg h-1 dosing) in healthy adult horses. STUDY DESIGN: Randomised experimental study with a Latin-square design. METHODS: Six adult healthy horses received each of the three treatments with a minimum 10 day washout period. BUP0 horses did not receive a patch (control). BUP20 horses received one patch (20 μg h-1) applied on the ventral aspect of the tail base resulting in a dose of 0.03-0.04 μg kg-1 h-1. BUP40 horses received two patches placed alongside each other (40 μg h-1) on the tail base resulting in a dose of 0.07-0.09 μg kg-1 h-1. Whole blood samples (for determination of buprenorphine concentration), physiological variables and thermal threshold testing were performed before (0 h) and at 2, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, and 96 h after patch application. The patches were removed 72 h following placement and were analyzed for residual buprenorphine content. RESULTS: Between the three groups, there was no change in physiological variables across timepoints as compared to baseline (p > 0.1). With the higher dose, there was a significant increase in thermal thresholds from baseline values from 2 h until 48 h and these values were significantly higher than the group receiving the lower patch dose for multiple timepoints up to 40 h. 40 μg h-1 patch led to consistent measurable plasma concentrations starting at 2 h up to 96 h, with the mean plasma concentrations of > 0.1 ng/ml from 4 h to 40 h. CONCLUSIONS: 20 μg h-1 and 40 μg h-1 patch doses were well tolerated by all horses. At higher dose, plasma buprenorphine concentrations were more consistently measurable and blunted thermal thresholds for 48 h vs. 32 h with 20 μg h-1 dosing as compared to control.

BackgroundPersons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations.MethodsHPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization.DiscussionThis trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care.Trial registrationClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

OBJECTIVE: To examine variables associated with engagement in (1) integrative health and medicine (IHM) and (2) nonpharmacologic modalities rather than opioids among United States adults with chronic pain. METHODS: Using the 2019 National Health Interview Survey, we examined sociodemographic, pain, and mental health predictors of (1) the sum of IHM modalities (ie, chiropractic care, yoga/Tai Chi, massage, or meditation/guided imagery) used to manage pain and (2) exclusive engagement in nonpharmacologic pain management modalities (ie, IHM, a chronic pain self-management program, support groups, or physical, rehabilitative, occupational, or talk therapy) or opioids in the past 3 months. RESULTS: Metropolitan residency, higher family income, higher education levels, increased number of pain locations, and increased frequency of pain limiting life/work activities were associated with increased odds of IHM engagement. Older age, male sex, non-Hispanic Black/African American race/ethnicity, and daily opioid use were associated with decreased odds of IHM engagement. Older age, male sex, and increased depressive symptoms were associated with decreases in the count of IHM modalities used to manage pain. Metropolitan residency, higher family income, and higher education levels were associated with increased odds of exclusive nonpharmacologic modality engagement. Older age and increasing frequency of pain limiting life/work activities were associated with decreased odds of exclusive nonpharmacologic modality engagement. CONCLUSIONS: We identified several contrasts between factors prevalent among individuals with chronic pain and factors associated with engagement in nonpharmacologic and IHM modalities. These results support efforts to address barriers to accessing these modalities among subpopulations of adults with chronic pain (eg, older adults, individuals identifying as Black/African American, rural residents, and those with lower levels of education and income).

ObjectivesThe purpose of this study was to evaluate the impact of pharmacist-driven naloxone training of resident physicians as part of discharge prescribing from an inpatient psychiatric unit.MethodsThis is a prospective pilot study in which psychiatric resident physicians (N = 21) were educated on naloxone administration, prescribing, and counseling. A ten-question survey was designed and delivered immediately pre- and post-training to assess resident knowledge of and comfort with naloxone prescribing. Respondents were asked to rate ten statements on a scale from 1 to 5, with 1 corresponding to "strongly disagree" and 5 corresponding to "strongly agree." The primary objective was to evaluate the impact of training on prescriber knowledge and attitudes using the designed questionnaire. The secondary objective was to assess the difference in naloxone prescribing pre- and post-training implementation. Descriptive statistics and paired t-tests were conducted to assess statistical significance.ResultsPrior to training, 11 resident physicians (approximately 50%) agreed or strongly agreed that they felt knowledgeable about naloxone and approximately 70% (n = 15) felt confident identifying patients who would benefit from naloxone at discharge. Only 10% of resident physicians (n = 2) felt comfortable counseling patients on and administering naloxone during an overdose pre-training compared to 100% after training. Thirty-seven patients were discharged and counseled on naloxone use during the study period.ConclusionPharmacist-driven naloxone training significantly increased physician knowledge and comfort prescribing naloxone and resulted in an increase in naloxone prescriptions upon discharge from an inpatient psychiatric unit.

Background and Objectives: Risky substance use (RSU) is common among people with chronic pain and is associated with worse pain treatment outcomes. Nonopioid treatment is recommended, but it is unknown whether people with RSU use different or fewer pain treatment modalities. This study describes use of different pain treatments by veterans with and without RSU and those receiving versus not receiving opioid medication. Methods: Veterans (N = 924) who filed service‐connected disability claims related to musculoskeletal conditions and rated their pain four or higher on the Numeric Rating Scale, reported on 25 different pain services in the preceding 90 days. Recent RSU was identified via Alcohol, Smoking, and Substance Involvement Test (ASSIST) cutoffs and/or nail sample toxicology. Results: Overall, RSU was not associated with number of provider‐delivered or self‐delivered pain modalities. Over‐the‐counter medications (71%), self‐structured exercise (69%), and nonopioid prescription medications (38%) were the most used modalities. Veterans receiving prescribed opioids (8.4%) were more likely to see primary care, receive injections, and attend exercise and/or meditation classes, compared to those without opioid prescriptions. Discussion and Conclusions: Opioid and nonopioid pain treatment utilization did not differ based on RSU, and those prescribed opioids were more likely to engage in other nonopioid pain treatments. Regardless of RSU, veterans appear willing to try provider‐delivered (58%) and self‐delivered (79%) pain treatment. Scientific Significance: In this first‐ever evaluation of 25 different pain treatment modalities among veterans with and without RSU, people with RSU did not use less treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Treatment with opioids is a mainstay in perioperative pain management. While the leading treatment paradigm has been procedure‐specific pain management, efforts regarding personalized pain treatment are increasing. The OPI•AID project aims to develop personalized algorithms for perioperative pain management, taking demographic, surgical, and anaesthesiologic factors into account. We will undertake five parallel reviews to illuminate current evidence on different aspects of individual responses to perioperative opioid treatment. Methods: Inclusion of adult populations in English‐written studies. Review‐specific searches are developed for the following databases: CENTRAL, MEDLINE, Embase, clinicaltrials.gov, and clinicaltrial.eu. Two authors will independently screen citations, extract data, and assess the risks of bias in each review (QUIPS, PROBAST and RoB2, as relevant). Conclusion: These reviews will evaluate various aspects of perioperative opioid treatment, including individualized treatment strategies, selection of specific opioids, and individual patient responses. These will guide future development of a personalized perioperative opioid treatment algorithm (OPI•AID) that will be validated and tested clinically against standard of care. [ABSTRACT FROM AUTHOR]

Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Microglia display similar morphological responses in the spinal cord after peripheral nerve injury (PNI). Consistent with this observation, functional studies have suggested that microglia activated by opioids or PNI engage common molecular mechanisms to induce hypersensitivity. In this article, we conducted deep RNA sequencing (RNA-seq) and morphological analysis of spinal cord microglia in male mice to comprehensively interrogate transcriptional states and mechanistic commonality between multiple models of OIH and PNI. After PNI, we identify an early proliferative transcriptional event across models that precedes the upregulation of histological markers of microglial activation. However, we found no proliferative transcriptional response associated with opioid-induced microglial activation, consistent with histological data, indicating that the number of microglia remains stable during morphine treatment, whereas their morphological response differs from PNI models. Collectively, these results establish the diversity of pain-associated microglial transcriptomic responses and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other central nervous system pathologies. [ABSTRACT FROM AUTHOR]

Many medications commonly used to treat neuropathic pain are associated with significant, dose-limiting adverse effects, including sedation, dizziness, and fatigue. These adverse effects are due to the activity of these medications within the central nervous system. The objective of this work was to investigate the interactions between peripherally restricted cannabinoid receptor and mu-opioid receptor (MOR) agonists on ongoing and evoked neuropathic pain behaviors in mouse models. RNAscope analysis of cannabinoid receptor type 1 (CB1R) and MOR mRNA demonstrated that the mRNA of both receptors is colocalized in both mouse and human dorsal root ganglion. Single-cell RNAseq of dorsal root ganglion from chronic constriction injury mice showed that the mRNA of both receptors (Cnr1 and Oprm1) is coexpressed across different neuron clusters. MycCB1R and FLAG-MOR were cotransfected into immortalized HEK-293T cells and were found to interact at a subcellular level. We also find that CB-13 (a peripherally restricted dual CB1R and cannabinoid receptor type 2 agonist) and DALDA (a peripherally restricted MOR agonist) both attenuate mechanical hypersensitivity in a murine model of neuropathic pain. Using isobolographic analysis, we demonstrate that when coadministered, these agents synergistically attenuate mechanical hypersensitivity. Importantly, combination dosing of these agents does not cause any detectable preferential behaviors or motor impairment. However, repeated dosing of these agents is associated with the development of tolerance to these drugs. Collectively, these findings suggest that leveraging synergistic pain inhibition between cannabinoid receptor and MOR agonists in peripheral sensory neurons may be worth examining in patients with neuropathic pain. [ABSTRACT FROM AUTHOR]

Given the high rates of physical trauma and pain among service members, opioid-prescribing practices and use patterns have significant implications for the well-being of service members and can affect military medicine and personnel readiness. This study measured the association between prescribed opioid and benzodiazepine medications and subsequently reported injuries (accidental, alcohol and drug related, self-inflicted, and violence related) among active duty military members. Participants were service members who entered the military between January 1, 2005, and June 30, 2010. In a nested case–control design, we compared individuals with injuries to individuals without injuries with respect to their opioid and benzodiazepine prescriptions in the 30 days before the injury of an index case. We used a multiintercept, logistic regression model to compare coefficient estimates by injury type. Overall, approximately 17% of individuals with an injury and 4% of individuals without an injury had a recorded opioid prescription. Individuals with an injury of any type had greater odds of prior exposure to opioid prescriptions than controls. Although a dose–response effect was observed for all injury types, it reached a plateau sooner for natural or environmental accidents and selfinflicted injuries relative to alcohol-related and drug-related injuries, violence-related injuries, vehicle accidents, accidental falls, and other accidents. Benzodiazepine prescriptions were found in 3.5% of individuals with an injury and 0.5% of individuals without an injury. The association between benzodiazepine prescriptions and injuries was strongest for natural and environmental accidents. [ABSTRACT FROM AUTHOR]

This article discusses the controversy surrounding pre-operative opioid tapering and its potential to advance personalized, patient-centered pain medicine. The use of opioids for chronic non-cancer pain management is common, but it is associated with negative outcomes in the peri-operative period, such as respiratory failure and surgical site infections. The article presents the findings of a pilot study that assessed the feasibility of a pharmacist-led opioid tapering program before elective hip or knee arthroplasty. The study found high adherence to the program and positive outcomes in terms of physical functioning and quality of life. However, the study has limitations, and further research is needed to determine the effectiveness of pre-operative opioid tapering in a broader patient population. [Extracted from the article]

This systematic review and meta-analysis aimed to inventory all outcome measures that are affected by tapering in chronic noncancer pain and to investigate the effectiveness of tapering. A literature search was conducted from inception to April 2024 in MEDLINE via PubMed, Web of Science, SCOPUS, EMBASE, and PsycINFO. The initial database search identified 3969 articles, which were screened by two independent reviewers. Studies evaluating pain medication tapering in adults with chronic noncancer pain were eligible for inclusion. In total, 57 and 34 articles were included in the systematic review and meta-analysis, respectively. Risk of bias assessment demonstrated poor, fair, and good quality in 30, 24, and three studies, respectively. Pain intensity was the most reported outcome measure, as reported in 28 studies. Furthermore, a random-effect three-level meta-analysis was performed. An overall effect size of 0.917 (95% confidence interval 0.61–1.22; P <0.001) was found, indicating a beneficial effect of tapering. In addition, a statistically significant improvement was demonstrated after tapering for pain intensity, headache disability, the number of headache days per month, anxiety, depression, the number of pills consumed per month, the number of days with medication intake per month, pain catastrophising, and pain interference. No statistically significant effect was observed for physical functioning, mental health-related quality of life, opioid use, pain self-efficacy, and physical health-related quality of life. This systematic review revealed a broad range of outcome measures affected by tapering. Owing to the high risk of bias of the included articles, the results of this meta-analysis must be interpreted with caution. CRD42023416343 (PROSPERO). [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy (AC) for colorectal cancer (CRC) has led to substantial improvement in survival. Several clinical trials advocate the initiation of AC within 6-8 weeks of surgical resection based on evidence of improved survival with early initiation of AC. We aim to evaluate factors that predict initiation and completion of AC, subsequently improving survival. Methods: We identified 451 patients who underwent resection for CRC between 2014 and 2022. One hundred ten patients had stage II/III colorectal cancer who underwent resection followed by AC. Multivariable logistic regression analysis was performed to identify factors significantly predicting delay in AC >8 weeks. Secondary outcomes included chemotherapy completion rate, recurrence-free survival, and overall survival. Results: The final analysis included 110 patients. The median time to initiation of adjuvant chemotherapy (TIAC) was 6.9 weeks (IQR: 5.8-9.5). In total, 36.4% of patients had a delay >8 weeks to initiation of AC, and only 40% completed treatment. The surgical approach (open vs laparoscopic vs robotic) had no effect on the TIAC. On multivariable logistic regression analysis, preoperative albumin ≥3.5 (OR = .31; 95% CI: .12-.80) was an independent predictor of timely initiation of AC. Completion of AC was associated with a higher overall survival. Discussion: Preoperative nutritional status predicted delay in initiation of AC. Patients with a delay in AC beyond eight weeks had a lower rate of AC completions and worse survival. It is imperative to optimize this aspect of treatment as it correlates with survival. [ABSTRACT FROM AUTHOR]

Introduction: This quality improvement initiative is a continued pursuit to optimize outcomes by iteratively improving our opioid sparing anesthesia protocol for tonsillectomy with or without adenoidectomy at our pediatric ambulatory surgical center through data driven Plan‐Do‐Study‐Act cycles. Methods: From 1/2015 through 12/2023, our standardized tonsillectomy protocol underwent nine procedure‐specific perioperative Plan‐Do‐Study‐Act cycles, three procedure‐specific postoperative prescription Plan‐Do‐Study‐Act cycles, and four general ambulatory surgical center enhanced recovery Plan‐Do‐Study‐Act cycles. We analyzed data from the medical record using statistical process control charts. The primary outcome measure was the percent of patients requiring intravenous opioid in the post anesthesia care unit. Secondary outcomes included maximum post anesthesia care unit pain score, the percent of patients requiring treatment for nausea and/or vomiting in the post anesthesia care unit, and the number of postoperative opioid prescription dosages. Balancing measures were average post anesthesia care unit length of stay, percent of patients with prolonged Post Anesthesia Care Unit length of stay (>120 min), and 30‐day reoperation rate. Results: A total of 5654 tonsillectomy with or without adenoidectomy cases were performed at our ambulatory surgical center from 2015 to 2023. The incidence of intravenous opioid administered in the post anesthesia care unit initially rose with opioid free anesthesia launch, but subsequently decreased below the target of 10%. Maximum post anesthesia care unit pain scores rose from mean 3.6 to 4.5, but subsequently returned to the baseline of 3.5, while the incidence of postoperative nausea and/or vomiting improved. The average post anesthesia care unit length of stay increased by 10 min with opioid free anesthesia; however, prolonged post anesthesia care unit stay and 30‐day reoperation rates were unchanged. Conclusions: The continued refinement of our opioid sparing anesthesia protocol has led to reduced perioperative and home opioid use, stable maximum post anesthesia care unit pain scores, and improved postoperative nausea and vomiting rates, with only a slight increase in mean post anesthesia care unit length of stay. [ABSTRACT FROM AUTHOR]

Deaths due to unintentional opioid overdose among youth living in the United States have risen at an extraordinary rate over the past 4 years.1 After remaining stable over the preceding decade, the rate of drug overdose deaths increased more than 2.3-fold from 2019 to 2021 to a record high of 5.49 deaths per 100,000 youth.1 This rise in fatal overdoses is largely due to increased prevalence of illicitly manufactured fentanyl in the drug supply. In 2021, fentanyl was identified in 77.1% of overdose deaths among US adolescents, a 23.5-fold increase from 2010, compared to 13.3% for benzodiazepines, 5.8% for prescription opioids, and 2.3% for heroin.1 Compared to other phases of the opioid crisis, fentanyl-related overdoses are characterized by extraordinarily broad geographic and sociodemographic reach. [ABSTRACT FROM AUTHOR]

Understanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated 1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC) and 2) how such effects are related to gene expression and receptor maps. Across 115 participants (37 control, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task. Using partial least squares regression, we investigated genes whose expression in the Allen Human Brain Atlas was associated with anatomical patterns of stress-related FC change. Finally, we correlated stress-related FC change maps with opioid and GABA A (gamma-aminobutyric acid A) receptor distribution maps derived from positron emission tomography. Results revealed robust effects of stress on global cortical connectivity, with increased global FC in frontoparietal and attentional networks and decreased global FC in the medial default mode network. Moreover, robust increases emerged in FC of the caudate, putamen, and amygdala with regions from the ventral attention/salience network, frontoparietal network, and motor networks. Such regions showed preferential expression of genes involved in cell-to-cell signaling (OPRM1 , OPRK1 , SST , GABRA3 , GABRA5), similar to previous genetic MDD studies. Acute stress altered global cortical connectivity and increased striatal connectivity with cortical regions that express genes that have previously been associated with imaging abnormalities in MDD and are rich in μ and κ opioid receptors. These findings point to overlapping circuitry underlying stress response, reward, and MDD. [ABSTRACT FROM AUTHOR]

Addictive, illicit drugs pose a high threat of relapse. The deaths related to illicit drugs have substantially increased in the last decade. Globally, the illicit drug trade poses a significant challenge to public health and law enforcement. It is essential to utilize advanced analytical methodologies that can characterize illegal substances precisely to monitor these drugs. Surfaced-enhanced Raman spectroscopy (SERS) has become a valuable tool, providing distinct capabilities for analyzing illegal substances. Surface enhancement enables far more sensitive detection and identification of illicit drugs by suppressing the fluorescence and enhancing the Raman signals. In this regard, a simple method with limited sample processing has been established to characterize illicit drugs that include methamphetamine (MAMP) (ice), bhang, marijuana (cannabis), opium, and diacetylmorphine (heroin). Moreover, principal component analysis (PCA) was employed for the identification of the characteristic SERS spectral features of these drugs. This article examines the potential application of SERS in the characterization of illicit substances, focusing on its ability to contribute significantly to law enforcement and forensic investigation. [ABSTRACT FROM AUTHOR]

Headaches are a common condition seen in the Emergency Department (ED), with numerous trials focused on improving care for these patients. However, there is limited recent large-scale, robust data available on the incidence, admission rates, evaluation, and treatment in the ED setting. This was a cross-sectional study of ED presentations for headache from 1/1/2016 to 12/31/2023 using the Epic Cosmos national database. All ED visits with headache-relevant ICD-10 coding were included. Outcomes included percentage of total ED visits, admission rates, computed tomography (CT) brain imaging, lumbar puncture (LP) performance, and medication administration. Medications were analyzed by class (NSAIDs, acetaminophen, dopamine antagonists, diphenhydramine, opioids, intravenous fluids, caffeine, and magnesium sulfate). Subgroup analyses were performed by specific types of dopamine antagonists. Of 188,482,644 ED encounters, 6,007,090 (3.2%) were due to headache. Of these, 246,082 (4.1%) were admitted. Nearly half (46.6%) of patients received at least one CT. Rates of CT head without contrast increased from 38.2% to 47.9% over time, while rates of CT angiography rose from 2.8% to 10.2%. 1.4% of all patients received an LP, with rates decreasing from 1.8% to 1.1% over time. The most common medication was NSAIDs (45.3%), followed by dopamine antagonists (44.8%), diphenhydramine (38.1%), acetaminophen (24.8%), opioids (16.3%), magnesium sulfate (0.2%), and caffeine (0.1%). 50.8% of patients received intravenous fluids. Rates of opioids declined over time, while dopamine antagonists, acetaminophen, and intravenous fluid administration increased. Headaches represent a common reason for ED presentation, with approximately 4% of patients being admitted. Imaging is frequently performed, with rises in CT without contrast and CT angiography rates over time, while LP rates have been declining. NSAIDs remain the most common medication given, with opioids declining over time while non-opioid agents such as dopamine antagonists have increased. These findings can help inform health policy initiatives, such as those focused on radiologic imaging and evidence-based medication administration. [ABSTRACT FROM AUTHOR]

Background: Machine learning (ML) has emerged as a method to determine patient-specific risk for prolonged postoperative opioid use after orthopedic procedures. Purpose: We sought to analyze the efficacy and validity of ML algorithms in identifying patients who are at high risk for prolonged opioid use following orthopedic procedures. Methods: PubMed, EMBASE, and Web of Science Core Collection databases were queried for articles published prior to August 2021 for articles applying ML to predict prolonged postoperative opioid use following orthopedic surgeries. Features pertaining to patient demographics, surgical procedures, and ML algorithm performance were analyzed. Results: Ten studies met inclusion criteria: 4 spine, 3 knee, and 3 hip. Studies reported postoperative opioid use over 30 to 365 days and varied in defining prolonged use. Prolonged postsurgical opioid use frequency ranged from 4.3% to 40.9%. C-statistics for spine studies ranged from 0.70 to 0.81; for knee studies, 0.75 to 0.77; and for hip studies, 0.71 to 0.77. Brier scores for spine studies ranged from 0.039 to 0.076; for knee, 0.01 to 0.124; and for hip, 0.052 to 0.21. Seven articles reported calibration intercept (range: –0.02 to 0.16) and calibration slope (range: 0.88 to 1.08). Nine articles included a decision curve analysis. No investigations performed external validation. Thematic predictors of prolonged postoperative opioid use were preoperative opioid, benzodiazepine, or antidepressant use and extremes of age depending on procedure population. Conclusions: This systematic review found that ML algorithms created to predict risk for prolonged postoperative opioid use in orthopedic surgery patients demonstrate good discriminatory performance. The frequency and predictive features of prolonged postoperative opioid use identified were consistent with existing literature, although algorithms remain limited by a lack of external validation and imperfect adherence to predictive modeling guidelines. [ABSTRACT FROM AUTHOR]

The opioid epidemic has had a strong impact on West Virginia, due to various social, economic, cultural, and environmental hardships. To aid users, Needle Exchange Programs (NEPs) were created to exchange used needles for new sterile ones and provide awareness of treatment and rehabilitation options. This study aimed to assess the effectiveness of NEPs in reducing HIV and Hepatitis C infections in West Virginia, and the subsequent decrease in healthcare costs. In 2018 and 2019, there was an HIV outbreak in Cabell County, with 85 cases requiring CDC intervention in 2019. This occurred after the county-run needle exchange was reduced. Kanawha County also shut down its NEPs in 2018, followed by another HIV outbreak between 1 January 2019 and 13 March 2021, with 65 people testing positive for HIV linked to injection drug use, which required CDC intervention. To rehabilitate the opioid addict population, research on relapse, quality of life, social inclusion, stable housing, habilitation, and treatment adherence should be conducted. Policymakers should also revise existing policies surrounding the provision of harm reduction services to document adequate procedures for SSP procedures. This research suggests that suspending and scaling down NEPs in West Virginia has increased HIV/HCV incidence. [ABSTRACT FROM AUTHOR]

Background: Long‐term opioid use is related to numerous harms and has uncertain efficacy for chronic, non‐cancer pain. Identification of individuals at risk for long‐term opioid use can help support treatment decisions. The aim of this study was to determine psychosocial factors associated with opioid use 6 months after a work‐related injury. Methods: This was a prospective observational cohort study incorporating surveys and administrative data. Eligibility included a workers' compensation claim for an injury between June 2019 and September 2021, no opioid use within 3 months before injury, and opioid use within 6 weeks after injury. The outcome was self‐reported opioid use at the 6‐month follow‐up survey (no use, use some days, or use most or every day). Multinomial logistic regression models were used to calculate relative risk ratios (RRRs) for associations between self‐reported psychosocial factors and long‐term opioid use. Results: Of the 1724 respondents, 301 (17.5%) reported taking long‐term opioids on some days and 87 (5.0%) reported taking long‐term opioids on most or every day. After adjustment for sociodemographic and clinical covariates, workers reporting work fear‐avoidance had a higher relative risk of opioid use most or every day, versus no opioid use at the 6‐month survey, compared to those without work fear‐avoidance (RRR = 1.95, 95% CI = 1.08, 3.50). Anxiety symptoms, depression symptoms, and recovery expectations were not associated with long‐term opioid use after covariate adjustment. Conclusions: Work fear‐avoidance was associated with long‐term opioid use in this study of injured workers. Addressing fears surrounding an injury and returning to work may help deter reliance on long‐term opioids. [ABSTRACT FROM AUTHOR]

Background and aims Design Setting Participants Measurements Findings Conclusions Involuntary civil commitment (ICC) is a legal process by which people are compulsorily admitted to substance use treatment. This study explored views about and promotion of ICC procedures for substance use disorders among public health‐public safety post‐overdose outreach programs and their outreach team members in Massachusetts, USA.In this mixed‐methods study, survey data were collected from post‐overdose outreach programs in 2019, and semi‐structured interviews were conducted with outreach team members in 2019 and 2020.Massachusetts, USA.We received 138 survey responses and conducted 38 interviews with post‐overdose outreach team members (law enforcement officers, recovery coaches, social workers and harm reductionists) who were majority male (57%) and white (66%).We used the survey instrument to categorize programs as more (discussed ICC at 50% or more of outreach encounters) or less ICC focused (discussed ICC at less than 50% of outreach encounters) and to identify program characteristics that corresponded with each categorization. Semi‐structured interviews explored staff perceptions of ICC effectiveness.Among 138 programs, 36% (n = 50) discussed ICC at 50% or more of outreach encounters. Discussing ICC at a majority of visits was positively associated with abstinence‐only program philosophies (36% v. 6%, P < 0.001) and collaborating with drug courts (60% v. 30%, P < 0.001), but negatively associated with naloxone distribution (48% v. 75%, P < 0.001) and referring to syringe service programs (26% v. 65%, P < 0.001). Qualitative interviews identified three themes: 1) some programs viewed ICC as a first line tool to engage overdose survivors in treatment; 2) other programs considered ICC a last resort, skeptical of its benefits and concerned about potential harms; 3) families commonly initiated discussions about ICC, reportedly out of desperation.Promotion of involuntary civil commitment (ICC) appears to vary widely across post‐overdose outreach programs in Massachusetts, USA, with approaches ranging from seeing it as a first step to treatment to being a tool of last resort. Demand for ICC among family members may relate to inadequate access to voluntary treatment. Family interest in ICC appears to be driven by inadequate availability of treatment and other services. ICC at post‐overdose outreach visits should be limited, if used at all. [ABSTRACT FROM AUTHOR]

Background: The utilization patterns of opioid analgesics and the proportion of long-term opioid use after surgery in Norway is largely unknown. Methods: This study aimed to estimate the proportion of one-year long-term prescription opioid use among all Norwegian postoperative opioid users. Complete data from central health registries (NPR, NorPD, Statistics Norway, CoDR) were linked via the personal identification number unique to all citizens. The study period was January 1st 2010 until December 31st 2019. Long-term opioid use was defined as at least two opioid dispensings within two subsequent 90-day periods, with a minimum average use of 10 MME/day for the first 90 days. Results: The study population consisted of 693 495 post-operative opioid users (53.6% women), whereof 73.2% had not used opioids the year before surgery (new users). Among the postoperative opioid users, 3.8% were one-year long-term opioid users. The corresponding figures for new and previous opioid users were 0.4% and 13.1%, respectively. The highest proportions of long-term opioid use were found after transluminal endoscopy, eye surgery and assessments related to surgical procedures. In previous opioid users, the proportion of one-year long-term use was higher among women than men in all age groups, a difference that increased with age. Conclusions: The proportion of postoperative long-term opioid use in Norway is generally low. We detected higher proportions of long-term opioid use after certain types of surgery, but our crude surgery definition warrants further examination. Previous opioid users pose a particular challenge in the management of postoperative pain. Trial registration: The study used national health registry data from the period 2010–2019. A pre-registered analysis plan is available at Open Science Framework. [ABSTRACT FROM AUTHOR]

Aims Design Setting Participants Measurements Findings Conclusions To understand how the US public defines recovery from opioid misuse and the recovery‐related resources it views as most helpful, and to compare differences by opioid misuse history and demographic characteristics.Observational study of data from the nationally representative AmeriSpeak® Panel survey administered in October/November 2021.United States.6515 adults (≥ 18 years).Respondents ranked 10 definitions of recovery (religious in nature; spiritual in nature; physical/mental in nature; contributing to society; enhanced quality of life; seeking professional help; having a sense of purpose; moderate/controlled substance use; no drug use; abstaining from all substance use) and 9 resources that might contribute to recovery (primary care physician; intensive inpatient program; residential rehabilitation program; self‐help group; therapist/psychologist/social worker; prescribed medication; talking to family/friends; spiritual/natural healer; faith‐based organization). We explored differences in rankings by opioid misuse history (personal vs. family/friend vs. no history) and demographic characteristics (race, sex, age) using multivariable ordinal logistic regression.Seeking professional help was the most endorsed recovery definition overall [mean (M) = 6.97, standard error (SE) = 0.03]. Those with personal opioid misuse history ranked enhanced quality of life (B = 0.16, P = 0.049) and having a sense of purpose (B = 0.16, P = 0.029) significantly higher, and ranked abstaining from substance use (B = ‐0.20, P = 0.009) significantly lower as recovery definitions than those without a history of opioid misuse. Compared with White respondents, Black (B = 0.60, P < 0.001) and Hispanic (B = 0.55, P < 0.001) respondents defined recovery as more religious in nature. Residential rehabilitation program was identified as the most helpful resource for recovery (M = 7.16, SE = 0.02), while prescribed medication received a relatively low ranking overall (M = 4.05, SE = 0.03). Those with family/friend opioid misuse history ranked prescribed medication as less helpful than others (B = ‐0.14, P = 0.003).The general US public's views around recovery from opioid misuse appear to focus on abstinence and formal treatment receipt, while people with a history of opioid misuse place less emphasis on abstinence and greater emphasis on other aspects of well‐being. [ABSTRACT FROM AUTHOR]

Introduction: Effective adjunctive therapeutic treatments for patients with opioid use disorder (OUD) on medication for OUD (MOUD) in primary care settings are needed to address high rates of mental illness and stress. Behavioral activation (BA) is a brief, evidence-based therapy that has potential to improve quality of life in people with OUD. The purpose of this pilot study was to evaluate the feasibility and acceptability of values-based BA (VBA) as an adjunct treatment for patients receiving MOUD in primary care. Methods: Participants were recruited for a single-arm pilot trial of BA in a primary care setting. VBA was adapted for people with OUD and included 4-6 sessions delivered over 12 weeks with a behavioral health consultant, either inperson or virtually. Feasibility was assessed as recruitment percent and pace and retention percent. Acceptability was assessed with the Client Satisfaction Questionnaire-8 (CSQ-8). Participants completed self-report measures of well-being, depression, substance use, and psychological processes of change at baseline, mid-intervention (6-weeks), and post-intervention (12-weeks). Participants engaged in a brief interview about their experiences at the end of the intervention. Results: Twenty-one participants enrolled in the intervention (66.7% female, M age = 44.0 years, 19% of those invited). Participants completed an average of 5.1 BA sessions (SD = 1.6) and most (90%) were retained through 12 weeks. Participants rated the intervention as highly acceptable on the CSQ-8 (M = 30.4/32.0, SD = 1.6). In qualitative interviews, participants reported that working with the therapist and setting values-based goals were helpful, while also recommending more tailoring to patients' needs and offering the program early in MOUD treatment. Preliminary efficacy data suggest the program was associated with small to moderate improvements in life satisfaction (Cohen's d = 0.25) and positive affect (d = 0.62), whereas there were no changes in depression (d = 0.09) or negative affect (d = -0.07) in a group with low depression at baseline. Discussion: VBA adapted for patients on MOUD in primary care was feasible to deliver and acceptable to participants. Minor modifications to the target population and treatment manual could increase the program's impact. Future studies will test the efficacy of the intervention in improving quality of life and OUD treatment outcomes. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The anterior quadratus lumborum (QL) block may be used for postoperative pain management for intra‐abdominal surgeries, but the evidence is uncertain. We aimed to investigate the benefit and harm of the anterior QL block compared to placebo/no block for intra‐abdominal surgery.We searched Medline, Embase, and CENTRAL for randomized controlled trials investigating anterior QL block for postoperative pain management for adult patients undergoing any intra‐abdominal surgery. The two co‐primary outcomes were cumulative 24‐h opioid consumption and serious adverse events. We performed meta‐analysis, trial sequential analysis (TSA), assessed the risk of bias, and present the certainty of evidence with the Grading of Recommendations, Assessment, Development and Evaluation approach.Thirty‐five trials randomizing 2418 patients were included in the meta‐analyses. Anterior QL block may reduce cumulative 24‐h intravenous opioid consumption compared to placebo/no block (MD −10.42 mg, 96.7% CI −14.83 to −6.01, TSA‐adjusted CI −17.03 to −3.82, p < .01). Two trials reported on SAEs. Anterior QL block may have little to no effect on the number of serious adverse events compared to placebo (RR 1.49, 96.7% CI 0.19 to 11.47, p = .68), but the evidence is very uncertain. All trial results were assessed as being high risk of bias.The anterior QL block may reduce cumulative 24‐h opioid consumption. Reported serious adverse events were few and the anterior QL block may have little to no effect on the number of SAEs, but the evidence was very uncertain. [ABSTRACT FROM AUTHOR]