Methadone Withdrawal-Induced Psychosis: A Case Report.

Methadone is a synthetic full µ-opioid receptor agonist and N-methyl-D-aspartate antagonist given to patients who have recently stopped using illicit opioids or are tapering off chronic opioid pain medication. Maintenance treatment with methadone is today the most widespread and effective way to treat opiate addiction, which achieves abstinence, decreases morbidity and mortality, improves quality of life, and reduces crime genesis, among other benefits. It is also approved by the Food and Drug Administration for treating moderate-to-severe pain that remains unresponsive to nonopioid medications. Patients sometimes abruptly discontinue the medication for several reasons and sometimes suffer distressing but non-life-threatening withdrawal symptoms. More common withdrawal symptoms include anxiety, agitation, rhinorrhea, nausea, and vomiting, like other opioid agonist medications. Psychosis has been reported in some rare cases of methadone withdrawal. However, more research is required because, although psychotic symptoms have been described in different case reports after the reduction or withdrawal of methadone, they have not been sufficient. This case report contributes to the literature on rare manifestations of psychosis in patients who abruptly discontinue the use of methadone.

The Relationship Between Preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Pain Intensity Scores and Early Postoperative Pain and Opioid Consumption After Lumbar Fusion.

Background The Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and pain intensity measures quantify separate dimensions of pain from the patient's perspective. This study aimed to assess differences in these outcomes and to evaluate whether baseline PROMIS pain scores could be used as a leading indicator of increased pain and opioid consumption during early recovery after lumbar fusion. Methods A retrospective review of 199 consecutive patients undergoing posterolateral fusion (PLF) at a single institution was performed. All patients underwent one to three level lumbar PLF and preoperatively completed the PROMIS pain intensity and PROMIS pain interference measures. Multivariate linear regression was used to assess the relationship between preoperative PROMIS scores and postoperative pain numeric rating scale (NRS) and oral morphine milligram equivalents (OMME) by day after controlling for age, sex, and body mass index (BMI). Results In comparison to patients with the lowest preoperative pain intensity scores, those with the highest scores required significantly more OMME on postoperative day (POD) zero and one (both p<0.05) and had higher pain NRS on POD one (p=0.02). Patients with the highest pain interference scores reported higher pain NRS on POD zero (p=0.02) but required similar OMME at all time points. After controlling for age, sex, and BMI, each one-point increase in preoperative PROMIS pain interference scores was associated with increased OMME on POD zero (ß=0.29, p=0.04) and POD one (ß=0.64, p=0.03). Conclusions Patients with high pain intensity reported higher levels of pain and required more opioids during the first 24 hours postoperatively, while those with high pain interference reported higher levels of pain on the day of surgery but utilized similar amounts of opioids. After risk adjustment, increased baseline PROMIS pain interference scores - but not pain intensity - were associated with increased opioid use. These results suggest that both measures should be considered when identifying patients at risk for increased pain and opioid consumption after PLF.

Nalmefene, an opioid receptor modulator, aggravates atherosclerotic plaque formation in apolipoprotein E knockout mice by enhancing oxidized low-density lipoprotein uptake in macrophages.

Nalmefene, an antagonist of mu- and delta-opioid receptors and a partial agonist of kappa-opioid receptors, has shown promise in reducing alcohol consumption among patients with alcohol dependence. Opioid receptors play pivotal roles in various physiological processes, including those related to peripheral inflammatory diseases such as colitis and arthritis, as well as functions in the immune system and phagocytosis. Atherosclerosis, a chronic inflammatory disease, progresses through the phagocytosis and uptake of oxidized low-density lipoprotein (oxLDL) by macrophages in atherosclerotic plaques. Despite this knowledge, it remains unclear whether nalmefene influences the formation of atherosclerotic plaques and increases the risk of serious cardiovascular events. This study aims to elucidate the impact of nalmefene on atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and peritoneal macrophages in vitro. In this experiment, 8-week-old male ApoE KO mice were fed a high-fat diet intraperitoneally administered either vehicle (saline) or nalmefene (1 mg and 3 mg kg-1 day-1) for 21 days. Oil red O-staining and immunohistochemistry with an anti-MOMA2 (monocyte/macrophage) antibody showed that a dose-dependent increase in atherosclerotic plaque formation and augmentation of macrophage-rich plaque formation in ApoE-KO mice. Further investigations focused on the effects of nalmefene on the expression of scavenger receptor CD36 in RAW264.7 cells, conducted through western blotting analysis. Nalmefene demonstrated a significant increase in CD36 protein expression in RAW264.7 cells. To explore the impact on oxidized LDL uptake in peritoneal macrophages, cells were treated with nalmefene (300 µg/mL) for 24 h, followed by the addition of DiI-labeled oxLDL (DiI-oxLDL) for 4 h. Nalmefene significantly enhanced DiI-oxLDL uptake in macrophages. Additionally, treatment with nalmefene (300 µg/mL) for 24 h decreased the mRNA expression of mu-, delta-, and kappa-opioid receptors in RAW264.7 cells. In conclusion, nalmefene may augment oxLDL uptake by macrophages through increased CD36 expression and decreased opioid receptor, thereby contributing to atherosclerotic plaque formation and vulnerability. Consequently, the use of nalmefene may be associated with an elevated risk of cardiovascular events.

Two-year Opioid Prescription Trends in Local Sanitary Agency Naples 3 South, Campania Region, Italy. Descriptive Analyses and AI-based Translational Perspectives.

Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.

Frontline Perspectives on Buprenorphine for the Management of Chronic Pain.

Due to the prevalence of chronic pain and high-impact chronic pain in the US, a significant percentage of the population is prescribed opioids for pain management. However, opioid use disorder is associated with reduced quality of life, along with fatal opioid overdoses, and is a significant burden on the US economy. Considering the clinical needs of patients with intractable chronic pain and the potential harms associated with prescribed and illicit opioids in our communities, having a deep understanding of current treatment options, supporting evidence, and clinical practice guidelines is essential for optimizing treatment selections. Buprenorphine is a Schedule III opioid with a unique mechanism of action, allowing effective and long-lasting analgesia at microgram doses with fewer negative side effects and adverse events, including respiratory depression, when compared with other immediate-release, long-acting, and extended-release prescription opioids. Due to its relatively lower risk for overdose and misuse, buprenorphine was recently added to the Clinical Practice Guideline for the Use of Opioids in the Management of Chronic Pain as a first-line treatment for chronic pain managed by opioids by the US Departments of Defense and Veterans Affairs, and the Department of Health and Human Services recommends that buprenorphine be made available for the treatment of chronic pain. In this narrative review, we discuss the different buprenorphine formulations, clinical efficacy, advantages for older adults and other special populations, clinical practice guideline recommendations, and payer considerations of buprenorphine and suggest that buprenorphine products approved for chronic pain should be considered as a first-line treatment for this indication.

Predictors of persistent opioid use in bladder cancer patients undergoing radical cystectomy: A SEER-Medicare analysis.

PURPOSE: To evaluate patient and provider characteristics that predict persistent opioid use following radical cystectomy for bladder cancer including non-opioid naïve patients. METHODS: Patients undergoing cystectomy between July 2007 and December 2015 were identified using the SEER-Medicare database. Opioid exposure was identified before and after cystectomy using Medicare Part D data. Multivariable analyses were used to identify predictors of the primary outcomes: persistent opioid use (prescription 3-6 months after surgery) and postoperative opioid prescriptions (within 30 days of surgery). Secondary outcomes included physician prescribing practices and rates of persistent opioid use in their patient cohorts. RESULTS: A total of 1,774 patients were included; 29% had prior opioid exposure. Compared to opioid-naïve patients, non-opioid naïve patients were more frequently younger, Black, and living in less educated communities. The percentage of persistent postoperative use was 10% overall and 24% in non-opioid naïve patients. Adjusting for patient factors, opioid naïve individuals were less likely to develop persistent use (OR 0.23) while a 50-unit increase in oral morphine equivalent per day prescribed following surgery nearly doubled the likelihood of persistent use (OR 1.98). Practice factors such as hospital size, teaching affiliation, and hospital ownership failed to predict persistent use. 29% of patients filled an opioid prescription postoperatively. Opioid naïve patients (OR 0.13) and those cared for at government hospitals (OR 0.59) were less likely to fill an opioid script along with those residing in the Northeast. Variability between physicians was seen in prescribing practices and rates of persistent use. CONCLUSIONS: Non-opioid naïve patients have higher rates of post-operative opioid prescription than opioid-naïve patients. Physician prescribing practices play a role in persistent use, as initial prescription amount predicts persistent use even in non-opioid naïve patients. Significant physician variation in both prescribing practices and rates of persistent use suggest a role for standardizing practices.

Detecting DSM-5 Opioid and Methamphetamine Use Disorders With the UNCOPE Screen.

BACKGROUND: The most recent wave of the opioid epidemic has contributed to record number of drug overdoses. Most fatal outcomes are associated with opioids and methamphetamine; two substances that tend to be used at high rates among criminal justice populations. Despite the steady rise in the number of overdoses in local detention centers, many correctional facilities do not conduct routine screens for opioid and methamphetamine use disorders. This study examines the utility of the UNCOPE, a 6-item brief screen, to detect probable Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) diagnoses for these 2 specific substance use disorders (SUDs). The study also examines key indicators of these specific SUDs. METHODS: Data were collected from comprehensive substance use assessments conducted with 717 adults who were recently admitted to 4 county jails. RESULTS: Findings indicate that 3 positive UNCOPE responses accurately detected 99.8% of opioid use disorder diagnoses and 98.7% of methamphetamine use disorder diagnoses. Receiver operating characteristic curve results generate an area under the curve at 0.99 for severe opioid use cases and 0.98 for severe methamphetamine use cases. Subsequent analyses indicate 2 of the 6 items on the UNCOPE function to accurately identify 100% of cases classified with opioid use disorder and 99.6% of cases classified with methamphetamine use disorder. CONCLUSIONS: Evidence suggests that UNCOPE is a practical and efficient approach to identifying opioid and methamphetamine use disorders. In addition, 2 items can serve as an ultra-brief method to detecting these conditions at the time of admission to detention centers.

"To prescribe or not to prescribe, that is the question": Perspectives on opioid prescribing for chronic, cancer-related pain from clinicians who treat pain in survivorship.

BACKGROUND: Opioid pain management in cancer survivorship is a complex and understudied topic. METHODS: The authors conducted in-depth, qualitative interviews to understand clinician approaches to opioid pain management in chronic cancer pain and to generate ideas for improvement. They used a rigorous, inductive, qualitative, descriptive approach to examine clinician (n = 20) perspectives about opioid pain management in survivorship, including oncologists (n = 5), palliative care clinicians (n = 8), primary care clinicians (n = 5), and pain management specialists (n = 2). RESULTS: The findings indicated that no consistent medical home exists for chronic pain management in cancer survivors and that there are fundamental differences in how each subspecialty approaches chronic pain management in survivorship (e.g., "Do we think of this as noncancer pain or cancer pain?… This is in this limbo zone-this gray zone-because it's cancer-related pain, right?"). Simultaneously, clinicians are influenced by their peers' perceptions of their opioid prescribing decisions, sparking intraprofessional tension when disagreement occurs. In these instances, clinicians described overthinking and doubting their clinical decision-making as well as a sense of judgment, pressure, and/or shame. Finally, clinicians acknowledged a fear of consequences for opioid prescribing decisions. Specifically, participants cited conflict with patients, sometimes escalating to aggression and threats of violence, as well as potential disciplinary actions and/or legal consequences. CONCLUSIONS: Participants suggested that opportunities to improve chronic cancer pain care include developing clear, systematic guidance for chronic cancer pain management, facilitating clinician communication and consultation, creating tailored survivorship care plans in partnership with patients, and developing accessible, evidence-based, complementary pain treatments.

Overdose from Unintentional Fentanyl Use when Intending to Use a Non-opioid Substance: An Analysis of Medically Attended Opioid Overdose Events.

Fentanyl-mixed and substituted heroin is well-documented, but less is known about unintentional fentanyl use among people using stimulants. To determine the prevalence of and racial and ethnic disparities in unintentional fentanyl use among people experiencing a medically attended opioid overdose, we reviewed 448 suspected non-fatal overdose cases attended by a community paramedic overdose response team in San Francisco from June to September 2022. We applied a case definition for opioid overdose to paramedic records and abstracted data on intended substance use prior to overdose. Among events meeting case criteria with data on intended substance use, intentional opioid use was reported by 57.3%, 98.0% of whom intended to use fentanyl. No intentional opioid use was reported by 42.7%, with most intending to use stimulants (72.6%), including methamphetamine and cocaine. No intentional opioid use was reported by 58.5% of Black, 52.4% of Latinx, and 28.8% of White individuals (p = 0.021), and by 57.6% of women and 39.5% of men (p = 0.061). These findings suggest that unintentional fentanyl use among people without opioid tolerance may cause a significant proportion of opioid overdoses in San Francisco. While intentional fentanyl use might be underreported, the magnitude of self-reported unintentional use merits further investigation to confirm this phenomenon, explore mechanisms of use and disparities by race and ethnicity, and deploy targeted overdose prevention interventions.

Storage, Disposal, and Use of Opioids Among Cancer Patients in Central China: A Multi-Center Cross-Sectional Study.

OBJECTIVE: Unsafe opioid-related practices can lead to abuse, diversion, and accidental overdoses. In this study, we aimed to describe the patterns and beliefs regarding the storage, disposal, and use of opioids among Chinese patients with cancer in their home settings, which remain unclear. METHODS: A multicenter cross-sectional survey was conducted in Hubei Province from October 2022 to June 2023. We collected information on the storage, disposal, and use of opioids among cancer pain inpatients in the oncology department. Logistic regression was used to estimate the factors associated with unsafe disposal and use of opioids. RESULTS: The survey included 221 patients with a median age of 62 years. Only 3.2% stored their opioids under lock and key, and 49.8% were unaware of proper disposal methods. Nearly one-fifth (19.5%) reported having received information on the safe storage (14.0%) and/or disposal (10.0%) of opioids. A total of 44.3% reported unsafe use by sharing (1.8%), losing (4.1%), or taking opioids at a higher dose than prescribed (42.5%). Patients who did not receive information on the safe disposal of opioids (OR = 4.57, P = .0423), had a history of alcohol use (OR = 1.91, P = .0399), and used opioids other than morphine (OR = 2.31, P = .0461) had higher odds of unsafe disposal practices. Individuals with an associate degree/bachelor's degree or above were less likely to dispose of (OR = 0.36, P = .0261) and use (OR = 0.31, P = .0127) opioids unsafely. CONCLUSION: A significant proportion of Chinese patients with cancer exhibit unsafe practices in the storage, disposal, and use of opioids. The study highlights an urgent need for implementing routine education programs and drug "take-back" initiatives to improve opioid-related practices.

Observational evidence linking psychotropic medicines to the dispensing of opioid agents in later life.

BACKGROUND: The use of opioid medicines is common in developed countries, particularly among older adults and those with mental health disorders. It is unclear if the association between mental disorders and opioid medicines is causal, or is due to reverse causality or confounding. METHODS: We used a 10% random sample of the Australian Pharmaceutical Benefits Scheme (years 2012-2022) to examine the cross-sectional, case-control and longitudinal association between the dispensing of antidepressants, anxiolytics, hypnotics, antipsychotics and lithium, and opioid medicines. We used logistic regression, structural equation models (SEM), and Cox regression to analyze the data. Analyses were adjusted for age (years), sex, and number of non-psychotropic medicines dispensed during the year. RESULTS: The 2022 file contained 804 334 individuals aged 50 years or over (53.1% women), of whom 181 690 (22.6%) received an opioid medicine. The adjusted odds ratio of being dispensed opioid medicines was 1.44 (99% CI = 1.42-1.46) for antidepressants, 1.97 (99% CI = 1.92-2.03) for anxiolytics, 1.55 (99% CI = 1.51-1.60) for hypnotics, 1.32 (99% CI = 1.27-1.38) for antipsychotics, and 0.60 (99% CI = 0.53-0.69) for lithium. Similar associations were noticed when we compared participants who were or not dispensed opioid medicines in 2022 for exposure to psychotropic agents between 2012 and 2021. SEM confirmed that this association was not due to reverse causality. The dispensing of antidepressants was associated with increased adjusted hazard (HR) of subsequent dispensing of opioid medicines (HR = 1.29, 99% CI = 1.27-1.30). Similar associations were observed for anxiolytics, hypnotics and antipsychotics, but not lithium. CONCLUSIONS: The dispensing of opioid medicines is higher among older individuals exposed to antidepressants, anxiolytics, hypnotics and antipsychotics than those who are not. These associations are not due to reverse causality or study design. Preventive strategies seeking to minimise the risk of inappropriate use of opioid medicines in later life should consider targeting this high-risk population.

Integrated care van delivery of evidence-based services for people who inject drugs: A cluster-randomized trial.

BACKGROUND AND AIMS: People who inject drugs (PWID) are at risk for adverse outcomes across multiple dimensions. While evidence-based interventions are available, services are often fragmented and difficult to access. We measured the effectiveness of an integrated care van (ICV) that offered services for PWID. DESIGN, SETTING AND PARTICIPANTS: This was a cluster-randomized trial, which took place in Baltimore, MD, USA. Prior to randomization, we used a research van to recruit PWID cohorts from 12 Baltimore neighborhoods (sites), currently served by the city's mobile needle exchange program. INTERVENTION AND COMPARATOR: We randomized sites to receive weekly visits from the ICV (n = 6) or to usual services (n = 6) for 14 months. The ICV offered case management; buprenorphine/naloxone; screening for HIV, hepatitis C virus and sexually transmitted infections; HIV pre-exposure prophylaxis; and wound care. MEASUREMENTS: The primary outcome was a composite harm mitigation score that captured access to evidence-based services, risk behaviors and adverse health events (range = 0-15, with higher numbers indicating worse status). We evaluated effectiveness by comparing changes in the composite score at 7 months versus baseline in the two study arms. FINDINGS: We enrolled 720 cohort participants across the study sites (60 per site) between June 2018 and August 2019: 38.3% women, 72.6% black and 85.1% urine drug test positive for fentanyl. Over a median of 10.4 months, the ICV provided services to 734 unique clients (who may or may not have been cohort participants) across the six intervention sites, including HIV/hepatitis C virus testing in 577 (78.6%) and buprenorphine/naloxone initiation in 540 (74%). However, only 52 (7.2%) of cohort participants received services on the ICV. The average composite score decreased at 7 months relative to baseline, with no significant difference in the change between ICV and usual services (difference in differences: -0.31; 95% confidence interval: -0.70, 0.08; P = 0.13). CONCLUSIONS: This cluster-randomized trial in Baltimore, MD, USA, found no evidence that weekly neighborhood visits from a mobile health van providing injection-drug-focused services improved access to services and outcomes among people who injected drugs in the neighborhood, relative to usual services. The van successfully served large numbers of clients but unexpectedly low use of the van by cohort participants limited the ability to detect meaningful differences.

A systematic review exploring healthcare professionals' perceptions of take-home naloxone dispensing in acute care areas.

AIMS: To explore healthcare professionals' perceptions and experiences of take-home naloxone initiatives in acute care settings to gain an understanding of issues facilitating or impeding dispensing. DESIGN: Systematic literature review. DATA SOURCES: Cochrane, MEDLINE and CINAHL were searched from 15/03/2021 to 18/03/2021, with a follow-up search performed via PubMed on 22/03/2021. The years 2011 to 2021 were included in the search. REVIEW METHODS: A systematic literature review focused on qualitative studies and quantitative survey designs. Synthesis without meta-analysis was undertaken using a thematic analysis approach. RESULTS: Seven articles from the United States of America (5), Australia (1) and Canada (1) with 750 participants were included in the review. Results indicate ongoing stigma towards people who use drugs with preconceived moral concerns regarding take-home naloxone. There was confusion regarding roles and responsibilities in take-home naloxone dispensing and patient education. Similarly, there was a lack of clarity over logistical and financial issues. CONCLUSION: Take-home naloxone is a vital harm reduction initiative. However, barriers exist that prevent the optimum implementation of these initiatives. IMPACT: What is already known: Deaths due to opioid overdose are a global health concern, with take-home naloxone emerging as a key harm reduction scheme. Globally, less than 10% of people who use drugs have access to treatment initiatives, including take-home naloxone. An optimum point of distribution of take-home naloxone is post-acute hospital care. WHAT THIS PAPER ADDS: There is role confusion regarding responsibility for the provision of take-home naloxone and patient education. This is exacerbated by inconsistent provision of training and education for healthcare professionals. Logistical or financial concerns are common and moral issues are prevalent with some healthcare professionals questioning the ethics of providing take-home naloxone. Stigma towards people who use drugs remains evident in some acute care areas which may impact the use of this intervention. Implications for practice/policy: Further primary research should examine what training and education methods are effective in improving the distribution of take-home naloxone in acute care. Education should focus on reduction of stigma towards people who use drugs to improve the distribution of take-home naloxone. Standardized care guidelines may ensure interventions are offered equally and take-home naloxone 'champions' could drive initiatives forward, with support from harm reduction specialists. REPORTING METHOD: This has adhered to the PRISMA reporting guidelines for systematic reviews. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Cost of start-up activities to implement a community-level opioid overdose reduction intervention in the HEALing Communities Study.

BACKGROUND: Communities That HEAL (CTH) is a novel, data-driven community-engaged intervention designed to reduce opioid overdose deaths by increasing community engagement, adoption of an integrated set of evidence-based practices, and delivering a communications campaign across healthcare, behavioral-health, criminal-legal, and other community-based settings. The implementation of such a complex initiative requires up-front investments of time and other expenditures (i.e., start-up costs). Despite the importance of these start-up costs in investment decisions to stakeholders, they are typically excluded from cost-effectiveness analyses. The objective of this study is to report a detailed analysis of CTH start-up costs pre-intervention implementation and to describe the relevance of these data for stakeholders to determine implementation feasibility. METHODS: This study is guided by the community perspective, reflecting the investments that a real-world community would need to incur to implement the CTH intervention. We adopted an activity-based costing approach, in which resources related to hiring, training, purchasing, and community dashboard creation were identified through macro- and micro-costing techniques from 34 communities with high rates of fatal opioid overdoses, across four states-Kentucky, Massachusetts, New York, and Ohio. Resources were identified and assigned a unit cost using administrative and semi-structured-interview data. All cost estimates were reported in 2019 dollars. RESULTS: State-level average and median start-up cost (representing 8-10 communities per state) were $268,657 and $175,683, respectively. Hiring and training represented 40%, equipment and infrastructure costs represented 24%, and dashboard creation represented 36% of the total average start-up cost. Comparatively, hiring and training represented 49%, purchasing costs represented 18%, and dashboard creation represented 34% of the total median start-up cost. CONCLUSION: We identified three distinct CTH hiring models that affected start-up costs: hospital-academic (Massachusetts), university-academic (Kentucky and Ohio), and community-leveraged (New York). Hiring, training, and purchasing start-up costs were lowest in New York due to existing local infrastructure. Community-based implementation similar to the New York model may have lower start-up costs due to leveraging of existing infrastructure, relationships, and support from local health departments.

The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.

Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model. Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature (p > 0.063). There was no significant effect of treatment on heart rate (p = 0.364). There was a significant effect of time (p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h. Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.

Low-dose Initiation of Buprenorphine/naloxone for the Management of Chronic Non-cancer Pain in Patients on Long-term Opioid Therapy: A Case Series.

Background: Buprenorphine may provide superior analgesia to full opioid agonist therapy and reverse the effects of opioid-induced hyperalgesia, while having a favorable safety profile and fewer adverse effects, in chronic non-cancer pain treatment. Low-dose initiation of buprenorphine is a useful strategy for patients on long-term opioid therapy because it avoids the need for moderate opioid withdrawal required for traditional buprenorphine initiations. However, there are few published reports of low-dose initiation regimens in the setting of chronic pain. Aims: The aim of the study was to describe a case series of individuals living with chronic pain who were transitioned from long-term full opioid agonist therapy onto sublingual buprenorphine/naloxone using low-dose initiation regimens. Methods: This study is a retrospective case series that included all patients who received care at an outpatient chronic pain clinic and were scheduled for low-dose initiation of buprenorphine/naloxone between March 2020 and December 2022. Data were collected through a retrospective review of electronic medical records and results were analyzed using descriptive statistics. Results: Eighteen patients underwent transitions from their baseline opioids onto buprenorphine/naloxone using a low-dose initiation regimen. Of those patients, 17 successfully completed the initiation (94.44%), 12 experienced adverse effects during the initiation (66.67%), with only one patient requiring treatment discontinuation, and all adverse effects resolved once maintenance doses of buprenorphine/naloxone were established. The mean Clinical Global Impression-Improvement score after initiation was 2 (1-5). Conclusion: Low-dose initiation is an effective approach to transition patients with chronic non-cancer pain from long-term opioid therapy to buprenorphine/naloxone without major complications or worsening pain.

Contexte: La buprénorphine peut offrir une analgésie supérieure à celle d'un traitement par agonistes opioïdes complet et inverser les effets de l'hyperalgésie induite par les opioïdes, tout en présentant un profil d'innocuité favorable et moins d'effets indésirables dans le traitement de la douleur chronique non cancéreuse. L'initiation à faible dose de la buprénorphine est une stratégie utile pour les patients sous traitement opioïde à long terme, car elle évite le besoin de sevrage des opioïdes modéré nécessaire pour les traitements traditionnels à base de buprénorphine. Cependant, il existe peu de rapports publiés sur les régimes d'initiation à faible dose dans le cadre de la douleur chronique.Objectifs: L'objectif de cette étude était de décrire une série de cas d'individus vivant avec une douleur chronique qui sont passés d'un traitement opioïde complet à long terme à un traitement par buprénorphine sublinguale/naloxone en ayant recours à des régimes d'initiation à faible dose.Méthodes: Cette étude est une série de cas rétrospective incluant tous les patients pris en charge dans une clinique externe de traitement de la douleur chronique et pour lesquels un schéma d'initiation à faible dose de buprénorphine/naloxone a été programmé entre mars 2020 et décembre 2022. Les données ont été collectées par le biais d'un examen rétrospectif des dossiers médicaux électroniques et les résultats ont été analysés à l'aide de statistiques descriptives.Résultats: Dix-huit patients ont fait la transition des opioïdes de base à la buprénorphine/naloxone en utilisant un régime d'initiation à faible dose. Parmi ces patients, 17 ont terminé l'initiation avec succès (94,44 %), 12 ont présenté des effets indésirables pendant l'initiation (66,67 %) et un seul patient a dû interrompre son traitement. Tous les effets indésirables ont disparu une fois les doses d'entretien de buprénorphine/naloxone établies. Le score d'impression clinique globale-amélioration moyen après le début du traitement était de 2 (1-5).Conclusion: L'initiation à faible dose est une approche efficace pour faire passer les patients souffrant de douleur chronique non cancéreuse d'un traitement opioïde à long terme à la buprénorphine/naloxone sans complications majeures ni aggravation de la douleur.

Successful Use of Intravenous Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Pediatric Patients.

Objectives Methylnaltrexone is U.S. Food and Drug Administration (FDA) approved as a subcutaneous injection for adults with opioid-induced constipation (OIC). Case series have described the use of methylnaltrexone for OIC in the pediatric oncology population. There are limited data describing its intravenous use in critically ill pediatric patients. Methods We conducted a retrospective observational study at St. Louis Children's Hospital. Patients less than 18 years old who received at least one dose of intravenous methylnaltrexone while admitted to an intensive care unit between January 2016 and August 2019 were included. The primary outcome was documented laxation within 24 hours of methylnaltrexone administration. Results Sixteen patients received a total of 34 doses of intravenous methylnaltrexone. Patients received a median of 1.69 (interquartile range [IQR], 0.9-4.86) morphine milligram equivalents per kilogram per 24 hours, over a median of 14 days (IQR, 11-30), before methylnaltrexone administration. The median dose of methylnaltrexone was 0.15 mg/kg (IQR, 0.15-0.16). Ten patients (63%) responded to the first dose of methylnaltrexone, and 14 patients (88%) responded to at least one dose. Overall, 26 doses (76%) led to patient response. Four patients (25%) experienced adverse events (emesis, abdominal pain) after methylnaltrexone administration. No signs or symptoms of opioid withdrawal were documented. Conclusions Intravenous methylnaltrexone appears to be safe and effective in treating OIC in critically ill pediatric patients. No serious adverse events or signs of opioid withdrawal were observed after single and repeat dosing. Patients responded to methylnaltrexone with varying opioid dosing and durations prior to administration.

The effectiveness of ambulatory continuous popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia in patients undergoing foot or ankle surgery (CAREFREE trial); a randomized, open label, non-inferiority trial.

STUDY OBJECTIVE: Management of pain after foot and ankle surgery remains a concern for patients and healthcare professionals. This study determined the effectiveness of ambulatory continuous popliteal sciatic nerve blockade, compared to standard of care, on overall benefit of analgesia score (OBAS) in patients undergoing foot or ankle surgery. We hypothesized that usage of ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care. DESIGN: Single center, randomized, non-inferiority trial. SETTING: Tertiary hospital in the Netherlands. PATIENTS: Patients were enrolled if ≥18 years and scheduled for elective inpatient foot or ankle surgery. INTERVENTION: Patients were randomized to ambulatory continuous popliteal sciatic nerve blockade or standard of care. MEASUREMENTS: The primary outcome was the difference in OBAS, which includes pain, side effects of analgesics, and patient satisfaction, measured daily from the first to the third day after surgery. A non-inferiority margin of 2 was set as the upper limit for the 90% confidence interval of the difference in OBAS score. Mixed-effects modeling was employed to analyze differences in OBAS scores over time. Secondary outcome was the difference in opioid consumption. MAIN RESULTS: Patients were randomized to standard of care (n = 22), or ambulatory continuous popliteal sciatic nerve blockade (n = 22). Analyzing the first three postoperative days, the OBAS was significantly lower over time in the ambulatory continuous popliteal sciatic nerve blockade group compared to standard of care, demonstrating non-inferiority (-1.9 points, 90% CI -3.1 to -0.7). During the first five postoperative days, patients with ambulatory continuous popliteal sciatic nerve blockade consumed significantly fewer opioids over time compared to standard of care (-8.7 oral morphine milligram equivalents; 95% CI -16.1 to -1.4). CONCLUSIONS: Ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care with single shot popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia.

Evidence-based Cesarean Delivery: Preoperative Management (Part 7).

The preoperative preparation for cesarean delivery is a multistep approach for which protocols should exist at each hospital system. These protocols should be guided by the findings of this review. The interventions reviewed and recommendations made for this review have a common goal of decreasing maternal and neonatal morbidity and mortality related to cesarean delivery (CD). The preoperative time period starts prior to the patient's arrival to the hospital and ends immediately prior to skin incision. Skin cleansing in addition to CDC recommendations of showering with either soap or an antiseptic solution at least the night prior to a procedure has not been shown to further decrease rates of infection. Hair removal at the cesarean skin incision is not necessary, however if preferred by the surgical team then clipping or depilatory creams should be used rather than shaving. Preoperative enema is not recommended. A clear liquid diet may be ingested up to 2 hours prior and a light meal up to 6 hours prior to CD. Consider giving a preoperative carbohydrate drink to non-diabetic patients up to 2 hours prior to planned CD. Weight-based intravenous (IV) cefazolin is recommended 60 minutes prior to skin incision: 1-2g IV for patients without obesity and 2g for patients with obesity or weight ≥ 80kg. Adjunctive azithromycin 500mg IV is recommended for patients with labor or rupture of membranes. Preoperative gabapentin can be considered as may decrease pain scores with movement in the postoperative period. Tranexamic acid (1g in 10-20mL of saline or 10mg/kg IV) is recommended prophylactically for patients at high-risk of postpartum hemorrhage, and can be considered in all patients. Routine use of mechanical venous thromboembolism prophylaxis is recommended preoperatively and is to be continued until the patient is ambulatory. Music, active warming of the patient, and adequate operating room temperature improves outcomes for the patient and neonate, respectively. Noise levels should allow clear communication between teams, however a specific decibel level has not been defined in the data. Patient positioning with left lateral tilt decreases hypotensive episodes compared to right lateral tilt, which is not recommended. Manual displacers result in fewer hypotensive episodes than left lateral tilt. Both vaginal and skin preparation should be performed with either chlorhexidine (preferred) or povidone-iodine. Placement of an indwelling urinary catheter is not necessary. Non-adhesive drapes are recommended. Cell salvage, while effective for high-risk patients, is not recommended for routine use. Maternal supplemental oxygen does not improve outcomes. A surgical safety checklist (including a timeout) is recommended for all CDs.