Opioid Availability Research Articles

Chronic olanzapine treatment leads to increased opioid receptor expression and changes in feeding regulating neurons in the female rat hypothalamus

Opioid receptor antagonists have shown increasing promise as an adjunct therapy to psychotropic medication. The goal is to reduce the weight gain and metabolic adverse effects that are associated with certain second-generation antipsychotics, such as olanzapine and clozapine. In this study, female rats were treated for 4 weeks with a long-acting injectable formulation of olanzapine to assess effects on hypothalamic feeding regulation. Using quantitative spatial in situ hybridization and receptor autoradiography, expression levels of the mu, kappa and delta opioid receptors were defined in the five hypothalamic areas: paraventricular nucleus (PVN), arcuate nucleus (ARC), ventromedial nucleus (VMN), dorsomedial nucleus (DMN) and lateral hypothalamus (LH). In addition, hypothalamic neuron number and size were estimated using the unbiased optical fractionator and spatial rotator methods. Hyperphagia was observed after only 24hours of olanzapine treatment, with continued weight gain throughout the duration of the study. In contrast, the observed food intake reversed to control levels after 2 weeks of olanzapine treatment. Chronic olanzapine treatment increased expression of kappa opioid receptor mRNA and receptor availability in the PVN, as well as increased mu opioid receptor availability in the PVN, ARC and VMN. These changes were accompanied by fewer anorexigenic proopiomelanocortin-expressing neurons of the ARC and corticotropin-releasing hormone expressing neurons of the PVN. This study links olanzapine-driven metabolic effects to increased opioid receptor expression in the hypothalamus, thus providing a rationale for the positive effects of using opioid receptor antagonists to relieve olanzapine adverse effects.

State opioid prescribing laws and associations with radiotherapy delays and radiotherapy completion.

122 Background: In July 2018, Missouri introduced a 7-day limit for initial opioid prescriptions, though there was an exemption for cancer-related pain. However, some worry that the exemptions may be inadequate for patients with cancer who experience cancer-related pain. Since some courses of radiotherapy can cause pain (eg, mucositis, esophagitis), appropriate opioid access is important for helping patients complete radiotherapy in a timely manner, which is associated with oncologic outcomes. Methods: Patients with cancer of all ages treated with radiotherapy from 2018-2019 at a large academic institution in Missouri were identified. More recent data were excluded due to the COVID-19 pandemic and Missouri Medicaid expansion. Trends over time in the proportion of missed/delayed radiotherapy fractions, incomplete radiotherapy courses, and a composite measure of excessive delays (≥5 days) or incomplete course were evaluated in linear and linear probability models. Additional analyses included patients from Illinois, an adjacent state without opioid prescribing legislation, and we subsequently performed difference-in-differences analyses comparing the outcomes from pre- to post- Missouri opioid legislation between the states. We conducted unadjusted analyses as well as analyses adjusted for age, sex, site, radiotherapy modality and fractions, as well as other covariates that could impact access to radiotherapy (ZIP code deprivation, distance from the facility, insurance status, and social work referral for unmet needs). Subgroup analyses focused on patients with head and neck cancer and lung cancer receiving definitive radiotherapy, who are at high risk of radiotherapy-related pain. Results: A total of 2613 and 1518 patients from Missouri and Illinois were identified, respectively. 4.7% of fractions were missed/delayed, 3.7% of patients did not complete treatment, and 8.1% of patients had either an incomplete course or excessive delays. There were no statistically significant increases (ie, worsening) in any outcome in any quarter after opioid policy implementation, and there were significant decreases in the composite outcome in multiple post-policy quarters in both unadjusted and adjusted analyses. In difference-in-differences analyses comparing trends over time with patients from Illinois, there were no significant associations of policy implementation with any of the outcomes. Results were similar in subgroup analyses for patients with head and neck and lung cancers. Conclusions: Missouri legislation limiting opioid prescribing for non-cancer-related pain was not associated with significant changes in a patient’s ability to undergo radiotherapy. Limitations of the study include evaluation of a single center in a single state and the lack of other intermediate outcomes important to patients including access to opioid medication itself, which we will examine in future work.

Opioid access barriers for cancer pain relief in Vietnam: A qualitative study.

154 Background: Although the World Health Organization designates opioids as an essential medication and recommends them as the cornerstone for managing moderate to severe cancer pain, their accessibility is severely restricted, particularly in low and middle-income countries. Despite Vietnam's early endeavors in the advancement of palliative care, including a revised opioid prescription policy in 2008, opioid use for cancer pain remains suboptimal, with oral morphine available only in a few major hospitals. To inform comprehensive strategies for improving opioid access, this study aims to explore the views of healthcare providers, regulators, cancer patients, and caregivers in Vietnam on the barriers to safely accessing opioids for cancer pain management. Methods: We conducted a qualitative, descriptive study and recruited five healthcare providers, six cancer patients and caregivers, and six regulators (i.e., policymakers in the Ministry of Health, heads or deputy heads of pharmacy, oncology, or palliative care departments) across Vietnam via purposeful sampling technique. Data were collected using semi-structured interviews, and the audio recordings were transcribed verbatim and subjected to inductive content analysis using a Framework Method. Results: Five categories of barriers were identified: 1) Patient-related barriers (fear of addiction and other side effects, morphine's association with impending death, negative administration experiences, religious beliefs); 2) Professional-related barriers (knowledge and experience deficit, fear of addiction and other side effects, concerns about opioid diversion and associated liabilities, lack of guidance, education, and training); 3) Medicine-related barriers (limited oral morphine availability, limited domestic pharmaceutical manufacturers and suppliers, supply interruptions, poor variety of opioid types and formulations, difficulties accessing parenteral opioids); 4) Services delivery barriers (scarce palliative and home care services); 5) Regulatory barriers (lack of information on opioid distribution channels, difficulties obtaining confirmation letters for patients' opioid usage needs, overly strict regulation enforcement). Conclusions: Barriers to opioid access for cancer pain control in Vietnam are multifactorial and mutually reinforcing, necessitating interdisciplinary solutions to overcome them. This approach should involve enhancing education about the appropriate use and management of opioids, along with current opioid policies for patients, communities, healthcare providers, and regulators; enacting and implementing policies mandating oral morphine availability at local health facilities; expanding palliative care services; utilizing telemedicine; and establishing an electronic opioid prescription monitoring system.

Patterns and Outcomes of Opioid Use Before and After Hospitalization for Critical Illness: A Population-Based Cohort Study.

Background: Hospitalization represents a major access point for prescription opioids, yet little is known regarding patterns and outcomes of opioid exposures before and after hospitalization for critical illness. Methods: This is an observational, population-based cohort study of adults (≥18 years) hospitalized for critical illness from 2010 to 2019. Multivariable models assess associations between opioid exposures prior to hospitalization, classified according to the Consortium to Study Opioid Risks and Trends, and posthospitalization opioid exposures and clinical outcomes through 1-year posthospitalization. Results: Of 11 496 patients, 6318 (55%) were men with a median age of 66 (51, 79) years and 40% (n = 4623) surgical admissions. Prehospitalization opioid availability included 8449 (73%) none, 2117 (18%) short-term, 471 (4%) episodic, and 459 (4%) long-term. Thirty-nine percent (4144/10 708) of hospital survivors were discharged with opioids, with higher prescribing rates for surgical admissions (55%). Greater preadmission opioid exposures were associated with higher prevalent opioid availability at 1 year (odds ratio [95% confidence interval] 24.1 [18.3-31.8], 9.42 [7.18-12.3], and 2.55 [2.08-3.12] for long-term, episodic, and short-term exposures, respectively, vs none, P < .001). Greater preadmission opioid exposures were associated with longer hospitalizations (1.13 [1.04-1.23], 1.15 [1.06-1.25], and 1.08 [1.04-1.13] multiplicative increase in geometric mean, P < .001), more readmissions (hazard ratio [HR] 2.08 [1.74-2.49], 1.88 [1.56-2.26], and 1.48 [1.33-1.64], P < .001), and higher 1-year mortality (HR 1.59 [1.28-1.98], 1.75 [1.41-2.18], and 1.49 [1.32-1.69], P < .001). Similar associations were observed across surgical and nonsurgical admissions. Conclusions: Prehospitalization opioid exposures in survivors of critical illness are associated with clinical outcomes through 1 year and may serve as important prognostic markers.

Opioid Access among Advanced Cancer Patients in Low- and Middle-Income Countries in Asia

ContextMost cancer-associated pain is experienced in low- and middle-income countries (LMICs) due to inequitable access to opioids. ObjectiveTo determine opioid access as estimated by both patients and providers and to understand patient and facility-level factors influencing access among patients with advanced cancer in LMICs in Asia using the Behavioral Model of Health Services Use. MethodsThe APPROACH cross-sectional study was conducted in seven LMICs in Asia, involving in-depth surveys with providers and advanced cancer patients. A hierarchical logistic regression model was used to assess predisposing (i.e. individual factors), enabling (i.e. health care system and facility-level resources) and need (i.e. pain severity) factors predicting opioid access. ResultsAmong patient participants (n=1,933), approximately 40% reported opioid use. Meanwhile 80% of facilities, as reported by providers, indicated at least half of their advanced cancer patients receive oral morphine prescriptions. Predisposing characteristics factored in the least in the model, with patient education positively associated with access (Odds ratio (OR): 1.01; 95% CI=1.00, 1.03). Facility-level enabling resources, factoring the most, included oral morphine prescription duration >14 days (OR: 1.27; 95% CI=1.05, 1.53) and the extent of physician palliative care training (extensive (>160 hours) OR: 3.95; CI=3.19, 4.88; basic (up to 40 hours) OR: 1.03; CI=1.03, 1.04). Patient need as indicated by greater pain severity predicted access (OR: 1.55; CI=1.47, 1.64). ConclusionStudy findings emphasize the importance of palliative care training—even a minimal amount—in supporting access to opioids for advanced cancer patients. This study also highlights pragmatic site-level policies, such as extended morphine prescription durations, enabling access.

Knowledge and attitude towards the use of pain medications according to WHO cancer pain analgesic ladder in tertiary care hospitals of Pakistan.

To assess the knowledge and attitude of practicing physicians and surgeons towards the use of pain medication according to the World Health Organisation cancer pain analgesic ladder, the current study was conducted at tertiary care hospitals of the four provinces of Pakistan. Professionals having experience of treating cancer patients for >2 years were included. Data was collected using a self-administered questionnaire sent to each participant using Google Forms. Of the 630 physicians approached, 133(21%) responded. Of them, 74(55.64%) participants were familiar with the World Health Organisation analgesic ladder. There was a significant difference in the frequency of using the ladder based on age (p<0.05). Most participants 31(23%) reported the nonavailability of the recommended drugs as the reason for not following the analgesic ladder. There is a strong need to educate physicians and surgeons about the World Health Organisation analgesic ladder, and to make strategies to improve opioid availability in Pakistan.

Analysis of opioid analgesics consumption in Africa: a longitudinal study from a 20-year continental perspective

Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa. This longitudinal study has updated and expanded upon the International Narcotics Control Board data obtained from 1999 to 2021, assessing opioid consumption trends across all African countries. The defined daily doses for statistical purposes (SDDD) was used to determine the changes in opioid consumption in Africa. In addition, we used sub-analyses of the data to delve into individual substances, income levels, cancer incidence, cancer mortality, and sub-regional cluster analysis (based on the language spoken) to identify possible disparities and inform further research and tailored solutions. Our results indicate a persistently low and stagnant trend in opioid consumption between 2001-03 and 2019-21, from 73 SDDD (95% CI 69-77) to 55 SDDD (32-79). In-depth analysis revealed a morphine consumption increase from 735 SDDD in 1999 to 1115 SDDD in 2021. Moreover, opioid consumption was closely related to country-level income levels, with most of the low-income and lower-middle-income African countries reporting low opioid consumption. Notably, the escalating incidence and mortality rates associated with cancer in Africa indicated a misalignment with the trajectory of opioid use. Additionally, French-speaking African countries exhibited lower opioid usage than the rest of the continent, suggesting avenues for research into cultural, political, and social aspects. In the context of global doubling in opioid consumption, Africa has shown insufficient and stagnant opioid consumption during the last 20 years. These findings underscore the need for policy reform to facilitate safe and responsible opioid access in Africa, particularly for legitimate indications such as cancer pain and palliative care. None. For the French translation of the abstract see Supplementary Materials section.

Curbing the Opioid Crisis: Optimal Dynamic Policies for Preventive and Mitigating Interventions

Problem statement: This paper addresses the challenge of effectively responding to the opioid epidemic stemming from prescription pills through a public health lens. It centers on the strategic distribution of resources across diverse interventions aimed at preventing and mitigating the consequences of opioid use disorder (OUD) and overdose occurrences. Methodology: This paper proposes a decision aid tool built on the expected utility theory that leverages a Susceptible-Infected-Removed compartmental model to simulate the dynamics of the epidemic in a population. This model then feeds into a Markov Decision Process (MDP) model to generate optimal policies upon the current state of the epidemic. The optimal policies allocate the intervention budget to primary preventive and mitigating interventions in each decision period by minimizing the cost of fatal overdoses relative to the population’s number of individuals with OUD, considering the impact magnitude of each intervention, based on the current state of the epidemic. A 10-year simulation of the epidemic’s progression is conducted to assess the dynamic efficacy of the proposed decision tool. Results: The findings reveal an average reduction of 29% in total costs compared to the scenario without interventions and a decrease of 12% in total costs on average compared to the scenario with a 50-50 allocation. The extensive sensitivity analysis of key parameters validates the decision aid tool. We observe that it is optimal to allocate a significant portion of the budget to prevention when the rate of opioid pill acquisition rises. Even with a heightened rate of fatal overdoses, it remains optimal to mostly invest in preventive interventions, as long as fatal overdose rates are lower than opioid access rates. Practical implications: This study provides practitioners with a tool to effectively address the opioid epidemic and enhance public health by deciding how to allocate their budget to various levels of intervention.

High prevalence of severe pain is associated with low opioid availability in patients with advanced cancer: Combined database study and nationwide questionnaire survey in Japan.

Opioid availability for the palliative care of patients with advanced cancer is increasing globally. However, opioid availability remains extremely low in Japan. We investigated whether pain is appropriately controlled by low-dose opioid prescriptions in patients with advanced cancer in Japan. A web-based nationwide survey for caregivers from 2000 community comprehensive support care centers was performed in Japan to assess details about pain in the 30 days before patients died of end-stage cancer. Separately, the data for opioid prescription doses and medical services in the 90 days before the death of patients with cancer were extracted from a health insurance claim database. Responses from 1034 responders were retrieved and 665 patients were included. In total, 254 patients (38.2%) complained of severe-to-intolerable cancer-related pain. The median cumulative prescription dose of opioids in the 90 days before patient death was 311.0 mg by oral morphine equivalent doses. Multiple regression analyses across prefectures revealed that the proportion of patients with severe-to-intolerable cancer-related pain was negatively associated with the cumulative opioid consumption expressed as morphine-equivalent doses within 90 days before death. The very low availability of opioids for patients with end-stage cancer could result in high rate of severe-to-intolerable cancer-related pain patients. There were several limitations in this study, and the interpretations of the findings should be carefully. However, the increase in the absolute dose of opioids could improve the palliative care framework to the pain control levels of the global standard.

Opioid Therapy for Cancer Pain in Vietnam: Knowledge, Attitudes, and Perceived Barriers Among Health Care Professionals, Policymakers, and Regulators.

We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.

Human metabolism of four synthetic benzimidazole opioids: isotonitazene, metonitazene, etodesnitazene, and metodesnitazene

Following isotonitazene scheduling in 2019, the availability of alternative 2-benzylbenzimidazole opioids (nitazenes) on the global drug market increased, resulting in many fatalities worldwide. Nitazenes are potent µ-opioid receptor agonists with strong narcotic/analgesic effects, and their concentrations in biological matrices are low, making the detection of metabolite biomarkers of consumption crucial to document use in clinical and forensic settings. However, there is little to no data on the metabolism of the most recently available nitazenes, especially desnitro-analogues. The aim of the research was to assess isotonitazene, metonitazene, etodesnitazene, and metodesnitazene human metabolism and identify specific metabolite biomarkers of consumption. The four analogues were incubated with 10-donor-pooled human hepatocytes, and the incubates were analyzed by liquid chromatography-high-resolution tandem mass spectrometry and data mining with Compound Discoverer (Thermo Scientific); the analysis was supported by in silico metabolite predictions with GLORYx open-access software. Metabolites were identified in postmortem blood and/or urine samples from two metonitazene-positive and three etodesnitazene-positive cases following the same workflow, with and without glucuronide hydrolysis in urine, to confirm in vitro results. Twelve, nine, twenty-two, and ten metabolites were identified for isotonitazene, metonitazene, etodesnitazene, and metodesnitazene, respectively. The main transformations were N-deethylation at the N,N-diethylethanamine side chain, O-dealkylation, and further O-glucuronidation. In vitro and autopsy results were consistent, demonstrating the efficacy of the 10-donor-pooled human hepatocyte model to predict human metabolism. We suggest the parent and the corresponding O-dealkyl- and N-deethyl-O-dealkyl metabolites as biomarkers of exposure in urine after glucuronide hydrolysis, and the corresponding N-deethyl metabolite as additional biomarker in blood.

County-level factors associated with a mismatch between opioid overdose mortality and availability of opioid treatment facilities.

Opioid overdose deaths in the United States remain a major public health crisis. Little is known about counties with high rates of opioid overdose mortality but low availability of opioid use disorder (OUD) treatment facilities. We sought to identify characteristics of United States (US) counties with high rates of opioid overdose mortality and low rates of opioid treatment facilities. Rates of overdose mortality from 3,130 US counties were compared with availability of opioid treatment facilities that prescribed or allowed medications for OUD (MOUD), from 2018-2019. The outcome variable, "risk-availability mismatch" county, was a binary indicator of a high rate (above national average) of opioid overdose mortality with a low (below national average) rate of opioid treatment facilities. Covariates of interest included county-level sociodemographics and rates of insurance, unemployment, educational attainment, poverty, urbanicity, opioid prescribing, depression, heart disease, Gini index, and Theil index. Multilevel logistic regression, accounting for the clustering of counties within states, was used to determine associations with being a "risk-availability mismatch" county. Of 3,130 counties, 1,203 (38.4%) had high rates of opioid overdose mortality. A total of 1,098 counties (35.1%) lacked a publicly-available opioid treatment facility in 2019. In the adjusted model, counties with an additional 1% of: white residents (odds ratio, OR, 1.02; 95% CI, 1.01-1.03), unemployment (OR, 1.11; 95% CI, 1.05-1.19), and residents without insurance (OR, 1.04; 95% CI, 1.01-1.08) had increased odds of being a mismatch county. Counties that were metropolitan (versus non-metropolitan) had an increased odds of being a mismatch county (OR, 1.85; 95% CI, 1.45-2.38). Assessing mismatch between treatment availability and need provides useful information to characterize counties that require greater public health investment. Interventions to reduce overdose mortality are unlikely to be effective if they do not take into account diverse upstream factors, including sociodemographics, disease burden, and geographic context of communities.

271 Evaluation of treatment for opioid use disorder across North Carolina: a study protocol

OBJECTIVES/GOALS: Our objectives are to: 1) characterize opioid treatment providers in North Carolina according to payment methods accepted and ability to provide medications for opioid use disorder and 2) use geomapping technology to characterize geographic access to treatment for opioid use disorder in NC. METHODS/STUDY POPULATION: We will identify opioid treatment providers using resources published by SAMHSA and NC DHHS. We will characterize all providers identified according to provision of medications for opioid use disorder, payment or insurance accepted, and services provided. ArcGIS will be used to characterize geographic distribution of treatment resources after filtering for these key characteristics and determine access according to driving radius. RESULTS/ANTICIPATED RESULTS: We anticipate that the geographic analysis of opioid treatment provider availability will reveal limited access to treatment, particularly in rural areas. We anticipate that further filtering for factors such as provision of medications for opioid use disorder--a first-line, evidence-based intervention—and payment or insurance accepted will demonstrate that the availability of evidence-based, financially accessible treatment for opioid use disorder in North Carolina is critically limited. DISCUSSION/SIGNIFICANCE: We anticipate that an analysis of treatment options available for opioid use disorder, particularly when considering insurance status and drive times, will clearly demonstrate the need for development and expansion of opioid treatment options, and in which areas those efforts are likely to have the highest impact.

Decreasing Opioid Addiction and Diversion Using Behavioral Economics Applied Through a Digital Engagement Solution: Protocol for a Randomized Controlled Trial.

Despite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted. Leveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT). A team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery. This study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024. Through this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record. ClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079. PRR1-10.2196/52882.

Opioid Receptor Mu 1 Gene (OPRM1) A118G Polymorphism and Emotional Modulation of Pain.

The A118G polymorphism in the opioid receptor mu 1 gene (OPRM1) is associated with decreased opioid receptor availability, altered emotion, and increased pain. Given that emotions modulate pain (positive emotions inhibit pain, negative emotions enhance pain), we predicted that G allele carriers would experience impaired emotional modulation of pain compared to non-G allele carriers. Emotional pictures (ie, erotica, neutral, attack) from the International Affective Picture System were used by permission from the authors to experimentally manipulate emotions in 64 adult participants while painful electrocutaneous stimulations were delivered in a cross-sectional study. Ratings of arousal and valence/pleasure were made in response to pictures, and pain ratings and a physiological measure of spinal nociception (ie, nociceptive flexion reflex, NFR) were collected in response to painful stimulations. Secondary analyses were conducted to examine the relationship between the A118G polymorphism and emotional modulation of pain/NFR. Exposure to emotional pictures elicited similar changes in valence, but G-carriers rated erotic pictures as more arousing. In non-carriers, pain was facilitated by attack pictures and pain and NFR were inhibited by erotic pictures relative to neutral pictures. Among G-carriers, pain was facilitated by negative emotional pictures but there was no pain or NFR inhibition by positive emotional pictures. The altered response to pleasant stimuli further supports the role of opioids in appetitive behavior and describes how the A118G polymorphism may prevent carriers from inhibiting pain during pleasure.

Metamizole outperforms meloxicam in sepsis: insights on analgesics, survival and immunomodulation in the peritoneal contamination and infection sepsis model.

Limited availability and side effects of opioids have led to an increased use of non-opioid analgesia in animal disease models. However, by affecting the immune-inflammatory reactions, analgesia may disrupt the resolution of the host inflammation and modulate the survival in septic animals. This study used a clinically relevant sepsis mouse model of peritoneal contamination and infection (PCI) to investigate the antinociceptive and anti-inflammatory properties of two non-opioid analgesics. Adult C57BL/6J mice were intraperitoneally injected with a human feces suspension and received either no analgesics (Non-A), Meloxicam, or Metamizole orally. The mice were monitored for pain and illness. Mortality was assessed at 7 days post-PCI. A separate group of mice was sacrificed 24 hours after infection. Blood, peritoneal lavage fluid (PLF), liver, and spleen were harvested for pathogen load quantification via qPCR, macrophage phenotyping, neutrophil infiltration/activation, and systemic/tissue cytokine release by flow cytometry. Meloxicam but not Metamizole reduced the mortality of septic mice by 31% on day 7 compared to the Non-A group. Both analgesics effectively alleviated pain but did not affect illness severity, body weight, and temperature. Meloxicam quadrupled the bacterial burden in the blood and PLF. In high IL-6 responders, Meloxicam treatment was associated with reduced circulating IL-10 and IL-1β compared to the Non-A septic group. In low IL-6 responders, Meloxicam increased circulating MCP-1 levels and decreased PGE2 levels compared to Non-A septic mice. Notably, Meloxicam reduced spleen neutrophil infiltration by 20% compared to two other sepsis groups. Metamizole and Meloxicam effectively relieved pain and increased the animals' basal activity in the PCI sepsis model. Meloxicam prolonged survival yet triggered maladaptive responses due to its immunosuppressive features that decreased tissue bacterial clearance during sepsis. In contrast, Metamizole constitutes a safe and effective non-opioid alternative for analgesic control in the non-surgical PCI sepsis model.

Application of Roy Adaptation Model: Using Artificial Intelligence-driven Immersive Virtual Reality As a Novel Technology for Cancer Pain Management among Patients with Advanced Breast Cancer

Background: Patients with advanced breast cancer often experience severe physical and psychological symptoms, including pain. Poor pain management is still prevalent despite the widespread availability of opioids as well as guidelines from the World Health Organization, professional training, and the availability of pain management alternatives. Consequently, researchers and healthcare practitioners have directed their efforts towards non-pharmacological approaches, such as artificial intelligence and virtual reality. Recently, AI technology has been used to develop advanced virtual reality systems that adapt and respond to human behavior in a highly intelligent and interactive manner. Purpose: This study aimed to structure a conceptual framework guided by the Roy Adaptation Model (RAM) for implementing AI-driven immersive VR in managing pain among patients with advanced breast cancer. Methods: A conceptual study framework was structured to use artificial intelligence-driven immersive virtual reality as a novel technology for pain management among patients with advanced breast cancer guided by the (RAM). Results: According to the proposed conceptual framework, it has been determined that healthcare providers can use the structured conceptual framework guided by the Roy Adaptation Model to adapt a nursing-based intervention, such as AI-driven Immersive VR for pain management among patients with advanced breast cancer. Adopting this intervention will help patients achieve a state of adaptation by addressing various modes of adaptation to manage pain, including physiological-physical mode, self-concept mode, role function mode, and independence mode. Conclusion: Roy Adaptation Model (RAM) is a highly valuable conceptual framework that plays a crucial role in guiding the use of artificial intelligence-driven immersive virtual reality as a novel technology for pain management among patients with advanced breast cancer. Implications for Nursing: By utilizing RAM, nurses can enhance their abilities to facilitate effective innovative nursing interventions such as artificial intelligence-driven immersive virtual reality for cancer pain management and to identify all of the related stimuli that directly lead to an increase in the intensity of cancer pain and have a significant influence on the effectiveness of the nursing intervention. Keywords: Breast cancer, Chronic cancer pain, Roy adaptation model, Artificial intelligence-driven immersive virtual reality

National Palliative Care Strategy in a Conflict Affected Country: A Jordanian Demonstration Project

ContextPalliative care (PC) integration is vital, as endorsed by the World Health Organization. Yet, Jordan, a Middle Eastern country with limited resources, faces ongoing challenges despite efforts to improve palliative and home care. Establishing a national PC strategic framework, with government and stakeholder consensus, is essential for ensuring universal access to high-quality palliative care. However, processes for achieving this, particularly in the Middle East, are underreported. ObjectivesThis study delineates the process of developing Jordan's National Palliative and Home Care Strategic Framework, reflecting on its five-year impact. Additionally, it identifies barriers to PC progress in Jordan and offers recommendations to stakeholders. MethodsWe conducted a rapid review and analyzed reports, minutes, meetings, and publications. The sequential framework development involved content and situational analysis, expert review, transparent expert consultation, multistage consensus procedures, and high-level advocacy meetings. ResultsThe National Palliative and Home Care Strategic Framework encompasses six domains: 1) policy, 2) finance, 3) service delivery, 4) opioid access, 5) capacity building, and 6) information, research, monitoring, and evaluation. Government endorsement in April 2018 ignited national engagement, driving policy, service delivery, workforce development, education, training, and research progress. Nonetheless, workforce shortages, limited opioid access, and inadequate funding persist as barriers. ConclusionJordan's collaborative development of the inaugural National Palliative and Home Care Strategic Framework, endorsed by the government and stakeholders, provides a comprehensive roadmap for PC advancement. While it promises improved services, effective solutions to workforce and opioid access issues are crucial for successful implementation.

Toward a Psychological Model of Chemical Coping with Opioids in Cancer Care.

• Outline the risk factors involved with opioid accessibility in patients receiving treatment for cancer.• Identify factors to address in order to mitigate risk for opioid misuse during cancer care. Most patients with advanced cancer receive treatment for related pain. Opioid accessibility, however, is a risk factor for misuse, which can present care challenges and quality-of-life concerns. There is a lack of consistent universal screening prior to initiation of opioid prescribing. One crucial issue in treating this population is adequately identifying and mitigating risk factors driving opioid misuse. Drawing on theory and research from addiction science, psychology, palliative care, and oncology, the presented conceptual framework suggests that risk factors for opioid misuse during cancer care can be stratified into historical, current, malleable, and unmalleable factors. The framework identifies necessary factors to address in order to mitigate risk for opioid misuse during cancer care, and offers key directions for future research.

Should We Use COMM (Current Opioid Misuse Measure) to Screen for Opioid Abuse in Patients With Cancer Pain?

Growing concerns about opioid use disorder (OUD) and the resulting decrease in opioid availability for patients with cancer pain highlight the need for reliable screening tools to identify the subset of patients at increased risk for aberrant opioid use. Our study examines the utility of Current Opioid Misuse Measure (COMM) recommended by the NCCN Clinical Practice Guidelines in Oncology for Adult Cancer Pain. We analyzed prospectively collected patient-reported outcomes of 444 consecutive patients with cancer seen in pain clinics of a cancer center at 2 time points within 100 days. The relationship of COMM to other OUD screening tools, pain, opioid doses, patient demographics, and mortality was examined using univariate and multivariable logistic regression. We also examined individual items of COMM for face validity. Among 444 patients who completed pain surveys at 2 time points, 157 (35.4%) did not complete COMM surveys. Using a COMM cutoff of ≥13, a total of 84 patients (29.3%; 84/287) scored positive for aberrant drug use. As patients remained on opioids for 49 to 100 days, the likelihood of improving COMM score (turning from positive to negative) was 6.1 times greater than the reverse. The number of patients with COMM ≥13 was 3.8 times higher than the number of patients with CPT diagnostic codes for OUD, 5.3 times higher than those with a positive urine drug screening, and 21 times higher than those with a positive CAGE (Cut Down, Annoyed, Guilty, Eye-Opener Questionnaire) score. COMM ≥13 was not associated with pain relief response (worst pain intensity score ≥2 points on the Brief Pain Inventory), opioid doses, gender, or age. Contrary to the intended use of COMM to identify aberrant opioid use, COMM ≥13 predicted mortality: patients with COMM ≥13 were 1.9 times more likely to die within 12 months. Our study found that using COMM in a cancer population may significantly overestimate the risk of opioid misuse. Using COMM without modifications can create an additional barrier to cancer pain management, such as limiting appropriate opioid use.