Are We Enhancing Recovery After Neonatal Surgery? Assessment of Enhanced Recovery After Surgery Principles for Ostomy Takedown.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) guidelines in adults have demonstrated reduced complications, length of stay, and cost. However, neonatal ERAS studies are limited and translation of adult ERAS guidelines to neonates is challenging. Furthermore, the knowledge, perception, and practice of neonatal ERAS guidelines is largely unknown. Our aim is to address this practice gap by determining current practice of the 2020 neonatal intestinal surgery ERAS guidelines at our institution and evaluating postoperative outcomes. METHODS: A retrospective study was conducted of patients <1 y who underwent elective ostomy takedown at a single-center tertiary children's hospital between 2013 and 2023. A 13-point ERAS score was developed. Demographics, clinical course, pain management, nutrition, ERAS scores, and outcomes were analyzed using descriptive statistics, logistic and negative binomial regression. RESULTS: One hundred eighty-six patients met the inclusion criteria. At surgery, the median age was 124 d (interquartile range [IQR] 81-220) and median weight was 4360 g (IQR 2920-7200). The median ERAS score was 6 (IQR 5-7). The highest scores were for appropriate (97.9%) and timely (91.9%) prophylactic antibiotics, and the lowest for preventing intraoperative hypothermia (14.5%), limiting opioids (9.1%), and early enteral feeding postoperatively (24.7%). Surgical site infection occurred in 14.5% and median length of stay was 28 (IQR 5-127) d. CONCLUSIONS: Our institution's current practice of the 2020 neonatal intestinal surgery ERAS guidelines was poor. We identified opportunities for improvement including postoperative antibiotic administration, prevention of intraoperative hypothermia, nutrition, and pain management. Future studies will focus on implementation of neonatal ERAS guidelines at our institution and evaluation of adherence and outcomes.

Utility of The PROMIS-10 Global Mental Health T-Score to Identify Patients at Risk for Poor Post-Surgical Outcomes Following Total Hip Arthroplasty.

BACKGROUND: Mental illness is a known risk factor for poor postoperative outcomes following total hip arthroplasty (THA); however, the relationship between a patients overall mental health and recovery from THA is not as well established. Using the preoperative Patient-Reported Outcomes Measurement Information System (PROMIS-10) Mental Health T-score (MHT), the purpose of this study was to understand the association between mental health and postoperative outcomes up to one year following THA. METHODS: This was a retrospective chart review of patients undergoing elective primary THA. Patients who did not have a formal diagnosis of a mental illness condition were divided based on their MHT (above average [AA] > 50, average [A] 40 to 50, below average [BA] < 40). Postsurgical parameters included inpatient opioid consumption and patient satisfaction, and 1-year post-surgery self-reported pain and patient-reported outcomes scores. A total of 972 patients were included in this study (AA 61.2%, A 33.1%, BA 5.7%). RESULTS: After controlling for confounders, multivariate models demonstrated that the MHT was an independent predictor of pain, opioid consumption, patient-reported outcomes, and satisfaction. Patients in the AA group overall demonstrated better outcomes and required fewer opioids than those in the BA group. CONCLUSION: The MHT can be used as a preoperative screening tool that can identify an at-risk group that has not been previously described. An MHT < 40 was associated with poor postoperative outcomes, increased pain and opioid consumption, and lower overall satisfaction scores.

Effectiveness of pain medication tapering in chronic pain patients: a systematic review and meta-analysis.

BACKGROUND: 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. METHODS: A literature search was conducted from inception to April 2024 in MEDLINE via PubMed, Web of Science, SCOPUS, EMBASE, and PsycINFO. RESULTS: 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. CONCLUSIONS: 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. SYSTEMATIC REVIEW PROTOCOL: CRD42023416343 (PROSPERO).

Liposomal bupivacaine plus intrathecal hydromorphone associated with shortened length of stay and decreased opioid use in pediatric patients following posterior spinal fusion surgery.

PURPOSE: We aimed to determine if the use of intrathecal (IT) hydromorphone and/or liposomal bupivacaine (LB) decreased the amount of postoperative and post-discharge opioids for pediatric patients undergoing fusion (PSF) surgery to treat adolescent idiopathic scoliosis (AIS). METHODS: A retrospective review of AIS patients undergoing PSF surgery was conducted. Hospital LOS, and inpatient and post-discharge opioid use were compared. Opioid use was reported as oral morphine equivalents (OMEs). RESULTS: Three groups were formed from 186 patients: the control (CG) (n = 39), the IT hydromorphone only (IT) (n = 58), and the liposomal bupivacaine with intrathecal hydromorphone (LB + IT) group (n = 89). The mean LOS were 4.8, 4.2, and 3.5 days for the CG, IT, and LB + IT groups, respectively, with the LB + IT group being shorter than both the CG (p < 0.001) and IT groups (p < 0.001). The mean inpatient OMEs were 106.3/day, 69.2/day, and 30.0/day for the CG, IT, and LB + IT groups, respectively, with each group being significantly different than each other (all pairwise comparisons, p < 0.001). The mean total OMEs that patients were prescribed post-discharge were 693.6 in the CG, 581.1 in the IT, and 359.4 in the LB + IT group (F(2,183) = 14.5, p < 0.001), with the LB + IT group being prescribed significantly less than both the IT (p = 0.003) and CG groups (p < 0.001). CONCLUSION: Both the use of IT hydromorphone and LB were associated with shortened LOS and fewer total and per day in-hospital OMEs; however, the group who received both IT and LB (LB + IT) had the greatest decrease in LOS, and both inpatient and post-discharge OME usage. LEVEL OF EVIDENCE: Level III (retrospective comparative study).

The devastating dance between opioid and housing crises: Evidence from OxyContin reformulation.

Housing instability and drug misuse are two of the United States' most pressing challenges, each bearing profound health and societal consequences. A crucial yet largely underexplored question is the extent to which the opioid crisis has intensified housing instability. Our study ventures into this relatively uncharted nexus, investigating how the OxyContin reformulation, a pivotal moment in the U.S. opioid epidemic, impacted eviction rates. Employing a dose-response Difference-in-Differences model and analyzing eviction data from 2004 to 2016, we demonstrate that the OxyContin reformulation precipitated a significant increase in evictions, especially in areas with weak eviction protections or limited access to psychiatric treatment resources. Channel analyses reveal increased marijuana initiation and heightened mental and physical health issues following the reformulation. Moreover, the OxyContin reformulation leads to greater reliance on the Supplemental Nutrition Assistance Program, signaling an escalated financial strain on governmental resources. Finally, we find evidence of increased marital disruption post-reformulation. Our findings underscore the urgent need for collaborative efforts between public health and housing authorities to address both the opioid and housing crises.

Heavy burden of non-fatal overdose among people who inject drugs in San Francisco, 2022.

BACKGROUND: Drug overdose deaths increased by 50 % between 2017 and 2021 in San Francisco. Little is known about non-fatal overdose, which heralds future risk for morbidity and overdose death. We assessed non-fatal overdose, access to drug treatment, and overdose prevention service utilization among people who inject drugs (PWID) in San Francisco in 2022. METHODS: Data were from the National HIV Behavioral Surveillance (NHBS), a cross-sectional survey among PWID recruited by respondent-driven sampling from June-December 2022. Participants self-reported their experience of overall overdose. Logistic regression analysis identified factors associated with non-fatal overdose. RESULTS: Of 521 PWID, 120 (23.0 %) experienced non-fatal overdose; 207 (39.7 %) frequently injected methamphetamine and 175 (33.6 %) frequently injected heroin in the past 12 months. PWID who experienced non-fatal overdose were more likely to reside in the low-income neighborhoods (25.9 % vs. other neighborhoods 16.8 %, p = 0.022) in the past 12 months. Less than half (43.7 %) of PWID who experienced non-fatal overdose received overdose treatment. Compared to those who did not try to access treatment, adjusted odds of non-fatal overdose was 1.89 times higher among PWID who attempted to access drug treatment but were unable to (p = 0.035, 95 % CI 1.05-3.43); and 1.86 times higher among PWID who attempted to obtain medications to treat drug use but were unable to in the past 12 months (p = 0.049, 95 % CI: 1.00-3.43). CONCLUSIONS: Non-fatal overdose was highly prevalent among PWID, including those who frequently inject stimulants. Public health surveillance will need to be vigilant in monitoring stimulant use and tracking fentanyl contamination in non-opioid drugs. PWID who were most engaged in harm reduction practices were also the most likely to experience non-fatal overdose. Expansion of substance use and overdose treatment, naloxone, fentanyl test strips, and safe drug use education are needed to reduce risk of overdose deaths among PWID.

Effect of cryoablation in Nuss bar placement on opioid utilization and length of stay.

BACKGROUND: Our institution recently transitioned from paravertebral nerve blocks (PVBs) to intercostal nerve cryoablation (INC) for pain control following minimally invasive repair of pectus excavatum (MIRPE). This study aimed to determine how INC affected the operative time, length of stay, complication rates, inpatient opioid use, and outpatient prescription of opioids at a single center. METHODS: A retrospective review was performed at a single pediatric referral center of all patients who underwent MIRPE between 2018 and 2023. Patient demographics, operative details, and perioperative course were collected. The use of INC versus PVB was recorded. Univariate analyses were performed using Wilcoxon rank sum tests for continuous variables and chi-squared tests for categorical variables. RESULTS: 255 patients were included with a median age of 15 years, median BMI of 18.50 kg/m2, and median Haller index of 4.40. INC was utilized in 41% (105/255), and 59% (150/255) received PVB. The two groups did not differ significantly in BMI, Haller index, or complications, though the INC patients were older by 1 year (15.0 vs. 16.0, p = 0.034). INC was associated with an increased operative time (INC: 92 min vs. PVB: 67 min, p < 0.001), decreased length of stay (3 vs. 4 days, p = < 0.001), more than twofold decrease in inpatient opioids per day (INC: 16 MME vs. PVB: 41 MME, p < 0.001), and a fourfold decrease in the amount of opioids prescribed at discharge (INC: 90 MME vs. PVB: 390 MME, p < 0.001). CONCLUSION: INC after MIRPE significantly decreased both the inpatient opioid utilization and our outpatient prescribing practices while also decreasing our overall length of stay without increasing complications. LEVEL OF EVIDENCE: Level III.

Opioid Misuse by Adults with Chronic Pain: The Impact of Illness and Medication Beliefs.

BACKGROUND: Why do some adults with chronic pain misuse their prescription opioids when others do not? Based on the extended Common-Sense Model, the study evaluated whether adults' beliefs about their pain have an indirect effect on risk of opioid misuse through beliefs about opioids when controlling for depression. METHODS: The sample included 297 adult participants in the U.S. recruited from Prolific, an online crowdsourcing website. Study measures included the Illness Perception Questionnaire-Revised (IPQ-R; protective and threat-related illness beliefs about chronic pain), the Beliefs about Medicines Questionnaire-Specific subscale (BMQ-Specific; concern and necessity medication beliefs about prescription opioids), and the Current Opioid Misuse Measure (COMM; risk of current opioid misuse). This cross-sectional parallel mediation analysis was conducted using MPlus. RESULTS: After controlling for depression, the indirect effect of protective illness beliefs on opioid misuse risk through concern medication beliefs (b = -0.01, 95% CI (-0. 038, -0.001), and the indirect effect of threat-related illness beliefs on opioid misuse risk through necessity medication beliefs (b = 0.02, 95% CI (0.004, 0.036) were significant. The full model explained 35% of the variance of opioid misuse risk. CONCLUSIONS: Adults with chronic pain with stronger protective beliefs about pain were less likely to have concerns about their opioids and were at lower risk for opioid misuse, while those with greater threat-related beliefs about pain were more likely to believe that their opioids were necessary and be at greater risk for opioid misuse. Results have implications for medical and mental health providers and future research.

Chronic inflammatory pain reduces fentanyl intake during early acquisition of fentanyl self-administration, but does not change motivation to take fentanyl in male and female rats.

The co-occurrence of chronic pain and opioid misuse has led to numerous preclinical investigations of pain-opioid interactions to examine how pain manipulations alter the reinforcing properties of opioids. However, preclinical investigations of chronic pain effects on opioid drug self-administration have produced inconsistent results. Our previous work demonstrated that established fentanyl self-administration is resistant to change by induction of chronic inflammatory pain (Complete Freund's Adjuvant; CFA) in male and female rats, while other laboratories have shown that CFA increased fentanyl self-administration in male but not female rats when pain induction precedes self-administration, which may be a critical factor in determining the effects of chronic pain on self-administration. The present study was designed similarly to Higginbotham et al. (2022) to test the effects of CFA on fentanyl self-administration in rats that underwent pain prior to acquisition of fentanyl self-administration. Male and female rats treated with hindpaw CFA or saline were trained to intravenously self-administer (IVSA) fentanyl for 3 weeks under limited access to fentanyl (2 h per day) conditions. After 3 weeks of fentanyl IVSA acquisition, we tested motivation to take fentanyl using progressive ratio testing and dose-response testing. CFA male and female rats self-administered less fentanyl than saline-treated controls during week 1 of acquisition, but not during weeks 2-3 of acquisition. Intra-session analysis of week 1 data demonstrated that chronic inflammatory pain suppressed fentanyl intake towards the end of week 1 and at the end of each operant session. We also report no effects of chronic inflammatory pain on motivation to take fentanyl. We discuss potential methodological explanations for differences between these results and prior reports. Our findings demonstrate that CFA temporarily suppresses fentanyl IVSA in animals without changing motivation to take fentanyl or promoting escalation of opioid use, suggesting that chronic inflammatory pain is unlikely to promote long-term risk of opioid misuse.

Clinical implications of opioid parent-metabolite ratios.

BACKGROUND: The opioid epidemic has underscored the importance of urine drug testing in the management of chronic pain. However, interpreting test results can be challenging, especially in scenarios where medications may have been directly added to urine samples to simulate compliance. METHODS: We conducted a retrospective analysis of 9,690 opioid testing results using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study aimed to define the expected ratios between parent drugs and metabolites for eight commonly prescribed opioids. Cases with a parent-metabolite ratio above the 95th percentile were subjected to chart review. RESULTS: A total of 13 cases appeared likely consistent with simulated compliance with buprenorphine, 2 with methadone, 14 with oxycodone, and one with hydrocodone. The unusual patterns of parent-metabolite ratio can also be associated with hyperacute drug exposures/use, pharmaceutical impurity, or underlying liver enzyme deficiency. Furthermore, patients who failed the decision limits could exhibit other illicit use or aberrant behaviors. CONCLUSION: Laboratories conducting LC-MS/MS-based opioid testing can more objectively identify anomalies by analyzing parent-metabolite ratios. When in consultation with providers, laboratories can point to these data when suggesting the possibility of simulated compliance and help identify cases warranting further investigation.

Providers' use of pharmacogenetic testing to inform opioid prescribing among veterans.

Aim: To survey Veterans Health Administration providers who prescribed tramadol or codeine to patients with known genotyping for cytochrome 2D6 (CYP2D6) to ascertain awareness of their patient's pharmacogenetic (PGx) test status, whether these results influenced prescribing, perceived benefit of PGx testing, and resources needed to obtain and deliver PGx testing information.Materials & methods: A provider survey was conducted of those who prescribed tramadol or codeine in a patient genotyped for CYP2D6.Results: Of 876 eligible providers, 220 completed the survey. Ten percent were aware that their patient received a PGx test, 64% had not ordered any PGx test related to any medication in the prior year, 55% strongly agreed or agreed that PGx testing is or will be valuable to guide pain medication prescriptions, 29% felt that the evidence base for PGx testing is very strong or moderately strong, 22% responded likely or extremely likely to order a future PGx test, and 51% felt that it would be either very important or fairly important to have a local subject matter expert as a resource for PGx testing.Conclusion: There are modifiable factors that the Veterans Health Administration could address to optimize PGx testing for pain management.

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Managing Cancer Pain in Hospitalized Patients with Comorbid Opioid Use Disorder with Buprenorphine: A Case Series.

Data indicate that one in five patients with cancer might be at risk for nonmedical opioid use and its extreme form, opioid use disorder (OUD). Buprenorphine is one of the few medications available for the management of patients with co-occurring OUD and chronic pain. Care for these patients can be challenging and require the expertise of specialist clinicians with a deep understanding of addiction and cancer pain. Regrettably, these specialist clinicians may not always be available and accessible when patients are admitted to the hospital. Reports on how primary non-specialist clinicians without access to specialist addiction services navigate the care of such patients in the inpatient setting are limited. We hereby describe the care of three patients with OUD receiving buprenorphine who were hospitalized for cancer pain.

Clinical pain management: Current practice and recent innovations in research.

Chronic pain affects one in five adults. It is not only a major cause of disability for individual patients but also a driver of costs for entire healthcare systems. Treatment of pain remains a challenge, and the use of opioids has further led to a concurrent opioid epidemic. In this review, we discuss current standard treatment options for chronic pain, including pharmacological, behavioral, and interventional treatments. In addition, we review ongoing research in different areas that will potentially unlock new therapies.

Impact of Complementary Health Approaches on Opioid Prescriptions Among Veterans with Musculoskeletal Disorders-A Retrospective Cohort Study.

To examine whether complementary and integrative health approaches mitigate opioid prescriptions for pain and whether the relationship differs by post-dramatic stress disorder (PTSD) diagnosis, we followed 1,993,455 Veterans with musculoskeletal disorders during 2005-2017 using Veterans Healthcare Administration electronic health records. Complementary and integrative health (CIH) approaches were defined as ≥1 primary care visits for meditation, Yoga, and acupuncture etc using natural language processing. Opioid prescriptions were ascertained from pharmacy dispensing records. A propensity score was estimated and used to match one control Veteran to each CIH recipient. Over the 2-year follow-up period after the index diagnosis, 140,902 (7.1%) Veterans received ≥ 1 modalities. Among the matched analytic sample (272,296 Veterans), the likelihood of dispensing opioid prescriptions was significantly lower for Veterans in the CIH group than their controls [adjusted hazard ratio (aHR), 0.45 (95% Confidence Intervals (CI): 0.44-0.46)]. The association did not differ between Veterans with [aHR: 0.46 (95% CI: 0.45-0.47)] and without [aHR: 0.44 (95% CI: 0.43-0.45)] PTSD. In sensitivity analyses, the exposure group had 3.82 (95% CI: 3.76-3.87) months longer restricted mean survival time to opioid initiation, 2% (95% CI: 4%-1%) lower morphine equivalent and 17% lower total days' supply (95% CI: 18%-16%). The relationship remains significant but was attenuated after eliminating waiting time for the exposure group (aHR, 0.63 (95% CI: 0.62-0.64)). These observations suggest that CIH approaches may help reduce opioid prescriptions for Veterans with musculoskeletal disorders and related pain. The impact of the timing of receiving such approaches warrants further investigation. PERSPECTIVE: This article presents a quasi-experimental investigation into potential benefit of complementary and integrative health approaches (CIH) on de-prescribing opioids. The findings may potentially help clinicians who are seeking non-pharmacological alternative options to manage patient pain and opioid dependence".

Persistent pain, long-term opioids, and restoring trust in the patient-clinician relationship.

The erosion of trust in the patient-clinician relationship is an underappreciated, and vital, component of the prescription opioid crisis. Drawing from lived experience of patients and clinicians, and a narrative evidence review, this report discusses how opioid use for persistent pain can impact the patient-clinician relationship from the vantage points of the patient and the family physician. For patients, the stress of dealing with persistent pain, misalignment with clinicians regarding goals of care, experiences of disrespect and stigma, fear of abrupt tapers, and frustration with a fragmented health system, all combine to breed a lack of trust. Clinicians, for their part, experience challenges due to inadequate resources for pain management and opioid safety, pressure to deprescribe opioids rapidly, inconsistent prescribing practices of colleagues, 'policing' opioid prescriptions when concern arises for opioid use disorder and adversarial relationships with frustrated patients wary of clinician intentions. As a result, many clinicians struggle to maintain a therapeutic relationship with patients in great need of empathy and healing. To support implementation of evidence-based guidelines and achieve public health goals of safer prescribing and reducing harm from prescription opioids, we recommend steps health systems and clinicians can take to rebuild trust in the patient-clinician relationship, enable patient-centered pain care, and embed patient perspectives into opioid safety processes. PERSPECTIVE: Erosion of patient-clinician trust is a barrier to implementing evidence-based guidelines that aim to improve opioid safety. This paper explores lived patient and clinician experiences and recommends steps for health systems and clinicians to rebuild this trust as a strategy to actualize the benefits of adherence to these guidelines.

The preponderance of opioid overdoses among middle-aged individuals in the US: Analysis of 911 dispatch data - Q1 2018 to Q3 2023.

BACKGROUND: Opioid overdoses have increased at a concerning rate in recent years. Middle-aged individuals have been reported as an age group of high concern for opioid overdoses. The purpose of this study was to assess trends in opioid overdose 911 dispatches between Q1 2018 and Q3 2023 among different age groups. It was hypothesized that the steepest increase in dispatches would be among middle-aged individuals. METHODS: We assessed age-related trends in opioid-related 911 dispatches using emergency medical service (EMS) data collected by biosptial, io. Data encompassed all 50 states and were broken into yearly quarters between Q1 2018 and Q3 2023. Age groups included younger- (10 to 29), middle- (30 to 49), and older-aged (50 to 69) individuals. Joinpoint regression was utilized to examine these trends. RESULTS: There were a total of 1,420,298 opioid-related 911 dispatches reported. Most were reported among middle-aged individuals, accounting for 48.9 % (n = 682,132) of all dispatches. Significant increases in dispatches were identified overall between Q1 2018 and Q2 2021 (ß = 0.096, SE = 0.006, P ≤ 0.001). The steepest increase was identified among middle-aged individuals between Q1 2018 and Q2 2021 (ß = 0.104, SE = 0.007, P ≤ 0.001). There was a significant decrease in dispatches among younger-aged individuals between Q2 2021 and Q3 2023 (ß = -0.024, SE = 0.011, P = .036). CONCLUSION: Middle-aged individuals experienced significant increases in opioid-related 911 dispatches between Q1 2018 and Q2 2021, and had the steepest increase compared to the other age groups. Conversely, younger-aged individuals have experienced a recent decrease in dispatches. These findings support previous indications that middle-aged individuals are at significant risk for opioid overdose. Additional research is necessary to identify geographic and demographic factors that may affect these trends.

Prescription opioid use in Israel - the tide has risen, but it's not a tidal wave.

The devastating human and financial costs of the ongoing global opioid crisis underscore the need for comprehensive public health strategies, effective treatment programs, and robust policy interventions to mitigate its impact. Regarding Israel, numerous reports highlight a steady increase since 2000 in prescription opioid use and the shift to more potent opioids particularly fentanyl, particularly among more marginalized population groups. In response to growing concern in the country about the rise in prescription opioid use and the consequential risk of opioid use disorder, the Israeli government, together with the country's health service providers, implemented a series of measures to monitor and regulate opioid prescriptions and balance the need for effective pain management with the prevention of opioid abuse and its associated harms. A national opioid data monitoring system is being established, alongside the provision of addiction training for health professionals, the integration of treatment services for opioid use disorder into the nationalized primary healthcare system, and the expansion of harm reduction strategies to mitigate the health risks associated with opioid use. Additional funding for opioid-related research, and for the broader fields of addictions and mental health, is vital. In conclusion, the sum of the evidence suggests that Israel is not facing an "opioid crisis" Continued commitment, resources, and innovative approaches will be crucial to ensure that the rising tide of opioid use in Israel, particularly during and in the aftermath of the ongoing war, will not become a tidal wave.

Opioid system and related ligands: from the past to future perspectives.

Chronic pain is a pathological condition affecting about 30% of population. It represents a relevant social-health issue worldwide, and it is considered a significant source of human suffering and disability, strongly affecting patients' quality of life. Despite several pharmacological strategies to guarantee an adequate pain management have been proposed over the years, opioids still represent one of the primary choices for treating moderate-to-severe pain in both cancer and non-cancer patients. However, chronic use of opioids often leads to numerous side effects, including respiratory depression, constipation, analgesic tolerance, and opioid-induced hyperalgesia (OIH), which can strongly limit their use. Given the fundamental role of opioid system in pain relief, this review provides a general overview about the main actors (endogenous opioid peptides and receptors) involved in its modulation. Furthermore, this review explores the action and the limitations of conventional clinically used opioids and describes the efficacy and safety profile of some promising analgesic compounds. A deeper understanding of the molecular mechanisms behind both analgesic effects and adverse events could advance knowledge in this field, thus improving chronic pain treatment.

Predictors of emergency medical transport refusal following opioid overdose in Washington, DC.

BACKGROUND AND AIMS: Patient initiated transport refusal during Emergency Medical Service (EMS) opioid overdose encounters has become an endemic problem. This study aimed to quantify circumstantial and environmental factors which predict refusal of further care. DESIGN: In this cross-sectional analysis, a case definition for opioid overdose was applied retrospectively to EMS encounters. Selected cases had sociodemographic and situational/incident variables extracted using patient information and free text searches of case narratives. 50 unique binary variables were used to build a logistic model. SETTING: Prehospital EMS overdose encounters in Washington, DC, USA, from July 2017 to July 2023. PARTICIPANTS: Of EMS encounters in the study timeframe, 14 587 cases were selected as opioid overdoses. MEASUREMENTS: Predicted probability for covariates was the outcome variable. Model performance was assessed using Stratified K-Fold Cross-Validation and scored with positive predictive value, sensitivity and F1. Prediction accuracy and McFadden's pseudo-R squared are also determined. FINDINGS: The model achieved a predictive accuracy of 78% with a high positive predictive value (0.83) and moderate sensitivity (0.68). Bystander type influenced the refusal outcome, with decreased refusal probability associated with family (nondescript) (-28%) and parents (-16%), while presence of a girlfriend increased it (+28%). Negative situational factors like noted physical trauma (-62%), poor weather (-14%) and lack of housing (-14%) decreased refusal probability. Characteristics of the emergency response team, like a prior crew member encounter (+20%) or crew experience <1 year (-36%), had a variable association with transport. CONCLUSIONS: Refusal of emergency transport for opioid overdose cases in Washington, DC, USA, has expanded by 43.8% since 2017. Several social, environmental and systematic factors can predict this refusal. Logistic regression models can be used to quantify broad categories of behavior in surveillance medical research.