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One of the most underdiagnosed and undertreated non-motor symptoms of Parkinson's Disease is chronic pain. This is generally treated with analgesics which is not always effective and can cause several side-effects. Therefore, new ways to reduce chronic pain are needed. Several experimental studies show that CT-optimal touch can reduce acute pain. However, little is known about the effect of CT-optimal touch on chronic pain. The aim of the current study is to investigate whether CT-optimal touch can reduce the chronic pain experience in Parkinson patients. In this intervention study, 17 Parkinson patients underwent three conditions; no touch, CT-optimal touch and CT non-optimal touch with a duration of one week each. During each touch week, participants received touch from their partners twice a day for 15 minutes. Results show that both types of touch ameliorate the chronic pain experience. Furthermore, it appears that it is slightly more beneficial to apply CT-optimal touch also because it is perceived as more pleasant. Therefore, we argue that CT-optimal touch might be used when immediate pain relief is needed. Importantly, this study shows that CT-optimal touch can reduce chronic pain in Parkinson's Disease and can be administered by a partner which makes it feasible to implement CT-optimal touch as daily routine.

Objective: This study aimed to provide a comprehensive overview of self-medication practices among students by conducting a bibliometric analysis of the available scientific literature. This research highlights the importance of promoting safe and responsible healthcare behaviors among students. Methods: A systematic search was conducted in the Scopus database to retrieve all peer-reviewed English articles and reviews published from 1968 onwards. The retrieved documents were analyzed to identify publication trends, citation counts, top journals, geographical distribution, and emerging research themes. Results: The findings indicate a significant increase in published literature about student self-medication over the past fifteen years. However, it was observed that the citation count for these documents was lower than expected, suggesting a need for increased attention toward this critical topic. The analysis also identified several hot topics in student self-medication, including the misuse of over-the-counter medications, dietary supplements, and psychoactive substances. The inappropriate use of antibiotics and the self-medication of mental health issues, such as anxiety and depression, were also identified as significant problems. Conclusions and recommendations: Self-medication among students is a complex and critical issue that requires immediate attention. This study highlights the urgent need for greater awareness and education regarding responsible self-medication practices among students. New policies, interventions, and strategies should be developed to address malpractices, misconceptions, and harmful practices related to self-medication. Educational institutions and health authorities should play a crucial role in providing students with mental health resources and support services. Collaborative efforts among healthcare providers, universities, and policymakers are required to consider this issue as public health priority, establish counseling centers

The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. While much previous work has emphasized the role of descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We describe pain-related activity throughout this circuit and report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings substantially revise current models of the DPMS and establish a supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.

BACKGROUND: Opioid use after revision total hip arthroplasty (rTHA) has not been well characterized. The purpose of this study was to characterize preoperative, perioperative, and postoperative opioid use during rTHA. METHODS: Patients undergoing revision THA from 2010 to 2018 were screened for opioid use 3 months before revision surgery and tracked 24 months postoperatively. Patients were categorized as naïve or tolerant. Opioid prescriptions and average morphine milligram equivalents (MME) were compared between the two groups. RESULTS: One hundred twenty-four of 247 patients (50%) in the tolerant group averaged a preoperative MME of 23.7 mg/day. Postoperatively, tolerant patients received significantly higher daily MME at all time points, including at 3 months 31.4 versus 18.1 mg/day (P < 0.001), 6 months 19.9 versus 2.95 mg/day (P < 0.001), 12 months 14.3 versus 3.5 mg/day (P < 0.001), and 24 months 10.7 versus 2.17 mg/day (P < 0.001). Tolerant patients were more likely to have a prescription at 6 months (44% versus 22%), 12 months (41.4% versus 24%), and 24 months (38% versus 19.3%) (P < 0.001, P = 0.002, P < 0.001, respectively). DISCUSSION: Opioid-tolerant patients had higher postoperative MME requirements for longer recovery duration. Both groups reduced opioid use at 3 months and plateaued at 6 months. These findings can help the revision surgeon counsel patients and expectations.

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.

OBJECTIVES: Patients receiving chiropractic spinal manipulation (CSM) for low back pain (LBP) are less likely to receive any opioid prescription for subsequent pain management. However, the likelihood of specifically being prescribed tramadol, a less potent opioid, has not been explored. We hypothesised that adults receiving CSM for newly diagnosed radicular LBP would be less likely to receive a tramadol prescription over 1-year follow-up, compared with those receiving usual medical care. DESIGN: Retrospective cohort study. SETTING: US medical records-based dataset including >115 million patients attending academic health centres (TriNetX, Inc), queried 9 November 2023. PARTICIPANTS: Opioid-naive adults aged 18-50 with a new diagnosis of radicular LBP were included. Patients with serious pathology and tramadol use contraindications were excluded. Variables associated with tramadol prescription were controlled via propensity matching. INTERVENTIONS: Patients were divided into two cohorts dependent on treatment received on the index date of radicular LBP diagnosis (CSM or usual medical care). PRIMARY AND SECONDARY OUTCOME MEASURES: Risk ratio (RR) for tramadol prescription (primary); markers of usual medical care utilisation (secondary). RESULTS: After propensity matching, there were 1171 patients per cohort (mean age 35 years). Tramadol prescription was significantly lower in the CSM cohort compared with the usual medical care cohort, with an RR (95% CI) of 0.32 (0.18 to 0.57; p<0.0001). A cumulative incidence graph demonstrated that the reduced incidence of tramadol prescription in the CSM cohort relative to the usual medical care cohort was maintained throughout 1-year follow-up. Utilisation of NSAIDs, physical therapy evaluation and lumbar imaging was similar between cohorts. CONCLUSIONS: This study found that US adults initially receiving CSM for radicular LBP had a reduced likelihood of receiving a tramadol prescription over 1-year follow-up. These finding

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

BackgroundWe aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population.MethodsWe included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models.ResultsAmong 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6).ConclusionsPain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

BACKGROUND: Patients with limited English proficiency (LEP) may have worse health outcomes and differences in processes of care. Language status may particularly affect situations that depend on communication, such as symptom management or end-of-life (EOL) care. OBJECTIVE: The objective of this study was to assess whether opioid prescribing and administration differs by English proficiency (EP) status among hospitalized patients receiving EOL care. METHODS: This single-center retrospective study identified all adult patients receiving comfort care on the general medicine service from January 2013 to September 2021. We assessed for differences in the quantity of opioids administered (measured by oral morphine equivalents [OME]) by patient LEP status using multivariable linear regression, controlling for other patient and medical factors. RESULTS: We identified 2652 patients receiving comfort care at our institution during the time period, of whom 1813 (68%) died during the hospitalization. There were no significant differences by LEP status in terms of mean OME per day (LEP received 30.8 fewer OME compared to EP, p = .91) or in the final 24 h before discharge (LEP received 61.7 more OME compared to EP, p = .80). CONCLUSION: LEP was not associated with differences in the amount of opioids received for patients whose EOL management involved standardized order sets for symptom management at our hospital.

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

Aim To explore registered nurses' experiences with pain management in patients with opioid use disorder (OUD) in home care. Design Qualitative explorative-descriptive design. Methods Data were collected via nine individual semi-structured interviews with registered nurses working in home care meeting patients with OUD. Data were analysed using systematic text condensation. Results Three categories were identified: Reciprocity in relationships and a professional approach enhance pain management; Discrepancies between guidelines, patient-reported pain and RNs' observations challenge pain management; and Interprofessional collaboration makes or breaks pain management.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder t

BACKGROUND: The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses. RESULTS: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour. CONCLUSIONS: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation.

Aim To explore registered nurses' experiences with pain management in patients with opioid use disorder (OUD) in home care. Design Qualitative explorative-descriptive design. Methods Data were collected via nine individual semi-structured interviews with registered nurses working in home care meeting patients with OUD. Data were analysed using systematic text condensation. Results Three categories were identified: Reciprocity in relationships and a professional approach enhance pain management; Discrepancies between guidelines, patient-reported pain and RNs' observations challenge pain management; and Interprofessional collaboration makes or breaks pain management.

Aim To explore registered nurses' experiences with pain management in patients with opioid use disorder (OUD) in home care. Design Qualitative explorative-descriptive design. Methods Data were collected via nine individual semi-structured interviews with registered nurses working in home care meeting patients with OUD. Data were analysed using systematic text condensation. Results Three categories were identified: Reciprocity in relationships and a professional approach enhance pain management; Discrepancies between guidelines, patient-reported pain and RNs' observations challenge pain management; and Interprofessional collaboration makes or breaks pain management.

Aim To explore registered nurses' experiences with pain management in patients with opioid use disorder (OUD) in home care. Design Qualitative explorative-descriptive design. Methods Data were collected via nine individual semi-structured interviews with registered nurses working in home care meeting patients with OUD. Data were analysed using systematic text condensation. Results Three categories were identified: Reciprocity in relationships and a professional approach enhance pain management; Discrepancies between guidelines, patient-reported pain and RNs' observations challenge pain management; and Interprofessional collaboration makes or breaks pain management.

Opioids are the cornerstone of cancer pain management. However, the type and dosing regimen required to achieve satisfactory pain control differs between individuals causing unpredictable analgesia and adverse effects. This leads to multiple hospital admissions, increased appointments, and even increased death rates. The observed variability in opioid response has been attributed to numerous functional gene variants. A genetic test that could determine the likelihood of clinical benefit or adverse effects from a certain opioid would provide an opportunity to significantly improve patient pain and symptom outcomes. This thesis starts with a review of current evidence of pharmacogenomics for opioid use in cancer. Through a combination of laboratory and clinical research methods, this list of candidate gene variants is then used to systematically examine the role of pharmacogenomics for opioid use to provide the basis for a precision medicine approach to pain control in cancer. Data from a longitudinal registry of patients receiving opioids for cancer related pain is used to conduct multiomic (clinical, genetic, transcriptomic) and pharmacokinetic analyses to investigate differences in opioid treatment response. The opioid prescription patterns in advanced cancer are then mapped to understand if pharmacogenomic guided prescribing is practical in the real-world setting. Genes involved in neuroimmune pathways, particularly within two key pathways in innate immune signalling (TLR4 pathway and ARRB2 pathway) demonstrated associations with opioid response outcomes (dose, pain, adverse effects). New information is also presented on the associations between genotype combinations for two important genes (COMT and OPRM1) and opioid response outcomes. Together, these genes were found to be important for the interindividual variability in opioid response within this registry. Additionally, the concentrations of plasma oxycodone and its metabolites were found to be potentially imp

Aim To explore registered nurses' experiences with pain management in patients with opioid use disorder (OUD) in home care. Design Qualitative explorative-descriptive design. Methods Data were collected via nine individual semi-structured interviews with registered nurses working in home care meeting patients with OUD. Data were analysed using systematic text condensation. Results Three categories were identified: Reciprocity in relationships and a professional approach enhance pain management; Discrepancies between guidelines, patient-reported pain and RNs' observations challenge pain management; and Interprofessional collaboration makes or breaks pain management.

Aim: To explore registered nurses' experiences with pain management in patients with opioid use disorder (OUD) in home care. Design: Qualitative explorative-descriptive design. Methods: Data were collected via nine individual semi-structured interviews with registered nurses working in home care meeting patients with OUD. Data were analysed using systematic text condensation. Results: Three categories were identified: Reciprocity in relationships and a professional approach enhance pain management; Discrepancies between guidelines, patient-reported pain and RNs' observations challenge pain management; and Interprofessional collaboration makes or breaks pain management.

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

People who nonmedically use drugs (PWUD) face intricate social issues that suppress self-actualization, communal integration, and overall health and wellness. Strengths-based approaches, an under-used pedagogy and practice in addiction medicine, underscore the significance of identifying and recognizing the inherent and acquired skills, attributes, and capacities of PWUD. A strengths-based approach engenders client affirmation and improves their capacity to reduce drug use-related harms by leveraging existing capabilities. Exploring this paradigm, we conducted and analyzed interviews with 46 PWUD who were clients at syringe services programs in New York City and rural southern Illinois, two areas with elevated rates of opioid-related morbidity and mortality, to assess respondents perceived strengths. We located two primary thematic modalities in which strengths-based ethos is expressed: individuals (1) being and advocate and resource for harm reduction knowledge and practices and (2) engaging in acts of continuous self-actualization. These dynamics demonstrate PWUD strengths populating and manifesting in complex ways that both affirm and challenge humanist and biomedical notions of individual agency, as PWUD refract enacted, anticipated, and perceived stigmas. In conclusion, programs that blend evidence-based, systems-level interventions on drug use stigma and disenfranchisement with meso and micro-level strengths-based interventions that affirm and leverage personal identity, decision-making capacity, and endemic knowledge may help disrupt health promotion cleavages among PWUD.

PURPOSE: The pupil displays chaotic oscillations, also referred to as pupillary unrest in ambient light (PUAL). As pain has previously been shown to increase pupillary unrest, the quantitative assessment of PUAL has been considered a possible tool to identify and quantify pain. Nevertheless, PUAL is affected by various states, such as vigilance, cognitive load, or emotional arousal, independent of pain. Furthermore, systematically applied opioids are known to reduce PUAL, thus potentially limiting its usefulness to detect pain or changes in pain intensity. To test the hypothesis that PUAL can reliably identify changes in pain intensity in a clinical setting, we measured PUAL in patients experiencing substantial pain relief when regional anesthesia interventions were applied after surgery. METHODS: We conducted an observational study at an academic surgery centre following institutional review board approval. Eighteen patients with unsatisfactory pain control following surgery underwent regional anesthesia procedures to improve pain control. We used infrared pupillometry to assess pupillary unrest before and after the regional block. We then compared the changes in pupillary unrest with the changes in pain scores (numeric rating scale [NRS], range 0-10). RESULTS: Eighteen patients received epidural anesthesia (n = 14) or peripheral nerve blocks (n = 4), resulting in improvement of mean (standard deviation [SD]) NRS pain scores from 7.2 (1.7) to 1.9 (1.8) (difference in means, -2.2; 95% confidence interval [CI], -6.3 to -4.1; P < 0.001). Nevertheless, pupillary unrest did not change as pain decreased; the mean (SD) PUAL was 0.113 (0.062) before analgesia and 0.112 (0.068) after analgesia (difference in means, -0.001; 95% CI, -0.018 to 0.015; P = 0.88). CONCLUSION: In this prospective observational study, pupillometric measurements of pupillary unrest did not identify changes in pain intensity in a postoperative, predominantly opioid-exposed patient population. Whil

BackgroundThe rates of suicide and opioid use disorder (OUD) among pregnant and postpartum women continue to increase. This research characterized OUD and suicide attempts among Medicaid-enrolled perinatal women and examined prenatal OUD diagnosis as a marker for postpartum suicide attempts.MethodsData from Oregon birth certificates, Medicaid eligibility and claims files, and hospital discharge records were linked and analyzed. The sample included Oregon Medicaid women aged 15-44 who became pregnant and gave live births between January 2008 and January 2016 (N = 61,481). Key measures included indicators of suicide attempts (separately for any means and opioid poisoning) and OUD diagnosis, separately assessed during pregnancy and the one-year postpartum period. Probit regression was used to examine the overall relationship between prenatal OUD diagnosis and postpartum suicide attempts. A simultaneous equations model was employed to explore the link between prenatal OUD diagnosis and postpartum suicide attempts, mediated by postpartum OUD diagnosis.ResultsThirty-three prenatal suicide attempts by any means were identified. Postpartum suicide attempts were more frequent with 58 attempts, corresponding to a rate of 94.3 attempts per 100,000. Of these attempts, 79% (46 attempts) involved opioid poisoning. A total of 1,799 unique women (4.6% of the sample) were diagnosed with OUD either during pregnancy or one-year postpartum with 53% receiving the diagnosis postpartum. Postpartum suicide attempts by opioid poisoning increased from 55.5 per 100,000 in 2009 to 105.1 per 100,000 in 2016. The rate of prenatal OUD also almost doubled over the same period. Prenatal OUD diagnosis was associated with a 0.15%-point increase in the probability of suicide attempts by opioid poisoning within the first year postpartum. This increase reflects a three-fold increase compared to the rate for women without a prenatal OUD diagnosis. A prenatal OUD diagnosis was significantly associated wit

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

Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor (MC1R) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed.

Despite the worldwide prevalence and huge burden of pain, pain is an undertreated phenomenon. Currently used analgesics have several limitations regarding their efficacy and safety. The discovery of analgesics possessing a novel mechanism of action has faced multiple challenges, including a limited understanding of biological processes underpinning pain and analgesia and poor animal-to-human translation. Computational pharmacology is currently employed to face these challenges. In this review, we discuss the theory, methods, and applications of computational pharmacology in pain research. Computational pharmacology encompasses a wide variety of theoretical concepts and practical methodological approaches, with the overall aim of gaining biological insight through data acquisition and analysis. Data are acquired from patients or animal models with pain or analgesic treatment, at different levels of biological organization (molecular, cellular, physiological, and behavioral). Distinct methodological algorithms can then be used to analyze and integrate data. This helps to facilitate the identification of biological molecules and processes associated with pain phenotype, build quantitative models of pain signaling, and extract translatable features between humans and animals. However, computational pharmacology has several limitations, and its predictions can provide false positive and negative findings. Therefore, computational predictions are required to be validated experimentally before drawing solid conclusions. In this review, we discuss several case study examples of combining and integrating computational tools with experimental pain research tools to meet drug discovery challenges.

The study aimed to investigate the prevalence and characteristics of pain in different ulcer types and to identify factors associated with pain experience in patients with lower-extremity ulcers. A cross-sectional single-centre study was performed, including 130 newly referred outpatients with lower-extremity ulcers. Pain intensity was measured with a visual analog scale (VAS) and pain characteristics with the short form mcgill pain questionnaire-2 (SF-MPQ-2). The mean pain intensity was 29.5 (SD 31.8) at rest and 35.5 (SD 34.1) during movement (0–100 VAS). 61.5% of the patients experienced pain (VAS > 0) at rest and 70.8% during movement. Moderate to severe pain at rest was seen in 39.2% and in 43.8% of patients during movement. The mean total score on SF-MPQ-2 (range 0–220) was 35.9 (SD 32.6). Most of the patients described pain as intermittent (mean 11.8 SD 13.9). Analgesics were prescribed for 78% of the patients. Ulcer type (i.e., arterial, immunological, pressure and venous) and age were associated with pain severity, and women had a significantly lower well-being score than men. Prevalence of pain in patients with lower-extremity ulcers was high across different ulcer aetiologies. Pain intensity and quality must be assessed to obtain adequate pain management.

The study aimed to investigate the prevalence and characteristics of pain in different ulcer types and to identify factors associated with pain experience in patients with lower-extremity ulcers. A cross-sectional single-centre study was performed, including 130 newly referred outpatients with lower-extremity ulcers. Pain intensity was measured with a visual analog scale (VAS) and pain characteristics with the short form mcgill pain questionnaire-2 (SF-MPQ-2). The mean pain intensity was 29.5 (SD 31.8) at rest and 35.5 (SD 34.1) during movement (0–100 VAS). 61.5% of the patients experienced pain (VAS > 0) at rest and 70.8% during movement. Moderate to severe pain at rest was seen in 39.2% and in 43.8% of patients during movement. The mean total score on SF-MPQ-2 (range 0–220) was 35.9 (SD 32.6). Most of the patients described pain as intermittent (mean 11.8 SD 13.9). Analgesics were prescribed for 78% of the patients. Ulcer type (i.e., arterial, immunological, pressure and venous) and age were associated with pain severity, and women had a significantly lower well-being score than men. Prevalence of pain in patients with lower-extremity ulcers was high across different ulcer aetiologies. Pain intensity and quality must be assessed to obtain adequate pain management.

BACKGROUND: Over the past decades, opioid prescriptions have increased in the Netherlands. The Dutch general practitioners' guideline on pain was recently updated and now aims to reduce opioid prescriptions and high-risk opioid use for non-cancer pain. The guideline, however, lacks practical measures for implementation.OBJECTIVE: This study aims to determine practical components for a tool that should assist Dutch primary care prescribers and implements the recently updated guideline to reduce opioid prescriptions and high-risk use.METHODS: A modified Delphi approach was used. The practical components for the tool were identified based on systematic reviews, qualitative studies, and Dutch primary care guidelines. Suggested components were divided into Part A, containing components designed to reduce opioid initiation and stimulate short-term use, and Part B, containing components designed to reduce opioid use among patients on long-term opioid treatment. During three rounds, a multidisciplinary panel of 21 experts assessed the content, usability, and feasibility of these components by adding, deleting, and adapting components until consensus was reached on the outlines of an opioid reduction tool.RESULTS: The resulting Part A consisted of six components, namely education, opioid decision tree, risk assessment, agreements on dosage and duration of use, guidance and follow-up, and interdisciplinary collaboration. The resulting Part B consisted of five components, namely education, patient identification, risk assessment, motivation, and tapering.CONCLUSIONS: In this pragmatic Delphi study, components for an opioid reduction tool for Dutch primary care-givers are identified. These components need further development, and the final tool should be tested in an implementation study.

Molecular mechanisms of the interaction between opioidergic and dopaminergic processing during pain-related experiences in the human brain are still incompletely understood. This is partially due to the invasive nature of the available techniques to visualize and measure metabolic activity. Positron Emission Tomography (PET) radioligand studies using radioactive substances are still the only available modality to date that allows for the investigation of the molecular mechanisms in the human brain. The most commonly studied PET radiotracers are [11C]-carfentanil (CFN) and [11C]- or [18F]-diprenorphine (DPN), which bind to opioid receptors, and [11C]-raclopride (RAC) and [18F]-fallypride (FAL) tracers, which bind to dopamine receptors. The current meta-analysis examines pain-related studies that used aforementioned opioid and dopamine radioligands in an effort to consolidate the available data into the most likely activated regions. Our primary goal was to identify regions of shared opioid/dopamine neurotransmission during pain-related experiences using within-subject approach. Seed-based d Mapping (SDM) analysis of previously published voxel coordinate data showed that opioidergic activations were strongest in the bilateral caudate, thalamus, right putamen, cingulate gyrus, midbrain, inferior frontal gyrus, and left superior temporal gyrus. The dopaminergic studies showed that the bilateral caudate, thalamus, right putamen, cingulate gyrus, and left putamen had the highest activations. We were able to see a clear overlap between opioid and dopamine activations in a majority of the regions during pain-related experiences, though there were some unique areas of dopaminergic activation such as the left putamen. Regions unique to opioidergic activation included the midbrain, inferior frontal gyrus, and left superior temporal gyrus. Here we provide initial evidence for the functional overlap between opioidergic and dopaminergic processing during aversive states in humans

BackgroundCommonly prescribed antidepressants (paroxetine, fluoxetine, duloxetine, bupropion) inhibit bioconversion of several prodrug opioid medications to their active metabolite, potentially decreasing analgesic effect. There is a paucity of studies assessing the risk-benefit of concomitant administration of antidepressants and opioids.Research design and methodsObservational study of adult patients taking antidepressants prior to scheduled surgery using 2017-2019 electronic medical record data to assess perioperative use of opioids and to determine the incidence and risk factors for developing postoperative delirium. We conducted a generalized linear regression with the Gamma log-link to assess the association between use of antidepressants and opioids and a logistic regression to assess the association between antidepressants use and the likelihood of developing postoperative delirium.ResultsAfter controlling for patient demographic and clinical characteristics, and postoperative pain, use of inhibiting antidepressants was associated with 1.67 times greater use of opioids per hospitalization day (p = 0.00154), a two-fold increase in the risk for developing postoperative delirium (p = 0.0224), and an estimated average of four additional days of hospitalization (p < 0.00001) compared to use of non-inhibiting antidepressants.ConclusionsCareful consideration to drug-drug interactions and risk of related adverse events remains critical in the safe and optimal management of postoperative pain in patients taking concomitantly antidepressants.

The minimization of pain in research animals is a scientific and ethical necessity. Carprofen is commonly used for pain management in mice; however, some data suggest that the standard dosage of 5 mg/kg may not provide adequate analgesia after surgery. We hypothesized that a higher dose of carprofen in mice would reduce pain-associated behaviors and improve analgesia without toxic effects. A pharmacokinetic study was performed in mice given carprofen subcutaneously at 10 or 20 mg/kg. Plasma concentrations were measured at 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h after dosing (n = 3 per time point and treatment). At these doses, plasma levels were above the purported therapeutic level for at least 12 and 24 h, respectively, with respective half-lives of 14.9 and 10.2 h. For the efficacy study, 10 mice per group received anesthesia with or without an ovariectomy. Mice were then given 5 or 10 mg/kg of carprofen, or saline subcutaneously every 12 h. Orbital tightening, arched posture, wound licking, rearing, grooming, nesting behavior, and activity were assessed before surgery and at 4, 8, 12, 24, and 48 h after surgery. The von Frey responses were assessed before and at 4, 12, 24, and 48 h after surgery. The efficacy study showed that all surgery groups had significantly higher scores for orbital tightening, arched posture, and wound licking than did the anesthesia-only groups at 4, 8, 12, and 24-h time points. At the 8 h time point, the surgery groups treated with carprofen had significantly lower arched posture scores than did the surgery group treated with saline only. No significant differences were found between carprofen treatment groups for rearing, grooming, von Frey, activity, or nesting behavior at any time point. These results indicate that subcutaneous carprofen administered at these doses does not provide sufficient analgesia to alleviate postoperative pain in female CD1 mice.

IntroductionDrug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled with stark health inequities demands a close examination of opioid use disorder (OUD) treatment barriers and swift consideration of policy changes.DesignThe aim of this buprenorphine policy analysis is to summarize existing buprenorphine barriers and present policy solutions to improve access and actualize the contributions of Advanced Practice Registered Nurses (APRNs).MethodsThe policy analysis follows five sequential steps: (1) defining the problem, (2) identifying key stakeholders, (3) assessing the landscape of relevant policies, (4) describing viable policy options, and (5) making final recommendations.ResultsAlthough there are laudable efforts to improve buprenorphine access, such as the new buprenorphine guidelines issued in April 2021, without larger-scale changes to federal, state, and scope of practice laws, overdose rates will continue to rise. We recommend a multipronged policy approach to improve buprenorphine treatment access, including eliminating the DEA X waiver, improving OUD education, and adopting full practice authority for APRNs in all states.ConclusionIncremental change is no longer sufficient to address opioid overdose deaths. Bolder and coordinated policy action is possible and necessary to empower the full clinical workforce to apply evidence-based life-saving treatments for OUD. The critical contributions of nurses in advancing equitable access to OUD care are emphasized in the National Academy of Medicine's Report, Future of Nursing: Charting a Path to Achieve Health Equity. Nurses are named as instrumental in improving buprenorphine access. Policy changes that acknowledge and build on evidence-based treatment expansion strategies are sorely needed.Clinical relevanceOne of the most robust tools to combat opioid overdose deaths is buprenorphine, a partial opioid

Substance use disorder is a growing public health challenge in the United States. People who use drugs may be more vulnerable to ambient heat due to the effects of drugs on thermoregulation and their risk environment. There have been limited population-based studies of ambient temperature and drug-related morbidity. We examined short-term associations between daily ambient temperature and emergency department (ED) visits for use or overdose of amphetamine, cocaine and opioids in California during the period 2005 to 2019. Daily ZIP code-level maximum, mean, and minimum temperature exposures were derived from 1-km data Daymet products. A time-stratified case-crossover design was used to estimate cumulative non-linear associations of daily temperature for lag days 0 to 3. Stratified analyses by patient sex, race, and ethnicity were also conducted. The study included over 3.4 million drug-related ED visits. We found positive associations between daily temperature and ED visits for all outcomes examined. An increase in daily mean temperature from the 50th to the 95th percentile was associated with ED visits for amphetamine use (OR = 1.072, 95% CI: 1.058, 1.086), cocaine use (OR = 1.044, 95% CI: 1.021, 1.068 and opioid use (OR = 1.041, 95% CI: 1.025, 1.057). Stronger positive associations were also observed for overdose: amphetamine overdose (OR = 1.150, 95% CI: 1.085, 1.218), cocaine overdose (OR = 1.159, 95% CI: 1.053, 1.276), and opioid overdose (OR = 1.079, 95% CI: 1.054, 1.106). In summary, people who use stimulants and opioids may be a subpopulation sensitive to short-term higher ambient temperature. Mitigating heat exposure can be considered in harm reduction strategies in response to the substance use epidemic and global climate change.

BACKGROUND AND AIMS: Low outcome prevalence, often observed with opioid-related outcomes, poses an underappreciated challenge to accurate predictive modeling. Outcome class imbalance, where non-events (i.e. negative class observations) outnumber events (i.e. positive class observations) by a moderate to extreme degree, can distort measures of predictive accuracy in misleading ways, and make the overall predictive accuracy and the discriminatory ability of a predictive model appear spuriously high. We conducted a simulation study to measure the impact of outcome class imbalance on predictive performance of a simple SuperLearner ensemble model and suggest strategies for reducing that impact. DESIGN, SETTING, PARTICIPANTS: Using a Monte Carlo design with 250 repetitions, we trained and evaluated these models on four simulated data sets with 100 000 observations each: one with perfect balance between events and non-events, and three where non-events outnumbered events by an approximate factor of 10:1, 100:1, and 1000:1, respectively. MEASUREMENTS: We evaluated the performance of these models using a comprehensive suite of measures, including measures that are more appropriate for imbalanced data. FINDINGS: Increasing imbalance tended to spuriously improve overall accuracy (using a high threshold to classify events vs non-events, overall accuracy improved from 0.45 with perfect balance to 0.99 with the most severe outcome class imbalance), but diminished predictive performance was evident using other metrics (corresponding positive predictive value decreased from 0.99 to 0.14). CONCLUSION: Increasing reliance on algorithmic risk scores in consequential decision-making processes raises critical fairness and ethical concerns. This paper provides broad guidance for analytic strategies that clinical investigators can use to remedy the impacts of outcome class imbalance on risk prediction tools.

The anterior cingulate cortex (ACC) processes the affective component of pain, whereas the primary somatosensory cortex (S1) is involved in its sensory-discriminative component. Injection of morphine in the ACC has been reported to be analgesic, and endogenous opioids in this area are required for pain relief. Mu opioid receptors (MORs) are expressed in both ACC and S1; however, the identity of MOR-expressing cortical neurons remains unknown. Using the Oprm1-mCherry mouse line, we performed selective patch clamp recordings of MOR+ neurons, as well as immunohistochemistry with validated neuronal markers, to determine the identity and laminar distribution of MOR+ neurons in ACC and S1. We found that the electrophysiological signatures of MOR+ neurons differ significantly between these 2 areas, with interneuron-like firing patterns more frequent in ACC. While MOR+ somatostatin interneurons are more prominent in ACC, MOR+ excitatory neurons and MOR+ parvalbumin interneurons are more prominent in S1. Our results suggest a differential contribution of MOR-mediated modulation to ACC and S1 outputs. We also found that females had a greater density of MOR+ neurons compared with males in both areas. In summary, we conclude that MOR-dependent opioidergic signaling in the cortex displays sexual dimorphisms and likely evolved to meet the distinct function of pain-processing circuits in limbic and sensory cortical areas.

BACKGROUND: Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD. METHODS: The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups usin

BACKGROUND: In the US, over 200 lives are lost from opioid overdoses each day. Accurate and prompt diagnosis of opioid use disorders (OUD) may help prevent overdose deaths. However, international classification of disease (ICD) codes for OUD are known to underestimate prevalence, and their specificity and sensitivity are unknown. We developed and validated algorithms to identify OUD in electronic health records (EHR) and examined the validity of OUD ICD codes. METHODS: Through four iterations, we developed EHR-based OUD identification algorithms among patients who were prescribed opioids from 2014 to 2017. The algorithms and OUD ICD codes were validated against 169 independent gold standard EHR chart reviews conducted by an expert adjudication panel across four healthcare systems. After using 2014-2020 EHR for validating iteration 1, the experts were advised to use 2014-2017 EHR thereafter. RESULTS: Of the 169 EHR charts, 81 (48%) were reviewed by more than one expert and exhibited 85% expert agreement. The experts identified 54 OUD cases. The experts endorsed all 11 OUD criteria from the Diagnostic and Statistical Manual of Mental Disorders-5, including craving (72%), tolerance (65%), withdrawal (56%), and recurrent use in physically hazardous conditions (50%). The OUD ICD codes had 10% sensitivity and 99% specificity, underscoring large underestimation. In comparison our algorithm identified OUD with 23% sensitivity and 98% specificity. CONCLUSIONS AND RELEVANCE: This is the first study to estimate the validity of OUD ICD codes and develop validated EHR-based OUD identification algorithms. This work will inform future research on early intervention and prevention of OUD.

BACKGROUND: Historically, overdose mortality rates among Hispanics have been lower than non-Hispanics. The purpose of this analysis was to characterize the U.S. overdose crisis among Hispanics compared to non-Hispanics. METHODS: We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research (WONDER) platform to obtain drug overdose mortality rates per 100,000 population between 2010 and 2021 for Hispanics and non-Hispanics. We examined the relative percent change and specific drug involvement (2010-2021) and state-level disparities (2010-2020) among Hispanics versus non-Hispanics. We calculated rate ratios by state and annual percent change in total and for each specific drug. Statistical analyses were performed using R software version 4.0.3 (R Project for Statistical Computing). RESULTS: Nationally, from 2010 to 2021, Hispanic overdose rates rose from 5.6 to 21.7 per 100,000, an increase of 287.5 % compared to 13.5-35.1 per 100,000, an increase of 160 % among non-Hispanics. The average annual percent change was 12 % for Hispanics and 9 % for non-Hispanics. The three most common drug classes involved in overdose deaths among both groups included: Fentanyls and synthetic opioids; cocaine; and prescription opioids. Hispanic overdose rates were higher than non-Hispanic rates in New Mexico, Colorado, Massachusetts, and Pennsylvania in 2020, versus only Michigan in 2010. CONCLUSIONS: We observed disparities in overdose mortality growth among Hispanics compared to non-Hispanics from 2010 to 2021. These disparities highlight the urgency to develop community-centered solutions that take into consideration the social and structural inequalities that exacerbate the effects of the opioid overdose crisis on Hispanic communities.

Traditional methods for site-specific drug delivery in the brain are slow, invasive, and difficult to interface with recordings of neural activity. Here, we demonstrate the feasibility and experimental advantages of in vivo photopharmacology using caged opioid drugs that are activated in the brain with light after systemic administration in an inactive form. To enable bidirectional manipulations of endogenous opioid receptors in vivo, we developed photoactivatable oxymorphone (PhOX) and photoactivatable naloxone (PhNX), photoactivatable variants of the mu opioid receptor agonist oxymorphone and the antagonist naloxone. Photoactivation of PhOX in multiple brain areas produced local changes in receptor occupancy, brain metabolic activity, neuronal calcium activity, neurochemical signaling, and multiple pain- and reward-related behaviors. Combining PhOX photoactivation with optical recording of extracellular dopamine revealed adaptations in the opioid sensitivity of mesolimbic dopamine circuitry in response to chronic morphine administration. This work establishes a general experimental framework for using in vivo photopharmacology to study the neural basis of drug action.

OBJECTIVES: Assess associations between social networks and urban American Indian/Alaska Native emerging adults alcohol, cannabis, and opioid use and intentions. METHOD: American Indian/Alaska Native participants ages 18-25 (N = 150; 86% female) were recruited across the United States from 12/20 to 10/21 via social media. Participants named up to 15 people whom they talked with most over the past 3 months and reported who (a) used alcohol and cannabis heavily or used other drugs (e.g., opioid use), (b) engaged in traditional practices, and (c) provided support. They also reported past 3-month alcohol, cannabis, and opioid use and intentions to use. RESULTS: Having a higher proportion of network members engaging in regular cannabis and heavy alcohol use (but not other drugs) was associated with more frequent cannabis use and stronger cannabis use intentions. Participants with higher proportions of members engaging in heavy alcohol use, regular cannabis use, or other drug use and who did not engage in traditional practices were more likely to report cannabis use and greater intentions to use cannabis and drink alcohol. In contrast, participants with higher proportions of network members engaging in traditional practices and who did not report heavy alcohol use, regular cannabis use, or other drug use were less likely to report intentions to use cannabis or drink alcohol. CONCLUSIONS: Findings emphasize what many studies have shown among various racial/ethnic groups-having network members who use substances increases the chance of use. Findings also highlight that traditional practices may be an important part of the prevention approach for this population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pain is common and variable in its severity among hospitalized patients with cancer. Although biopsychosocial factors are well established as modulators of chronic pain, less is known about what patient-level factors are associated with worse pain outcomes among hospitalized cancer patients. This prospective cohort study included patients with active cancer presenting to the emergency department (ED) with pain severity of ≥4/10 and followed pain outcomes longitudinally throughout hospital admission. Baseline demographic, clinical, and psychological factors were assessed on ED presentation, and daily average clinical pain ratings and opioid consumption during hospitalization were abstracted. Univariable and multivariable generalized estimating equation analyses examined associations of candidate biopsychosocial, demographic, and clinical predictors with average daily pain and opioid administration. Among 113 hospitalized patients, 73% reported pain as the primary reason for presenting to the ED, 43% took outpatient opioids, and 27% had chronic pain that predated their cancer. Higher pain catastrophizing ( B = 0.1, P ≤ 0.001), more recent surgery ( B = -0.2, P ≤ 0.05), outpatient opioid use ( B = 1.4, P ≤ 0.001), and history of chronic pain before cancer diagnosis ( B = 0.8, P ≤ 0.05) were independently associated with greater average daily pain while admitted to the hospital. Higher pain catastrophizing ( B = 1.6, P ≤ 0.05), higher anxiety ( B = 3.7, P ≤ 0.05), lower depression ( B = -4.9, P ≤ 0.05), metastatic disease ( B = 16.2, P ≤ 0.05), and outpatient opioid use ( B = 32.8, P ≤ 0.001) were independently associated with higher daily opioid administration. Greater psychological distress, especially pain catastrophizing, as well as pain and opioid use history, predicted greater difficulty with pain management among hospitalized cancer patients, suggesting that early assessment of patient-level characteristics may help direct consultation for more intensive pharmaco

BACKGROUND: Overprescription of opioids after surgery remains common. Residual and unnecessarily prescribed opioids can provide a reservoir for nonmedical use. This study therefore tested the hypothesis that a decision-support tool embedded in electronic health records guides clinicians to prescribe fewer opioids at discharge after inpatient surgery. METHODS: This study included 21,689 surgical inpatient discharges in a cluster randomized multiple crossover trial from July 2020 to June 2021 in four Colorado hospitals. Hospital-level clusters were randomized to alternating 8-week periods during which an electronic decision-support tool recommended tailored discharge opioid prescriptions based on previous inpatient opioid intake. During active alert periods, the alert was displayed to clinicians when the proposed opioid prescription exceeded recommended amounts. No alerts were displayed during inactive periods. Carryover effects were mitigated by including 4-week washout periods. The primary outcome was oral morphine milligram equivalents prescribed at discharge. Secondary outcomes included combination opioid and nonopioid prescriptions and additional opioid prescriptions until day 28 after discharge. A vigorous state-wide opioid education and awareness campaign was in place during the trial. RESULTS: The total postdischarge opioid prescription was a median [quartile 1, quartile 3] of 75 [0, 225] oral morphine milligram equivalents among 11,003 patients discharged when the alerts were active and 100 [0, 225] morphine milligram equivalents in 10,686 patients when the alerts were inactive, with an estimated ratio of geometric means of 0.95 (95% CI, 0.80 to 1.13; P = 0.586). The alert was displayed in 28% (3,074 of 11,003) of the discharges during the active alert period. There was no relationship between the alert and prescribed opioid and nonopioid combination medications or additional opioid prescriptions written after discharge. CONCLUSIONS: A decision-support tool i

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce pain and has become a core strategy to decrease opioid use, but there is a lack of data to describe encouraging use when admitting patients using electronic health record systems. OBJECTIVE: Assess an electronic health record system to increase ordering of NSAIDs for hospitalized adults. DESIGNS, SETTINGS AND PARTICIPANTS: We performed a cluster randomized controlled trial of clinicians admitting adult patients to a health system over a 9-month period. Clinicians were randomized to use a standard admission order set. INTERVENTION: Clinicians in the intervention arm were required to actively order or decline NSAIDs; the control arm was shown the same order but without a required response. MAIN OUTCOME AND MEASURES: The primary outcome was NSAIDs ordered and administered by the first full hospital day. Secondary outcomes included pain scores and opioid prescribing. RESULTS: A total of 20,085 hospitalizations were included. Among these hospitalizations, patients had a mean age of 58 years, and a Charlson comorbidity score of 2.97, while 50% and 56% were female and White, respectively. Overall, 52% were admitted by a clinician randomized to the intervention arm. NSAIDs were ordered in 2267 (22%) interventions and 2093 (22%) control admissions (p = .10). Similarly, there were no statistical differences in NSAID administration, pain scores, or opioid prescribing. Average pain scores (0-5 scale) were 3.36 in the control group and 3.39 in the intervention group (p = .46). There were no differences in clinical harms. CONCLUSIONS AND RELEVANCE: Requiring an active decision to order an NSAID at admission had no demonstrable impact on NSAID ordering. Multicomponent interventions, perhaps with stronger decision support, may be necessary to encourage NSAID ordering.

Use of pharmaceuticals is continuously increasing globally and their residues are recognized as a risk for theenvironment. The aim of this study was to investigate drug utilization patterns of analgesics in relation toenvironmental hazard in the region surrounding Sweden’s largest drinking water source, Lake Mälaren. This wasexamined using sales data on pharmaceuticals from the Swedish E-health Agency. The total sales of analgesics(non-steroidal anti-inflammatory drugs, paracetamol, other non-opioid analgesics, and opioids) for both humanand veterinary use in the region were analyzed for the years 2016 to 2020, in relation to the inherent environmental hazard for each active pharmaceutical ingredient (API). We found that a total of 454 tons of analgesicswere sold in the region during these 5 years. Classifications of environmental hazard were available for 16 out ofthe 45 studied APIs, accounting for 98.8% of the total mass in kilograms. Paracetamol, ibuprofen, and acetylsalicylic acid, which are all classified as low-hazard compounds, were the most commonly sold APIs. Diclofenac, the only pharmaceutical classified as high-hazard, was the fifth most commonly sold API, with a total soldmass of 2321 kg. The majority of the total sold mass of analgesics originated from dispensed prescriptions forhuman use in urban areas. Visualization of drug sales for humans and animals in different settings can be used toidentify the environmental burden of pharmaceuticals. Based on our study, we suggest that additional measuresto reduce the impacts of pharmaceuticals on the environment should primarily be directed to prescribing physicians in urban areas and campaigns targeted at the high over-the-counter sales of diclofenac. Moreover, it isimportant to address the fact that many pharmaceuticals currently have limited data on environmental hazard.

Use of pharmaceuticals is continuously increasing globally and their residues are recognized as a risk for theenvironment. The aim of this study was to investigate drug utilization patterns of analgesics in relation toenvironmental hazard in the region surrounding Sweden’s largest drinking water source, Lake Mälaren. This wasexamined using sales data on pharmaceuticals from the Swedish E-health Agency. The total sales of analgesics(non-steroidal anti-inflammatory drugs, paracetamol, other non-opioid analgesics, and opioids) for both humanand veterinary use in the region were analyzed for the years 2016 to 2020, in relation to the inherent environmental hazard for each active pharmaceutical ingredient (API). We found that a total of 454 tons of analgesicswere sold in the region during these 5 years. Classifications of environmental hazard were available for 16 out ofthe 45 studied APIs, accounting for 98.8% of the total mass in kilograms. Paracetamol, ibuprofen, and acetylsalicylic acid, which are all classified as low-hazard compounds, were the most commonly sold APIs. Diclofenac, the only pharmaceutical classified as high-hazard, was the fifth most commonly sold API, with a total soldmass of 2321 kg. The majority of the total sold mass of analgesics originated from dispensed prescriptions forhuman use in urban areas. Visualization of drug sales for humans and animals in different settings can be used toidentify the environmental burden of pharmaceuticals. Based on our study, we suggest that additional measuresto reduce the impacts of pharmaceuticals on the environment should primarily be directed to prescribing physicians in urban areas and campaigns targeted at the high over-the-counter sales of diclofenac. Moreover, it isimportant to address the fact that many pharmaceuticals currently have limited data on environmental hazard.

Use of pharmaceuticals is continuously increasing globally and their residues are recognized as a risk for theenvironment. The aim of this study was to investigate drug utilization patterns of analgesics in relation toenvironmental hazard in the region surrounding Sweden’s largest drinking water source, Lake Mälaren. This wasexamined using sales data on pharmaceuticals from the Swedish E-health Agency. The total sales of analgesics(non-steroidal anti-inflammatory drugs, paracetamol, other non-opioid analgesics, and opioids) for both humanand veterinary use in the region were analyzed for the years 2016 to 2020, in relation to the inherent environmental hazard for each active pharmaceutical ingredient (API). We found that a total of 454 tons of analgesicswere sold in the region during these 5 years. Classifications of environmental hazard were available for 16 out ofthe 45 studied APIs, accounting for 98.8% of the total mass in kilograms. Paracetamol, ibuprofen, and acetylsalicylic acid, which are all classified as low-hazard compounds, were the most commonly sold APIs. Diclofenac, the only pharmaceutical classified as high-hazard, was the fifth most commonly sold API, with a total soldmass of 2321 kg. The majority of the total sold mass of analgesics originated from dispensed prescriptions forhuman use in urban areas. Visualization of drug sales for humans and animals in different settings can be used toidentify the environmental burden of pharmaceuticals. Based on our study, we suggest that additional measuresto reduce the impacts of pharmaceuticals on the environment should primarily be directed to prescribing physicians in urban areas and campaigns targeted at the high over-the-counter sales of diclofenac. Moreover, it isimportant to address the fact that many pharmaceuticals currently have limited data on environmental hazard.

Use of pharmaceuticals is continuously increasing globally and their residues are recognized as a risk for theenvironment. The aim of this study was to investigate drug utilization patterns of analgesics in relation toenvironmental hazard in the region surrounding Sweden’s largest drinking water source, Lake Mälaren. This wasexamined using sales data on pharmaceuticals from the Swedish E-health Agency. The total sales of analgesics(non-steroidal anti-inflammatory drugs, paracetamol, other non-opioid analgesics, and opioids) for both humanand veterinary use in the region were analyzed for the years 2016 to 2020, in relation to the inherent environmental hazard for each active pharmaceutical ingredient (API). We found that a total of 454 tons of analgesicswere sold in the region during these 5 years. Classifications of environmental hazard were available for 16 out ofthe 45 studied APIs, accounting for 98.8% of the total mass in kilograms. Paracetamol, ibuprofen, and acetylsalicylic acid, which are all classified as low-hazard compounds, were the most commonly sold APIs. Diclofenac, the only pharmaceutical classified as high-hazard, was the fifth most commonly sold API, with a total soldmass of 2321 kg. The majority of the total sold mass of analgesics originated from dispensed prescriptions forhuman use in urban areas. Visualization of drug sales for humans and animals in different settings can be used toidentify the environmental burden of pharmaceuticals. Based on our study, we suggest that additional measuresto reduce the impacts of pharmaceuticals on the environment should primarily be directed to prescribing physicians in urban areas and campaigns targeted at the high over-the-counter sales of diclofenac. Moreover, it isimportant to address the fact that many pharmaceuticals currently have limited data on environmental hazard.

BackgroundThe nocebo response refers to the phenomenon where non-specific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Non-specific factors are also likely to influence AE occurrence following administration of active pharmacological treatments. ObjectiveThis meta-analysis aimed to estimate the nocebo response in dentistry by assessing the AEs prevalence in placebo- and active arms of randomised controlled trials (RCTs) assessing analgesic treatment following third molar (M3) surgery. MethodsA systematic search was performed in PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies had to report the number of patients experiencing at least one drug-related AE (patients with AE >= 1) separately for the active and placebo arms. The proportion of patients with AE >= 1 and drug-related dropouts were pooled, and risk differences (RDs) between patients in the placebo- and active arm were calculated. ResultsIn 50 independent RCTs of 47 identified articles, the pooled rates of patients with AE >= 1 were 22.8% in the placebo arm and 20.6% in the active arm. The pooled rates of drug-related dropout were 0.24% in the placebo arm and 0.08% in the active arm. There were no significant RDs in patients with AE >= 1 and drug-related dropouts. ConclusionThese results show that patients in the placebo arm reported AEs to the same extent as patients receiving active treatment, suggesting that most AEs in analgesic medication following M3 surgery may be attributed to the nocebo phenomenon.

Background: The nocebo response refers to the phenomenon where non-specific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Non-specific factors are also likely to influence AE occurrence following administration of active pharmacological treatments. Objective: This meta-analysis aimed to estimate the nocebo response in dentistry by assessing the AEs prevalence in placebo- and active arms of randomised controlled trials (RCTs) assessing analgesic treatment following third molar (M3) surgery. Methods: A systematic search was performed in PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies had to report the number of patients experiencing at least one drug-related AE (patients with AE ≥ 1) separately for the active and placebo arms. The proportion of patients with AE ≥ 1 and drug-related dropouts were pooled, and risk differences (RDs) between patients in the placebo- and active arm were calculated. Results: In 50 independent RCTs of 47 identified articles, the pooled rates of patients with AE ≥ 1 were 22.8% in the placebo arm and 20.6% in the active arm. The pooled rates of drug-related dropout were 0.24% in the placebo arm and 0.08% in the active arm. There were no significant RDs in patients with AE ≥ 1 and drug-related dropouts. Conclusion: These results show that patients in the placebo arm reported AEs to the same extent as patients receiving active treatment, suggesting that most AEs in analgesic medication following M3 surgery may be attributed to the nocebo phenomenon.