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BACKGROUND: Prescription opioids are commonly prescribed postoperatively and increase the risk of diversion or misuse when left unused and accessible. Despite awareness of the risks associated with unused opioids, harm reduction strategies like safe storage and drug take-back events may be limited by inconvenience and patient-specific barriers to access. OBJECTIVES: To evaluate a quality improvement project designed to facilitate at-home disposal of unused opioids after day surgery. METHODS: An observational, prospective quality improvement project was conducted in patients undergoing elective outpatient surgery at Newton-Wellesley Hospital from December 2019 to June 2020. Upon discharge, eligible patients received a Deterra® drug disposal packet, which deactivates unused medication. Follow-up surveys assessed packet use and reasons for nonuse one to two weeks after surgery. RESULTS: 106 participants received a disposal packet and responded to the survey. Among the 67 respondents with unused medication, 30% used the packet. Women were more likely to use the packet than men (predicted probability 30.2% vs. 10.4%, p = .033), and patients aged 18-25 were more likely to use the packet than those aged 26-40 (40.0% vs. 9.5%, p = .049). The most common reasons for packet nonuse included procrastination, holding onto prescriptions in case of future pain, and waiting to dispose of multiple medications. CONCLUSION: The majority of patients surveyed had unused opioids one to two weeks after surgery, and approximately one in three patients with unused doses utilized the disposal packet. Common reasons for nonuse included procrastination and concerns about needing future medication for pain. Going forward, safe drug disposal efforts may emphasize improved patient education, partial prescription fill options, or alert systems to remind patients to safely dispose of unused medication.

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PURPOSE: The aim of this study was to examine the impact of detoxification from prescription opioids on the quality of life (QoL) and pain levels among patients reliant on these medications for chronic pain management. OBJECTIVE: Long-term use of opioids for pain management may lead to a range of adverse effects, including tolerance, dependence, significant societal costs, and a decline in overall quality of life (QoL). Despite these challenges, there is a limited amount of research focusing on the effects of detoxification and its impact on the QoL for patients with chronic pain tolerant to prescription opioids. METHODS: This prospective study included 45 patients who underwent elective detoxification from prescription opioids. Prescription opioids were discontinued during the detoxification treatment in 44 of the 45 cases. QoL was monitored using SF-36v2™ questionnaires administered before detoxification, on the day of discharge, and at least six months after detoxification. Pain levels were assessed using Visual Analogue Scale (VAS) scores before and after the detoxification process. RESULTS: The study was fully completed by 30 patients. At the third SF-36v2™ evaluation, 25 out of 30 patients (83.3%) reported the detoxification treatment as beneficial to their overall health status compared to that before the treatment, and SF-36v2™ questionnaires after detoxification were significantly higher than before the treatment (p < 0.001). A decreased pain level right after the detoxification was reported by 44 of the 45 patients (97.7%), with a significant average reduction of 4.51 points observed (p < 0.001). CONCLUSIONS: The observed enhancement in QoL, significant reduction in pain, and cessation of opioid use in most patients with chronic pain tolerant to prescription opioids following opioid detoxification indicate that this method of treatment can be safely and effectively administered and must be considered for chronic pain patients.

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Objective: This study aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and mortality in long-term prescription opioid users. Methods: The study included 1856 long-term prescription opioid users from the National Health and Nutrition Examination Survey (NHANES, 2001-2018). Mortality status were determined by matching with the National Death Index (NDI) records until December 31, 2019. Multivariable Cox proportional hazard models were constructed to assess the association. Results: Over a median follow-up period of 7.75 years, there were 443 cases of all-cause mortality, including 135 cardiovascular disease (CVD) deaths and 94 cancer deaths. After multivariable adjustment, participants with serum 25(OH)D concentrations within 50.00 to <75.00 nmol/L and ≥ 75 nmol/L had a lower risk of all-cause mortality, with hazard ratios (HRs) of 0.50 (95% confidence interval [CI] 0.29, 0.86) and 0.54 (95% CI 0.32, 0.90), respectively. Nevertheless, no significant association was found between serum 25(OH)D concentrations and the risk of CVD or cancer mortality. The RCS analysis revealed a non-linear association of serum 25(OH)D concentration with all-cause mortality (p for non-linear = 0.01). Per 1-unit increment in those with serum 25(OH)D concentrations <62.17 nmol/L corresponded to a 2% reduction in the risk of all-cause mortality (95% CI 0.97, 1.00), but not changed significantly when 25(OH)D concentrations ≥62.17 nmol/L. Conclusion: In conclusion, a non-linear association existed between serum 25(OH)D concentrations and all-cause mortality in long-term prescription opioid users. Maintaining serum 25(OH)D concentrations ≥62.17 nmol/L may be beneficial in preventing all-cause mortality in this population.

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Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. The hippocampal formation is known to participate in memory and learning processes and has been documented to contribute to opioid dependence. Accordingly, the present study assessed molecular and cellular alterations in the hippocampal formation of Wistar rats intraperitoneally administered with 50 mg/kg tramadol or tapentadol for eight alternate days. Alterations were found in serum hydrogen peroxide, cysteine, homocysteine, and dopamine concentrations upon exposure to one or both opioids, as well as in hippocampal 8-hydroxydeoxyguanosine and gene expression levels of a panel of neurotoxicity, neuroinflammation, and neuromodulation biomarkers, assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of hippocampal formation sections showed increased glial fibrillary acidic protein (GFAP) and decreased cluster of differentiation 11b (CD11b) protein expression, suggesting opioid-induced astrogliosis and microgliosis. Collectively, the results emphasize the hippocampal neuromodulator effects of tramadol and tapentadol, with potential behavioral implications, underlining the need to prescribe and use both opioids cautiously.

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Changes in chronic noncancer pain treatment have led to decreases in prescribing of opioids and increases in the availability of medical cannabis, despite its federal prohibition. Patients may face barriers to establishing new care with a physician based on use of these treatments. We compared physician willingness to accept patients based on prescription opioid, cannabis, or other pain treatment use. This study of 36 states and Washington, DC, with active medical cannabis programs surveyed physicians who treat patients with chronic noncancer pain between July 13 and August 4, 2023. Of 1000 physician respondents (34.5% female, 63.2% White, 78.1% primary care), 852 reported accepting new patients with chronic pain. Among those accepting new patients with chronic pain, more physicians reported that they would not accept new patients taking prescription opioids (20.0%) or cannabis (12.7%) than those taking nonopioid prescription analgesics (0.1%). In contrast, 68.1% reported willingness to accept new patients using prescribed opioids on a daily basis. For cannabis, physicians were more likely to accept new patients accessing cannabis through medical programs (81.6%) than from other sources (60.2%). Access to care for persons with chronic noncancer pain appears to be the most restricted among those taking prescription opioids, although patients taking cannabis may also encounter reduced access.

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Background: Chronic non-cancer pain affects 20% of Americans. This is significantly impacted by the ongoing opioid crisis and reduced opioid dispensing. Public perceptions additionally shape pain management strategies. Purpose: This study explores public attitudes toward prescription opioids for chronic non-cancer pain. We aim to understand how public attitudes are influenced by the evolving opioid crisis and shifting opioid use patterns. Methods: In Michigan, 823 adults participated in a Qualtrics survey on attitudes toward nonmedical and medical prescription opioid use. Multivariable logistic regression was performed to identify factors associated with beliefs that doctors prescribe opioids for too long (Model 1) and chronic pain patients should transition to alternative treatments (Model 2). Results: About half (49.4%) of respondents believed doctors keep patients on prescription opioids for too long, while two-thirds (65.7%) agreed chronic pain patients should be tapered off medications. Knowing someone who misused opioids and perceptions of substance use (e.g. perceived risk of prescription opioid misuse, stigma toward chronic pain patients, perceived prevalence of prescription opioid misuse, and awareness of fentanyl) were associated with greater odds of believing doctors keep patients on opioids too long. Demographics (age and education), substance use histories and perceptions (e.g. perceived risk and stigma) were associated with greater odds of believing patients should be tapered off their medication. Conclusions: These findings inform strategies to correct public misperceptions, emphasizing the importance of personal experience, perceived risks, and stigmatization of chronic pain patients. This insight can guide effective pain management for those with chronic non-cancer pain.

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BACKGROUND: Overprescription of opioids has led to increased misuse of opioids, resulting in higher rates of overdose. The workplace can play a vital role in an individual's intentions to misuse prescription opioids with injured workers being prescribed opioids, at a rate 3 times the national average. For example, health care workers are at risk for injuries, opioid dispensing, and diversion. Intervening within a context that may contribute to risks for opioid misuse while targeting individual psychosocial factors may be a useful complement to interventions at policy and prescribing levels. OBJECTIVE: This pilot study assessed the effects of a mobile-friendly opioid misuse intervention prototype tailored for health care workers using the preparation phase of a multiphase optimization strategy design. METHODS: A total of 33 health care practitioners participated in the pilot intervention, which included 10 brief web-based lessons aimed at impacting psychosocial measures that underlie opioid misuse. The lesson topics included: addiction beliefs, addiction control, Centers for Disease Control and Prevention guidelines and recommendations, beliefs about patient-provider relationships and communication, control in communicating with providers, beliefs about self-monitoring pain and side effects, control in self-monitoring pain and side effects, diversion and disposal beliefs, diversion and disposal control, and a conclusion lesson. Using a treatment-only design, pretest and posttest surveys were collected. A general linear repeated measures ANOVA was used to assess mean differences from pretest to posttest. Descriptive statistics were used to assess participant feedback about the intervention. RESULTS: After completing the intervention, participants showed significant mean changes with increases in knowledge of opioids (+0.459; P<.001), less favorable attitudes toward opioids (-1.081; P=.001), more positive beliefs about communication with providers (+0.205; P=.01), more positive beliefs about pain management control (+0.969; P<.001), and increased intentions to avoid opioid use (+0.212; P=.03). Of the 33 practitioners who completed the program, most felt positive about the information presented, and almost 70% (23/33) agreed or strongly agreed that other workers in the industry should complete a program like this. CONCLUSIONS: While attempts to address the opioid crisis have been made through public health policies and prescribing initiatives, opioid misuse continues to rise. Certain industries place workers at greater risk for injury and opioid dispensing, making interventions that target workers in these industries of particular importance. Results from this pilot study show positive impacts on knowledge, attitudes, and beliefs about communicating with providers and pain management control, as well as intentions to avoid opioid misuse. However, the dropout rate and small sample size are severe limitations, and the results lack generalizability. Results will be used to inform program revisions and future optimization trials, with the intention of providing insight for future intervention development and evaluation of mobile-friendly eHealth interventions for employees.

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Prescription opioid misuse (POM) among people living with HIV (PLWH) is a serious concern due to risks related to dependence and overdose, and PLWH may be at higher risk for POM due to psychosocial stressors including psychological distress. However, scant POM research has examined the role of HIV-related stigma (e.g., internalized stigma, enacted stigma) in POM among PLWH. Guided by minority stress theory, this study examined a hypothesized serial mediation among enacted stigma, internalized stigma, psychological distress, and POM within a sample of Chinese PLWH with pain symptoms enrolled in a wave (between November 2017 and February 2018) of a longitudinal cohort study in Guangxi (n = 116). Models were tested individually for six enacted stigma experiences, controlling for key demographic and health-related variables (e.g., CD4 + count). Results showed HIV-related workplace discrimination was the most common stigma experience (12%,) and 10.3% of PLWH reported POM. Indirect effect analyses showed that internalized stigma was indirectly associated with POM through psychological distress. Internalized stigma and psychological distress mediated the association between workplace discrimination and POM. Family discrimination, gossip, and healthcare discrimination were directly associated with POM. This study suggests that Chinese PLWH may engage in POM to cope with psychological distress that is rooted in HIV-related stigma and highlights the important context of workplace discrimination for PLWH. Implications for interventions to reduce POM among PLWH are discussed.

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BACKGROUND: A wide range of opioid misuse motives have been documented in the literature, including to relieve physical pain, feel good/get high, relax, manage feelings/emotions, sleep, and moderate the effects of other substances. Despite a rise in opioid misuse among African Americans over the last 2 decades, their motivations for misuse remain unclear. Much of the research on opioid misuse motivations either rely on samples with little racial diversity or do not stratify their findings by race. As a result, less is known about the specific reasons why African Americans engage in opioid misuse. The objective of this study, therefore, was to identify and explain the most common motives for misusing opioids among African Americans. Qualitative interview data are also presented to explain/contextualize the most prevalent motivations. METHODS: This study used data from the Florida Minority Health Survey, a mixed-methods project that included online surveys (n = 303) and qualitative in-depth interviews (n = 30) of African Americans. Data collection was conducted from August 2021 to February 2022 throughout Southwest Florida. RESULTS: Analyses revealed that while some (33.9%) misused opioids for purposes of recreation/sensation seeking (eg, feel good/get high), the majority (66.1%) were attempting to self-treat perceived medical symptoms (eg, physical pain, anxiety/trauma, withdrawals, insomnia). CONCLUSIONS: This study contributes to a better understanding of why some African Americans engage in opioid misuse and findings highlight the need for interventions to be trauma informed and address unmanaged physical pain among African Americans. Given that most studies on motivations are quantitative in nature, the study contributes to the literature by capturing the voices of African Americans who use drugs.

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BACKGROUND: Only a small proportion of individuals who initiate nonmedical use of prescription opioids (NUPO) transition to heroin, suggesting that more nuanced aspects of NUPO may be better indicators of risk for escalating opioid use trajectories. This study leveraged panel data to identify NUPO typologies based on NUPO characteristics associated with opioid risk trajectories (route of administration, motives) and compared rates of heroin initiation at follow-up across typologies. METHODS: Latent class analyses were run among respondents with no history of heroin use from the Monitoring the Future Panel Study (base year N=10,408) at modal ages 18, 19/20, 21/22, 23/24, and 25/26. Indicators included oral NUPO, nonoral NUPO, and NUPO motives to experiment, have a good time with friends, get high, escape problems, manage pain, relax, and sleep. Heroin initiation at follow-ups through modal age 29/30 was predicted from class membership. RESULTS: No NUPO, self-medication (oral, manage pain), recreational (oral, nonoral, experiment, get high, have a good time with friends), and mixed-motive (all routes, all motives) classes emerged. Heroin initiation rates did not differ across no NUPO and self-medication classes; recreational and mixed-motives classes initiated heroin at higher rates than the other classes and comparable rates to each other. Non-NUPO drug use prior to heroin initiation was prevalent in recreational and mixed-motive classes. CONCLUSIONS: NUPO does not uniformly or uniquely increase risk for heroin initiation. Leveraging more nuanced indicators of risk for heroin use and targeting polysubstance use in addition to opioid-specific programming may enhance the efficacy of public health efforts.

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RATIONALE: Prescription opioid use and misuse have increased rapidly in many Western countries in the past decade. Patients (mis)using opioids are at risk of presenting to the emergency department (ED) with opioid-related problems. European data concerning prescription opioid (mis)use among the ED population is lacking. AIMS AND OBJECTIVES: This study aims to determine prevalence of prescription opioid use, misuse, and opioid use disorder (OUD) among Dutch ED patients. Secondary objectives were to explore factors associated with prescription opioid misuse and the number of patients discharged with a new opioid prescription. METHODS: In a cross-sectional multicenter study at three hospitals in the Netherlands, adult ED patients were screened for current prescription opioid use. Opioid users filled out questionnaires regarding opioid (mis)use, and underwent a structured interview to assess OUD criteria. The primary outcomes were prevalence rates of (1) current prescription opioid use, (2) prescription opioid misuse (based on a Current Opioid Misuse Measure [COMM] score > 8), (3) OUD, based on DSM-5 criteria. Independent T-tests, Pearson χ2 and Fisher's Exact tests were used to analyse differences in characteristics between groups. RESULTS: A total of 997 patients were screened, of which 15% (n = 150) used prescription opioids. Out of 93 patients assessed, 22.6% (n = 21) showed signs of prescription opioid misuse, and 9.8% (n = 9, 95% CI: 4.5-17.8) fulfilled criteria for OUD. A medical history of psychiatric disorder was significantly more common in patients with prescription opioid misuse and OUD. CONCLUSION: This study shows that prescription opioid use is relatively common in ED patients in the Netherlands, compared to the overall population. Over one fifth of these patients shows signs of opioid misuse or OUD. Awareness among ED personnel about the high prevalence of prescription opioid (mis)use in their population is critical for signalling opioid-related problems.

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Non-medical prescription opioid use (NMPOU) is the use of opioids without a prescription or in a way different from how they were prescribed and is the fourth most common type of drug use in the United States. Separate research has shown that trauma-related shame is linked to posttraumatic stress disorder (PTSD) and, respectively, opioid use. However, no study to date has empirically examined the association between trauma-related shame and NMPOU among individuals with PTSD symptoms. Forty adults with clinical or subclinical PTSD who reported engaging in NMPOU at least one day in the prior month before the study completed 28 days of daily surveys. Trauma-related shame was measured at baseline. NMPOU and underlying motives to engage in NMPOU were assessed once daily via a smartphone app. Twenty-four participants (60 %) reported NMPOU over the 28-day period. After controlling for PTSD symptoms and covariates, mixed models showed that higher trauma-related shame significantly predicted higher risk of daily NMPOU (B = 0.06, SE = 0.03, t = 2.14, p=.03). After controlling for false discovery rates, trauma-related shame also significantly predicted NMPOU due to the following motives (p's < 0.031): to manage depression/sadness, to manage anxiety, to manage other stress/worry, and to get high. Among individuals with PTSD, higher baseline trauma-related shame prospectively and positively predicted greater NMPOU over a four-week daily monitoring period. Findings suggest a need to attend to trauma-related shame and its impact on subsequent motivations to engage in NMPOU. Future research should examine how treatments may effectively target trauma-related shame to reduce NMPOU and more severe PTSD symptoms.

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BACKGROUND: Given significant risks associated with long-term prescription opioid use, there is a need for non-pharmacological interventions for treating chronic pain. Activating patients to manage chronic pain has the potential to improve health outcomes. The ACTIVATE study was designed to evaluate the effectiveness of a 4-session patient activation intervention in primary care for patients on long-term opioid therapy. METHODS: The two-arm, pragmatic, randomized trial was conducted in two primary care clinics in an integrated health system from June 2015-August 2018. Consenting participants were randomized to the intervention (n = 189) or usual care (n = 187). Participants completed online and interviewer-administered surveys at baseline, 6- and 12- months follow-up. Prescription opioid use was extracted from the EHR. The primary outcome was patient activation assessed by the Patient Activation Measure (PAM). Secondary outcomes included mood, function, overall health, non-pharmacologic pain management strategies, and patient portal use. We conducted a repeated measure analysis and reported between-group differences at 12 months. RESULTS: At 12 months, the intervention and usual care arms had similar PAM scores. However, compared to usual care at 12 months, the intervention arm demonstrated: less moderate/severe depression (odds ratio [OR] = 0.40, 95%CI 0.18-0.87); higher overall health (OR = 3.14, 95%CI 1.64-6.01); greater use of the patient portal's health/wellness resources (OR = 2.50, 95%CI 1.42-4.40) and lab/immunization history (OR = 2.70, 95%CI 1.29-5.65); and greater use of meditation (OR = 2.72; 95%CI 1.61-4.58) and exercise/physical therapy (OR = 2.24, 95%CI 1.29-3.88). At 12 months, the intervention arm had a higher physical health measure (mean difference 1.63; 95%CI: 0.27-2.98). CONCLUSION: This trial evaluated the effectiveness of a primary care intervention in improving patient activation and patient-reported outcomes among adults with chronic pain on long-term opioid therapy. Despite a lack of improvement in patient activation, a brief intervention in primary care can improve outcomes such as depression, overall health, non-pharmacologic pain management, and engagement with the health system. TRIAL REGISTRATION: The study was registered on 10/27/14 on ClinicalTrials.gov (NCT02290223).

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BACKGROUND AND AIMS: Public health measures introduced to contain the spread of the SARS-CoV-2 virus likely affected opioid supply and demand, as well as the patterns and contexts of opioid use. We measured opioid-related harms during the first 2 years of COVID-19 restrictions in Victoria, Australia. DESIGN: We adopted an interrupted time series analysis design using interventional autoregressive integrated moving average (ARIMA) models. Opioid-related ambulance attendance data between January 2015 and March 2022 were extracted from the National Ambulance Surveillance System. SETTING: Victoria, Australia. PARTICIPANTS: Patients (≥15 years) attended to by an ambulance for opioid-related harms. MEASUREMENTS: Monthly opioid-related ambulance attendances for three drug types: heroin, prescription opioids and opioid agonist therapy (OAT) medications. FINDINGS: The monthly rate of heroin-related attendances fell by 26% immediately after the introduction of COVID-19 restrictions. A reduced rate of heroin-related attendances was observed during COVID-19 restrictions, resulting in 2578 averted heroin-related attendances. There was no change in the rate of attendances for extra-medical OAT medications or prescription opioids. CONCLUSIONS: Strict COVID-19 restrictions in Victoria, Australia appear to have resulted in a substantial reduction in heroin-related ambulance attendances, perhaps because of border closures and restrictions on movement affecting supply, changing patterns of drug consumption, and efforts to improve access to OAT. Despite policy changes allowing longer OAT prescriptions and an increased number of unsupervised doses, we found no evidence of increased harms related to the extra-medical use of these medications.

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OBJECTIVES: This study sought to examine associations between U.S. adolescents' perceived racism and discrimination (PRD) at school and current substance use. METHODS: Data were drawn from the Adolescent Behaviors and Experiences Survey (ABES), a probability sample of U.S. high school students in 2021 (n = 7705). Multivariable regression models were conducted to examine associations of PRD with current (past 30-day) use of tobacco products, marijuana, alcohol, and prescription opioid misuse. Interaction effects of PRD and demographic factors were tested. RESULTS: Among participants in the 2021 ABES, PRD was associated with higher odds of current use of tobacco (AOR = 1.3, p = 0.03), marijuana (AOR = 1.3, p = 0.03), alcohol (AOR = 1.2, p = 0.03), and misuse of prescription opioids (AOR = 1.6, p = 0.004). The effects of PRD on current tobacco and alcohol use differed by Hispanic and non-Hispanic adolescents (interaction effect = 0.007 and 0.01, respectively) with higher odds among Hispanic youth than among non-Hispanic counterparts. The associations of PRD and current tobacco use, marijuana use, alcohol use, and misuse of prescription opioids were moderated by sex with more pronounced effects on males than females. CONCLUSIONS: Efforts to promote awareness and create support environments that value diversity and inclusivity at school are needed to mitigate adolescent exposure to racism and discrimination.

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We understand the current crisis of overdose deaths to be driven by widespread opioid use, characterized by distinct 'waves' of drug use. The first wave was driven by prescription opioids, the second by heroin, and the third by illicit, non-pharmaceutical fentanyl and fentanyl analogues (henceforth, fentanyl). The purpose of this study is to describe opioid initiation within each of the three waves from the perspective of people who use illicit opioids, with a focus on emerging pathways into fentanyl use. The authors recruited sixty people reporting past-30-day illicit opioid use in Dayton, Ohio. Participants completed a brief survey and a semi-structured in-depth qualitative interview, conducted from March to November 2020 with a total of 13 in-person and 47 virtual interviews. The qualitative interviews were transcribed in their entirety and analyzed thematically using NVivo 12. We noted supply-side changes as influencing trajectories in all three waves. However, we also noted differences in the experiences of prescription opioid and heroin initiation, with these trajectories influenced by pharmacological effects, pain management, curiosity, intergenerational use, pricing, and peers. In comparison, most participants were unaware that they were initiating fentanyl, and many reported overdosing with their first use of fentanyl. We identified a trajectory into fentanyl with limited to no prior heroin use among a few participants. The increased risk of overdose with initiation into fentanyl use further emphasizes the need for an expansion of naloxone distribution and the implementation of more comprehensive measures, such as overdose prevention centers, drug testing, and a safer supply. Further research on the dynamics of the ongoing overdose death crisis in the era of fentanyl and the 4th wave of the overdose crisis is critical in developing responsive prevention and intervention strategies.

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Researchers have found considerable evidence in the past 20 years that perinatal opioid exposure leads to an increased risk of developmental disorders in offspring that persist into adulthood. The use of opioids to treat pain concerning pregnancy, delivery, and postpartum complications has been rising. As a result, communities have reported a 300-400 % increase in Neonatal Opioid Withdrawal Syndrome (NOWS). NOWS represents the initial stage of several behavioral, phenotypic, and synaptic deficits. This review article summarizes the Developmental Outcomes of Perinatal Exposure (DOPE) to prescription opioids. Moreover, we also seek to connect these findings to clinical research that describes DOPE at multiple stages of life. Since specific mechanisms that underlie DOPE remain unclear, this article aims to provide a framework for conceptualizing across all ages and highlight the implications they may have for longevity.

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The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.

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Background: Epidemiological studies suggest chronic and recurrent pain affects around a quarter of children, while 8% report intense and frequent pain. The long-term implications of chronic pain in childhood are uncertain. Using electronic health records (EHRs) we used both disease codes and medicines prescription records to investigate the scale of chronic pain and long-term analgesic use in children and young people (CYP), and if chronic pain and/or use of analgesic medicines at an early age is associated with substance misuse, use of prescription opioids, and poor mental health in adulthood. Methods: We conducted a cohort study using data from IQVIA Medical Research Data UK. We identified individuals aged 2-24 with exposure to either a diagnostic code indicating chronic pain (diagnosis-exposed), repeat prescription for medicines commonly used to treat pain (prescription-exposed), or both. Follow-up began at 25, and the unexposed population acted as comparators. We calculated hazard ratios (HR) for mental health and substance misuse outcomes, and rate ratios (RR) for opioid prescriptions in adulthood. Additionally, we investigated which diagnoses, if any, were over-represented in the prescription-exposed subgroup. Findings: The cohort constituted 853,625 individuals; 146,431 had one or more of the exposures of interest (diagnosis-exposed = 115,101, prescription-exposed = 20,298, both-exposed = 11,032), leaving 707,194 as comparators. Median age at index exposure was 18.7 years (IQR 14.7-22.3). On average during follow-up, the pooled exposed group had, respectively, a 31% and 17% higher risk of adverse mental health and substance misuse outcomes (adjusted HR [95% CI] of 1.31 [1.29-1.32] and 1.17 [1.11-1.24]). Exposed individuals also received prescription opioids at double the rate of unexposed individuals on average during follow-up (adjusted RR 2.01 [95% CI 1.95-2.10]). Outcomes varied between exposure subgroups, with prescription- and both-exposure tending to have worse outcomes. Unlike these two subgroups, in the diagnosis-exposed subgroup we did not detect a greater risk of substance misuse. Interpretation: Chronic pain in CYP is associated with increased prescription opioid use and adverse mental health outcomes in adulthood, as is repeat prescription for analgesic medicines, but only the latter is also associated with substance misuse in adulthood. It is essential to avoid the harms of under-treating pain in CYP while giving due consideration to the risks posed by analgesic medicines. Early recognition of chronic pain in CYP and utilising non-pharmacological management options may help minimise overprescribing, and long-term reliance on dependence-forming-drugs. Funding: AL is an NIHR funded academic clinical fellow, and was supported by funding from UCLH Charities while carrying out this work. RS and DS are part of the Advanced Pain Discovery Platform and were supported by a UKRI and Versus Arthritis grant (MR/W002566/1) as part of the Consortium Against Pain Inequality. AW was supported by the Wellcome Trust (220558/Z/20/Z).

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OBJECTIVE: The COVID-19 pandemic contributed to healthcare disruptions for patients with chronic pain. Following initial disruptions, national policies were enacted to expand access to long-term opioid therapy (LTOT) for chronic pain and opioid use disorder (OUD) treatment services, which may have modified risk of opioid overdose. We examined associations between LTOT and/or OUD with fatal and non-fatal opioid overdoses, and whether the pandemic moderated overdose risk in these groups. METHODS: We analyzed New York State Medicaid claims data (3/1/2019-12/31/20) of patients with chronic pain (N = 236,391). We used generalized estimating equations models to assess associations between LTOT and/or OUD (neither LTOT or OUD [ref], LTOT only, OUD only, and LTOT and OUD) and the pandemic (03/2020-12/2020) with opioid overdose. RESULTS: The pandemic did not significantly (ns) affect opioid overdose among patients with LTOT and/or OUD. While patients with LTOT (vs. no LTOT) had a slight increase in opioid overdose during the pandemic (pre-pandemic: aOR:1.65, 95% CI:1.05, 2.57; pandemic: aOR:2.43, CI:1.75,3.37, ns), patients with OUD had a slightly attenuated odds of overdose during the pandemic (pre-pandemic: aOR:5.65, CI:4.73, 6.75; pandemic: aOR:5.16, CI:4.33, 6.14, ns). Patients with both LTOT and OUD also experienced a slightly reduced odds of opioid overdose during the pandemic (pre-pandemic: aOR:5.82, CI:3.58, 9.44; pandemic: aOR:3.70, CI:2.11, 6.50, ns). CONCLUSIONS: Findings demonstrated no significant effect of the pandemic on opioid overdose among people with chronic pain and LTOT and/or OUD, suggesting pandemic policies expanding access to chronic pain and OUD treatment services may have mitigated the risk of opioid overdose.

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