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Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6‐dependent opioids while on CYP2D6‐inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6‐dependent opioids utilizing electronic health records data from the University of Florida Health (2015–2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine‐treated patients exposed to CYP2D6‐inhibitor antidepressants (n = 7,043) had a higher crude rate of pain‐related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6‐inhibitor antidepressant‐exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27–2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control. [ABSTRACT FROM AUTHOR]

The purpose of our study was to assess how an academic health center (AHC) mentor academy program affected mentor competence and optimized the mentor-mentee relationship. Mixed methods were used to assess the effectiveness of an AHC mentor program at a clinical translational science institute (CTSI). Twenty biomedical research faculty mentors took a validated survey and submitted reflective writings to discover if they corroborated or refuted statistically significant survey results. There was a significant improvement in participants' confidence of mentor skills, integral mentoring quality, and the extent to which they fulfill mentees' expectations. Males provided constructive feedback and helped mentees develop goal strategies more often compared to females. Reflective writings supported these findings yet refuted two survey findings. The use of a mixed methods approach offers novel insight into how mentoring programs benefit translational research mentoring capacity building and raises questions about the sole use of surveys as evidence of program effectiveness.

Simple Summary: Pain is a common symptom that affects individuals with cancer. This study, using data from the National Health Interview Survey, explored how household income relates to chronic pain among cancer survivors. It found that lower-income survivors, those below 200% of the federal poverty level (FPL), were more likely to report chronic pain lasting at least 3 months and pain that significantly limited their daily activities. Compared to higher-income survivors (at least 400% FPL), those with lower incomes had higher odds of experiencing chronic pain and its impact on daily life. Additionally, opioid use for pain management was more common among lower-income survivors, while higher-income survivors tended to use alternative methods like yoga, chiropractic care, and physical therapy. This study emphasizes the need for targeted efforts to address healthcare disparities and improve pain management for all cancer survivors, regardless of their income level. Pain is a prevalent issue among cancer patients, yet its link with socioeconomic status has not been thoroughly examined. This study investigated chronic pain (lasting ≥3 months) and high-impact pain (chronic pain limiting activities) among cancer survivors based on household income relative to the federal poverty level (FPL), using data from the National Health Interview Survey (2019–2020). Of the 4585 participants with a history of solid cancers, 1649 (36.3%) reported chronic pain and 554 (12.6%) reported high-impact chronic pain. After adjustment, participants with incomes < 200% FPL had significantly higher odds of chronic pain (adjusted odds ratio [aOR]: 1.60, 95% CI: 1.25–2.05) and high-impact chronic pain (aOR: 1.73, 95% CI: 1.09–2.74) compared to those with incomes ≥ 400% FPL. Opioid use for chronic pain was most prevalent among those with incomes < 200% FPL (28.3%) compared to those with 200–399% (21.3%) and ≥400% (19.0%). Higher-income participants reported greater use of alternative pain management methods such as yoga (50.5%), chiropractic care (44.8%), and physical therapy (44.3%). This study highlights the association between household income and chronic pain outcomes among cancer survivors, emphasizing the necessity for targeted interventions to mitigate healthcare access disparities and improve pain management for all individuals affected by cancer. [ABSTRACT FROM AUTHOR]

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6‐guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT‐PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6‐impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6‐guided trial recommendations. The primary study outcome is the 3‐month absolute change in the composite pain intensity score assessed using Patient‐Reported Outcomes Measurement Information System (PROMIS) measures. Follow‐up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment. [ABSTRACT FROM AUTHOR]

The nature of pharmacokinetic interactions between cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids and antidepressants among older nursing home residents is unclear. In this study of nursing home residents, concomitant use of CYP2D6-metabolized opioids with CYP2D6-inhibiting antidepressants was associated with higher adjusted rate ratios of worsening pain, pain-related hospitalization, pain-related emergency department visits, and opiate use disorder. These findings suggest the need for caution in prescribing these agents in older patients. Visual Abstract. Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents: The nature of pharmacokinetic interactions between cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids and antidepressants among older nursing home residents is unclear. In this study of nursing home residents, concomitant use of CYP2D6-metabolized opioids with CYP2D6-inhibiting antidepressants was associated with higher adjusted rate ratios of worsening pain, pain-related hospitalization, pain-related emergency department visits, and opiate use disorder. These findings suggest the need for caution in prescribing these agents in older patients. Background: Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents. Objective: To investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs). Design: Retrospective cohort study using a target trial emulation framework. Setting: 100% Medicare NH sample linked to Minimum Data Set (MDS) from 2010 to 2021. Participants: Long-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use. Intervention: Initiating CYP2D6-inhibiting versus CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for 1 day or more. Measurements: Clinical outcomes were worsening pain, physical function, and depression from baseline to quarterly MDS assessments and were analyzed using modified Poisson regression models. The ORAE outcomes included counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose and were analyzed with negative binomial or Poisson regression models. All models were adjusted for baseline covariates via inverse probability of treatment weighting. Results: Among 29 435 identified residents, use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher adjusted rate ratio of worsening pain (1.13 [95% CI, 1.09 to 1.17]) and higher adjusted incidence rate ratios of pain-related hospitalization (1.37 [CI, 1.19 to 1.59]), pain-related ED visit (1.49 [CI, 1.24 to 1.80]), and OUD (1.93 [CI, 1.37 to 2.73]), with no difference in physical function, depression, and opioid overdose. Limitation: Findings are generalizable to NH populations only. Conclusion: Use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with worsening pain and increased risk for most assessed ORAEs among older NH residents. Primary Funding Source: National Institute on Aging. [ABSTRACT FROM AUTHOR]

Background Injury, prevalent and potentially associated with prescription opioid use among older adults, has been implicated as a warning sign of serious opioid-related adverse events (ORAEs) including opioid misuse, dependence, and poisoning, but this association has not been empirically tested. The study aims to examine the association between incident injury after prescription opioid initiation and subsequent risk of ORAEs and to assess whether the association differs by recency of injury among older patients. Methods and findings This nested case-control study was conducted within a cohort of 126,752 individuals aged 65 years or older selected from a 5% sample of Medicare beneficiaries in the United States between 2011 and 2018. Cohort participants were newly prescribed opioid users with chronic noncancer pain who had no injury or ORAEs in the year before opioid initiation, had 30 days or more of observation, and had at least 1 additional opioid prescription dispensed during follow-up. We identified ORAE cases as patients who had an inpatient or outpatient encounter with diagnosis codes for opioid misuse, dependence, or poisoning. During a mean follow-up of 1.8 years, we identified 2,734 patients who were newly diagnosed with ORAEs and 10,936 controls matched on the year of cohort entry date and a disease risk score (DRS), a summary score derived from the probability of an ORAE outcome based on covariates measured prior to cohort entry and in the absence of injury. Multivariate conditional logistic regression was used to estimate ORAE risk associated with any and recency of injury, defined based on the primary diagnosis code of inpatient and outpatient encounters. Among the cases and controls, 68.0% (n = 1,859 for cases and n = 7,436 for controls) were women and the mean (SD) age was 74.5 (6.9) years. Overall, 54.0% (n = 1,475) of cases and 46.0% (n = 1,259) of controls experienced incident injury after opioid initiation. Patients with (versus without) injury after opioid therapy had higher risk of ORAEs after adjustment for time-varying confounders, including diagnosis of tobacco or alcohol use disorder, drug use disorder, chronic pain diagnosis, mental health disorder, pain-related comorbidities, frailty index, emergency department visit, skilled nursing facility stay, anticonvulsant use, and patterns of prescription opioid use (adjusted odds ratio [aOR] = 1.4; 95% confidence interval (CI) 1.2 to 1.5; P < 0.001). Increased risk of ORAEs was associated with current ([less than or equal to]30 days) injury (aOR = 2.8; 95% CI 2.3 to 3.4; P < 0.001), whereas risk of ORAEs was not significantly associated with recent (31 to 90 days; aOR = 0.93; 95% CI 0.73 to 1.17; P = 0.48), past (91 to 180 days; aOR = 1.08; 95% CI 0.88 to 1.33; P = 0.51), and remote (181 to 365 days; aOR = 0.88; 95% CI 0.73 to 1.1; P = 0.18) injury preceding the incident diagnosis of ORAE or matched date. Patients with injury and prescription opioid use versus those with neither in the month before the ORAE or matched date were at greater risk of ORAEs (aOR = 5.0; 95% CI 4.1 to 6.1; P < 0.001). Major limitations are that the study findings can only be generalized to older Medicare fee-for-service beneficiaries and that unknown or unmeasured confounders have the potential to bias the observed association toward or away from the null. Conclusions In this study, we observed that incident diagnosis of injury following opioid initiation was associated with subsequent increased risk of ORAEs, and the risk was only significant among patients with injury in the month before the index date. Regular monitoring for injury may help identify older opioid users at high risk for ORAEs., Author(s): Yu-Jung Jenny Wei 1,2,3,*, Cheng Chen 4, Ting-Yuan David Cheng 5, Siegfried O. Schmidt 6, Roger B. Fillingim 7, Almut G. Winterstein 1,2,8 Introduction Older adults in the United [...]

Negative pain beliefs are associated with adverse pain outcomes; however, less is known regarding how positive, adaptive factors influence pain and functioning. These relationships are especially important to examine in older adults with pain, given increased disability and functional limitations in this population. We investigated whether pain resilience moderated the relationships between negative pain beliefs (fear-avoidance, pain catastrophizing) and pain outcomes (functional performance, movement-evoked pain) in sixty older adults with low back pain. Higher pain resilience was associated with lower fear-avoidance (p < .05) and pain catastrophizing (p = .05). After controlling for demographic variables, higher fear-avoidance (p = .03) and catastrophizing (p = .03) were associated with greater movement-evoked pain in individuals with low pain resilience, but not among those high in resilience. No significant moderation effects were observed for functional performance. Resilience may attenuate the relationship between negative psychological processes and pain-related disability, highlighting the need for interventions that enhance pain resilience in older adults., Author(s): Shreela Palit [sup.1] , Roger B. Fillingim [sup.1] , Emily J. Bartley [sup.1] Author Affiliations: (1) grid.15276.37, 0000 0004 1936 8091, Department of Community Dentistry and Behavioral Science, Pain [...]