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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 [...]

Background Despite the rising number of older adults with medical encounters for opioid misuse, dependence, and poisoning, little is known about patterns of prescription opioid dose and their association with risk for opioid-related adverse events (ORAEs) in older patients. The study aims to compare trajectories of prescribed opioid doses in 6 months preceding an incident ORAE for cases and a matched control group of older patients with chronic noncancer pain (CNCP). Methods and findings We conducted a nested case-control study within a cohort of older ([greater than or equal to]65 years) patients diagnosed with CNCP who were new users of prescription opioids, assembled using a 5% national random sample of Medicare beneficiaries from 2011 to 2018. From the cohort with a mean follow-up of 2.3 years, we identified 3,103 incident ORAE cases with [greater than or equal to]1 opioid prescription in 6 months preceding the event, and 3,103 controls matched on sex, age, and time since opioid initiation. Key exposure was trajectories of prescribed opioid morphine milligram equivalent (MME) daily dosage over 6 months before the incident ORAE or matched controls. Among the cases and controls, 2,192 (70.6%) were women, and the mean (SD) age was 77.1 (7.1) years. Four prescribed opioid trajectories before the incident ORAE diagnosis or matched date emerged: gradual dose discontinuation (from [less than or equal to]3 to 0 daily MME, 1,456 [23.5%]), gradual dose increase (from 0 to >3 daily MME, 1,878 [30.3%]), consistent low dose (between 3 and 5 daily MME, 1,510 [24.3%]), and consistent moderate dose (>20 daily MME, 1,362 [22.0%]). Few older patients ( Conclusions In this sample of older patients who are Medicare beneficiaries, 4 prescription opioid dose trajectories were identified, with most prescribed doses below 90 daily MME within 6 months before ORAE or matched date. An increased risk for ORAE was observed among older patients with a gradual increase in dose or among those with a consistent low-to-moderate dose of prescribed opioids when compared to patients with opioid dose discontinuation. Whether older patients are susceptible to low opioid doses warrants further investigations., Author(s): Yu-Jung Jenny Wei 1,2,*, Cheng Chen 1, Motomori O. Lewis 1, Siegfried O. Schmidt 3, Almut G. Winterstein 1,2,4 Introduction The number of older adults who had medical encounters [...]

Background Gabapentinoids are increasingly prescribed to manage chronic noncancer pain (CNCP) in older adults. When used concurrently with opioids, gabapentinoids may potentiate central nervous system (CNS) depression and increase the risks for fall. We aimed to investigate whether concurrent use of gabapentinoids with opioids compared with use of opioids alone is associated with an increased risk of fall-related injury among older adults with CNCP. Methods and findings We conducted a population-based cohort study using a 5% national sample of Medicare beneficiaries in the United States between 2011 and 2018. Study sample consisted of fee-for-service (FFS) beneficiaries aged [greater than or equal to]65 years with CNCP diagnosis who initiated opioids. We identified concurrent users with gabapentinoids and opioids days' supply overlapping for [greater than or equal to]1 day and designated first day of concurrency as the index date. We created 2 cohorts based on whether concurrent users initiated gabapentinoids on the day of opioid initiation (Cohort 1) or after opioid initiation (Cohort 2). Each concurrent user was matched to up to 4 opioid-only users on opioid initiation date and index date using risk set sampling. We followed patients from index date to first fall-related injury event ascertained using a validated claims-based algorithm, treatment discontinuation or switching, death, Medicare disenrollment, hospitalization or nursing home admission, or end of study, whichever occurred first. In each cohort, we used propensity score (PS) weighted Cox models to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of fall-related injury, adjusting for year of the index date, sociodemographics, types of chronic pain, comorbidities, frailty, polypharmacy, healthcare utilization, use of nonopioid medications, and opioid use on and before the index date. We identified 6,733 concurrent users and 27,092 matched opioid-only users in Cohort 1 and 5,709 concurrent users and 22,388 matched opioid-only users in Cohort 2. The incidence rate of fall-related injury was 24.5 per 100 person-years during follow-up (median, 9 days; interquartile range [IQR], 5 to 18 days) in Cohort 1 and was 18.0 per 100 person-years during follow-up (median, 9 days; IQR, 4 to 22 days) in Cohort 2. Concurrent users had similar risk of fall-related injury as opioid-only users in Cohort 1(aHR = 0.97, 95% CI 0.71 to 1.34, p = 0.874), but had higher risk for fall-related injury than opioid-only users in Cohort 2 (aHR = 1.69, 95% CI 1.17 to 2.44, p = 0.005). Limitations of this study included confounding due to unmeasured factors, unavailable information on gabapentinoids' indication, potential misclassification, and limited generalizability beyond older adults insured by Medicare FFS program. Conclusions In this sample of older Medicare beneficiaries with CNCP, initiating gabapentinoids and opioids simultaneously compared with initiating opioids only was not significantly associated with risk for fall-related injury. However, addition of gabapentinoids to an existing opioid regimen was associated with increased risks for fall. Mechanisms for the observed excess risk, whether pharmacological or because of channeling of combination therapy to high-risk patients, require further investigation. Clinicians should consider the risk-benefit of combination therapy when prescribing gabapentinoids concurrently with opioids., Author(s): Cheng Chen 1, Almut G. Winterstein 1,2,3, Wei-Hsuan Lo-Ciganic 1,2, Patrick J. Tighe 4, Yu-Jung Jenny Wei 1,2,* Introduction Amid the opioid epidemic in the US, the proportion of [...]

INTRODUCTION: Limited evidence exists on the associations of discontinuing versus continuing long‐term opioid therapy (LTOT) with pain intensity, physical function, and depression among patients with Alzheimer's disease and related dementias (ADRD). METHODS: A cohort study among 138,059 older residents with mild‐to‐moderate ADRD and receipt of LTOT was conducted using a 100% Medicare nursing home sample. Discontinuation of LTOT was defined as no opioid refills for ≥ 60 days. Outcomes were worsening pain, physical function, and depression from baseline to quarterly assessments during 1‐ and 2‐year follow‐ups. RESULTS: The adjusted odds of worsening pain and depressive symptoms were 29% and 5% lower at the 1‐year follow‐up and 35% and 9% lower at the 2‐year follow‐up for residents who discontinued versus continued LTOT, with no difference in physical function. DISCUSSION: Discontinuing LTOT was associated with lower short‐ and long‐term worsening pain and depressive symptoms than continuing LTOT among older residents with ADRD. Highlights: Discontinuing long‐term opioid therapy (LTOT) was associated with lower short‐ and long‐term worsening pain.Discontinuing LTOT was related to lower short‐ and long‐term worsening depression.Discontinuing LTOT was not associated with short‐ and long‐term physical function. [ABSTRACT FROM AUTHOR]

Background With governments' increasing efforts to curb opioid prescription use and limit dose below the Centers for Disease Control and Prevention (CDC)-recommended threshold of 90 morphine milligram equivalents per day, little is known about prescription opioid patterns preceding opioid use disorder (OUD) or overdose. This study aimed to determine prescribed opioid fills and dose trajectories in the year before an incident OUD or overdose diagnosis using a 2005-2016 commercial healthcare database. Methods and findings This cross-sectional study identified individuals aged 18 to 64 years with incident OUD or overdose in the United States. We measured the prevalence of opioid prescription fills and trajectories of opioid morphine equivalent dose (MED) prescribed during the 12-month period before the diagnosis. Of 227,038 adults with incident OUD or overdose, 33.1% were aged 18 to 30 years, 52.9% were males, and 85.0% were metropolitan residents. Half (50.5%) of the patients had a diagnosis of chronic pain, 32.7% had depression, and 20.3% had anxiety. Overall, 79,747 (35.1%) patients filled no opioid prescription in the 12 months before OUD or overdose diagnosis, with the proportion significantly increasing between 2006 and 2016 (adjusted prevalence ratio, 1.86; 95% CI 1.79-1.93; P < 0.001). Patients without (versus with) prescribed opioids tended to be younger males and metropolitan and Northeast US residents. Of 145,609 patients who filled opioid prescriptions, 5 distinct prescribed daily dose trajectories preceding diagnosis emerged: consistent low dose ( Conclusions In this study, we found that absence of opioid prescription fills in the year before incident OUD or overdose diagnosis was prevalent, and the majority of the patients received prescription opioid doses below the risk threshold of 90 mg MED. An increasing proportion of high-risk patients could be missed by current programs solely based on opioid prescribing and dispensing information in this new era of limited access to prescription opioids., Author(s): Yu-Jung Jenny Wei 1,2,*, Cheng Chen 1, Roger Fillingim 3,4, Siegfried O. Schmidt 5, Almut G. Winterstein 1,2,6 Introduction Opioid use disorder (OUD) has significant public health consequences including [...]

Quality of care rather than price is the main concern in health care. However, does price not matter at all? To investigate what quality and cost factors influence whether patients [...]

Purpose: We evaluated the generalizability and accuracy of the IBM® MarketScan® Health Risk Assessment (HRA) data to assess its suitability as supplement to linked claims data. Methods: We identified adult private insurance enrollees in the IBM® MarketScan® Commercial Claims & Encounters (CC&E) and HRA databases between 2012 and 2017. In the claims data, for each enrollee, we sampled the first calendar year with continuous enrollment indicating full capture of claims data and extracted linked HRA survey data if available. We compared HRA participants and non‐participants considering demographics, prevalences of chronic conditions, and healthcare utilization. Including the subsample with HRA data only, we estimated the negative predictive value (NPV) of obesity and smoking reported in the HRA against diagnosis code in the claims data. Results: Between 2012 and 2017, 2 693 444 and 31 450 000 of HRA and non‐HRA participants were included in the study, respectively. Chronic diseases were similarly distributed between the two populations, with hypertension and hyperlipidemia representing the highest prevalence difference (1.4%). The two samples showed similar healthcare utilization. The proportion of false‐negatives for obesity and smoking information when relying on the HRA data compared to patients with positive diagnosis based on claims data was low (<1%). Prevalence estimates of both variables were similar to national estimates. Conclusion: Our findings suggest that the overall HRA population may represent the overall claims population and HRA provides certain data elements with satisfactory accuracy. [ABSTRACT FROM AUTHOR]

While the Minimum Data Set (MDS) 3.0 has adopted Patient Health Questionnaire (PHQ)-9 to screen for depression and rephrased language for behavioral symptoms among nursing home residents, it remains unclear how well the assessment data agree with medical records. Using a retrospective review of MDS 3.0 linked to medical records between October 2010 and November 2017, we included residents with at least one quarterly or short-term (day 30 or day 60) MDS 3.0 assessment of depression PHQ-9 (n = 446) or behavioral symptoms (n = 460). For each resident of each cohort, we randomly selected an eligible MDS 3.0 depression and behavioral symptom assessment and compared against the respective medical diagnoses recorded within 30 days before the MDS 3.0 assessment. Percent agreement was high for depression (90.1%) and behavioral symptoms (89.3%). Negative agreement was high for depression (94.8%) and behavioral symptoms (94.3%), while positive agreement was low for both conditions (4.3% and 10.9%). MDS 3.0 depression and behavioral symptoms had high overall and negative agreement, but low positive agreement with clinician diagnoses. MDS 3.0 data may be useful in ruling out depression and behavioral symptoms. Confirmation of the findings in a representative sample of nursing homes is warranted. [ABSTRACT FROM AUTHOR]