Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents : A Target Trial Emulation Study.

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.

Use of CYP2D6 Inhibitors with CYP2D6 Opioids: Association with Emergency Department Visits for Pain.

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.

Short- and long-term safety of discontinuing chronic opioid therapy among older adults with Alzheimer's disease and related dementia.

Background: Limited evidence exists on the short- and long-term safety of discontinuing versus continuing chronic opioid therapy (COT) among patients with Alzheimer's disease and related dementias (ADRD).

Methods: This cohort study was conducted among 162,677 older residents with ADRD and receipt of COT using a 100% Medicare nursing home sample. Discontinuation of COT was defined as no opioid refills for ≥90 days.

Sociodemographic Characteristics of Adverse Event Reporting in the USA: An Ecologic Study.

Introduction: The Food and Drug Administration Adverse Event Reporting System (FAERS) is a vital source of new drug safety information, but whether adverse event (AE) information collected from these systems adequately captures experiences of the overall United States (US) population is unknown.

Objective: To examine determinants of consumer AE reporting in the USA.

Methods: Five-year AE reporting rate per 100,000 residents per US county were calculated, mapped, and quartiled for AE reports received directly from consumers between 2011 and 2015.

Prevalence and trend of central nervous system-active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study.

Background: Limited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, depression, or epilepsy, conditions managed by CNS-active medications.

Methods: A multi-year, cross-sectional study using 2012-2021 MarketScan Commercial Claims data was conducted among adults aged 30 to 64 years with EOD and those without EOD but having a diagnosis of chronic pain, depression, or epilepsy as comparison groups. For each disease cohort, the primary outcome was CNS-active medication polypharmacy defined as concurrent use of ≥ 3 CNS-active medications on the US Beers Criteria list that overlapped for > 30 consecutive days during 12 months following a randomly selected medical encounter with the disease diagnosis.

Pain intensity, physical function, and depressive symptoms associated with discontinuing long-term opioid therapy in older adults with Alzheimer's disease and related dementias.

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.

Experimental Revelation of Surface and Bulk Lattices in Faceted Cu O Crystals.

Semiconductor crystals have generally shown facet-dependent electrical, photocatalytic, and optical properties. These phenomena have been proposed to result from the presence of a surface layer with bond-level deviations. To provide experimental evidence of this structural feature, synchrotron X-ray sources are used to obtain X-ray diffraction (XRD) patterns of polyhedral cuprous oxide crystals.

Association of injury after prescription opioid initiation with risk for opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case-control study.

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.

Perioperative Use of Gabapentinoids and Risk for Postoperative Long-Term Opioid Use in Older Adults Undergoing Total Knee or Hip Arthroplasty.

Background: Gabapentinoids are recommended by guidelines as a component of multimodal analgesia to manage postoperative pain and reduce opioid use. It remains unknown whether perioperative use of gabapentinoids is associated with a reduced or increased risk of postoperative long-term opioid use (LTOU) after total knee or hip arthroplasty (TKA/THA).

Methods: Using Medicare claims data from 2011 to 2018, we identified fee-for-service beneficiaries aged ≥ 65 years who were hospitalized for a primary TKA/THA and had no LTOU before the surgery.

Trajectories of prescription opioid dose and risk of opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case-control study.

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 (≥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.

Concurrent use of prescription gabapentinoids with opioids and risk for fall-related injury among older US Medicare beneficiaries with chronic noncancer pain: A population-based cohort study.

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.

Concurrent Use of Prescription Opioids and Gabapentinoids in Older Adults.

Introduction: Concurrent use of prescription opioids with gabapentinoids may pose risks of serious drug interactions. Yet, little is known about the trends in and patient characteristics associated with concurrent opioid-gabapentinoid use among older Medicare opioid users with chronic noncancer pain.

Methods: A cross-sectional study was conducted among Medicare older beneficiaries (aged ≥65 years) with chronic noncancer pain who filled ≥1 opioid prescription within 3 months after a randomly selected chronic noncancer pain diagnosis (index date) in a calendar year between 2011 and 2018.

Discontinuation of Long-Term Opioid Therapy in Patients With Versus Without Dementia.

Introduction: Discontinuation of long-term opioid therapy has increased in recent years, but whether this trend extends to patients with Alzheimer disease and related dementia remains unclear.

Methods: Medicare data from 2011 to 2018 were analyzed to compare the trends in the use and discontinuation of long-term opioid therapy between patients with and without Alzheimer disease and related dementia who had chronic noncancer pain. Outcome measures were annual proportions of (1) patients who received long-term opioid therapy and (2) long-term opioid therapy users who subsequently discontinued opioids for ≥30, 60, or 90 days during 12-month follow-up.

Generalizability and accuracy of IBM MarketScan health risk assessment instrument data for augmentation of commercial claims data.

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.

Quality of opioid prescribing in older adults with or without Alzheimer disease and related dementia.

Background: Pain is common among individuals with Alzheimer's disease and related dementias (ADRD), and use of opioids has been increasing over the last decade. Yet, it is unclear to what extent opioids are appropriately prescribed for patients with ADRD and whether the appropriateness of opioid prescribing differs by ADRD status. The objective of this study is to compare the quality of opioid prescribing among patients with or without ADRD who have chronic noncancer pain.

Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Exacerbations Among Patients With Type 2 Diabetes.

Objective: Emerging data from animal and human pilot studies suggest potential benefits of glucagon-like peptide 1 receptor agonists (GLP-1RA) on lung function. We aimed to assess the association of GLP-1RA and chronic lower respiratory disease (CLRD) exacerbation in a population with comorbid type 2 diabetes (T2D) and CLRD.

Research Design And Methods: A new-user active-comparator analysis was conducted with use of a national claims database of beneficiaries with employer-sponsored health insurance spanning 2005-2017.

Utilization Patterns of Skeletal Muscle Relaxants Among Commercially Insured Adults in the United States from 2006 to 2018.

Objective: To examine the prevalence and duration of skeletal muscle relaxant (SMR) treatment among commercially insured adults in the United States.

Methods: We used the MarketScan Research Database to identify a cohort of adults 18 to 64 years who had ≥2-year continuous enrollment between 2005 and 2018. We estimated the prevalence of SMR treatment using a repeated cross-sectional design and derived treatment duration using the Kaplan-Meier method.

Validation of algorithms to estimate gestational age at birth in the Medicaid Analytic eXtract-Quantifying the misclassification of maternal drug exposure during pregnancy.

Purpose: Accurate ascertainment of gestational age (GA) has been a challenge in perinatal epidemiologic research. To date, no study has validated GA algorithms in Medicaid Analytic eXtract (MAX).

Methods: We linked livebirths of mothers enrolled in Medicaid ≥30 days after delivery in 1999-2010 MAX to state birth certificates.

Agreement of Minimum Data Set 3.0 depression and behavioral symptoms with clinical diagnosis in a nursing home.

Objectives: 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.

Design: Using a retrospective review of MDS 3.

Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population-Based Cohort Study.

The recent opioid prescribing guideline cautions about the concomitant prescribing of opioids and skeletal muscle relaxants (SMRs) given the additive central nervous system depressant effect. However, the clinical relevance remains unclear. In this retrospective cohort study, we compared the risk of opioid overdose associated with concomitant use of opioids and SMRs vs.

Towards Automating Adverse Event Review: A Prediction Model for Case Report Utility.

Introduction: The rapidly expanding size of the Food and Drug Administration's (FDA) Adverse Event Reporting System database requires modernized pharmacovigilance practices. Techniques to systematically identify high utility individual case safety reports (ICSRs) will support safety signal management.

Objectives: The aim of this study was to develop and validate a model predictive of an ICSR's pharmacovigilance utility (PVU).

Trends in prescription opioid use and dose trajectories before opioid use disorder or overdose in US adults from 2006 to 2016: A cross-sectional study.

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.

Concomitant Use of Quinolones and Stimulants and the Risk of Adverse Cardiovascular Symptoms: A Retrospective Cohort Study.

Objective: To examine whether concomitant use of quinolones and stimulants increases the risk of cardiac events in adults.

Study Design: A retrospective cohort study of privately insured adults using MarketScan claims data from 2008 to 2015.

Patients: Stimulant (methylphenidate or mixed amphetamine salts) users (18-65 yrs old) with continuous health plan enrollment for the 6 months (baseline) prior to the first dispensation (index date) of oral quinolones or comparators (amoxicillin ± clavulanate or azithromycin).