Applying evidence-based cross-disciplinary concepts helps to explain the heterogeneity in pain, function, and biological measures in individuals with knee pain with/at risk of osteoarthritis.

Introduction: Factors contributing to individual differences in knee osteoarthritis remain elusive. Dispositional traits and socioeconomic status are independent predictors of mental and physical health, although significant variability remains. Dispositional traits serve as the biological interface for life experiences.

Design and development of a machine-learning-driven opioid overdose risk prediction tool integrated in electronic health records in primary care settings.

Background: Integrating advanced machine-learning (ML) algorithms into clinical practice is challenging and requires interdisciplinary collaboration to develop transparent, interpretable, and ethically sound clinical decision support (CDS) tools. We aimed to design a ML-driven CDS tool to predict opioid overdose risk and gather feedback for its integration into the University of Florida Health (UFHealth) electronic health record (EHR) system.

Methods: We used user-centered design methods to integrate the ML algorithm into the EHR system.

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.

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.

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.

Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review.

While the Food and Drug Administration's black-box warnings caution against concurrent opioid and benzodiazepine (OPI-BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995-08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0).

Characterizing DNA methylation in prescription opioid users with chronic musculoskeletal pain.

Introduction: Many patients with chronic pain use prescription opioids. Epigenetic modification of the μ-opioid receptor 1 () gene, which codes for the target protein of opioids, may influence vulnerability to opioid abuse and response to opioid pharmacotherapy, potentially affecting pain outcomes.

Objective: Our objective was to investigate associations of clinical and sociodemographic factors with DNA methylation in patients with chronic musculoskeletal pain on long-term prescription opioids.

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.

A randomized, cross-over trial of metoprolol succinate formulations to evaluate PK and PD end points for therapeutic equivalence.

There are limited comparison data throughout the dosing interval for generic versus brand metoprolol extended-release (ER) tablets. We compared the pharmacokinetics (PKs) and pharmacodynamics of brand name versus two generic formulations (drugs 1 and 2) of metoprolol ER tablets with different time to maximum concentration (T ) in adults with hypertension. Participants were randomized to equal drug doses (50-150 mg/day) administered in one of two sequences (brand-drug1-brand-drug2 or brand-drug2-brand-drug1) and completed 24-h PK, digital heart rate (HR), ambulatory blood pressure (BP), and HR studies after taking each formulation for greater than or equal to 7 days.

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.

Uncontrolled Pain and Risk for Depression and Behavioral Symptoms in Residents With Dementia.

Objectives: Limited cohort studies have assessed the association between uncontrolled pain and risk for behavioral and psychological symptoms of dementia (BPSDs). We conducted a longitudinal cohort study to examine whether associations exist between uncontrolled pain and risk for 2 common BPSDs-depression and behavioral symptoms-among long-term care (LTC) residents with Alzheimer disease and related dementia (ADRD).

Design: This retrospective cohort study analyzed quarterly data from the 5% Medicare sample linked to Minimum Data Set (MDS) 3.

Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease.

We aimed to determine the potential value of panel-based pharmacogenetic (PGx) testing in patients with chronic pain or gastroesophageal reflux disease (GERD) who underwent single-gene PGx testing to guide opioid or proton pump inhibitor (PPI) therapy, respectively. Of 448 patients included (chronic pain, n = 337; GERD, n = 111), mean age was 57 years, 68% were female, and 73% were white. Excluding opiates for the pain cohort and PPIs for the GERD cohort, 76.

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.

Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening.

Objective: Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).

Research Design And Methods: A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.

Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores.

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S-metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.

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.

Trends in prior receipt of prescription opioid or adjuvant analgesics among patients with incident opioid use disorder or opioid-related overdose from 2006 to 2016.

Background: With increasing efforts to scrutinize and reduce opioid prescribing, limited data exist on the recent trend in receipt of prescription pain medications before diagnosis of opioid use disorder (OUD) or opioid-related overdose (OD).

Methods: Using 2005-2016 Truven MarketScan Commercial Claims databases, we assessed trends in annual 1) incidence of OUD or OD and 2) prevalence of receipt of prescription opioids or four commonly-prescribed adjuvant analgesics among patients newly diagnosed with OUD/OD. Trends were examined in the overall sample and by 3 age groups, including youths (≤18 years), adults (19-64 years), and older adults (≥65 years).

Challenges and lessons learned from clinical pharmacogenetic implementation of multiple gene-drug pairs across ambulatory care settings.

Purpose: Incorporating a patient's genotype into the clinical decision-making process is one approach to precision medicine. The University of Florida (UF) Health Precision Medicine Program is a pharmacist-led multidisciplinary effort that has led the clinical implementation of six gene-drug(s) pairs to date. This study focuses on the challenges encountered and lessons learned with implementing pharmacogenetic testing for three of these: CYP2D6-opioids, CYP2D6/CYP2C19-selective serotonin reuptake inhibitors, and CYP2C19-proton pump inhibitors within six pragmatic clinical trials at UF Health and partners.

CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial.

Purpose: CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control.

Methods: Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design.

Clinical application of pharmacogenetics in pain management.

There is growing experience translating genomic data into clinical practice, as seen with the Implementing GeNomics In pracTicE (IGNITE) network. A primary example is the influence of CYP2D6 genotype on the beneficial and adverse effects of some opioids. Clinical recommendations exist to guide drug therapy based on CYP2D6 genotype for codeine, tramadol, oxycodone and hydrocodone, although the level of supporting evidence differs by drug.

Trends in Florida's Prescription Drug Monitoring Program registration and utilization: Implications for increasing voluntary use.

Objective: Effective use of state prescription drug monitoring programs (PDMPs) to track controlled substance prescribing and dispensing may help mitigate the current opioid crisis. Our objective was to examine trends in registration for and use of Florida's PDMP by physicians and pharmacists, from 2013 to 2016. We discuss implications for PDMP uptake and policy.

The effect of EHR-integrated patient-reported outcomes on satisfaction with chronic pain care.

Objectives: Given its complexity, chronic noncancer pain presents an opportunity to use health information technology (IT) to improve care experiences. The objective of this study was to assess whether integrating patient-reported outcomes (PROs) data in an electronic health record (EHR) affects provider and patient satisfaction with chronic noncancer pain care.

Study Design: We conducted a pragmatic cluster randomized trial involving 4 family medicine clinics.

Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans.

African Americans suffer a higher prevalence of hypertension compared with other racial/ethnic groups. In this study, we performed a pharmacogenomic genome-wide association study of blood pressure (BP) response to β-blockers in African Americans with uncomplicated hypertension. Genome-wide meta-analysis was performed in 318 African American hypertensive participants in the 2 Pharmacogenomic Evaluation of Antihypertensive Responses studies: 150 treated with atenolol monotherapy and 168 treated with metoprolol monotherapy.

Pharmacogenetics: Using Genetic Information to Guide Drug Therapy.

Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.

PTPRD gene associated with blood pressure response to atenolol and resistant hypertension.

Objective: The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-blocker atenolol.

Methods: Genome-wide association analysis of BP response to atenolol monotherapy was performed in 233 white participants with uncomplicated hypertension in the pharmacogenomic evaluation of antihypertensive responses study. Forty-two polymorphisms with P less than 10 for association with either diastolic or systolic response to atenolol monotherapy were validated in four independent groups of hypertensive individuals (total n = 2114).