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Introduction: Medical cannabis (MC) is available upon certification for one of several qualifying conditions in Florida, USA. Previous studies suggested that some people seek cannabis for medical conditions/symptoms beyond those legally permitted. However, data remain limited on patient motives for seeking MC and their experiences around its impact on their health. We aimed to compare reported qualifying conditions for MC certification with the most frequently self-reported reasons for using MC while assessing the alignment between the two and understanding the perceived impacts of MC on self-reported conditions and symptoms. Methods: We conducted a cross-sectional study using survey data from the Medical Marijuana and Me (M3) Data Bank of individuals receiving MC in Florida, USA, in 2022. Participants were recruited via convenience sampling from nine MC clinics/clinic networks across Florida and were asked to fill out an online survey. The study measures included sociodemographic variables, self-reported health conditions, self-reported main reasons for using MC, self-reported qualifying conditions for MC certification, and self-reported perceived impact of MC on health conditions. We cross-tabulated reported qualifying conditions and reasons for MC use and reported the perceived impact per condition. Results: A total of 632 participants completed the survey, of whom 396 (62.66%) were female and 471 (74.53%) were non-Hispanic white. The median (IQR) age was 45 (35, 58). The most frequently reported qualifying conditions were post-traumatic stress disorder (PTSD) (n = 187, 29.59%), a condition not on the qualifying conditions list (n = 175, 27.69%), medical conditions of the same kind/comparable to those listed (n = 140, 22.15%), and chronic nonmalignant pain (n = 62, 25.63%). The top ten most frequently reported reasons for using MC were anxiety (n = 383, 60.60%), chronic pain (n = 278, 43.99%), depression (n = 252, 39.87%), PTSD (n = 220, 34.81%), headaches/migraine (n = 134, 21.20%), fibromyalgia (n = 67, 10.60%), attention-deficit hyperactivity disorder (ADHD) (n = 59, 9.34%), bipolar disorder (n = 53, 8.39%), high blood pressure (n = 41, 6.49%), and cancer (n = 18,2.85%). Of respondents, 70–90% with each qualifying condition reported it as one of the main reasons for using MC. Most respondents reported improvement of anxiety (n = 430/451, 95.34%), depression (n = 381/392, 97.20%), chronic pain (n = 305/310, 98.39%), insomnia/sleeping problems (n = 225/295, 86.44%), PTSD (n = 247/270, 91.48%), headaches/migraine (n = 172/218, 78.90%), ADHD (n = 82/123, 66.67%), bipolar disorder (n = 79/89, 88.76%), and fibromyalgia (n = 77/82, 93.90%). Most respondents were unsure/reported no change in blood pressure (n = 93/162, 57.41%). A small percentage reported perceived worsening impacts on their conditions. Conclusion: Qualifying conditions and self-reported reasons for using MC aligned for most respondents. Yet, a notable proportion of respondents sought MC for broader treatment effects beyond those delineated by the officially recognized qualifying conditions in Florida, USA. Most patients perceived positive effects, including those with limited available evidence on efficacy.

Abstract Background Although administrative claims data have a high degree of completeness, not all medically attended Respiratory Syncytial Virus-associated lower respiratory tract infections (RSV-LRTIs) are tested or coded for their causative agent. We sought to determine the attribution of RSV to LRTI in claims data via modeling of temporal changes in LRTI rates against surveillance data. Methods We estimated the weekly incidence of LRTI (inpatient, outpatient, and total) for children 0–4 years using 2011–2019 commercial insurance claims, stratified by HHS region, matched to the corresponding weekly NREVSS RSV and influenza positivity data for each region, and modelled against RSV, influenza positivity rates, and harmonic functions of time assuming negative binomial distribution. LRTI events attributable to RSV were estimated as predicted events from the full model minus predicted events with RSV positivity rate set to 0. Results Approximately 42% of predicted RSV cases were coded in claims data. Across all regions, the percentage of LRTI attributable to RSV were 15–43%, 10–31%, and 10–31% of inpatient, outpatient, and combined settings, respectively. However, when compared to coded inpatient RSV-LRTI, 9 of 10 regions had improbable corrected inpatient LRTI estimates (predicted RSV/coded RSV ratio

Abstract 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 Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no‐function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no‐function allele carriers. However, the influence of patient‐specific demographic, clinical, and other genetic factors on outcomes with genotype‐guided DAPT has not been defined. In addition, the impact of genotype‐guided de‐escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no‐function allele has not been investigated in a diverse, real‐world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient‐specific factors on clinical outcomes with CYP2C19‐guided DAPT, evaluate the safety and effectiveness of CYP2C19‐guided DAPT de‐escalation following PCI in a real‐world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real‐world population.

Abstract Real‐world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE. A total of 31 were in oncology and 54 were in non‐oncology therapeutic areas. Most were for indications in adults only (N = 42, 49.4%), while 13 were in pediatrics only (15.3%), and 30 were in both (35.3%). In terms of regulatory context, 59 cases (69.4%) were for an original marketing application, 24 (28.2%) were for label expansion, and 2 (2.4%) were for label modification. Most also received special regulatory designations (e.g., orphan indication, breakthrough therapy, fast track, conditional, and accelerated approvals). There were 42 cases that utilized RWE to support single‐arm trials. External data to support single‐arm trials were utilized in various ways across use cases, including direct matching, benchmarking, natural history studies as well as literature or previous trials. A variety of data sources were utilized, including electronic health records, claims, registries, site‐based charts. Endpoints in oncology use cases commonly included overall survival, progression‐free survival. In 13 use cases, RWE was not considered supportive/definitive in regulatory decision‐making due to design issues (e.g., small sample size, selection bias, missing data). Overall, RWE is utilized in regulatory approval processes for new indications/label expansion across various therapeutic areas with wide range of approaches. Multifaceted cross‐sector efforts are needed to further improve the quality and utility of RWE in regulatory decision‐making.

Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. Methods and Results Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P

The Consortium for Medical Marijuana Clinical Outcomes Research, a multi-university collaboration established by the state of Florida in the USA, hosted its third annual Cannabis Clinical Outcomes Research Conference (CCORC) in May 2023. CCORC was held as a hybrid conference, with a scientific program consisting of in-person sessions, with some sessions livestreamed to virtual attendees. CCORC facilitated and promoted up-to-date research on the clinical effects of medical cannabis, fostering collaboration and active involvement among scientists, policymakers, industry professionals, clinicians, and other stakeholders. Three themes emerged from conference sessions and speaker presentations: (1) disentangling conflicting evidence for the effects of medical cannabis on public health, (2) seeking solutions to address barriers faced when conducting clinical cannabis research – especially with medical cannabis use in special populations such as those who are pregnant, and (3) unpacking the data behind cannabis use and mental health outcomes. The fourth annual CCORC is planned for the summer of 2024 in Florida, USA.

Significant knowledge gaps regarding the effectiveness and safety of medical cannabis (MC) create clinical challenges for MC physicians, making treatment recommendations and patients choosing treatment among the growing number of options offered in dispensaries. Additionally, data describing the characteristics of people who use MC and the products and doses they receive are lacking. The Medical Marijuana and Me (M3) Study was designed to collect patient-centered data from MC users. We aim to describe preferred MC use patterns that patients report as “most effective” for specific health conditions and symptoms, identify user characteristics associated with such use patterns, characterize adverse effects, including cannabis use disorder, identify products and patient characteristics associated with adverse effects, describe concurrent prescription medication use, and identify concomitant medication use with potential drug-MC interaction risk. Among MC initiators, we also aim to quantify MC use persistence and identify reasons for discontinuation, assess MC utilization pattern trajectories over time, describe outcome trajectories of primary reasons for MC use and determine factors associated with different trajectories, track changes in concomitant substance and medication use after MC initiation, and identify factors associated with such changes. M3 is a combined study comprised of: (1) a prospective cohort of MC initiators completing surveys at enrollment, 3 months, and 9 months after MC initiation and (2) a cross-sectional study of current MC users. A multidisciplinary committee including researchers, physicians, pharmacists, patients, and dispensary personnel designed and planned study protocols, established study measures, and created survey questionnaires. M3 will recruit 1,000–1,200 participants aged ≥18 years, with ∼50% new and ∼50% current MC patients from MC clinics across Florida, USA. Study enrollment started in May 2022 and will continue until the target number of patients is achieved. Survey domains include sociodemographic characteristics, physical and mental health, cannabis use history, reasons for MC use and discontinuation, MC products and use patterns, concurrent use of prescription medications and other substances, and side effects. Data collected in the M3 Study will be available for interested researchers affiliated with the Consortium for Medical Marijuana Clinical Outcomes Research. The M3 Study and Databank will be the largest cohort of current and new MC users in Florida, USA, which will provide data to support MC-related health research necessary to inform policy and clinical practice and ultimately improve patient outcomes.

The Consortium for Medical Marijuana Clinical Outcomes Research, a multi-university collaboration established by the state of Florida in the USA, hosted its second annual Cannabis Clinical Outcomes Research Conference (CCORC) in May 2022. CCORC was held as a hybrid conference, with a scientific program consisting of in-person and virtual sessions. CCORC fostered and disseminated current research on clinical outcomes of medical marijuana while stimulating collaboration and engagement between the scientific community, policymakers, industry representatives, clinicians, and other interested stakeholders. Three themes emerged from conference sessions and speakers: (1) disentangling research findings comparing use and outcomes of medical and nonmedical cannabis, (2) addressing barriers and promoting facilitators for clinical cannabis research, and (3) resolving uncertainties around cannabis dosing. The third annual CCORC is planned for the summer of 2023 in Florida, USA.

Abstract Background RSV-incidence estimates obtained from routinely-collected healthcare data (e.g., MarketScan) are commonly adjusted for under-reporting using test positivity reported in national Surveillance Systems (NREVSS). However, NREVSS lacks detail on patient-level characteristics and the validity of applying a single positivity estimate across diverse patient groups is uncertain. We aimed to describe testing practices and test positivity across subgroups of private health insurance enrollees in the US and illustrate the possible magnitude of misclassification when using NREVSS to correct for RSV under ascertainment. Methods Using billing records, we determined distributions of RSV-test claims and test positivity among a national sample of private insurance enrollees. Tests were considered positive if they coincided with an RSV-diagnosis. We illustrated the influence of positivity variation across sub-populations when accounting for untested acute respiratory infections. Results Most tests were for children (age 0–4: 65.8%) and outpatient encounters (78.3%). Test positivity varied across age (0–4: 19.8%, 5–17: 1.8%, adults: 0.7%), regions (7.6–16.1%), settings (inpatient 4.7%, outpatient 14.2%), and test indication (5.0–35.9%). When compared to age, setting or indication-specific positivity, bias due to using NREVSS positivity to correct for untested ARIs ranged from − 76% to 3556%. Conclusions RSV-test positivity depends on the characteristics of patients for whom those tests were ordered. NREVSS-based correction for RSV-under-ascertainment underestimates the true incidence among children and overestimate rates among adults. Demographic-specific detail on testing practice and positivity can improve the accuracy of RSV-incidence estimates.

Background Although respiratory syncytial virus (RSV) immunoprophylaxis is recommended for high-risk infants, the American Academy of Pediatrics (AAP) recommends against immunoprophylaxis in the same season following a breakthrough hospitalization due to limited risk for a second hospitalization. Evidence in support of this recommendation is limited. We estimated population-based re-infection rates from 2011–2019 in children Materials and methods Using claims data from private insurance enrollees, we established cohorts of children Results Over the 8 assessed seasons/years (N = 6,705,979) and across all age groups annual inpatient and outpatient infection rates were 0.14% and 1.29%, respectively. Among children with a first infection, annual inpatient and outpatient re-infection rates were 0.25% (95% confidence interval (CI) = 0.22–0.28) and 3.44% (95% CI = 3.33–3.56), respectively. Both infection and re-infection rates declined with age. Conclusion While medically-attended re-infections contributed numerically only a fraction of the total RSV infections, re-infections among those with previous infection in the same season were of similar magnitude as the general infection risk, suggesting that a previous infection may not attenuate the risk for a re-infection.

Background Knowledge of real‐world antihypertensive use is limited to prevalent hypertension, limiting our understanding of how treatment evolves and its contribution to persistently poor blood pressure control. We sought to characterize antihypertensive initiation among new users. Methods and Results Using Medicaid and Medicare data from the OneFlorida+ Clinical Research Consortium, we identified new users of ≥1 first‐line antihypertensives (angiotensin‐converting enzyme inhibitor, calcium channel blocker, angiotensin receptor blocker, thiazide diuretic, or β‐blocker) between 2013 and 2021 among adults with diagnosed hypertension, and no antihypertensive fill during the prior 12 months. We evaluated initial antihypertensive regimens by class and drug overall and across study years and examined variation in antihypertensive initiation across demographics (sex, race, and ethnicity) and comorbidity (chronic kidney disease, diabetes, and atherosclerotic cardiovascular disease). We identified 143 054 patients initiating 188 995 antihypertensives (75% monotherapy; 25% combination therapy), with mean age 59 years and 57% of whom were women. The most commonly initiated antihypertensive class overall was angiotensin‐converting enzyme inhibitors (39%) followed by β‐blockers (31%), calcium channel blockers (24%), thiazides (19%), and angiotensin receptor blockers (11%). With the exception of β‐blockers, a single drug accounted for ≥75% of use of each class. β‐blocker use decreased (35%–26%), and calcium channel blocker use increased (24%–28%) over the study period, while initiation of most other classes remained relatively stable. We also observed significant differences in antihypertensive selection across demographic and comorbidity strata. Conclusions These findings indicate that substantial variation exists in initial antihypertensive prescribing, and there remain significant gaps between current guideline recommendations and real‐world implementation in early hypertension care.

The Cannabis Clinical Outcomes Research Conference (CCORC) 2021 was held virtually on April 8 and 9, 2021. The conference was hosted by the Consortium for Medical Marijuana Clinical Outcomes Research, a research organization instituted by the state legislature of Florida in the United States. The inaugural annual CCORC 2021 was organized as a scientific meeting to foster and disseminate research on medical marijuana (MM) clinical outcomes, while promoting engagement among MM researchers, patients, clinicians, policymakers, and industry partners. Key conference themes included: (a) the disconnect between policy, practice, and evidence and steps towards reconciliation, (b) approaches to overcome common barriers to MM research, and (c) the use of focused translational approaches utilizing both mechanistic and clinical research methodology to tackle the complexities of MM outcomes. CCORC 2022 is planned for spring 2022 in Orlando, Florida, United States.

Objective: More patients are turning to medical marijuana as an alternative treatment, yet there are apparent knowledge gaps on the risk benefit of medical marijuana for a variety of indications. This study aimed to determine the priorities for medical marijuana research from the perspective of multiple stakeholders including patients, clinicians, and industry representatives. Methods: An anonymous survey was administered to attendees of the 2019 American Medical Marijuana Physicians Association annual meeting in Orlando, Florida. Respondents completed the survey on paper or smartphone via Qualtrics. The survey included questions on demographics and medical marijuana research priorities under the following broad categories: clinical conditions, safety issues, marijuana types, populations, and others. Results: Forty-six participants (56.5% female, mean age = 51.6 ± 14.1) responded to the survey. A majority were medical marijuana qualified physicians in Florida (56.5%), 30.5% other physicians or clinicians, and 21.7% medical marijuana patients (multiple choices allowed). The top conditions prioritized for research by this group were chronic pain, cancer, and anxiety, and the top priority safety issues were dosing/product choice, complications from smoking/vaping, and drug interactions. Regarding marijuana types, the group prioritized research on THC/CBD ratios, different modes of consumption, and terpenes. Conclusions: Findings from this survey indicate that medical marijuana stakeholders perceived a broad range of research topics as priorities. More research is needed to advance the evidence in these areas and provide guidance to patients, physicians, and the medical marijuana industry.

Abstract 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. Methods A nationally representative cohort study of Medicare beneficiaries aged 50 years or older who had chronic pain but who had no cancer, hospice, or palliative care from 2011 to 2015. Four indicators of potentially inappropriate opioid prescribing were measured in patients residing in communities (75,258 patients with and 435,870 patients without ADRD); five indicators were assessed in patients in nursing homes (NHs) (37,117 patients with and 5128 patients without ADRD). Each indicator was calculated as the proportion of eligible patients with inappropriate opioid prescribing in the year after a chronic pain diagnosis. Differences in proportions between ADRD and non-ADRD groups were estimated using a generalized linear model adjusting for covariates through inverse probability weighting. Results Patients with ADRD versus those without had higher concurrent use of opioids and central nervous system–active drugs (community 44.1% vs 33.3%; NH 58.8% vs 54.1%, both P

In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016–2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn’s disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson’s disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.

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 ≥65 years with CNCP diagnosis who initiated opioids. We identified concurrent users with gabapentinoids and opioids days’ supply overlapping for ≥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. In a cohort study, Cheng Chen and colleagues investigate associations between concurrent use of gabapentinoids and opioids and risk of fall-related injury, compared with use of opioids alone, among adults aged 65 years or older with chronic noncancer pain in the United States. Author summary Why was this study done? Prescriptions for gabapentinoids, commonly coadministered with opioids to manage chronic pain, have tripled among older adults in the past decade. Concurrent use of prescription opioids and gabapentinoids may potentiate central nervous system (CNS) depression and result in falls and related injuries, but this association has not been formally investigated. What did the researchers do and find? We conducted a population-based cohort study among older Medicare beneficiaries with chronic noncancer pain (CNCP) who initiated prescription opioids. We assembled 2 cohorts from opioid initiators: Cohort 1 included 6,733 patients initiating opioids and gabapentinoids simultaneously and 27,092 matched controls initiating opioids only, and Cohort 2 included 5,709 patients initiating gabapentinoids after opioid initiation and 22,388 matched controls continuing with opioids only. We found that concurrent gabapentinoid–opioid use was not associated with risk of fall-related injury in Cohort 1 but was associated with a 69% higher risk of fall-related injury in Cohort 2, when compared with use of opioid only. What do these findings mean? In this sample of older Medicare beneficiaries with CNCP, initiating gabapentinoids and opioids simultaneously compared with initiating opioids only was not associated with risks for fall-related injury. However, addition of gabapentinoids to an existing opioid regimen was associated with increased risks for fall-related injury. Clinicians should consider the risk–benefit of combination therapy when prescribing gabapentinoids concurrently with opioids.

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. From the cohort with a mean follow-up of 2.3 years, we identified 3,103 incident ORAE cases with ≥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 ≤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. Yu-Jung Jenny Wei and colleagues study patterns of prescribed opioid doses in the 6 months before an opioid-related adverse event among Medicare beneficiaries with chronic non-cancer pain in the US. Author summary Why was this study done? The number of older adults with medical encounters for opioid-related adverse events (ORAEs) has increased over the past decade. Yet, little is known about patterns of prescription opioid dose and their association with risk for ORAEs among older patients. What did the researchers do and find? We assessed trajectories of opioid morphine milligram equivalent (MME) dose prescribed during the 6 months before an incident ORAE for 3,103 cases and during the 6 months before the equivalent date for 3,103 controls who did not experience an ORAE, selected from a cohort of Medicare older patients diagnosed with chronic noncancer pain who were new users of prescription opioids. We found four prescription opioid dose trajectories, with most prescribed doses below 90 daily MME before ORAE or matched date. We also found that compared to patients with gradual dose discontinuation (from ≤3 to 0 daily MME), those with gradual dose increase (from 0 to >3 daily MME), consistent low dose (between 3 and 5 daily MME), and consistent moderate low (>20 daily MME) had a higher risk for ORAEs. What do these findings mean? An increased risk for ORAE was observed among older patients who had a gradual increase in dose or among those who had 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.

We aimed to estimate the utility of panel‐based pharmacogenetic testing of patients undergoing percutaneous coronary intervention (PCI). Utilization of Clinical Pharmacogenetic Implementation Consortium (CPIC) level A/B drugs after PCI was estimated in a national sample of IBM MarketScan beneficiaries. Genotype data from University of Florida (UF) patients (n = 211) who underwent PCI were used to project genotype‐guided opportunities among MarketScan beneficiaries with at least one (N = 105,547) and five (N = 12,462) years of follow‐up data. The actual incidence of genotype‐guided prescribing opportunities was determined among UF patients. In MarketScan, 50.0% (52,799/105,547) over 1 year and 68.0% (8,473/12,462) over 5 years had ≥ 1 CPIC A/B drug besides antiplatelet therapy prescribed, with a projected incidence of genotype‐guided prescribing opportunities of 39% at 1 year and 52% at 5 years. Genotype‐guided prescribing opportunities occurred in 32% of UF patients. Projected and actual incidence of genotype‐guided opportunities among two cohorts supports the utility of panel‐based testing among patients who underwent PCI.

Artificial intelligence, in particular machine learning (ML), has emerged as a key promising pillar to overcome the high failure rate in drug development. Here, we present a primer on the ML algorithms most commonly used in drug discovery and development. We also list possible data sources, describe good practices for ML model development and validation, and share a reproducible example. A companion article will summarize applications of ML in drug discovery, drug development, and postapproval phase.

Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss‐of‐function (LOF) variant carriers versus non‐carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real‐world outcomes with the clinical implementation of CYP2C19‐guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all‐cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life‐threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39–0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71–1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real‐world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy.

Background: Little is known about the clinical training or practice experiences among physicians who certify patients for medical marijuana. The objective of this study was to determine information sources, factors influencing recommendations, clinical practices in patient assessment, communications, and recommendations, and priority areas for additional training among physicians who certify patients for medical marijuana. Methods: A cross-sectional state-wide anonymous survey of registered medical marijuana physicians in Florida between June and October 2020 was administered. Numerical responses were quantified using counts and percentages. The frequencies for “often” and “always” responses were aggregated when appropriate. Results: Among 116 respondents, the mean (standard deviation) age was 57 (12) years old, and 70% were male. The most frequently used information sources were research articles (n = 102, 95%), followed by online sources (n = 99, 93%), and discussions with other providers and dispensary staff (n = 84, 90%). Safety concerns were most influential in patient recommendations (n = 39, 39%), followed by specific conditions (n = 30, 30%) and patient preferences (n = 26, 30%). Ninety-three physicians (92%) reported they “often” or “always” perform a patient physical exam. Eighty-four (77%) physicians provided specific administration route recommendations. Half (n = 56) “often” or “always” provided specific recommendations for Δ-9-tetrahydrocannabinol: cannabidiol ratios, while 69 (62%) “often” or “always” provided specific dose recommendations. Online learning/training modules were the most preferred future training mode, with 88 (84%) physicians “likely” or “very likely” to participate. The top 3 desired topics for future training were marijuana-drug interactions (n = 84, 72%), management of specific medical conditions or symptoms (n = 83, 72%), and strategies to reduce opioids or other drugs use (n = 78, 67%). Conclusions: This survey of over 100 medical marijuana physicians indicates that their clinical practices rely on a blend of research and anecdotal information sources. While physicians report clinical factors as influential during patient recommendation, patient assessment practices and treatment regimen recommendations vary substantially and rely on experimental approaches. More research is needed to inform evidence-based practice and training, especially considering details on drug interactions, risk-benefit of treatment for specific clinical conditions, and strategies to reduce opioid use.

The application of modeling and simulation (M&S) tools to biological, physiological, and clinical data has great potential to enhance drug development and regulatory decision making. The strategic development of multidisciplinary projects aimed at integrating methodologies from different disciplines may bridge between preclinical and clinical drug development as well as between academic curiosity and clinical practice. Herein we review the history and present the state of M&S approaches as well as our vision for future challenges and applications.

Abstract Background There exists limited data on the association between unhealthy body weight and chronic pain, and whether this association is explained by frailty status of older adults. Methods We included older adults aged ≥65 years from the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Chronic pain was defined by self-reported pain lasting for ≥3 months in the past year. Body mass index (BMI) was categorized as underweight, normal, overweight, and obese. Participants were dichotomized as frail or non-frail based on a validated frailty index calculated as the proportion of the number of deficits present to a total of 45 possible deficits ascertained in NHANES. We used modified Poisson regression models to estimate prevalence ratios (PRs) and their 95% confidence intervals (CIs). Results Of 3693 older participants, one in six (15.9%) experienced chronic pain, with higher prevalence among the underweight (24.6%) and obese (20.2%) group. Frailty versus non-frailty was independently associated with BMI (PR = 1.25, 95% CI = 1.16–1.36 for underweight; and PR = 1.15, 95% CI = 1.07–1.22 for obese), and chronic pain (PR = 2.84, 95% CI = 2.18–3.69). After adjustment for frailty, the association between BMI and chronic pain decreased from PR = 1.82 to 1.64 for the underweight and 1.41 to 1.33 for the obese group. We did not observe an interaction effect between frailty and BMI. Conclusions Unhealthy body weight was associated with increased chronic pain and the associations were partially explained by frailty status of older adults. Our findings generate hypotheses for further investigations of the interplay of these chronic conditions in older adults.

Medication therapy is an important component of the comprehensive treatment plan designed to maintain or improve health. If patients do not take prescribed medications correctly or are non-adherent, less successful therapy occurs. Reasons given for noncompliance include cost, misunderstanding the therapy, side effects, forgetfulness, or a belief that the medication is not effective or necessary. This study had two goals, the first was to evaluate medication use while simultaneously assessing knowledge, compliance, tolerance, and perceived efficacy. Drug-related problems, if any, were also identified. The second goal was to develop methods to improve patient outcomes based upon identified problems. For eight weeks, all patients attending four rural North Central Florida clinics were asked to participate in this study by completing a short questionnaire and personal interview. A significant inverse correlation (p