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BACKGROUND: Currently available medications for chronic osteoarthritis pain are only moderately effective, and their use is limited in many patients because of serious adverse effects and contraindications. The primary surgical option for osteoarthritis is total joint replacement (TJR). The objectives of this study were to describe the treatment history of patients with osteoarthritis receiving prescription pain medications and/or intra-articular corticosteroid injections, and to estimate the incidence of TJR in these patients. METHODS: This retrospective, multicenter, cohort study utilized health plan administrative claims data (January 1, 2013, through December 31, 2019) of adult patients with osteoarthritis in the Innovation in Medical Evidence Development and Surveillance Distributed Database, a subset of the US FDA Sentinel Distributed Database. Patients were analyzed in two cohorts: those with prevalent use of "any pain medication" (prescription non-steroidal anti-inflammatory drugs [NSAIDs], opioids, and/or intra-articular corticosteroid injections) using only the first qualifying dispensing (index date); and those with prevalent use of "each specific pain medication class" with all qualifying treatment episodes identified. RESULTS: Among 1 992 670 prevalent users of "any pain medication", pain medications prescribed on the index date were NSAIDs (596 624 [29.9%] patients), opioids (1 161 806 [58.3%]), and intra-articular corticosteroids (323 459 [16.2%]). Further, 92 026 patients received multiple pain medications on the index date, including 71 632 (3.6%) receiving both NSAIDs and opioids. Altogether, 20.6% of patients used an NSAID at any time following an opioid index dispensing and 17.2% used an opioid following an NSAID index dispensing. The TJR incidence rates per 100 person-years (95% confidence interval [CI]) were 3.21 (95% CI: 3.20-3.23) in the "any pain medication" user cohort, and among those receiving "each specific pain medication class" were NSAIDs, 4.63 (95% CI: 4.58-4.67); opioids, 7.45 (95% CI: 7.40-7.49); and intra-articular corticosteroids, 8.05 (95% CI: 7.97-8.13). CONCLUSIONS: In patients treated with prescription medications for osteoarthritis pain, opioids were more commonly prescribed at index than NSAIDs and intra-articular corticosteroid injections. Of the pain medication classes examined, the incidence of TJR was highest in patients receiving intra-articular corticosteroids and lowest in patients receiving NSAIDs.
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Artroplastia de Reemplazo , Dolor Crónico , Osteoartritis , Corticoesteroides/efectos adversos , Adulto , Analgésicos Opioides/uso terapéutico , Antiinflamatorios no Esteroideos , Artroplastia de Reemplazo/efectos adversos , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/epidemiología , Estudios de Cohortes , Humanos , Incidencia , Osteoartritis/tratamiento farmacológico , Osteoartritis/epidemiología , Osteoartritis/cirugía , Estudios RetrospectivosRESUMEN
Corneal epithelial wound healing is a multifaceted process that encompasses cell proliferation, migration, and communication from the corneal stroma. Upon corneal injury, bidirectional crosstalk between the epithelium and stroma via extracellular vesicles (EVs) has been reported. However, the mechanisms by which the EVs from human corneal keratocytes (HCKs), fibroblasts (HCFs), and/or myofibroblasts (HCMs) exert their effects on the corneal epithelium remain unclear. In this study, HCK-, HCF-, and HCM-EVs were isolated and characterized, and human corneal epithelial (HCE) cell migration was assessed in a scratch assay following PKH26-labeled HCK-, HCF-, or HCM-EV treatment. HCE cells proliferative and apoptotic activity following EV treatment was assessed. HCF-/HCM-EVs were enriched for CD63, CD81, ITGAV, and THBS1 compared to HCK-EV. All EVs were negative for GM130 and showed minimal differences in biophysical properties. At the proteomic level, we showed HCM-EV with a log >two-fold change in CXCL6, CXCL12, MMP1, and MMP2 expression compared to HCK-/HCF-EVs; these proteins are associated with cellular movement pathways. Upon HCM-EV treatment, HCE cell migration, velocity, and proliferation were significantly increased compared to HCK-/HCF-EVs. This study concludes that the HCM-EV protein cargo influences HCE cell migration and proliferation, and understanding these elements may provide a novel therapeutic avenue for corneal wound healing.
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Lesiones de la Cornea , Epitelio Corneal , Vesículas Extracelulares , Movimiento Celular , Lesiones de la Cornea/metabolismo , Células Epiteliales/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Miofibroblastos/metabolismo , ProteómicaRESUMEN
BACKGROUND: In population studies, vaping is often treated as a dichotomous exposure (present/absent) without consideration of specific vaping devices and materials being used. A survey instrument is needed to record specific vaping devices and materials. METHODS: We developed a database of 613 vaping device models and 3196 vaping liquid products, indexed by device brand, device type, liquid brand, liquid name and liquid flavour type. We developed a survey instrument to allow participants to report their vaping device and liquid from the indexed lists. The survey was pilot tested with a convenience sample of 208 adults (≥age 21). We validated the vaping device and liquid responses with a recontact survey. We report the proportion of respondents finding their products, characteristics of people finding their products and survey response times. RESULTS: Devices used most frequently in the past 30 days were electronic cigarettes (33% of respondents), vaping pens (28%) and vaping mods (16%). Fifty-seven per cent used liquids containing nicotine most frequently in the past 30 days, followed by liquids without nicotine (20%) and marijuana or hashish (10%). Most (85%) participants found their vaping device successfully (median 19.7 s) and 74% found their vaping liquid (median 19.8 s). Females and older adults were less likely to find their devices and liquids. Responses were validated for 91% and 76% of devices and e-liquids, respectively. CONCLUSIONS: This study demonstrated the feasibility of an internet-based survey instrument to record specific vaping factors for use in studies of vaping and health.
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Sistemas Electrónicos de Liberación de Nicotina , Fumar Marihuana/epidemiología , Nicotina/administración & dosificación , Vapeo/epidemiología , Adulto , Factores de Edad , Femenino , Aromatizantes/química , Humanos , Internet , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores Sexuales , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (n = 9), Europe (n = 3), and Japan (n = 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding. Meta-analysis of incidence rate ratios (IRR) and incidence rate differences (IRD) for each outcome, from each data source was executed using modified Poisson regression and Cochran-Mantel-Haenszel analysis. RESULTS: Of 9013 eligible baricitinib-treated patients, 7606 were propensity score-matched with TNFi-treated patients, contributing 5879 and 6512 person-years of baricitinib and TNFi exposure, respectively. Across data sources, 97 patients (56 baricitinib) experienced VTE during follow-up, 93 experienced MACE (54 baricitinib), and 321 experienced serious infection (176 baricitinib). Overall IRRs comparing baricitinib with TNFi treatment were 1.51 (95% CI 1.10, 2.08) for VTE, 1.54 (95% CI 0.93, 2.54) for MACE, and 1.36 (95% CI 0.86, 2.13) for serious infection. IRDs for VTE, MACE, and serious infection, respectively, were 0.26 (95% CI -0.04, 0.57), 0.22 (95% CI -0.07, 0.52), and 0.57 (95% CI -0.07, 1.21) per 100 person-years greater for baricitinib than TNFi. CONCLUSIONS: Overall results suggest increased risk of VTE with baricitinib versus TNFi, with consistent point estimates from the two largest data sources. A numerically greater risk was observed for MACE and serious infection when comparing baricitinib versus TNFi, with different point estimates from the two largest data sources. Findings from this study and their impact on clinical practice should be considered in context of limitations and other evidence regarding the safety and efficacy of baricitinib and other Janus kinase inhibitors. TRIAL REGISTRATION: EU PAS Register ( http://encepp.eu ), identifier #32271.