Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006–2021

Article

作者: Jokinen, Jussi ; Desai Boström, Adrian E ; Andersson, Peter ; Jarbin, Håkan ; Lundberg, Johan

BackgroundThis cross-sectional study examined nationwide real-world associations between anti-inflammatory agent fills and suicide-related death rates in 20-24-year-olds across the 21 Swedish regions during 2006-2021.MethodsNationwide Swedish registers were used to compare regional year-wise suicide-related mortality (SRM) and dispensations for anti-inflammatory agents (ATC-code: M01) in 20-24-year-olds. Dispensations for paracetamol (ATC-code: N02BE01) was applied as a control variable. Associations between regional year-wise SRM and dispensation rates were analyzed by sex-stratified zero-inflated generalized linear mixed effect models (GLMM). Dispensation rates of paracetamol and inflammatory agents were designated as independent fixed effects variables, and year and region constituted random-intercept effects.ResultsAcetic acid derivatives and related substances (M01AB) and propionic acid derivates (M01A3) accounted for ∼71% of measured dispensation fills for anti-inflammatory agents. Diclofenac fills constituted ∼98% of the former category, whereas dispensations for Ibuprofen (∼21%), Naproxen (∼62%) and Ketoprofen (∼13%) constituted the most prescribed agents in the latter category. Regional yearly dispensation rates of anti-inflammatory agents in 20-24-year-old females were inversely associated with female SRM (β = -0.095, p = 0.0393, 95% CI -0.186, -0.005) - independent of paracetamol rates, which were unassociated to SRM (p = 0.2094). Results were confirmed in validation analyses for anti-inflammatory agents (OR = 0.7232, p = 0.0354, 95% CI [OR] 0.5347, 0.9781). No association was demonstrated in males (p = 0.833).ConclusionAnti-inflammatory agent dispensation rates were independently associated to lower suicide-related death rates in female 20-24-year-olds. This adds to growing evidence implicating inflammatory processes in mental disorders, warranting trials focusing on the suicide preventative potential of anti-inflammatories in young adults.

2022-11-01·Allergy and Asthma Proceedings

Treatment options for moderate to severe atopic dermatitis

Review

作者: Wallace, Dana V.

Background:The treatment of chronic refractory moderate-to-severe atopic dermatitis (AD) has traditionally relied on broad-spectrum systemic anti-inflammatory agents. With the introduction of biologics and Janus kinase inhibitors (Jakinib), the step management of moderate-to-severe AD is rapidly changing; however, guidelines have yet to provide formal recommendations for how to best incorporate these agents into the treatment plan.Objective:To summarize the updated evidence-based medical treatment for AD, including a proposed position for biologics and Jakinibs in the treatment algorithm.Methods:A literature search of several medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from 2012 to 2022 on the treatment of moderate-to-severe AD was conducted to prepare this narrative review.Results:Emollients and topical corticosteroids are the mainstay for treating acute flares and for maintaining chronic control. Second-line topical agents include calcineurin inhibitors, e.g., tacrolimus and pimecrolimus; crisaborole; and ruxolitinib. For acute flares, cyclosporine is preferred over systemic corticosteroids. For chronic treatment, phototherapy should be considered before systemic anti-inflammatory agents. Of the traditional anti-inflammatory agents, cyclosporine is the first-line choice, with methotrexate and azathioprine equal secondary choices. Although abrocitinib may have better efficacy then dupilumab based on indirect comparisons, abrocitinib requires closer monitoring for adverse events. Based on package labeling, Jakinibs, e.g., abrocitinib and upadacitinib, should be used only after failure with other systemic agents, including biologics (e.g., dupilumab and tralokinumab). Biologics and Jakinibs should be considered before the traditional systemic anti-inflammatory agents.Conclusion:Clinicians should consider a modified step management for AD as they await the development of national and international guideline recommendations for how best to position the biologics and Jakinibs into the AD treatment algorithm.

2022-03-01·Foot & Ankle International2区 · 医学

Intra-Articular Synovial Fluid With Hematoma After Ankle Fracture Promotes Cartilage Damage In Vitro Partially Attenuated by Anti-Inflammatory Agents

2区 · 医学

Article

作者: Kraus, Virginia B. ; Adams, Samuel B. ; Allen, Nicholas B. ; Olson, Steven A. ; Abar, Bijan ; Danilkowicz, Richard M.

Background: Intra-articular ankle fracture (IAF) causes posttraumatic osteoarthritis (PTOA), but the exact mechanism is unknown. Proinflammatory mediators have been shown to be present in the synovial fluid fracture hematoma (SFFH) but have not been linked to cartilage damage. The purpose of this study was to determine if the SFFH causes cartilage damage and whether this damage can be attenuated by commercially available therapeutic agents. Methods: Synovial fluid was obtained from 54 IAFs and cultured with cartilage discs from the dome of fresh allograft human tali and randomly assigned to one of the following groups: (A) control—media only, (B) SFFH from days 0 to 2 after fracture, (C) SFFH from days 3 to 9, (D) SFFH from days 10 to 14, (E) group B + interleukin 1 receptor antagonist (IL-1Ra), and (F) group B + doxycycline. The cartilage discs underwent histological evaluation for cell survival and cartilage matrix components. The spent media were analyzed for inflammatory mediators. Results: Cartilage discs cultured with SFFH in groups B, C, and D demonstrated significantly increased production of cytokines, metalloproteinases (MMPs), and extracellular matrix breakdown products. Safranin O staining was significantly decreased in group B. The negative effects on cartilage were partially attenuated with the addition of either IL-1RA or doxycycline. There was no difference in chondrocyte survival among the groups. Conclusion: Exposure of uninjured cartilage to IAF SFFH caused activation of cartilage damage pathways evident through cartilage disc secretion of inflammatory cytokines, MMPs, and cartilage matrix fragments. The addition of IL-1Ra or doxycycline to SFFH culture partially attenuated this response. Clinical Relevance: IAFs create an adverse intra-articular environment consisting of significantly increased levels of inflammatory cytokines and MMPs able to damage cartilage throughout the joint. These data suggest that the acute addition of specific inflammatory inhibitors may decrease the levels of these proinflammatory mediators.

100 项与 Inflammatory disease (Illimis Therapeutics) 相关的药物交易

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