Immune-mediated thrombocytopenia and IL-6-mediated thrombocytosis observed in idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare haematological disorder characterized by generalized lymphadenopathy with atypical histopathological features and systemic inflammation caused by a cytokine storm involving interleukin-6 (IL-6). Three clinical subtypes are recognized: thrombocytopenia, anasarca, fever, renal dysfunction, organomegaly (iMCD-TAFRO); idiopathic plasmacytic lymphadenopathy (iMCD-IPL), involving thrombocytosis and hypergammaglobulinaemia; and iMCD-not otherwise specified (iMCD-NOS), which includes patients who do not meet criteria for the other subtypes. Disease pathogenesis is poorly understood, with potential involvement of infectious, clonal and/or autoimmune mechanisms. To better characterize iMCD clinicopathology and gain mechanistic insights into iMCD, we analysed complete blood counts, other clinical laboratory values and blood smear morphology among 63 iMCD patients grouped by clinical subtype. Patients with iMCD-TAFRO had large platelets, clinical severity associated with lower platelet counts and transfusion-resistant thrombocytopenia, similar to what is observed with immune-mediated destruction of platelets in immune thrombocytopenic purpura. Conversely, elevated platelet counts in iMCD-IPL were associated with elevated IL-6 and declined following anti-IL-6 therapy. Our data suggest that autoimmune mechanisms contribute to the thrombocytopenia in at least a portion of iMCD-TAFRO patients whereas IL-6 drives thrombocytosis in iMCD-IPL, and these mechanisms likely contribute to disease pathogenesis.

Treatment consistent with idiopathic multicentric Castleman disease guidelines is associated with improved outcomes.

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with an unknown etiology. Clinical presentation is heterogeneous, ranging from mild constitutional symptoms with lymphadenopathy to life-threatening multiorgan dysfunction. International, consensus treatment guidelines developed in 2018 relied upon a limited number of clinical trials and small case series; however, to our knowledge, real-world performance of these recommendations has not been subsequently studied. Siltuximab, a monoclonal antibody against interleukin 6 (IL6), is approved for the treatment of iMCD and recommended first-line, and tocilizumab, a monoclonal antibody directed against the IL6 receptor, is recommended when siltuximab is unavailable. Chemotherapy, rituximab, and immunomodulators are recommended as second- and third-line treatments based on limited evidence. Corticosteroid monotherapy is used by clinicians, although not recommended. Here, we draw upon the ACCELERATE Natural History Registry to inventory regimens and evaluate regimen response for 102 expert-confirmed iMCD cases. Siltuximab with/without (w/wo) corticosteroids was associated with a 52% response, whereas corticosteroid monotherapy was associated with a 3% response. Anti-IL6-directed therapy with siltuximab or tocilizumab demonstrated better response and more durability than was observed with rituximab w/wo corticosteroids. Cytotoxic chemotherapy was associated with a 52% response and was predominantly administered in patients characterized by thrombocytopenia, anasarca, fever, renal failure/reticulin fibrosis, and organomegaly. Our results provide evidence in support of current recommendations to administer anti-IL6 as first-line treatment, to administer cytotoxic chemotherapy in patients with severe refractory disease, and to limit corticosteroid monotherapy. Evidence remains limited for effective agents for patients who are refractory to anti-IL6-directed therapy. This trial was registered at www.clinicaltrials.gov as #NCT02817997.

Primary Perspectives in Meme Utilization as a Digital Driver for Medical Community Engagement and Education Mobilization: Pre-Post Study.

BACKGROUND: Memes have gone "viral," gaining increasing prominence as an effective communications strategy based on their unique ability to engage, educate, and mobilize target audiences in a call to action through a cost-efficient and culturally relevant approach. Within the medical community in particular, visual media has evolved as a means to influence clinical knowledge transfer. To this end, the GetWaivered (GW) project has leveraged memes as part of a behavioral economics toolkit to address one of the most critical public health emergencies of our time-the 20-year opioid epidemic. As part of a multidimensional digital awareness campaign to increase Drug Enforcement Administration (DEA)-X waiver course registration, GW investigated the results of meme usage in terms of impressions, website traffic, and ultimately user acquisition, as determined by web-based training enrollment and attendance outcomes. OBJECTIVE: The objective of this study was to determine the efficacy of implementing humor-based promotional content versus the traditional educational model, and how the translation of the increase in engagement would increase the participant count and website traffic for GW's remote DEA-X waiver training. METHODS: The approach to this study was based on 2 time frames (pre- and postcampaign). During April-July 2021, we developed a campaign via advertisements on Facebook, Twitter, Instagram, and the GW website to expand outreach. These memes targeted medical professionals with the ability to prescribe buprenorphine. The time frame of this campaign measured engagement metrics and compared values to preceding months (January-March 2021) for our GetWaivered website and social media pages, which translated to registrants for our remote DEA-X waiver training. RESULTS: By the end of July 2021, a total of 9598 individuals had visited the GW website. There was an average of 79.3 visitors per day, with the lowest number of daily visitors being 0 and the highest being 575. CONCLUSIONS: The use of memes may provide a medium for social media engagement (likes, comments, and shares) while influencing viewers to pursue a proposed action, such as e-training registration.

Analyzing opioid-use disorder websites in the United States: An optimized website usability study.

Background: As the United States continues to tackle the opioid epidemic, it is imperative for digital healthcare organizations to provide Internet users with accurate and accessible online resources so that they can make informed decisions with regards to their health. Objective: The primary objectives were to adapt and modify a previously established usability methodology from literature, apply this modified methodology in order to perform usability analysis of opioid-use-disorder (OUD)-related websites, and make important recommendations that OUD-related digital health organizations may utilize to improve their online presence. Methods: A list of 208 websites (later refined) was generated for usability testing using a modified Google Search methodology. Four keywords were chosen and used in the search: "DEA-X Waiver Training", "opioid-use-disorder (OUD) Initiatives", "Buprenorphine Assisted Treatment", and "Opioid-Use Disorder Websites". Usability analysis was performed concurrently with optimization of the methodology. OUD websites were analyzed and scored on several usability categories established by previous literature. Results: "DEA-X Waiver Training" yielded websites that scored the highest average in "Accessibility" (0.84), while "Opioid-Use Disorder Websites" yielded websites that scored the highest average in "Content Quality" (0.67). "Buprenorphine Assisted Treatment" yielded websites that scored the highest average across "Marketing" (0.52), "Technology" (0.89), "General Usability" (0.69), and "Overall Usability" (0.68). "Technology" and "Marketing" were the highest and lowest scoring usability categories, respectively. T-test analysis revealed that each usability, except "Marketing" had a pair of one or more keywords that were significantly different with a p-value that was equal to or less than 0.05. Conclusions: Based on the study findings, we recommend that digital organizations in the OUD space should improve their "General Usability" score by making their websites easier to find online. Doing so, may allow users, especially individuals in the OUD space, to discover accurate information that they are seeking. Based on the study findings, we also made important recommendations that OUD-related digital organizations may utilize in order to improve website usability as well as overall reach.

Opioid Use Disorder Education for Students and the Future of Opioid Overdose Treatment.

Opioid use disorder (OUD) is a major public health concern in the United States. The opioid crisis has taken hundreds of thousands of lives in the past 20 years, and it is predicted to take millions more. With the rising death tolls, it is essential that health care providers are able to use proper tools to treat OUD efficiently and effectively through medication-assisted treatment (MAT), particularly buprenorphine. Despite changes to buprenorphine regulations making it more accessible, clinicians have been slow to use buprenorphine to treat OUD. We believe that training student clinicians in evidence-based MAT and buprenorphine practices will address the training and competence barriers that hinder clinicians from prescribing buprenorphine to treat OUD. Students are in an ideal position to receive and benefit from this training and influence the medical community to better treat OUD.