The influence of different fibrates on apolipoprotein metabolism was investigated. Administration of fenofibrate provoked a dose-dependent decrease in plasma cholesterol concentration that was already evident after 1 day. Intestinal apolipoprotein (apo) A-I and apo A-IV mRNA levels remained fairly constant. In contrast, liver apo A-I, apo A-II, and apo A-IV mRNA levels decreased in a dose-dependent fashion, which was associated with a lower transcription rate of the apo A-I but not the apo A-II gene. The decline in hepatic apo A-I, apo A-II, and apo A-IV mRNA had already started after 1 day and was associated with a drop in plasma apo A-I and apo A-IV concentrations. Plasma apo E had already decreased after 1 day of fenofibrate, whereas apo B initially remained constant and increased only after 14 days of fenofibrate at the highest dose. Hepatic and intestinal apo B mRNA contents and liver, heart, kidney, and testis apo E mRNA contents were only marginally affected after treatment with fenofibrate. Liver low density lipoprotein receptor mRNA levels rose slightly after a 3-day administration of the highest dose of fenofibrate. Both clofibrate and gemfibrozil had effects comparable to those of fenofibrate on liver and intestinal apolipoprotein mRNA levels except for liver apo A-II mRNA, which decreased only marginally. Compared with fenofibrate, clofibrate caused similar changes in plasma cholesterol, apo A-I, apo A-IV, and apo E concentrations, whereas gemfibrozil increased plasma cholesterol and apo E without changing apo A-I and apo A-IV concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Conclusion Given the existing low degree of evidence, this study shows that there are no clear advantages of this medication in patients with cystic fibrosis and neuromuscular problems. Consequently, and given the high cost that palivizumab use implies, it would be necessary to establish protocols that define use condition and identification of patients that may benefit better from the treatment.
BackgroundOsteoarthritis (OA) is a chronic degenerative joint condition associated with joint pain, stiffness, and mobility problems. More than half of OA patients live with moderate or severe pain[1], impacting all aspects of their lives and decreasing their overall Quality of Life (QoL). Social listening enables insight generation beyond the healthcare setting, demonstrating a more comprehensive view on disease burden and patient experiences. This study utilizes a unique approach based on Artificial Intelligence that analyses high volumes of data both quantitatively and qualitatively of patient-authored content.ObjectivesThe study aims at exploring patient-generated online data as a source for capturing the real-world experience of OA patients, as reported by a large online population in the UK. A particular focus is on understanding the individually perceived disease burden in terms of symptoms, patient-reported QoL[2]and surgical treatment options.MethodsA sample of real-world data from online health communities in the UK was collected between Oct 2019 until Jan 2022, resulting in a data set comprising n=6,354 algorithmically identified OA patients and n=42,353 posts (documents). OA-specific concepts to identify patient experiences were algorithmically coded using supervised machine learning, natural language processing (NLP) and knowledge graph tagging. An algorithmic stack of 40+ dedicated NLP analyzers was applied to detect key concepts and their relations of the patient experience in the posts (symptoms, their severity, impacts on QoL facets, perception of treatment options). Data were collected and processed in an anonymized, secure, and reliable way to ensure privacy and ethical aspects.ResultsAge could be algorithmically determined for N=1,012 patients (16 % of total patients), 56% of whom are older than 50 years. Pain was the most discussed symptom (58% of patients; N=3,703). N=1,508 patients underwent surgeries, with hip (N=762) and knee replacements (N=674) as most reported procedures. Recreation & Leisure and Mobility were the most prominent QoL aspects (31% and 28% of patients). Healthcare availability (e.g. access to treatments) was raised by N=668 patients (11%); a proportion of these (N=150) also underwent hip or knee replacement, with more than half reporting having been on a “waiting list” for their surgical procedure.Figure 1 shows five QoL aspects most relevant for patients with knee or hip replacement, together with improvement or worsening of the respective QoL aspect. Notably, a majority of patients in both groups report mobility and healthcare availability to deteriorate rather than improve.Figure 1.Sankey chart illustrating improvement or worsening (right) of the five most mentioned QoL aspects (middle) of patients with a knee or hip replacement procedure (n=266 documents)ConclusionThis social listening study indicates pain as the most burdensome OA symptom and sheds light on the QoL impact of surgical procedures. Given limitations of social listening studies (e.g. number of identifiable age groups or gender)[3], the results need to undergo further validation by patient representatives and clinical experts. Yet, this novel method complements common approaches by providing an understanding of patients’ perspectives outside the clinic, representing the voices of vulnerable populations who may not otherwise participate in clinical or epidemiological studies.References[1]Jackson, J. et al. (2020) The Burden of Pain Associated with Osteoarthritis in the Hip or Knee from the Patient’s Perspective: A Multinational Cross-Sectional Study Adv Ther (2020) 37:3985–3999[2]Spies E, et al. (2022) Retrospective Social Listening Study of Patients Living with Systemic Lupus Erythematosus (SLE): Understanding the Patient Experience. ISPOR Europe 2022. Value in Health, Volume 25, Issue 12S (December 2022). New York: Elsevier Science, 2022.[3]Schmidt, A.L. et al. (2022): Applications of Quantitative Social Media Listening to Patient-centric Drug Development. Drug Discov Today: S1359-6446(22)00037-XAcknowledgementsThe project is funded by Grünenthal GmbH.Disclosure of InterestsNeil Betteridge Consultant of: Consultancy fees received from Grünenthal, Amgen, Galapagos, Lilly, Sanofi, Gudula Petersen Employee of: Grünenthal GmbH, Thomas Andreu Consultant of: Grünenthal GmbH provides funding for this project, Matthias Hartung Consultant of: Grünenthal GmbH provides funding for this project.
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