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Fara Fauzia; Promotor: Nurhayati Adnan; Kopromotor: Ratna Djuwita, Radiyati Umi Partan; Penguji: Asri C. Adisasmita, Sudarto Ronoatmodjo, Trisari Anggondowati, Laniyati Hamijoyo
Abstrak:

Pendahuluan. Artritis reumatoid (AR) adalah peradangan kronik autoimun yang terutama melibatkan persendian secara bilateral dan simetris. Walaupun memiliki prevalensi yang rendah namun jika tidak diterapi secara adekuat maka akan menimbulkan masalah persendian yang bersifat permanen, kecacatan dan gangguan fungsi sendi sehingga menimbulkan dampak secara ekonomi dan sosial pada individu yang mengalaminya. Penyakit AR ini tidak dapat disembuhkan namun penyakit ini harus tetap ditatalaksana untuk mencegah progresifitas dari penyakit itu sendiri dan saat ini  prediksi kegagalan atau keberhasilan terapi MTX belum pernah  dilakukan di Indonesia terutama pengembangan terhadap suatu sistem skoring yang aplikatif, hal ini menjadi  landasan  untuk melakukan analisis faktor-faktor yang memengaruhi kegagalan pengobatan metotreksat pada pasien AR dalam hal ini dalam skala rumah sakit yang menyesuaikan dengan kondisi di Indonesia dan melakukan pengembangan sistem skoring prediktor terhadap kegagalan monoterapi metotreksat. Metode. Penelitian menggunakan desain studi kohort retrospektif yang menggunakan data rekam medis elektronik (RME) pasien poli reumatologi penyakit dalam RSCM pada kurun waktu Oktober 2020 - September 2023. Dilakukan analisis deskriptif dan bivariat dengan menggunakan analisis chi-square yang dilanjutkan dengan analisis multivariat dengan analisis model Generalized Linear Model (GLM) dengan family Poisson untuk mendapatkan nilai koefisien, RR dengan interval kepercayaan 95% dari variabel independen terhadap kegagalan terapi monoterapi metotreksat yang dilanjutkan proses eliminasi variabel melalui metode backward. Hasil. Penelitian ini mendapatkan jumlah sampel sebanyak 215 subyek setelah melalui seleksi kriteria inklusi dan eksklusi, dan didapatkan hasil bahwa jumlah sendi nyeri ≥ 6 memiliki RR 1,52 (CI 95% 1,09-2,16), obesitas memiliki RR 1,41 (CI 95% 1,04-1,24), faktor peradangan LED memiliki RR 2,21 (CI 95%1,07-4,10) dan derajat aktifitas penyakit yang tinggi dengan RR 1,36 (CI 95% 1,03-1,79) adalah variabel yang memengaruhi kegagalan monoterapi metotreksat. Pada pembentukan skoring didapatkan skoring TOLD memiliki nilai kalibrasi dari Hosmer-Lemeshow goodness of fit sebesar 0,29 dan nilai diskriminasi area under curve (AUC) pada kurva receiver operating characteristics (ROC) sebesar 0,71 (CI 95% 0,65-0,78; p-value 0,03). Kesimpulan. Jumlah sendi nyeri ≥ 6, obesitas, faktor peradangan LED dan derajat aktifitas penyakit yang tinggi adalah variabel yang memengaruhi kegagalan monoterapi metotreksat dan pembentukan skoring prediksi TOLD memiliki nilai diskriminasi dan kalibrasi yang cukup baik


 

Introduction. Rheumatoid arthritis (RA) is a chronic autoimmune inflammation that mainly involves the joints bilaterally and symmetrically. Even though it has a low prevalence, if it is not treated adequately, it will cause permanent joint problems, disability and impaired joint function, causing economic and social impacts on the individuals who experience it. RA disease cannot be cured but this disease must still be managed to prevent progression of the disease itself and currently predictions of failure or success of MTX therapy have never been carried out in Indonesia, especially the development of an applicable scoring system, this is the basis for conducting analysis of factors that influence methotrexate treatment failure in RA patients, in this case on a hospital scale that adapts to conditions in Indonesia and develops a predictor scoring system for failure of methotrexate monotherapy. Methods. The study used a retrospective cohort study design using electronic medical record (RME) data from patients in the RSCM internal medicine rheumatology clinic in the period October 2020 - September 2023. Descriptive and bivariate analysis was carried out using chi-square analysis followed by multivariate analysis using Generalized model analysis. Linear Model (GLM) with the Poisson family to obtain coefficient values, RR with a 95% confidence interval of the independent variable for failure of methotrexate monotherapy therapy, followed by a variable elimination process using the backward method. Results. This study obtained a sample size of 215 subjects after going through selection criteria for inclusion and exclusion, and the results showed that the number of painful joints ≥ 6 had an RR of 1.52 (CI 95% 1.09-2.16), obesity had an RR of 1.41 (CI 95% 1.04-1.24), inflammatory factor ESR had RR 2.21 (CI 95% 1.07-4.10) and high degree of disease activity with RR 1.36 (CI 95% 1.03 -1.79) are variables that influences the failure of methotrexate monotherapy. In forming the scoring, it was found that TOLD scoring had a calibration value from the Hosmer-Lemeshow goodness of fit of 0.29 and an area under curve (AUC) discrimination value on the receiver operating characteristics (ROC) curve of 0.71 (CI 95% 0.65-0 .78; p-value 0.03). Conclusion. The number of painful joints ≥ 6, obesity, ESR inflammatory factors and a high degree of disease activity are variables that influence the failure of methotrexate monotherapy and the formation of TOLD prediction scoring has quite good discrimination and calibration values.

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D-545
Depok : FKM UI, 2024
S3 - Disertasi   Pusat Informasi Kesehatan Masyarakat
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Hotma Martogi Lorensi Hutapea; Promotor: Mondastri Korib Sudaryo; Kopromotor: Tri Yunis Miko Wahyono, Arli Aditya Parikesit; Penguji: Besral, Ratna Djuwita, Trisari Anggondowati, Sunarno, Adi Yulandi, Radiyati Umi Partan
Abstrak:
Latar Belakang: Long COVID adalah kondisi pasca infeksi SARS-CoV-2 yang ditandai oleh gejala yang bertahan ≥2 bulan, dengan kelelahan sebagai keluhan utama. Di Indonesia, tercatat sekitar 1.400 kasus COVID-19 aktif, dan berpotensi mengalami long COVID. Meskipun kelelahan umum terjadi, faktor risiko dan biomarker yang mendasarinya, baik pada long COVID maupun COVID-19 secara umum, belum sepenuhnya dipahami. Interleukin-6 (IL-6) diduga berperan dalam mekanisme kelelahan, tetapi hubungan antara varian virus SARS-CoV-2, kadar IL-6, dan gejala kelelahan masih belum jelas. Metode: Penelitian ini merupakan studi kohort ambispektif yang melibatkan pasien dewasa yang dirawat inap ≥5 hari karena COVID-19. Data klinis, demografis, dan riwayat vaksinasi diperoleh dari rekam medis. Gejala kelelahan dinilai menggunakan kuesioner Fatigue Assessment Scale (FAS), sedangkan long COVID dinilai melalui kuesioner terstruktur. Analisis regresi Cox digunakan untuk mengidentifikasi faktor risiko. IL-6 diukur dengan metode ELISA, dan analisis in-silico dilakukan untuk menilai hubungan mutasi ssRNA terhadap binding affinity TLR8 dan kadar IL-6. Hasil: Sebanyak 257 pasien terlibat dalam penelitian, dengan 30 subjek diambil darahnya untuk pemeriksaan IL-6. Enam faktor risiko ditemukan terkait dengan long COVID, yaitu riwayat kelelahan akut saat dirawat, penyakit ginjal kronis, status PCR positif saat keluar RS, trombositosis, status vaksinasi, dan kebiasaan olahraga. Eritrositopenia dan terapi oksigen berkorelasi dengan kelelahan long COVID, sedangkan kelelahan akut dan kebiasaan olahraga memengaruhi kelelahan COVID-19 umum. Varian Delta meningkatkan risiko long COVID namun menurunkan risiko kelelahan, dan kadar IL-6 tinggi berhubungan dengan kelelahan setelah dikendalikan oleh variabel confounding. Selain itu, ditemukan secara in-silico perbedaan skor binding affinity yang disebabkan mutasi pada ssRNA memengaruhi kadar IL-6 subjek. Kesimpulan: Long COVID, kelelahan long COVID dan kelelahan COVID-19 umum dipengaruhi oleh kombinasi faktor klinis, perilaku, dan varian virus. IL-6 berperan penting dalam patogenesis kelelahan, dengan kemungkinan pengaruh mutasi virus terhadap disregulasi imun. Kata kunci: coronavirus disease 2019, faktor risiko, interleukin 6, long COVID, penyintas COVID-19.

Background: Long COVID is a post-infection condition following SARS-CoV-2 infection characterized by symptoms lasting ≥2 months, with fatigue being the major complaint. In Indonesia, around 1,400 active COVID-19 cases have been recorded. These individuals have the potential to develop long COVID. Although fatigue is common, the underlying risk factors and biomarkers both in long COVID and in COVID-19 generally are not yet fully understood. Interleukin-6 (IL-6) is suspected to play a role in the mechanism of fatigue, but the relationship between SARS-CoV-2 variants, IL-6 levels, and fatigue symptoms remains unclear. Methods: This was an ambispective cohort study involving adult patients hospitalized for ≥5 days due to COVID-19. Clinical, demographic, and vaccination history data were collected from medical records. Fatigue status was assessed using the Fatigue Assessment Scale (FAS), and long COVID was evaluated through a structured questionnaire. Cox regression analysis was used to identify risk factors. IL-6 was measured using ELISA, and in-silico analysis was performed to assess the relationship ssRNA mutations based its binding affinity to TLR8. The binding affinity score was compared to IL-6 levels. Results: A total of 257 patients participated in the study, with blood samples for IL-6 testing collected from 30 subjects. Six risk factors were found to be associated with long COVID: history of acute fatigue during hospitalization, chronic kidney disease, PCR-positive status at hospital discharge, thrombocytosis, vaccination status, and exercise habits. Erythrocytopenia and oxygen therapy were correlated with long COVID fatigue, while acute fatigue and exercise habits influenced general COVID-19-related fatigue. After controlling for confounding variables, the Delta variant increased the risk of long COVID but had the lower risk of fatigue, and high IL-6 levels were associated with fatigue. Additionally, in-silico findings showed that mutations in ssRNA altered TLR8 binding affinity scores, which influenced IL-6 levels in subjects. Conclusion: Long COVID, long COVID fatigue, and general COVID-19-related fatigue are influenced by a combination of clinical, behavioral, and viral variant factors. IL-6 plays an important role in the pathogenesis of fatigue, with possible viral mutation effects contributing to immune dysregulation. Keywords: coronavirus disease 2019, COVID-19 survivors, interleukin 6, long COVID, risk factors.
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D-578
Depok : FKM-UI, 2025
S3 - Disertasi   Pusat Informasi Kesehatan Masyarakat
:: Pengguna : Pusat Informasi Kesehatan Masyarakat
Library Automation and Digital Archive