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Abstrak :
Varian virus dan Variasi genetik menjadi salah satu masalah dalam menentukan Farmakoterapi COVID-19. Mekanisme variasi orang-ke-orang dan antar-populasi dalam keamanan dan kemanjuran obat merupakan dasar untuk pengembangan obat yang rasional. Penelitian ini menggambarkan karakteristik dan profil Farmakoterapi pada pasien COVID-19 dan menganalisis hubungan profil Farmakoterapi dengan variasi gen ACE dan ACE2. Desain penelitian ini adalah cross sectional dengan pengambilan data profil Farmakoterapi dilakukan secara retrospektif dan Pemeriksaan Polimorfisme dilakukan pada 50 orang penyintas COVID-19 di RSUD Lahat yang terjangkit COVID-19 periode September 2020 hingga Agustus 2021. Hubungan profil Farmakoterapi dalam bentuk Penggunaan Antivirus dan Antibiotik serta durasinya terhadap Polimorfisme SNP gen ACE pada rs1799752 dan rs4331 dan gen ACE2 pada rs2014792 dengan menggunakan metode regresi logistik. Subjek penelitian terdiri dari 28 pasien rawat jalan dan 22 orang pasien rawat inap. Ada perbedaan karakteristik usia, tingkat stress dan status vaksinasi pada kelompok rawat inap dan rawat jalan. Sebanyak 98% pasien mendapatkan Antibiotik dan 84% pasien mendapatkan terapi Antivirus selama dalam terapi COVID-19. Antivirus yang digunakan selama terapi adalah Oseltamivir, Favipiravir dan Remdesivir dan Antibiotik yang digunakan adalah Azitromycin, Levofloxacin, Ceftriaxone dan Meropenem. Sebanyak 29 orang memiliki genotipe II, 14 orang memilik genotipe ID dan 7 orang mempunyai genotipe DD pada pada SNP rs1799752 gen ACE. Pada SNP rs4331 gen ACE 30 orang memiliki genotipe GG, 12 orang memiliki genotipe AG dan 8 orang memiliki genotipe AA. Dan pada SNP rs2014792 gen ACE2 18 orang memilik genotipe CC dan 32 orang memiliki genotipe CC. Secara statistik tidak hubungan signifikan antara polimorfisme gen ACE pada SNP rs1799752 dan rs4331 dan gen ACE2 pada rs2014792 dengan resiko rawat inap dan penggunaan Antivirus dan Antibiotik serta durasinya pada pasien COVID-19. ......One of the challenges in selecting COVID-19 Pharmacotherapy is the presence of viral variants and genetic variation. Mechanisms of person-to-person and interpopulation variation in drug safety and efficacy are the basis for rational drug development. This research describes the characteristics and profile of pharmacotherapy in COVID-19 patients and analyzes the relationship between pharmacotherapy profile and ACE and ACE2 gene variations. The study was crosssectional, involved the retrospective collection of pharmacotherapy profile data and the polymorphism testing on 50 COVID-19 survivors at Lahat Hospital who contracted the virus between September 2020 and August 2021. Use of logistic regression approach to examine the association between Pharmacotherapy profiles in the form of Antiviral and Antibiotic Use, as well as their duration, and SNP polymorphisms at rs1799752 and rs4331 of the ACE gene and rs2014792 of the ACE2 gene. There were 28 non-hospitalized and 22 hospitalized patients who participated in the study. Age, stress level, and vaccination status were all different between non-hospitalized and hospitalized groups. While undergoing COVID-19 therapy, up to 98% of patients received antibiotics, and 84% of patients received antiviral therapy. Oseltamivir, Favipiravir, and Remdesivir are the antivirals utilized throughout therapy. Azithromycin, Levofloxacin, Ceftriaxone, and Meropenem are the antibiotics. On SNP rs1799752 ACE gene, 29 participants had genotype II, 14 had genotype ID, and 7 had genotype DD. Thirty people had the GG genotype, twelve had the AG genotype, and eight had the AA genotype for the SNP rs4331 ACE gene. Additionally, 32 and 18 individuals with the CC genotype in the SNP rs2014792 ACE2 gene. The likelihood of hospitalization, the usage of antivirals and antibiotics, and the length of time those treatments were used in COVID-19 patients were not significantly associated with the ACE gene polymorphism at SNP rs1799752 and rs4331 or the ACE2 gene at rs2014792.

Abstrak :
Hipertensi merupakan penyakit penyerta yang paling umum ada pada penderita COVID-19. Faktor risiko seperti genetik, sosiodemografi, dan kondisi klinis awal diduga dapat memengaruhi kerentanan individu terhadap hipertensi dan COVID-19. Salah satu gen yang berhubungan dengan hipertensi adalah gen ACE. Penelitian ini bertujuan untuk mengkaji variasi genetik gen ACE dalam hubungannya dengan risiko kerentanan dan penanganan penyakit hipertensi dan COVID-19 menggunakan model populasi Palu-Sulawesi Tengah. Penelitian ini merupakan studi observasional dengan desain cross-sectional. Data faktor non-genetik diperoleh dari rekam medis dan kuesioner. Identifikasi variasi genetik dilakukan pada 4 lokasi pada gen ACE, yaitu rs1799752 (I/D) dengan metode PCR, dan rs4331 (A/G), rs4341 (G/C), dan rs4343 (G/A) dengan rhAmp SNP genotyping. Data faktor genetik dan non-genetik kemudian disusun menjadi model instrumen translasional. Studi melibatkan 136 subjek, dan analisis variasi genetik menunjukkan genotipe dominan untuk rs1799752 adalah II (50%), rs4331 adalah GG (51%), rs4341 adalah GG (100%), dan rs4343 adalah AA (65%). Varian alel D rs1799752, alel A rs4331, dan alel G rs4343 menunjukkan hubungan dengan kerentanan terhadap hipertensi, COVID-19, dan keparahan COVID-19. Analisis regresi menunjukkan bahwa jenis kelamin, usia, riwayat hipertensi, LDL, asam urat, glukosa darah, dan variasi genetik gen ACE adalah prediktor dalam menilai tingkat risiko hipertensi. Sementara itu, jenis kelamin, trigliserida, HDL, komorbiditas hipertensi, dan variasi genetik gen ACE adalah prediktor dalam menilai risiko terhadap kejadian COVID-19, sementara komorbiditas hipertensi, IMT, asam urat, dan variasi genetik gen ACE adalah prediktor dalam menilai risiko keparahan COVID-19. Asesmen prediksi instrumen translasional menunjukkan bahwa 31% dari kelompok hipertensi berisiko tinggi terhadap kejadian COVID-19 dan 46% memiliki berisiko sangat tinggi untuk mengalami keparahan yang lebih tinggi. Asesmen prediksi instrumen translasional hipertensi menunjukkan bahwa 22% subjek memiliki risiko sangat tinggi dan 23% diantaranya memerlukan penyesuaian pola terapi. Variasi gen ACE rs4331, rs1799752, dan rs4343, bersama dengan faktor risiko non-genetik, dapat digunakan sebagai prediktor untuk kejadian hipertensi, COVID-19, dan keparahan COVID-19. Variasi gen dan faktor non-genetik ini dapat dikembangkan menjadi model pengobatan presisi untuk mengevaluasi tingkat risiko dan penanganan individu terhadap hipertensi, COVID-19, dan keparahan COVID-19 di kalangan populasi Palu-Sulawesi Tengah secara translasional. ......Hypertension is the most common comorbidity in COVID-19 sufferers. Risk factors such as genetics, sociodemographics, and initial clinical conditions are thought to influence an individual's susceptibility to hypertension and COVID-19. One of the genes associated with hypertension is the ACE gene. This study examines the ACE gene's genetic variation in summary with the risk of developing hypertension and COVID-19 using the Palu-Central Sulawesi population model. This research is an observational study with a cross-sectional design. Data on non-genetic factors were obtained from medical records and questionnaires. Identification of genetic variations was carried out at 4 locations in the ACE gene, namely rs1799752 (I/D) using the PCR method, rs4331 (A/G), rs4341 (G/C), and rs4343 (G/A) using rhAmp SNP genotyping. Data on genetic and non-genetic factors are then compiled into a translational instrument model. The study involved 136 subjects, and analysis of genetic variations showed that the dominant genotype for rs1799752 was II (50%), rs4331 was GG (51%), rs4341 was GG (100%), and rs4343 was AA (65%). The variant D allele rs1799753, A allele rs4331, and G allele rs4343 showed an association with susceptibility to hypertension, COVID-19, and severity of COVID-19. Regression analysis showed that gender, age, history of hypertension, LDL, uric acid, blood glucose, and genetic variations of the ACE gene were predictors in assessing the level of hypertension risk. Meanwhile, gender, triglycerides, HDL, comorbid hypertension, and genetic variations of the ACE gene are predictors in determining the risk of COVID-19. In contrast, comorbid hypertension, BMI, uric acid, and genetic variations of the ACE gene are predictors in assessing the risk of COVID-19 severity. -19. The translational instrument prediction assessment showed that 31% of the hypertension group were at high risk of experiencing COVID-19, and 46% were at very high risk of experiencing higher severity. The translational instrument prediction assessment for hypertension showed that 22% of subjects had a very high risk, and 23% of them required adjustment of therapy patterns. ACE gene variations rs4331, rs1799752, and rs4343, together with non-genetic risk factors, can be used as predictors for the incidence of hypertension, COVID-19, and severity of COVID-19. These gene variations and non-genetic factors can be developed into a precision medicine model to evaluate the risk level and individual treatment of hypertension, COVID-19, and the severity of COVID-19 among the Palu-Central Sulawesi population in a translational.