Araştırma Çıktıları
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Item Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial(BMC, 2022-01-01) Chastre, Jean; Francois, Bruno; Bourgeois, Marc; Komnos, Apostolos; Ferrer, Ricard; Rahav, Galia; De Schryver, Nicolas; Lepape, Alain; Koksal, Iftihar; Luyt, Charles-Edouard; Sanchez-Garcia, Miguel; Torres, Antoni; Eggimann, Philippe; Koulenti, Despoina; Holland, Thomas L.; Ali, Omar; Shoemaker, Kathryn; Ren, Pin; Sauser, Julien; Ruzin, Alexey; Tabor, David E.; Akhgar, Ahmad; Wu, Yuling; Jiang, Yu; DiGiandomenico, Antonio; Colbert, Susan; Vandamme, Drieke; Coenjaerts, Frank; Malhotra-Kumar, Surbhi; Timbermont, Leen; Oliver, Antonio; Barraud, Olivier; Bellamy, Terramika; Bonten, Marc; Goossens, Herman; Reisner, Colin; Esser, Mark T.; Jafri, Hasan S.; Grp, C. O. M. B. A. C. T. E.-M.A.G.N.E.T. Evade StudyBackground: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. Methods: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe,Turkey, Israel, and the USA. Subjects >= 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose),or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. Results: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n =16/87Item Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey(ELSEVIER SCIENCE INC, 2021-01-01) Tanriover, Mine Durusu; Doganay, Hamdi Levent; Akova, Murat; Guner, Hatice Rahmet; Azap, Alpay; Akhan, Sila; Kose, Sukran; Erdinc, Fatma Sebnem; Akalin, Emin Halis; Tabak, Omer Fehmi; Pullukcu, Husnu; Batum, Ozgur; Yavuz, Serap Simsek; Turhan, Ozge; Yildirmak, Mustafa Taner; Koksal, Iftihar; Tasova, Yesim; Korten, Volkan; Yilmaz, Gurdal; Celen, Mustafa Kemal; Altin, Sedat; Celik, Ilhami; Bayindir, Yasar; Karaoglan, Ilkay; Yilmaz, Aydin; Ozkul, Aykut; Gur, Hazal; Unal, Serhat; Grp, CoronaVac StudyBackground CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. Methods This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 mu g inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0.5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. Findings Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 {[}65.1\%] in the vaccine group and 3568 {[}34.9\%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 {[}65.4\%] and 3470 {[}34.6\%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31.7 cases {[}14.6-59.3] per 1000 person-years) and 32 cases were reported in the placebo group (192.3 cases {[}135.7-261.1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83.5\% (95\% CI 65.4-92.1Item Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus(NATURE PORTFOLIO, 2022-01-01) Durie, Ian A.; Tehrani, Zahra R.; Karaaslan, Elif; Sorvillo, Teresa E.; McGuire, Jack; Golden, Joseph W.; Welch, Stephen R.; Kainulainen, Markus H.; Harmon, Jessica R.; Mousa, Jarrod J.; Gonzalez, David; Enos, Suzanne; Koksal, Iftihar; Yilmaz, Gurdal; Karakoc, Hanife Nur; Hamidi, Sanaz; Albay, Cansu; Spengler, Jessica R.; Spiropoulou, Christina F.; Garrison, Aura R.; Sajadi, Mohammad M.; Bergeron, Eric; Pegan, Scott D.Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40\% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains. There are currently no approved treatments for Crimean-Congo Hemorrhagic Fever Virus (CCHFV) infection. In this study, the authors structurally characterize the epitope targeted by protective non-neutralizing mouse and human antibodies and provide insights into their broad range potential against various CCHFV strains.Item Eliminating Viral Hepatitis in Turkey: Achievements and Challenges(GALENOS PUBL HOUSE, 2022-01-01) Akarca, Ulus Salih; Baykam, Nurcan; Guner, Rahmet; Gunsar, Fulya; Idilman, Ramazan; Kaymakoglu, Sabahattin; Koksal, Iftihar; Tabak, Fehmi; Yamazhan, TansuAfter the declaration Global Health Sector Strategy on Viral Hepatitis by the World Health Organization in 2016, the Turkish Government defined a national strategy covering 2018-2023 to reach goals by 2030. Following a participatory decision process and a series of workshops, the strategy was built on eight separate subheadings. Apart from the official Prevention and Control Program, two separate road maps for hepatitis B and C were developed to obtain targets accessible with the cooperation of the Viral Hepatitis Society and the Turkish Association for the Study of the Liver in 2018 and 2020, respectively. Up to 2023, achievements and the current situation of the National Viral Hepatitis Prevention and Control Program and the hepatitis B virus and hepatitis C virus road maps were assessed in detail on June 28th, 2022, by the subject matter experts in Turkey. Besides the officially reported achievement rate (42\%) of the Program in 2021, participants mentioned undesirable effects of the coronavirus disease-2019 pandemic, unregulated migration, low levels of professional and public awareness, and barriers to access to anti-viral treatment. Recommendations focused on increasing the efficiency of screening and surveillance by integrating the viral carrier identity of individuals into the national health information system, simplifying the drug supplement and treatment initiation process and insisting on education to raise awareness.Item Factors Affecting Adherence to Antiretroviral Treatment among HIV/AIDS Patients in Turkey(BILIMSEL TIP YAYINEVI, 2021-01-01) Nur Karakoc, Hanife; Kaya, Selcuk; Aydin, Merve; Koksal, IftiharIntroduction: Adherence to antiretroviral treatment (ART) is critical for the success of Human Immunodeficiency Virus (HIV) infection treatment. There is no approved consensus that defines adherence. In this study, it was aimed to examine the adherence rate of our patients with high-efficacy ART and to determine the factors affecting treatment adherence. Materials and Methods: Seventy-two patients admitted to the study between January 1, 2018 and July 31, 2018 with the diagnosis of HIV/AIDS who received ART for at least three months and agreed to participate in the study were included in the study. The effect of treatment adherence was investigated by examining the sociodemographic and clink characteristics and laboratory findings, and moods of the patients. Treatment adherence of the patients was evaluated with the Center for Adherence Support Evaluation (CASE) adherence questionnaire and pill counting method. The Hamilton Depression Rating Scale questionnaire was used to investigate the effect of depression severity on treatment adherence in patients. Results: Of the patients, 72.2\% were males and 27.8\% were females. Mean age of the patients was 44.9 +/- 14.8 years. Of the patients, 59.7\% were defined as treatment compatible. Sixty (83.3\%) patients used a single tablet regimen. The most commonly used combination was tenofovir alafenamide-emtricitabine-elvitegravir-cobicistate. Patients' age, disease duration, frequency of follow-up clinic depressive mood, substance use, and HIV positivity in their partners were found effective on treatment adherence. However, sex, marital and educational status, occupation, residential area, transmission route, duration on ART, ART regimen, ART treatment revision, recent CD4+ T lymphocyte count, recent viral load, side effect, additional treatments, antibiotic prophylaxis, smoking habit, alcohol use, comorbidity, co-infection were not statistically associated with treatment adherence. Conclusion: Sufficient awareness should be created by allocating enough time to patients, and patients should be followed up more frequently. Since alcohol and substance use affects treatment adherence, support should be sought from relevant institutions to limit alcohol and substance use in patients. Depressive mood is more common in HIV/AIDS patients compared to the normal population and negatively affects treatment adherence.Item An Evaluation of Chronic Hepatitis C Patients' Responses to Direct-Acting Antivirals According to Transient Elastography and Serum Biomarkers(GALENOS YAYINCILIK, 2022-01-01) Aydin, Nurten Nur; Koksal, IftiharObjectives: In this study, it was evaluated the changes in liver stiffness measurements measured by AST to Platelet Ratio index (APRI), Fibrosis 4 index (FIB-4), Age Platelet index (API), AST-ALT ratio (AAR) and transient elastography (TE) among the non-invasive fibrosis scores in chronic hepatitis C (CHC) patients treated with direct-acting agents (DM) and the effect of treatment. Materials and Methods: Ombitasvir-paritaprevir-ritonavir-dasabuvir +/- ribavirin (RBV) or sofosbuvir +/- ledipasvir (SOF +/- LDV) +/- RBV was given to the patients. Fibrosis scores were calculated with the biochemical data of the patients before the treatment, at the 4s . week of the treatment, at the end of treatment and at the sustained virological response 12 (SVR12) Liver stiffness measurements were recorded before treatment with TE and in SVR12. Post-treatment SVR12 responses were evaluated. Results: SVR12 was achieved in 97.9\% of 95 patients included in the study. Significant regression was found in APRI and FIB-4 scores, which are among the 4 serum fibrosis markers calculated in all patients (p<0.001, p<0.001). Liver stiffness was measured using TE in 75 patients. It was determined that the liver stiffness measurement (9.3 +/- 6.5 kPa) in SVR12 significantly decreased compared to the baseline (11.6 +/- 7.8 kPa) (p<0.001). Conclusion: DAA provides improvement in fibrosis scores and persistent viral response in patients. In our study, in which fibrosis was evaluated non-invasive methods, it was observed that there was a significant improvement in liver fibrosis with APRI, FIB-4 and TE measurements.