Browsing by Subject "Mortality"
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Item Open Access Adjuvant autologous melanoma vaccine for macroscopic stage III disease: survival, biomarkers, and improved response to CTLA-4 blockade(Hindawi Limited, 2016) Lotem, M.; Merims, S.; Frank, S.; Hamburger, T.; Nissan, A.; Kadouri, L.; Cohen, J.; Straussman, R.; Eisenberg, G.; Frankenburg, S.; Carmon, E.; Alaiyan, B.; Shneibaum, S.; Ayyildiz, Z. O.; Isbilen, M.; Senses, K. M.; Ron, I.; Steinberg, H.; Smith, Y.; Shiloni, E.; Gure, A. O.; Peretz, T.Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.Item Open Access Comparison of original EuroSCORE, EuroSCORE II and STS risk models in a Turkish cardiac surgical cohort(2013) Kunt, A.G.; Kurtcephe, M.; Hidiroglu, M.; Cetin L.; Kucuker, A.; Bakuy V.; Ruchan Akar, A.; Sener, E.OBJECTIVESThe aim of this study was to compare additive and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE II and the Society of Thoracic Surgeons (STS) models in calculating mortality risk in a Turkish cardiac surgical population.METHODSThe current patient population consisted of 428 patients who underwent isolated coronary artery bypass grafting (CABG) between 2004 and 2012, extracted from the TurkoSCORE database. Observed and predicted mortalities were compared for the additive/logistic EuroSCORE, EuroSCORE II and STS risk calculator. The area under the receiver operating characteristics curve (AUC) values were calculated for these models to compare predictive power.RESULTSThe mean patient age was 74.5 ± 3.9 years at the time of surgery, and 35.0% were female. For the entire cohort, actual hospital mortality was 7.9% (n = 34; 95% confidence interval [CI] 5.4-10.5). However, the additive EuroSCORE-predicted mortality was 6.4% (P = 0.23 vs observed; 95% CI 6.2-6.6), logistic EuroSCORE-predicted mortality was 7.9% (P = 0.98 vs observed; 95% CI 7.3-8.6), EuroSCORE II- predicted mortality was 1.7% (P = 0.00 vs observed; 95% CI 1.6-1.8) and STS predicted mortality was 5.8% (P = 0.10 vs observed; 95% CI 5.4-6.2). The mean predictive performance of the analysed models for the entire cohort was fair, with 0.7 (95% CI 0.60-0.79). AUC values for additive EuroSCORE, logistic EuroSCORE, EuroSCORE II and STS risk calculator were 0.70 (95% CI 0.60-0.79), 0.70 (95% CI 0.59-0.80), 0.72 (95% CI 0.62-0.81) and 0.62 (95% CI 0.51-0.73), respectively.CONCLUSIONSEuroSCORE II significantly underestimated mortality risk for Turkish cardiac patients, whereas additive and logistic EuroSCORE and STS risk calculators were well calibrated. © 2013 The Author 2013.Item Open Access Democracies linked to greater universal health coverage compared with autocracies, even in an economic recession(Project HOPE, 2021-08) Templin, T.; Dieleman, J. L.; Wigley, Simon; Mumford, J. E.; Miller-Petrie, M.; Kiernan, S.; Bollyky, T. J.Despite widespread recognition that universal health coverage is a political choice, the roles that a country’s political system plays in ensuring essential health services and minimizing financial risk remain poorly understood. Identifying the political determinants of universal health coverage is important for continued progress, and understanding the roles of political systems is particularly valuable in a global economic recession, which tests the continued commitment of nations to protecting their health of its citizens and to shielding them from financial risk. We measured the associations that democracy has with universal health coverage and government health spending in 170 countries during the period 1990–2019. We assessed how economic recessions affect those associations (using synthetic control methods) and the mechanisms connecting democracy with government health spending and universal health coverage (using machine learning methods). Our results show that democracy is positively associated with universal health coverage and government health spending and that this association is greatest for low-income countries. Free and fair elections were the mechanism primarily responsible for those positive associations. Democracies are more likely than autocracies to maintain universal health coverage, even amid economic recessions, when access to affordable, effective health services matters most.Item Open Access Demographics, treatment and outcomes of atrial fibrillation in a developing country: the population-based TuRkish Atrial Fibrillation (TRAF) cohort(Oxford University Press, 2017) Yavuz, B.; Ata, N.; Oto, E.; Katircioglu-Öztürk, D.; Aytemir, K.; Evranos, B.; Koselerli, R.; Ertugay, E.; Burkan, A.; Ertugay, E.; Gale, C. P.; Camm, A. J.; Oto, A.Aims: Although atrial fibrillation (AF) is increasingly common in developed countries, there is limited information regarding its demographics, co-morbidities, treatments and outcomes in the developing countries. We present the profile of the TuRkish Atrial Fibrillation (TRAF) cohort which provides real-life data about prevalence, incidence, comorbidities, treatment, healthcare utilization and outcomes associated with AF. Methods and results: The TRAF cohort was extracted from MEDULA, a health insurance database linking hospitals, general practitioners, pharmacies and outpatient clinics for almost 100% of the inhabitants of the country. The cohort includes 507 136 individuals with AF between 2008 and 2012 aged >18 years who survived the first 30 days following diagnosis. Of 507 136 subjects, there were 423 109 (83.4%) with non-valvular AF and 84 027 (16.6%) with valvular AF. The prevalence was 0.80% in non-valvular AF and 0.28% in valvular AF; in 2012 the incidence of non-valvular AF (0.17%) was higher than valvular AF (0.04%). All-cause mortality was 19.19% (97 368) and 11.47% (58 161) at 1-year after diagnosis of AF. There were 35 707 (7.04%) ischaemic stroke/TIA/thromboembolism at baseline and 34 871 (6.87%) during follow-up; 11 472 (2.26%) major haemorrhages at baseline and 10 183 (2.01%) during followup, and 44 116 (8.69%) hospitalizations during the follow-up. Conclusion: The TRAF cohort is the first population-based, whole-country cohort of AF epidemiology, quality of care and outcomes. It provides a unique opportunity to study the patterns, causes and impact of treatments on the incidence and outcomes of AF in a developing country. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017.Item Open Access Does control of rheumatic disease raise the standard of living in developing countries?(2009) Wigley, R.; Chopra, A.; Wigley, S.; Akkoyunlu-Wigley, A.[No abstract available]Item Open Access The impact of democracy and media freedom on under-5 mortality, 1961–2011(Elsevier Ltd, 2017) Wigley, S.; Akkoyunlu-Wigley, A.Do democracies produce better health outcomes for children than autocracies? We argue that (1) democratic governments have an incentive to reduce child mortality among low-income families and (2) that media freedom enhances their ability to deliver mortality-reducing resources to the poorest. A panel of 167 countries for the years 1961–2011 is used to test those two theoretical claims. We find that level of democracy is negatively associated with under-5 mortality, and that that negative association is greater in the presence of media freedom. These results are robust to the inclusion of country and year fixed effects, time-varying control variables, and the multiple imputation of missing values.Item Open Access The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelialmesenchymal transition in breast cancer(Impact Journals LLC, 2016) Raza, U.; Saatci, O.; Uhlmann, S.; Ansari, S. A.; Eyüpoglu, E.; Yurdusev, E.; Mutlu, M.; Ersan, P. G.; Altundağ, M. K.; Zhang, J. D.; Dogan, H. T.; Güler, G.; Şahin, Ö.Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPRCas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant-p53 which acts as a 'molecular switch' between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53- mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis.Item Open Access Validation of the EuroSCORE risk models in Turkish adult cardiac surgical population(Oxford University Press, 2011) Akar, A. R.; Kurtcephe, M.; Sener, E.; Alhan, C.; Durdu, S.; Kunt, A. G.; Güvenir, H. A.Objective: The aim of this study was to validate additive and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) models on Turkish adult cardiac surgical population. Methods: TurkoSCORE project involves a reliable web-based database to build up Turkish risk stratification models. Current patient population consisted of 9443 adult patients who underwent cardiac surgery between 2005 and 2010. However, the additive and logistic EuroSCORE models were applied to only 8018 patients whose EuroSCORE determinants were complete. Observed and predicted mortalities were compared for low-, medium-, and high-risk groups. Results: The mean patient age was 59.5 years (±12.1 years) at the time of surgery, and 28.6% were female. There were significant differences (all p< 0.001) in the prevalence of recent myocardial infarction (23.5% vs 9.7%), moderate left ventricular function (29.9% vs 25.6%), unstable angina (9.8% vs 8.0%), chronic pulmonary disease (13.4% vs 3.9%), active endocarditis (3.2% vs 1.1%), critical preoperative state (9.0% vs 4.1%), surgery on thoracic aorta (3.7% vs 2.4%), extracardiac arteriopathy (8.6% vs 11.3%), previous cardiac surgery (4.1% vs 7.3%), and other than isolated coronary artery bypass graft (CABG; 23.0% vs 36.4%) between Turkish and European cardiac surgical populations, respectively. For the entire cohort, actual hospital mortality was 1.96% (n = 157; 95% confidence interval (CI), 1.70-2.32). However, additive predicted mortality was 2.98% (p< 0.001 vs observed; 95%CI, 2.90-3.00), and logistic predicted mortality was 3.17% (p< 0.001 vs observed; 95%CI, 3.03-3.21). The predictive performance of EuroSCORE models for the entire cohort was fair with 0.757 (95%CI, 0.717-0.797) AUC value (area under the receiver operating characteristic, AUC) for additive EuroSCORE, and 0.760 (95%CI, 0.721-0.800) AUC value for logistic EuroSCORE. Observed hospital mortality for isolated CABG was 1.23% (n = 75; 95%CI, 0.95-1.51) while additive and logistic predicted mortalities were 2.87% (95%CI, 2.82-2.93) and 2.89% (95%CI, 2.80-2.98), respectively. AUC values for the isolated CABG subset were 0.768 (95%CI, 0.707-0.830) and 0.766 (95%CI, 0.705-0.828) for additive and logistic EuroSCORE models. Conclusion: The original EuroSCORE risk models overestimated mortality at all risk subgroups in Turkish population. Remodeling strategies for EuroSCORE or creation of a new model is warranted for future studies in Turkey. © 2011 European Association for Cardio-Thoracic Surgery.