Browsing by Author "Liu, H."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials
    (Springer, 2024) Liu, H.; Li, J.; Ziegemeier, E.; Adams, S.; McDade, E.; Clifford, D. B.; Cao, Y.; Wang, G.; Li, Y.; Mills, S. L.; Santacruz, A. M.; Belyew, S.; Grill, J. D.; Snider, B. J.; Mummery, C. J.; Surti, G.; Hannequin, D.; Wallon, D.; Berman, S. B.; Jimenez-Velazquez, I. Z.; Roberson, E. D.; van Dyck, C. H.; Honig, L. S.; Sanchez-Valle, R.; Brooks, W. S.; Gauthier, S.; Galasko, D.; Masters, C. L.; Brosch, J.; Hsiung, G. Y. R.; Jayadev, S.; Formaglio, M.; Masellis, M.; Clarnette, R.; Pariente, J.; Dubois, B.; Pasquier, F.; Bateman, R. J.; Llibre-Guerra, J. J.; DIAN-TU Study Team; Neurology, School of Medicine
    Background: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). Methods: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. Results: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. Conclusion: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.
  • Thumbnail Image
    Item
    Genetic variants in the folate metabolic pathway genes predict melanoma-specific survival
    (Oxford University Press, 2020-10) Dai, W.; Liu, H.; Liu, Y.; Xu, X.; Qian, D.; Luo, S.; Cho, E.; Zhu, D.; Amos, C.I.; Fang, S.; Lee, J.E.; Li, X.; Nan, H.; Li, C.; Wei, Q.; Epidemiology, School of Public Health
    Background: Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWASs) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. Objectives: To examine associations between SNPs in folate metabolic pathway genes and CMSS. Methods: We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively. Results: We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32-2·32, P = 9·96 × 10-5 ) and 2·05 (1·39-3·01, P = 2·84 × 10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. Conclusions: Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic? Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma-specific prognosis. A hypothesis-driven approach, by pooling the effects of single-nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add? Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma-specific survival (CMSS). What is the translational message? The identification of genetic variants will make a risk-prediction model possible for CMSS. The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma.
  • Thumbnail Image
    Item
    Prognostic factors in patients with poor-risk germ-cell tumors: a retrospective analysis of the Indiana University experience from 1990 to 2014
    (Oxford University Press, 2016-05) Adra, N.; Althouse, S.K.; Liu, H.; Brames, M.J.; Hanna, N.H.; Einhorn, L.H.; Albany, C.; Department of Medicine, School of Medicine
    BACKGROUND: Based on the risk stratification from the International Germ Cell Cancer Collaborative Group (IGCCCG), only 14% of patients with metastatic germ-cell tumors (GCT) had poor-risk disease with a 5-year progression-free survival (PFS) rate of 41% and a 5-year overall survival (OS) rate of only 48%. This analysis attempts to identify prognostic factors for patients with poor-risk disease. PATIENTS AND METHODS: We conducted a retrospective analysis of all patients with GCT diagnosed and treated at Indiana University from 1990 to 2014. Clinical and pathological characteristics were available for all patients and all of them were treated with cisplatin-etoposide-based chemotherapy. Cox proportional hazards models were used to target significant predictors of disease progression and mortality. A significance level of 5% was used in the analysis. RESULTS: We identified 273 consecutive patients with poor-risk GCT (PRGCT). Median follow-up time was 8 years (range 0.03-24.5). The 5-year PFS and OS rates were 58% [95% confidence interval (CI) 51% to 63%] and 73% (95% CI 67% to 78%), respectively. In multivariate survival analyses, multiple risk factors were associated with disease progression, including liver metastasis, brain metastasis, primary mediastinal nonseminomatous GCT (PMNSGCT), and elevation in logarithmic β-hCG. Significant predictors of mortality were PMNSGCT [hazard ratio (HR) 4.63, 95% CI 2.25-9.56; P < 0.001], brain metastasis (HR 3.30, 95% CI 1.74-6.23; P < 0.001), and increasing age (HR 1.03, 95% CI 1.01-1.06; P = 0.02). CONCLUSIONS: Patients with PMNSGCT, brain metastasis, or with increasing age are at higher risk of death than their counterparts. This contemporary cohort (1990-2014) of 273 patients with PRGCT had improved PFS and OS outcomes than those from the historical IGCCCG group of patients (1975-1990).