Project description:Introduction: Research incorporating resilience, a concept featuring a positive outcome despite some type of stressor, has the potential to identify possibilities for promotion of the well-being of older people. This study aims to gain insight into the value and potential applications of resilience in both research and care practice from the perspective of researchers and care professionals. Specifically, the value of two scientific approaches, the a priori (i.e., based on a priori definition of a stressor and outcome) and dynamical systems approaches (i.e., based on mathematically modeled patterns in the real-time response to perturbations), was explored. Methods: Focus groups were performed to explore the thoughts of academic researchers from different disciplines in the fields of aging and care and care professionals on the application of the concept of resilience, including the a priori and dynamical systems approaches. Analysis of these focus groups was based on the framework method. Results: Five focus groups were held with a total of nine researchers from different disciplines (e.g., epidemiology, sociology) and 15 older adult care professionals from different professions (e.g., elderly care physician, physiotherapist). The participants described resilience as a concept with value for both aging research and care through its positive connotation and comprehensiveness. Continued research was thought to play an important role in clearing up some of the existing ambiguity surrounding resilience. The importance of resilience in the context of both high- and low-intensity stressors was underscored. The a priori and dynamical systems approaches were considered to have their specific advantages and disadvantages on both conceptual and feasibility levels. Therefore, the use of both approaches, side by side and in combination, was suggested. Conclusion: This qualitative exploration among researchers and care professionals confirms that the concept of resilience, including the a priori and dynamical systems approaches, is valuable. However, more work is necessary before can be delivered on the potential of resilience in aging research and older adult care practice. Greater conceptual and operational clarity can be achieved through more qualitative studies on the concept that take the perspective of older people into account and through empirical studies that work with both approaches simultaneously and/or in combination.

Project description:Background. Bevacizumab, an antibody neutralizing Vascular Endothelial Growth Factor (VEGF), is licensed for the management of patients with advanced colon cancer. However, tumor biomarkers identifying the molecular tumor subsets most amenable to angiogenesis modulation are lacking. Patients and Methods. We profiled expession of 24526 genes by means of whole genome 24K DASL (c-DNA-mediated, Annealing, Selection and Ligation) arrays, (Illumina, CA) in 16 bevacizumab-treated patients with advanced colon cancer (Test set). Genes with correlation to 8-month Progression-free status were studied by means of qPCR in two independent colon cancer cohorts: 49 patients treated with bevacizumab+chemotherapy (Bevacizumab qPCR set) and 72 patients treated with chemotherapy only (Control qPCR set). Endpoints were best tumor response before metastasectomy (ORR) and progression-free survival (PFS). Results. Five genes were significantly correlated to 8-month progression-free status in the Test set: overexpression of KLF12 and downregulation of AGR2, ALDH6A1, MCM5, TFF2. In the two independent datasets, irinotecan- or oxaliplatin-based chemotherapy was administered as first-line treatment and metastasectomies were subsequently applied in 8-14% of patients. No prognostically significant gene classifier encompassing all five genes could be validated in the Bevacizumab or Control qPCR sets. The complex gene expression profile of all-low tumor (ALDH6A1+TFF2+MCM5) was strongly associated with ORR in the Bevacizumab qPCR set (ORR 85.7%, p=0.007), but not in the Control set (ORR 36.4%, p=0.747). The Odds Ratio for response for the all-low tumor (ALDH6A1+TFF2+MCM5) profile versus any other ALDH6A1+TFF2+MCM5 profile was 15 (p=0.018) in the Bevacizumab qPCR set but only 0.72 (p=0.63) in the Control set. The tumor expression profile of (KLF12-high+TFF2-low) was significantly associated with PFS only in the Bevacizumab qPCR set: bevacizumab-treated patients with (KLF12-high + TFF2-low) tumors had superior PFS (median 14 months, 95% CI 2-21) compared to patients with any other (KLF12+TFF2) expression profile (median PFS 7 months, 95% CI 5-10, p=0.021). The Hazard Ratio for disease progression for (KLF12-high + TFF2-low) versus any other KLF12+TFF2 expression profile was 2.92 (p=0.03) in the Validation and 1.29 (p=0.39) in the Control set. Conclusions. Our <three-stage> hypothesis-generating study failed to validate the prognostic significance of a five-gene classifier in mCRC patients. Exploratory analyses suggest two gene signatures that are potentially associated with bevazicumab benefit in patients with advanced colon cancer. 18 tumor tissue samples were analysed, no replicates

Project description:Background. Bevacizumab, an antibody neutralizing Vascular Endothelial Growth Factor (VEGF), is licensed for the management of patients with advanced colon cancer. However, tumor biomarkers identifying the molecular tumor subsets most amenable to angiogenesis modulation are lacking. Patients and Methods. We profiled expession of 24526 genes by means of whole genome 24K DASL (c-DNA-mediated, Annealing, Selection and Ligation) arrays, (Illumina, CA) in 16 bevacizumab-treated patients with advanced colon cancer (Test set). Genes with correlation to 8-month Progression-free status were studied by means of qPCR in two independent colon cancer cohorts: 49 patients treated with bevacizumab+chemotherapy (Bevacizumab qPCR set) and 72 patients treated with chemotherapy only (Control qPCR set). Endpoints were best tumor response before metastasectomy (ORR) and progression-free survival (PFS). Results. Five genes were significantly correlated to 8-month progression-free status in the Test set: overexpression of KLF12 and downregulation of AGR2, ALDH6A1, MCM5, TFF2. In the two independent datasets, irinotecan- or oxaliplatin-based chemotherapy was administered as first-line treatment and metastasectomies were subsequently applied in 8-14% of patients. No prognostically significant gene classifier encompassing all five genes could be validated in the Bevacizumab or Control qPCR sets. The complex gene expression profile of all-low tumor (ALDH6A1+TFF2+MCM5) was strongly associated with ORR in the Bevacizumab qPCR set (ORR 85.7%, p=0.007), but not in the Control set (ORR 36.4%, p=0.747). The Odds Ratio for response for the all-low tumor (ALDH6A1+TFF2+MCM5) profile versus any other ALDH6A1+TFF2+MCM5 profile was 15 (p=0.018) in the Bevacizumab qPCR set but only 0.72 (p=0.63) in the Control set. The tumor expression profile of (KLF12-high+TFF2-low) was significantly associated with PFS only in the Bevacizumab qPCR set: bevacizumab-treated patients with (KLF12-high + TFF2-low) tumors had superior PFS (median 14 months, 95% CI 2-21) compared to patients with any other (KLF12+TFF2) expression profile (median PFS 7 months, 95% CI 5-10, p=0.021). The Hazard Ratio for disease progression for (KLF12-high + TFF2-low) versus any other KLF12+TFF2 expression profile was 2.92 (p=0.03) in the Validation and 1.29 (p=0.39) in the Control set. Conclusions. Our <three-stage> hypothesis-generating study failed to validate the prognostic significance of a five-gene classifier in mCRC patients. Exploratory analyses suggest two gene signatures that are potentially associated with bevazicumab benefit in patients with advanced colon cancer.

Project description:This study aimed to examine the predictive validity of two internationally well-known instruments, the Modified Home Falls and Accidents Screening Tool (Modified HOME FAST) and the Modified Home Falls and Accidents Screening Tool-Self Report (Modified HOME FAST-SR), and the newly developed Thai Home Falls Hazard Assessment Tool (Thai-HFHAT) (69 items) in predicting falls among older Thai adults. It also aimed to examine the predictive validity of the two abbreviated versions (44 and 27 items) of the Thai-HFHAT, which were developed post hoc to accommodate older adults' limited literacy and poor vision and to facilitate the identification of high-impact home fall hazards that are prevalent in the Thailand context. A prospective cohort study was conducted among 450 participants aged 60 years and above who were assessed by the aforementioned tools at baseline, for which data on fall incidence were then collected during the one-year follow-up. The Cox proportional hazard model was applied to estimate hazard ratios (HRs); then, Harrell's C-statistics and receiver operating characteristic (ROC) analyses were conducted to identify the best cutoff point, sensitivity and specificity for each instrument. The results showed that the fall hazard rate was 2.04 times per 1,000 person-days. Taking into account both the predictive validity and applicability, the Thai-HFHAT (44 items) was found to be the most suitable screening tool due to its highest sensitivity and specificity (93% and 72%) at the cutoff score of 18. In conclusion, our study showed that these internationally validated home fall hazard assessment tools were quite applicable for Thailand, but further tailoring the tools into a specific local context yielded even more highly valid tools in predicting fall risk among older Thai adults. Although these findings were well reproducible by inferring from the internal validation results, further external validation in the independent population is necessary.

Dataset Information

Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients.

Background

Methods

Results

Conclusions

Publications

Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets