42 research outputs found
Walking speed, cognitive function and dementia risk in the English Longitudinal Study
Background: Physical and cognitive function decline with age. Slow walking speed has been associated with negative health outcomes and dementia is often preceded by cognitive decline. This study investigated walking speed, cognitive function and the interaction between changes in these measures in relation to dementia risk.
Method: Walking speed and cognition were assessed in 3,932 individuals aged ≥60 years at wave 1 (2002-03) and 2 (2004-05) of the English Longitudinal Study of Ageing. New dementia cases were assessed from wave 3 (2006-07) to wave 7 (2014-15). The associations were modelled using Cox proportional hazards regression.
Results: Participants with faster baseline walking speeds (HR 0.36; 95% CI 0.22 - 0.60) had a decreased risk of dementia. Those who had a greater decline in walking speed (waves 1 - 2 (HR 1.23; 95% CI 1.03 - 1.47) had an increased dementia risk. Participants with greater baseline cognition (HR 0.42; 95% CI 0.34 - 0.54) had a reduced dementia risk. Those who had a greater decline in cognition (waves 1-2) had a greater risk of dementia (HR 1.78; 95% CI 36 1.53 - 2.06). Change in walking speed and change in cognition did not interact significantly in relation to dementia risk (HR 1.01; 95% CI 0.88 – 1.17).
Conclusions: In this community-dwelling sample of English adults those with slower walking speeds and a greater decline in speed over time had an increased risk of developing dementia independent of changes in cognition. Further research is required to understand the mechanisms that may drive these associations
Predictors of colorectal cancer screening in diverse primary care practices
BACKGROUND: To explain why rates of colorectal cancer (CRC) screening including fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), colonoscopy (CS), and barium enema (BE), are low, this study assessed determinants of CRC screening from medical records. METHODS: Data were abstracted from patients aged ≥64 years selected from each clinician from 30 diverse primary care practices (n = 981). Measurements included the rates of annual FOBT, ever receiving FOBT, ever receiving FS/CS/BE under a combination variable, endoscopy/barium enema (EBE). RESULTS: Over five years, 8% had received annual FOBT, 53% had ever received FOBT and 22% had ever received EBE. Annual FOBT was negatively associated with female gender, odds ratio (OR) = .23; 95% confidence interval = .12–.44 and positively associated with routinely receiving influenza vaccine, OR = 2.55 (1.45–4.47); and more office visits: 3 to <5 visits/year, OR = 2.78 (1.41–5.51), and ≥5 visits/year, OR = 3.35 (1.52-7.42). Ever receiving EBE was negatively associated with age ≥75 years, OR = .66 (.46–.95); being widowed, OR = .59 (.38–.92); and positively associated with more office visits: 3 to <5 visits/year, OR = 1.83 (1.18–2.82) and ≥5 visits/year, OR = 2.01 (1.14–3.55). CONCLUSION: Overall CRC screening rates were low, but were related to the number of primary care office visits. FOBT was related to immunization status, suggesting the possible benefit of linking these preventive services
Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting
The dynamic relationship between cognitive function and walking speed:The English Longitudinal Study of Ageing
Cross-sectional studies show that older people with better cognition tend to walk faster. Whether this association reflects an influence of fluid cognition upon walking speed, vice versa, a bidirectional relationship or the effect of common causes is unclear. We used linear mixed effects models to examine the dynamic relationship between usual walking speed and fluid cognition, as measured by executive function, verbal memory and processing speed, in 2,654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relationship between walking speed and fluid cognition. After adjusting for age and sex, better performance on executive function, memory and processing speed was associated with less yearly decline in walking speed over the 6-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; and less yearly decline in each cognitive domain was associated with less yearly decline in walking speed. Effect sizes were small. After further adjustment for other covariates, effect sizes were attenuated but most remained statistically significant. We found some evidence that walking speed and the fluid cognitive domains of executive function and processing speed may change in parallel with increasing age. Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions.<br/
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Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls
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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring
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Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting