@article {11622, title = {Association of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention With Memory Decline in Older Adults Undergoing Coronary Revascularization}, journal = {JAMA}, volume = {325}, year = {2021}, pages = {1955-1964}, abstract = {It is uncertain whether coronary artery bypass grafting (CABG) is associated with cognitive decline in older adults compared with a nonsurgical method of coronary revascularization (percutaneous coronary intervention [PCI]).To compare the change in the rate of memory decline after CABG vs PCI.Retrospective cohort study of community-dwelling participants in the Health and Retirement Study, who underwent CABG or PCI between 1998 and 2015 at age 65 years or older. Data were modeled for up to 5 years preceding and 10 years following revascularization or until death, drop out, or the 2016-2017 interview wave. The date of final follow-up was November 2017.CABG (including on and off pump) or PCI, ascertained from Medicare fee-for-service billing records.The primary outcome was a summary measure of cognitive test scores and proxy cognition reports that were performed biennially in the Health and Retirement Study, referred to as memory score, normalized as a z score (ie, mean of 0, SD of 1 in a reference population of adults aged >=72 years). Memory score was analyzed using multivariable linear mixed-effects models, with a prespecified subgroup analysis of on-pump and off-pump CABG. The minimum clinically important difference was a change of 1 SD of the population-level rate of memory decline (0.048 memory units/y).Of 1680 participants (mean age at procedure, 75 years; 41\% female), 665 underwent CABG (168 off pump) and 1015 underwent PCI. In the PCI group, the mean rate of memory decline was 0.064 memory units/y (95\% CI, 0.052 to 0.078) before the procedure and 0.060 memory units/y (95\% CI, 0.048 to 0.071) after the procedure (within-group change, 0.004 memory units/y [95\% CI, -0.010 to 0.018]). In the CABG group, the mean rate of memory decline was 0.049 memory units/y (95\% CI, 0.033 to 0.065) before the procedure and 0.059 memory units/y (95\% CI, 0.047 to 0.072) after the procedure (within-group change, -0.011 memory units/y [95\% CI, -0.029 to 0.008]). The between-group difference-in-differences estimate for memory decline for PCI vs CABG was 0.015 memory units/y (95\% CI, -0.008 to 0.038; P = .21). There was statistically significant increase in the rate of memory decline after off-pump CABG compared with after PCI (difference-in-differences: mean increase in the rate of decline of 0.046 memory units/y [95\% CI, 0.008 to 0.084] after off-pump CABG), but not after on-pump CABG compared with PCI (difference-in-differences: mean slowing of decline of 0.003 memory units/y [95\% CI, -0.024 to 0.031] after on-pump CABG).Among older adults undergoing coronary revascularization with CABG or PCI, the type of revascularization procedure was not significantly associated with differences in the change of rate of memory decline.}, keywords = {cardiology, cardiothoracic surgery, ischemic heart disease}, isbn = {0098-7484}, doi = {10.1001/jama.2021.5150}, author = {Elizabeth L Whitlock and L Grisell Diaz-Ramirez and Alexander K Smith and W John Boscardin and Kenneth E Covinsky and Michael S. Avidan and M. Maria Glymour} } @article {11500, title = {Long-term individual and population functional outcomes in older adults with atrial fibrillation.}, journal = {Journal of the American Geriatrics Society}, volume = {69}, year = {2021}, pages = {1570-1578}, abstract = {

Background: Older adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability has not been previously characterized.

Methods: We performed a longitudinal, observational study in the nationally representative Health and Retirement Study (1992-2014). We included participants >=65 years with Medicare claims who met incident AF diagnosis claims criteria. We examined the association of incident stroke with three functional outcomes: independence with activities of daily living (ADL) and instrumental activities of daily living (IADL) and community-dwelling. We fit separate logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimate the contribution of strokes to the overall population burden of functional impairment using the method of recycled predictions.

Results: Among 3530 participants (median age 79 years, 53\% women, median CHA DS -VASc 5), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for population comorbidities, annually, ADL dependence increased by 4.4\%, IADL dependence increased by 3.9\%, and nursing home residence increased by 1.2\% (p<0.05 for all). Accounting for comorbidities, of those who experienced a stroke, 31.9\% developed new ADL dependence, 26.5\% developed new IADL dependence, and 8.6\% newly moved to a nursing home (p<0.05 for all). Considering all causes of function loss, 1.7\% of ADL disability-years, 1.2\% of IADL disability-years, and 7.3\% of nursing home years could be attributed to stroke over 7.4years.

Conclusion: Older adults lose substantial function over time following AF diagnosis, independent of stroke. Stroke was associated with a significant decline in function and an increase in the likelihood of nursing home move, but stroke did not accelerate subsequent disability accrual. Because of the high background rate of functional loss, stroke was not the dominant determinant of population-level disability in older adults with AF.

Impact statement: We certify that this work is novel. Little is known about long-term function (ADL, IADL, community-dwelling) among older adults with AF and the association with stroke. This nationally representative study finds a high rate of function loss independent of stroke, and among those who suffer a stroke, a dramatic and immediate decline in function. Because of the high rate of function loss independent of stroke and the relatively low rate of stroke, on a population level, stroke is not the dominant determinant of disability in older adults with AF.

}, keywords = {ADL disability, Atrial Fibrillation, community living, IADLS}, doi = {10.1101/2020.05.04.20091025}, author = {Anna L Parks and Sun Y Jeon and W John Boscardin and Michael A Steinman and Alexander K Smith and Margaret C Fang and Sachin J Shah} } @article {11579, title = {A Novel Method for Identifying a Parsimonious and Accurate Predictive Model for Multiple Clinical Outcomes.}, journal = {Computer Methods and Programs in Biomedicine}, volume = {204}, year = {2021}, pages = {106073}, abstract = {

BACKGROUND AND OBJECTIVE: Most methods for developing clinical prognostic models focus on identifying parsimonious and accurate models to predict a single outcome; however, patients and providers often want to predict multiple outcomes simultaneously. As an example, for older adults one is often interested in predicting nursing home admission as well as mortality. We propose and evaluate a novel predictor-selection computing method for multiple outcomes and provide the code for its implementation.

METHODS: Our proposed algorithm selected the best subset of common predictors based on the minimum average normalized Bayesian Information Criterion (BIC) across outcomes: the Best Average BIC (baBIC) method. We compared the predictive accuracy (Harrell{\textquoteright}s C-statistic) and parsimony (number of predictors) of the model obtained using the baBIC method with: 1) a subset of common predictors obtained from the union of optimal models for each outcome (Union method), 2) a subset obtained from the intersection of optimal models for each outcome (Intersection method), and 3) a model with no variable selection (Full method). We used a case-study data from the Health and Retirement Study (HRS) to demonstrate our method and conducted a simulation study to investigate performance.

RESULTS: In the case-study data and simulations, the average Harrell{\textquoteright}s C-statistics across outcomes of the models obtained with the baBIC and Union methods were comparable. Despite the similar discrimination, the baBIC method produced more parsimonious models than the Union method. In contrast, the models selected with the Intersection method were the most parsimonious, but with worst predictive accuracy, and the opposite was true in the Full method. In the simulations, the baBIC method performed well by identifying many of the predictors selected in the baBIC model of the case-study data most of the time and excluding those not selected in the majority of the simulations.

CONCLUSIONS: Our method identified a common subset of variables to predict multiple clinical outcomes with superior balance between parsimony and predictive accuracy to current methods.

}, keywords = {backward elimination, Bayesian Information Criterion, prognostic models, Survival Analysis, variable selection}, issn = {1872-7565}, doi = {10.1016/j.cmpb.2021.106073}, author = {L Grisell Diaz-Ramirez and Lee, Sei J and Alexander K Smith and Gan, Siqi and W John Boscardin} } @article {11523, title = {A Novel Metric for Developing Easy-to-Use and Accurate Clinical Prediction Models: The Time-cost Information Criterion.}, journal = {Medical Care}, volume = {59}, year = {2021}, pages = {418-424}, abstract = {

BACKGROUND: Guidelines recommend that clinicians use clinical prediction models to estimate future risk to guide decisions. For example, predicted fracture risk is a major factor in the decision to initiate bisphosphonate medications. However, current methods for developing prediction models often lead to models that are accurate but difficult to use in clinical settings.

OBJECTIVE: The objective of this study was to develop and test whether a new metric that explicitly balances model accuracy with clinical usability leads to accurate, easier-to-use prediction models.

METHODS: We propose a new metric called the Time-cost Information Criterion (TCIC) that will penalize potential predictor variables that take a long time to obtain in clinical settings. To demonstrate how the TCIC can be used to develop models that are easier-to-use in clinical settings, we use data from the 2000 wave of the Health and Retirement Study (n=6311) to develop and compare time to mortality prediction models using a traditional metric (Bayesian Information Criterion or BIC) and the TCIC.

RESULTS: We found that the TCIC models utilized predictors that could be obtained more quickly than BIC models while achieving similar discrimination. For example, the TCIC identified a 7-predictor model with a total time-cost of 44 seconds, while the BIC identified a 7-predictor model with a time-cost of 119 seconds. The Harrell C-statistic of the TCIC and BIC 7-predictor models did not differ (0.7065 vs. 0.7088, P=0.11).

CONCLUSION: Accounting for the time-costs of potential predictor variables through the use of the TCIC led to the development of an easier-to-use mortality prediction model with similar discrimination.

}, keywords = {Bayesian Information Criterion, Methodology}, issn = {1537-1948}, doi = {10.1097/MLR.0000000000001510}, author = {Lee, Sei J and Alexander K Smith and Ramirez-Diaz, Ledif G and Kenneth E Covinsky and Gan, Siqi and Chen, Catherine L and W John Boscardin} } @article {11657, title = {Pre-existing geriatric conditions in older adults with poor prognosis cancers.}, journal = {Journal of Clinical Oncology}, volume = {39}, year = {2021}, pages = {12044-12044}, abstract = {Background: Older adults with poor prognosis cancers are more likely to experience toxicity from cancer-directed therapies. Although geriatric assessment (GA) reduces chemotherapy toxicity by detecting pre-existing conditions, GA can be difficult for oncologists to perform because of limited time and resources. We aim to determine the prevalence of pre-existing geriatric conditions that could be detected if GA were performed during routine oncology care. Methods: We used the Health and Retirement Study (HRS) linked with Medicare (1998-2016) to identify adults age >65 with poor prognosis cancers (median overall survival < 1 year). The HRS is a biennial nationally representative survey that asks about pre-existing geriatric conditions. Using the interview prior to the cancer diagnosis, we determined the presence of conditions included in GA: functional status (i.e. difficulty with climbing stairs, walking one block, getting up from a chair, bathing or showering, taking medications, and managing money), falls and injurious falls, unintentional weight loss, self-rated health, social support, mentation, advanced care planning, use of pain or sleep medications, and mobility. To identify groups with the highest prevalence of pre-existing geriatric conditions, we stratified results by age (adjusted for gender) and gender (adjusted for age). Results: Our study included 2,121 participants. At the time of cancer diagnosis, mean age was 76, 51\% were female, 79\% were non-Hispanic White, 26\% had lung cancer, 14\% had a GI cancer, and 60\% had other metastatic cancers. Mean time between the HRS interview and cancer diagnosis was 12.7 months. The median overall survival of the entire cohort was 9.6 months with a 45\% 1-year survival rate. The adjusted prevalence of pre-existing geriatric concerns were as follows: 65\% had difficulty with climbing several flights of stairs, 27\% had difficulty with walking one block, 47\% had difficulty getting up from a chair after sitting down, 12\% had difficulty in bathing or showering, 6\% had difficulty taking medications, 11\% had difficulty in managing money, 35\% had a fall in the last 2 years with 12\% of participants reporting injury after their fall. Those who were aged 85+, vs those aged 65-74, had higher rates of conditions indicative of cognitive impairment (e.g. 12 vs 4\% had difficulty taking medications, p = 0.000, 26\% vs 6\% had difficulty managing money, p = 0.000) and physical impairments (e.g. 54\% vs 30\% had falls, respectively, p = 0.000). Rates of geriatric conditions indicative of physical impairment were higher in women vs men (e.g. 72\% vs 58\% had difficulty climbing stairs, p = 0.000 and 52\% vs 41\% had difficulty getting up from a chair, p = 0.000). Conclusions: Patients with poor prognosis cancers have high rates of pre-existing geriatric conditions that can be detected by GA. Geriatric assessments could find important impairments that could be addressed prior to cancer therapy to reduce adverse effects.12044Background: Older adults with poor prognosis cancers are more likely to experience toxicity from cancer-directed therapies. Although geriatric assessment (GA) reduces chemotherapy toxicity by detecting pre-existing conditions, GA can be difficult for oncologists to perform because of limited time and resources. We aim to determine the prevalence of pre-existing geriatric conditions that could be detected if GA were performed during routine oncology care. Methods: We used the Health and Retirement Study (HRS) linked with Medicare (1998-2016) to identify adults age >65 with poor prognosis cancers (median overall survival < 1 year). The HRS is a biennial nationally representative survey that asks about pre-existing geriatric conditions. Using the interview prior to the cancer diagnosis, we determined the presence of conditions included in GA: functional status (i.e. difficulty with climbing stairs, walking one block, getting up from a chair, bathing or showering, taking medications, and managing money), falls and injurious falls, unintentional weight loss, self-rated health, social support, mentation, advanced care planning, use of pain or sleep medications, and mobility. To identify groups with the highest prevalence of pre-existing geriatric conditions, we stratified results by age (adjusted for gender) and gender (adjusted for age). Results: Our study included 2,121 participants. At the time of cancer diagnosis, mean age was 76, 51\% were female, 79\% were non-Hispanic White, 26\% had lung cancer, 14\% had a GI cancer, and 60\% had other metastatic cancers. Mean time between the HRS interview and cancer diagnosis was 12.7 months. The median overall survival of the entire cohort was 9.6 months with a 45\% 1-year survival rate. The adjusted prevalence of pre-existing geriatric concerns were as follows: 65\% had difficulty with climbing several flights of stairs, 27\% had difficulty with walking one block, 47\% had difficulty getting up from a chair after sitting down, 12\% had difficulty in bathing or showering, 6\% had difficulty taking medications, 11\% had difficulty in managing money, 35\% had a fall in the last 2 years with 12\% of participants reporting injury after their fall. Those who were aged 85+, vs those aged 65-74, had higher rates of conditions indicative of cognitive impairment (e.g. 12 vs 4\% had difficulty taking medications, p = 0.000, 26\% vs 6\% had difficulty managing money, p = 0.000) and physical impairments (e.g. 54\% vs 30\% had falls, respectively, p = 0.000). Rates of geriatric conditions indicative of physical impairment were higher in women vs men (e.g. 72\% vs 58\% had difficulty climbing stairs, p = 0.000 and 52\% vs 41\% had difficulty getting up from a chair, p = 0.000). Conclusions: Patients with poor prognosis cancers have high rates of pre-existing geriatric conditions that can be detected by GA. Geriatric assessments could find important impairments that could be addressed prior to cancer therapy to reduce adverse effects.}, keywords = {Cancer, Geriatric Assessment, Medicare, Pre-existing Conditions}, isbn = {0732-183X}, doi = {10.1200/JCO.2021.39.15_suppl.12044}, author = {Tsang, Mazie and Gan, Siqi and Wong, Melisa L. and Louise C Walter and Alexander K Smith} }