New horizons in frailty identification via electronic frailty indices: early implementation lessons from experiences in England and the United States.

Frailty represents an integrative prognostic marker of risk that associates with a myriad of age-related adverse outcomes in older adults. As a concept, frailty can help to target scarce resources and identify subgroups of vulnerable older adults that may benefit from interventions or changes in medical management, such as pursing less aggressive glycaemic targets for frail older adults with diabetes. In practice, however, there are several operational challenges to implementing frailty screening outside the confines of geriatric medicine. Electronic frailty indices (eFIs) based on the theory of deficit accumulation, derived from routine data housed in the electronic health record, have emerged as a rapid, feasible and valid approach to screen for frailty at scale. The goal of this paper is to describe the early experience of three diverse groups in developing, implementing and adopting eFIs (The English National Health Service, US Department of Veterans Affairs and Atrium Health-Wake Forest Baptist). These groups span different countries and organisational complexity, using eFIs for both research and clinical care, and represent different levels of progress with clinical implementation. Using an implementation science framework, we describe common elements of successful implementation in these settings and set an agenda for future research and expansion of eFI-informed initiatives.

Insomnia Symptoms and Environmental Disruptors: A Preliminary Evaluation of Veterans in a Subacute Rehabilitation.

OBJECTIVES: Evaluate insomnia symptoms and environmental disruptors at admission and discharge in a subacute rehabilitation care setting. METHODS: Veterans (age ≥50) admitted to a Veterans Health Administration (VA) Hospital subacute rehabilitation between March and August 2022 completed baseline (N = 46) and follow up (N = 33) assessments with the Insomnia Severity Index (ISI), Sleep Need Questionnaire (SNQ), Epworth Sleepiness Scale (ESS), and an assessment of environmental sleep disruptors. Veterans were offered sleep resources after admission evaluations and outpatient referrals after discharge evaluations. Pearson correlation determined associations between length of stay (LOS), ISI, SNQ, and ESS scores at admission and discharge; chi-square and Wilcoxon Signed Rank Tests compared insomnia at admission and discharge. RESULTS: One-half of participants reported clinically meaningful insomnia symptoms and sleep needs at baseline with no significant change at discharge. Almost all (89.1%) Veterans reported sleep was disturbed by environmental factors, primarily staff awakenings. LOS was correlated with ESS scores at discharge (r = .52, p = .002). CONCLUSIONS: Environmental sleep disruption was common during a subacute rehabilitation admission and were not adequately addressed through sleep resources and treatment due to low uptake. CLINICAL IMPLICATIONS: Providers should assess sleep at admission and lessen environmental sleep disruptors by reducing noise, light, and non-essential awakenings at night.

Validation of algorithms to select patients with multiple myeloma and patients initiating myeloma treatment in the national Veterans Affairs Healthcare System.

BACKGROUND: We aimed to evaluate and compare the performance of multiple myeloma (MM) selection algorithms for use in Veterans Affairs (VA) research. METHODS: Using the VA Corporate Data Warehouse (CDW), the VA Cancer Registry (VACR), and VA pharmacy data, we randomly selected 500 patients from 01/01/1999 to 06/01/2021 who had (1) either one MM diagnostic code OR were listed in the VACR as having MM AND (2) at least one MM treatment code. A team reviewed oncology notes for each veteran to annotate details regarding MM diagnosis and initial treatment within VA. We evaluated inter-annotator agreement and compared the performance of four published algorithms (two developed and validated external to VA data and two used in VA data). RESULTS: A total of 859 patients were reviewed to obtain 500 patients who were annotated as having MM and initiating MM treatment in VA. Agreement was high among annotators for all variables: MM diagnosis (98.3% agreement, Kappa = 0.93); initial treatment in VA (91.8% agreement; Kappa = 0.77); and initial treatment classification (87.6% agreement; Kappa = 0.86). VA Algorithms were more specific and had higher PPVs than non-VA algorithms for both MM diagnosis and initial treatment in VA. We developed the "VA Recommended Algorithm," which had the highest PPV among all algorithms in identifying patients diagnosed with MM (PPV = 0.98, 95% CI = 0.95-0.99) and in identifying patients who initiated their MM treatment in VA (PPV = 0.93, 95% CI = 0.90-0.96). CONCLUSION: Our VA Recommended Algorithm optimizes sensitivity and PPV for cohort selection and treatment classification.

Mild Neurocognitive Disorder, Social Engagement, and Falls Among Older Primary Care Patients.

OBJECTIVES: (1) To estimate the association between social engagement (SE) and falls; (2) To examine the relation between mild neurocognitive disorder (MNCD) and falls by different levels of SE. DESIGN: We performed a secondary data analysis using prospective cohort study design. SETTING: Primary care. PARTICIPANTS: A total of 425 older adult primary care patients at risk for mobility decline (N=425). As previously reported, at baseline, 42% of participants exhibit MNCD. MAIN OUTCOME MEASURES: The outcome variable was the number of falls during 2 years of follow-up. Exposure variables at baseline included (1) MNCD identified using a cut-off of 1.5 SD below the age-adjusted mean on at least 2 measures within a cognitive performance battery and (2) SE, which was assessed using the social component of the Late-Life Function and Disability Instrument. High SE was defined as having a score ≥ median value (≥49 out of 100). All models were adjusted for age, sex, education, marital status, comorbidities, and pain status. RESULTS: Over 2 years of follow-up, 48% of participants fell at least once. MNCD was associated with a higher rate of falls, adjusting for the covariates (Incidence Rate Ratio=1.6, 95% confidence interval: 1.1-2.3). There was no significant association between MNCD and the rate of falls among people with high SE. In participants with low SE (having a score less than 49.5 out 100), MNCD was associated with a higher rate of falls as compared with participants with no neurocognitive disorder (No-NCD). CONCLUSIONS: Among participants with low SE, MNCD was associated with a higher rate of falls, but not among participants with high SE. The findings suggest that high SE may be protective against falls among older primary care patients with MNCD.

Trauma re-engagement and PTSD in older medically ill veterans: implications for trauma-informed care.

OBJECTIVES: We characterize rates and correlates of PTSD and of trauma re-engagement without PTSD in medically ill older Veterans, as well as supportive strategies, with the goal of advancing trauma-informed care. METHODS: We interviewed medically ill older Veterans (N = 88, M age 75.13, SD = 6.14) with primary care screening measures for PTSD and trauma re-engagement, and open-ended questions to assess supportive strategies. RESULTS: One-fifth (20.5%) presented with probable PTSD, associated with greater trauma exposures (r=.57, p<.001), whereas two-fifths (43.2%) reported re-engagement with military memories without PTSD, associated with having a spouse/partner (t = 2.27, p=.028). Of those who experienced trauma, half reported thinking more about the trauma recently and becoming more emotional on certain days. In response to the question 'What gives you strength as you think about the future with your illness' Veterans described support of family, healthcare, worldview, personal control, acceptance, and health behaviors. CONCLUSION: Memories of trauma are common with medical illness. Age-friendly trauma-informed care could consider factors that patients describe as sources of strength with illness.

Frailty and cardiovascular mortality in more than 3 million US Veterans.

AIMS: Frailty is associated with an increased risk of all-cause mortality and cardiovascular (CV) events. Limited data exist from the modern era of CV prevention on the relationship between frailty and CV mortality. We hypothesized that frailty is associated with an increased risk of CV mortality. METHODS AND RESULTS: All US Veterans aged ≥65 years who were regular users of Veteran Affairs care from 2002 to 2017 were included. Frailty was defined using a 31-item previously validated frailty index, ranging from 0 to 1. The primary outcome was CV mortality with secondary analyses examining the relationship between frailty and CV events (myocardial infarction, stroke, revascularization). Survival analysis models were adjusted for age, sex, ethnicity, geographic region, smoking, hyperlipidaemia, statin use, and blood pressure medication use. There were 3 068 439 US Veterans included in the analysis. Mean age was 74.1 ± 5.8 years in 2002, 76.0 ± 8.3 years in 2014, 98% male, and 87.5% White. In 2002, the median (interquartile range) frailty score was 0.16 (0.10-0.23). This increased and stabilized to 0.19 (0.10-0.32) for 2006-14. The presence of frailty was associated with an increased risk of CV mortality at every stage of frailty. Frailty was associated with an increased risk of myocardial infarction and stroke, but not revascularization. CONCLUSION: In this population, both the presence and severity of frailty are tightly correlated with CV death, independent of underlying CV disease. This study is the largest and most contemporary evaluation of the relationship between frailty and CV mortality to date. Further work is needed to understand how this risk can be diminished. KEY QUESTION: Can an electronic frailty index identify adults aged 65 and older who are at risk of CV mortality and major CV events? KEY FINDING: Among 3 068 439 US Veterans aged 65 and older, frailty was associated with an increased risk of CV mortality at every level of frailty. Frailty was also associated with an increased risk of myocardial infarction and stroke, but not revascularization. TAKE HOME MESSAGE: Both the presence and severity of frailty are associated with CV mortality and major CV events, independent of underlying CV disease.

Randomized controlled trial of geriatric consultation versus standard care in older adults with hematologic malignancies.

We conducted a randomized controlled trial in older adults with hematologic malignancies to determine the impact of geriatrician consultation embedded in our oncology clinic alongside standard care. From February 2015 to May 2018, transplant-ineligible patients aged ≥75 years who presented for initial consultation for lymphoma, leukemia, or multiple myeloma at Dana-Farber Cancer Institute (Boston, MA, USA) were eligible. Pre-frail and frail patients, classified based on phenotypic and deficit-accumulation approaches, were randomized to receive either standard oncologic care with or without consultation with a geriatrician. The primary outcome was 1-year overall survival. Secondary outcomes included unplanned care utilization within 6 months of follow-up and documented end-of-life (EOL) goals-of-care discussions. Clinicians were surveyed as to their impressions of geriatric consultation. One hundred sixty patients were randomized to either geriatric consultation plus standard care (n=60) or standard care alone (n=100). The median age of the patients was 80.4 years (standard deviation = 4.2). Of those randomized to geriatric consultation, 48 (80%) completed at least one visit with a geriatrician. Consultation did not improve survival at 1 year compared to standard care (difference: 2.9%, 95% confidence interval: -9.5% to 15.2%, P=0.65), and did not significantly reduce the incidence of emergency department visits, hospital admissions, or days in hospital. Consultation did improve the odds of having EOL goals-of-care discussions (odds ratio = 3.12, 95% confidence interval: 1.03 to 9.41) and was valued by surveyed hematologic-oncology clinicians, with 62.9%-88.2% of them rating consultation as useful in the management of several geriatric domains.

Association of Polypharmacy and Potentially Inappropriate Medications With Frailty Among Older Adults With Blood Cancers.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIMs) are common among older adults with blood cancers, but their association with frailty and how to manage them optimally remain unclear. PATIENTS AND METHODS: From 2015 to 2019, patients aged ≥75 years presenting for initial oncology consult underwent screening geriatric assessment. Patients were determined to be robust, prefrail, or frail via deficit accumulation and phenotypic approaches. We quantified each patient's total number of medications and PIMs using the Anticholinergic Risk Scale (ARS) and a scale we generated using the NCCN Medications of Concern called the Geriatric Oncology Potentially Inappropriate Medications (GO-PIM) scale. We assessed cross-sectional associations of PIMs with frailty in multivariable regression models adjusting for age, gender, and comorbidity. RESULTS: Of 785 patients assessed, 603 (77%) were taking ≥5 medications and 421 (54%) were taking ≥8 medications; 201 (25%) were taking at least 1 PIM based on the ARS and 343 (44%) at least 1 PIM based on the GO-PIM scale. Among the 468 (60%) patients on active cancer treatment, taking ≥8 medications was associated with frailty (adjusted odds ratio [aOR], 2.82; 95% CI, 1.92-4.17). With each additional medication, the odds of being prefrail or frail increased 8% (aOR, 1.08; 95% CI, 1.04-1.12). With each 1-point increase on the ARS, the odds of being prefrail or frail increased 19% (aOR, 1.19; 95% CI, 1.03-1.39); with each additional PIM based on the GO-PIM scale, the odds increased 65% (aOR, 1.65; 95% CI, 1.34-2.04). CONCLUSIONS: Polypharmacy and PIMs are prevalent among older patients with blood cancers; taking ≥8 medications is strongly associated with frailty. These data suggest careful medication reconciliation for this population may be helpful, and deprescribing when possible is high-yield, especially for PIMs on the GO-PIM scale.

Gait speed, survival, and recommended treatment intensity in older adults with blood cancer requiring treatment.

BACKGROUND: Brief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults who have blood cancer; however, little is known about whether such assessments are already captured within oncologists' "gestalt" assessments. METHODS: Gait speed was assessed in 782 patients ≥75 years of age who had blood cancer, with results reported to providers after treatment decisions were made; 408 patients required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN-based categorizations of oncologists' treatment intensity recommendations, including gait speed. RESULTS: The median survival by gait speed category was 10.8 months (<0.4 m/s), 18.6 months (0.4-0.6 m/s), 34.0 months (0.6-0.8 m/s), and unreached (>0.8 m/s). Univariable hazard ratios (HRs) for death increased for each lower category compared with ≥0.8 m/s (0.6-0.8 m/s: HR, 1.76; 0.4-0.6 m/s: HR, 2.30; <0.4 m/s: HR, 3.31). Gait speed predicted survival in multivariable Cox regression (all P < .05). In multivariable models including age, sex, and Eastern Cooperative Oncology Group performance status, gait speed did not predict oncologists' recommended treatment intensity (all P > .05) and did not add to a base model predicting recommended treatment intensity. CONCLUSION: In older adults with blood cancer who presented for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision making may improve optimal treatment selection.

Gait speed, grip strength, and clinical outcomes in older patients with hematologic malignancies.

This study aimed to evaluate whether gait speed and grip strength predicted clinical outcomes among older adults with blood cancers. We prospectively recruited 448 patients aged 75 years and older presenting for initial consultation at the myelodysplastic syndrome/leukemia, myeloma, or lymphoma clinic of a large tertiary hospital, who agreed to assessment of gait and grip. A subset of 314 patients followed for ≥6 months at local institutions was evaluated for unplanned hospital or emergency department (ED) use. We used Cox proportional hazard models calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for survival, and logistic regression to calculate odds ratios (ORs) for hospital or ED use. Mean age was 79.7 (± 4.0 standard deviation) years. After adjustment for age, sex, Charlson comorbidity index, cognition, treatment intensity, and cancer aggressiveness/type, every 0.1-m/s decrease in gait speed was associated with higher mortality (HR, 1.20; 95% CI, 1.12-1.29), odds of unplanned hospitalizations (OR, 1.33; 95% CI, 1.16-1.51), and ED visits (OR, 1.34; 95% CI, 1.17-1.53). Associations held among patients with good Eastern Cooperative Oncology Group performance status (0 or 1). Every 5-kg decrease in grip strength was associated with worse survival (adjusted HR, 1.24; 95% CI, 1.07-1.43) but not hospital or ED use. A model with gait speed and all covariates had comparable predictive power to comprehensive validated frailty indexes (phenotype and cumulative deficit) and all covariates. In summary, gait speed is an easily obtained "vital sign" that accurately identifies frailty and predicts outcomes independent of performance status among older patients with blood cancers.

Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy.

Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer's disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected in the early stages after TBI, and how TBI leads to tauopathy is unknown. Here we find robust cis P-tau pathology after TBI in humans and mice. After TBI in mice and stress in vitro, neurons acutely produce cis P-tau, which disrupts axonal microtubule networks and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, which we term 'cistauosis', appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis P-tau is a major early driver of disease after TBI and leads to tauopathy in chronic traumatic encephalopathy and Alzheimer's disease. The cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury.

A blueprint for success: Using an implementation framework to create a medication history technician pilot program.

BACKGROUND: Medication discrepancies at transitions of care may compromise patient safety. Trained pharmacy technicians can reduce harmful medication discrepancies at transitions of care by collecting medication histories. OBJECTIVE: We describe how to create a program integrating medication history technicians (MHTs) into the hospital discharge process using implementation science. PRACTICE DESCRIPTION: We created our MHT program at a Veterans Affairs (VA) hospital. PRACTICE INNOVATION: We used an evidence-based framework and implementation science to tailor our MHT program to meet local stakeholder needs. EVALUATION METHODS: We completed a literature review and review of current discharge practices. Then, we completed a workflow pilot, a needs assessment, and semistructured interviews with pharmacy technicians and pharmacists. We integrated these findings to identify barriers of MHT program implementation. Finally, we mapped these barriers to implementation strategies to create an MHT program implementation blueprint. RESULTS: The literature review and review of current discharge practices revealed opportunities for our program to reduce medication discrepancies. We applied these findings to our proof-of-concept workflow pilot, which reduced medication discrepancy rates at discharge. When we explored barriers in the needs assessment, we learned that 4 of 6 pharmacy technicians had some training conducting medication histories, but 5 of 6 requested additional training for the new MHT role. We explored these and additional barriers in semistructured interviews. Four themes emerged: elements of pharmacy technician training, challenges to implementation, program logistics and workflow, and pharmacy technician self-efficacy. We mapped barriers to implementation strategies to create an MHT program implementation blueprint, including developing pharmacy technician training materials, modifying our workflow, creating program evaluation materials, and strategizing how to overcome anticipated and current implementation barriers. CONCLUSIONS: We used implementation science to create a tailored MHT program. Others may adapt our implementation blueprint to fit local stakeholder needs.

There's no place like home-Integrating a pharmacist into the hospital-in-home model.

BACKGROUND: Hospital-in-home (HIH) is an innovative model that provides hospital-level care in a patient's home. Pharmacists can enhance the HIH model through medication reconciliation and medication optimization. OBJECTIVES: To integrate a clinical pharmacist into the HIH model and to conduct a formative evaluation of pharmacist contributions, including medication discrepancy resolution, cost savings, and cost avoidance. PRACTICE DESCRIPTION: This is a prospective quality improvement study conducted at the Veterans Affairs Boston Healthcare System. PRACTICE INNOVATION: We integrated a pharmacist into the HIH model. The pharmacist conducted a medication reconciliation at hospital discharge and after discharge through home video telehealth and provided longitudinal medication management. EVALUATION METHODS: We adapted the PRECEDE-PROCEED model to guide program implementation. We conducted a formative evaluation using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, evaluating the reach, efficacy, adoption, and implementation of the pharmacist in the HIH team. We calculated cost savings associated with pharmacist-managed home intravenous (IV) therapy, cost avoidance from deprescribing, and cost avoidance from earlier hospital discharge. RESULTS: The HIH program enrolled 102 patients from May 2019 to March 2020. The pharmacist completed 99 (97%) discharge and 95 (93%) postdischarge medication reconciliations, most of which 71 (75%) were conducted using home video telehealth. The pharmacist identified and resolved a total of 453 medication discrepancies: 181 (40%) at discharge and 272 (60%) during postdischarge medication reconciliation. A total of 84 (19%) discrepancies were considered high risk. The pharmacist managed 104 days of home IV therapy, resulting in a cost savings of approximately $17,000. The cost avoided by identifying and deprescribing 145 inappropriate medications was approximately $51,000. The cost avoided by earlier hospital discharge was $1.2 million. CONCLUSION: Integrating a pharmacist into the HIH model enables the detection and resolution of medication discrepancies. Cost savings from medication deprescribing, cost avoided from pharmacist-managed home IV therapy, and cost avoided from early hospital discharge totaled $1268 million.

Front-Line innovation: Rapid implementation of a nurse-driven protocol for care of outpatients with COVID-19.

AIMS AND OBJECTIVES: Our objective was to rapidly adapt and scale a registered nurse-driven Coordinated Transitional Care (C-TraC) programme to provide intensive home monitoring and optimise care for outpatient Veterans with COVID-19 in a large urban Unites States healthcare system. BACKGROUND: Our diffuse primary care network had no existing model of care by which to provide coordinated result tracking and monitoring of outpatients with COVID-19. DESIGN: Quality improvement implementation project. METHODS: We used the Replicating Effective Programs model to guide implementation, iterative Plan-Do-Study-Act cycles and SQUIRE reporting guidelines. Two transitional care registered nurses, and a geriatrician medical director developed a protocol that included detailed initial assessment, overnight delivery of monitoring equipment and phone-based follow-up tailored to risk level and symptom severity. We tripled programme capacity in time for the surge of cases by training Primary Care registered nurses. RESULTS: Between 23 March and 15 May 2020, 120 Veterans with COVID-19 were enrolled for outpatient monitoring; over one-third were aged 65 years or older, and 70% had medical conditions associated with poor COVID-19 outcomes. All Veterans received an initial call within a few hours of the laboratory reporting positive results. The mean length of follow-up was 8.1 days, with an average of 4.2 nurse and 1.3 physician or advanced practice clinician contacts per patient. The majority (85%) were managed entirely in the outpatient setting. After the surge, the model was disseminated to individual primary care teams through educational sessions. CONCLUSION: A model based on experienced registered nurses can provide comprehensive, effective and sustainable outpatient monitoring to high-risk populations with COVID-19.

Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older.

Importance: Data are limited regarding statin therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults 75 years and older. Objective: To evaluate the role of statin use for mortality and primary prevention of ASCVD in veterans 75 years and older. Design, Setting, and Participants: Retrospective cohort study that used Veterans Health Administration (VHA) data on adults 75 years and older, free of ASCVD, and with a clinical visit in 2002-2012. Follow-up continued through December 31, 2016. All data were linked to Medicare and Medicaid claims and pharmaceutical data. A new-user design was used, excluding those with any prior statin use. Cox proportional hazards models were fit to evaluate the association of statin use with outcomes. Analyses were conducted using propensity score overlap weighting to balance baseline characteristics. Exposures: Any new statin prescription. Main Outcomes and Measures: The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included a composite of ASCVD events (myocardial infarction, ischemic stroke, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention). Results: Of 326 981 eligible veterans (mean [SD] age, 81.1 [4.1] years; 97% men; 91% white), 57 178 (17.5%) newly initiated statins during the study period. During a mean follow-up of 6.8 (SD, 3.9) years, a total 206 902 deaths occurred including 53 296 cardiovascular deaths, with 78.7 and 98.2 total deaths/1000 person-years among statin users and nonusers, respectively (weighted incidence rate difference [IRD]/1000 person-years, -19.5 [95% CI, -20.4 to -18.5]). There were 22.6 and 25.7 cardiovascular deaths per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -3.1 [95 CI, -3.6 to -2.6]). For the composite ASCVD outcome there were 123 379 events, with 66.3 and 70.4 events/1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -4.1 [95% CI, -5.1 to -3.0]). After propensity score overlap weighting was applied, the hazard ratio was 0.75 (95% CI, 0.74-0.76) for all-cause mortality, 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality, and 0.92 (95% CI, 0.91-0.94) for a composite of ASCVD events when comparing statin users with nonusers. Conclusions and Relevance: Among US veterans 75 years and older and free of ASCVD at baseline, new statin use was significantly associated with a lower risk of all-cause and cardiovascular mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD.

Shared genetic architecture between metabolic traits and Alzheimer's disease: a large-scale genome-wide cross-trait analysis.

A growing number of studies clearly demonstrate a substantial link between metabolic dysfunction and the risk of Alzheimer's disease (AD), especially glucose-related dysfunction; one hypothesis for this comorbidity is the presence of a common genetic etiology. We conducted a large-scale cross-trait GWAS to investigate the genetic overlap between AD and ten metabolic traits. Among all the metabolic traits, fasting glucose, fasting insulin and HDL were found to be genetically associated with AD. Local genetic covariance analysis found that 19q13 region had strong local genetic correlation between AD and T2D (P = 6.78 × 10- 22), LDL (P = 1.74 × 10- 253) and HDL (P = 7.94 × 10- 18). Cross-trait meta-analysis identified 4 loci that were associated with AD and fasting glucose, 3 loci that were associated with AD and fasting insulin, and 20 loci that were associated with AD and HDL (Pmeta < 1.6 × 10- 8, single trait P < 0.05). Functional analysis revealed that the shared genes are enriched in amyloid metabolic process, lipoprotein remodeling and other related biological pathways; also in pancreas, liver, blood and other tissues. Our work identifies common genetic architectures shared between AD and fasting glucose, fasting insulin and HDL, and sheds light on molecular mechanisms underlying the association between metabolic dysregulation and AD.

Frailty, Implantable Cardioverter Defibrillators, and Mortality: a Systematic Review.

BACKGROUND: Evidence for the benefit of implantable cardioverter defibrillators (ICD) in preventing sudden cardiac death (SCD) in older adults is mixed; age alone may not predict benefit. Frailty may help identify patients in whom an ICD does not improve overall mortality risk. METHODS: Structured search of PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials on 1/31/2019, without language restriction, with terms for ICD, frailty, and mortality. Frailty was defined broadly using any validated single component (e.g., walking speed, weight loss) or multi-component tool (e.g., cumulative deficit index). Each study was assessed for quality and risk of bias. RESULTS: We identified and screened 2649 titles, reviewed 280 abstracts, and extracted 71 articles. Nine articles, including two RCTs, one prospective cohort, and six retrospective cohort studies met all criteria. The most common reason for exclusion was a lack of frailty definition. Frailty definitions were heterogeneous, including cumulative deficit models, low weight, and walking speed. Follow-up time for mortality differed: from days to > 6 years. All studies indicated that mortality was higher amongst individuals identified as frail, regardless of definition. In one RCT, slow walkers did not benefit from ICD therapy after 3 years. A cohort of 83,792 Medicare beneficiaries in an ICD registry reported higher 1-year mortality following ICD in those with frailty or dementia. Four studies reported an association between being underweight and increased mortality following ICD placement. CONCLUSION: Existing literature suggests that individuals with frailty may not benefit from ICD placement for primary prevention of SCD.

Cancer-related cognitive impairment and associated factors in a sample of older male oral-digestive cancer survivors.

OBJECTIVE: This study examines the demographic and clinical variables associated with cancer-related cognitive impairment (CRCI) in a sample of older, male, oral-digestive cancer survivors at VA Medical Centers in Boston and Houston. METHODS: A two-time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post-diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls. Paired t-tests examined cognitive change over time in the cancer group. Hierarchical linear regression examined variables potentially associated with cognitive impairment at 18 months. RESULTS: Forty-eight percent of cancer patients exhibited cognitive impairment 6 months post-cancer diagnosis, and 40% at 18 months. Cancer survivors were impaired relative to controls on measures of sustained attention, memory, and verbal fluency at 18 months, controlling for age. Older age, low hemoglobin, and cancer-related PTSD were associated with worse cognition at 18 months. CONCLUSIONS: CRCI is more frequent in older adults than reported in studies of younger adults and may be more frequent in men. Potential areas of intervention for CRCI include psychotherapy for cancer-related PTSD, treatment of anemia, and awareness of particularly vulnerable cognitive domains such as sustained attention, memory, and verbal fluency.

Geriatric Rehabilitation Should Not Be an Oxymoron: A Path Forward.

Older adults are the fastest growing segment of our population and contribute greatly to the high costs of health care. The primary concern among older adults seeking health care is maintaining or improving functional independence. This concern is the focus of both rehabilitative care and geriatric medicine; however, collaboration between these fields can be hampered by a lack of mutual understanding of the fundamental principles of the other field. We describe 3 steps that can be implemented at an organizational or individual level to bridge the fields of geriatric medicine and rehabilitation, allowing them to better serve older patients. These include (1) recognizing the interwoven concepts of multimorbidity, function, and frailty; (2) communicating with a common language; and (3) synthesizing our knowledge from both fields.

Investigating the genetic relationship between Alzheimer's disease and cancer using GWAS summary statistics.

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer's disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; r g = 0.17, P = 0.04), and specifically with breast cancer (ER-negative and overall; r g = 0.21 and 0.18, P = 0.035 and 0.034) and lung cancer (adenocarcinoma, squamous cell carcinoma and overall; r g = 0.31, 0.38 and 0.30, P = 0.029, 0.016, and 0.006). Estimating the genetic correlation in specific functional categories revealed mixed positive and negative signals, notably stronger at annotations associated with increased enhancer activity. This suggests a role of gene expression regulators in the shared genetic etiology between AD and cancer, and that some shared variants modulate disease risk concordantly while others have effects in opposite directions. Due to power issues, we did not detect cross-phenotype associations at individual SNPs. This genetic overlap is not likely driven by a handful of major loci. Our study is the first to examine the co-heritability of AD and cancer leveraging large-scale GWAS results. The functional categories highlighted in this study need further investigation to illustrate the details of the genetic sharing and to bridge between different levels of associations.