Identification of complier and noncomplier average causal effects in the presence of latent missing-at-random (LMAR) outcomes: a unifying view and choices of assumptions.

The study of treatment effects is often complicated by noncompliance and missing data. In the one-sided noncompliance setting where of interest are the complier and noncomplier average causal effects, we address outcome missingness of the latent missing at random type (LMAR, also known as latent ignorability). That is, conditional on covariates and treatment assigned, the missingness may depend on compliance type. Within the instrumental variable (IV) approach to noncompliance, methods have been proposed for handling LMAR outcome that additionally invoke an exclusion restriction-type assumption on missingness, but no solution has been proposed for when a non-IV approach is used. This article focuses on effect identification in the presence of LMAR outcomes, with a view to flexibly accommodate different principal identification approaches. We show that under treatment assignment ignorability and LMAR only, effect nonidentifiability boils down to a set of two connected mixture equations involving unidentified stratum-specific response probabilities and outcome means. This clarifies that (except for a special case) effect identification generally requires two additional assumptions: a specific missingness mechanism assumption and a principal identification assumption. This provides a template for identifying effects based on separate choices of these assumptions. We consider a range of specific missingness assumptions, including those that have appeared in the literature and some new ones. Incidentally, we find an issue in the existing assumptions, and propose a modification of the assumptions to avoid the issue. Results under different assumptions are illustrated using data from the Baltimore Experience Corps Trial.

The relationship between older adults' technology use, in-person engagement, and pandemic-related mental health.

OBJECTIVE: The objectives of this study are to 1) describe changes in in-person communication/activity and changes in older adult technology use during the COVID-19 pandemic and 2) examine whether less in-person communication/activity mediates the relationship between pandemic-related mental health and technology use. METHOD: Linear regressions (stratified by age and financial strain) and structural equation modeling were employed using a nationally representative, cross-sectional survey of 3,188 older adults from the 2020 National Health and Aging Trends Study's COVID-19 Questionairre. RESULTS: Older adults engaged in more technology-based activity (b = 0.24; p<.001), more technology-based health care communication (b = 0.22; p<.001), and more technology-based food acquisition (b = 0.21; p<.001) during the COVID-19 pandemic, as compared to before the pandemic. Results indicate that adults <80 years old demonstrated greater increases in technology-based activity, technology-based health communication, and technology-based food acquisition, compared to adults ≥80 years old. Change in in-person communication significantly mediated the relationship between pandemic-related mental health and technology-based communication (standardized coefficient= -0.012; p=.005), and change in in-person activity significantly mediated the relationship between pandemic-related mental health and technology-based activity (standardized coefficient= -0.017; p=.020). CONCLUSIONS: This study suggests that older adults are utilizing technology more, and therefore should be considered in technology design and dissemination. Technology use could be an important positive response to help those with pandemic related worries stay safely engaged with friends and family. Technologies should be produced that are modifiable for older adults with disabilities and affordable for older adults with fixed incomes.

Assessment of hearing and vision impairment in cohort studies collecting cognitive data in older adults.

INTRODUCTION: There are no standard practices for considering sensory impairment in studies measuring cognitive function among older adults. Exclusion of participants with impairments may inaccurately estimate the prevalence of cognitive impairment and dementia. METHODS: We surveyed prospective cohort studies measuring cognitive function in older adults, determined the proportion that excluded participants based on sensory impairment and the proportion that assessed each type of sensory impairment, and described the methods of sensory assessment. RESULTS: Investigators/staff from 85 (of 192 cohorts) responded; 6 (7%) excluded participants with severe impairment; 80 (94%) measured hearing and/or vision impairment, while 5 (6%) measured neither. Thirty-two (38%) cohorts assessed hearing objectively and 45 (53%) assessed vision objectively. DISCUSSION: Findings indicate variation in methods used to assess sensory impairment, with potential implications for resource allocation. To ensure equitable inclusion of study participants, consensus is needed on best practices standardized protocols for assessment and accommodations of sensory impairment.

Cognitive impairment burden in older and younger adults across the kidney transplant care continuum.

BACKGROUND: Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis. METHODS: To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two-center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1-year post-KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL] < 6 or instrumental activities of daily living [IADL] < 8). RESULTS: Among KT candidates, global cognitive impairment (18-34 years: 11.1%; 35-49 years: 14.0%; 50-64 years: 19.5%; ≥65 years: 22.0%) and severe cognitive impairment burden (18-34 years: 1.1%; 35-49 years: 3.0%; 50-64 years: 6.2%; ≥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18-34 years: 9.1%; 35-49 years: 6.1%; 50-64 years: 9.3%; ≥65 years: 15.7%) and severe cognitive impairment burden (18-34 years: 1.4%; 35-49 years: 1.4%; 50-64 years: 2.2%; ≥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1-year post-KT across all ages (18-34 years: 1.7%; 35-49 years: 3.4%; 50-64 years: 4.3%; ≥65 years: 6.5%), many still exhibited severe cognitive impairment (18-34 years: .0%; 35-49 years: 1.9%; 50-64 years: 2.4%; ≥65 years: 3.5%). CONCLUSION: Findings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community-dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age.

Frailty-a risk factor of global and domain-specific cognitive decline among a nationally representative sample of community-dwelling older adult U.S. Medicare beneficiaries.

OBJECTIVES: frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty-cognition link differs by cognitive domain remains unclear; however, it could lend insight into underlying mechanisms. METHODS: we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011-2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test. RESULTS: we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = -0.12 (standard deviations) SD/year, 95%CI: -0.15, -0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: -1.99, -1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: -0.89, -0.69). Associations differed by education for global cognitive function (Pinteraction < 0.001) and for each domain-specific outcome: CDT (Pinteraction < 0.001), orientation (Pinteraction < 0.001), immediate (Pinteraction < 0.001) and delayed (Pinteraction < 0.001) word recalls. CONCLUSION: frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical.

Role of high-resolution peripheral nerve magnetic resonance imaging in diagnosing median nerve tethering in a case of both-bone forearm fracture in a child.

Forearm fractures are common injuries in pediatric patients. We present a case of median nerve tethering as a complication of both-bone forearm fracture in a child, with an emphasis on MRI as an appropriate and important complement to clinical and electrodiagnostic examination. Early intervention is essential because delayed surgical management of median nerve tethering can result in poor clinical outcomes as a result of irreversible muscle denervation. In this case, we highlight the importance of MRI to facilitate management, including early surgical intervention when appropriate, in median neuropathy following forearm fractures.

Hearing impairment and missing cognitive test scores in a population-based study of older adults: The Atherosclerosis Risk in Communities neurocognitive study.

INTRODUCTION: Hearing impairment is associated with poor cognitive test performance in older adults. However, hearing's impact on cognitive test completion is poorly described, and missing cognitive data due to hearing impairment could misestimate the association. METHODS: We investigated if hearing impairment is associated with missing neurocognitive scores in 3678 adults (72-94 years). Hearing impairment was defined by the better-ear pure tone average of speech-frequency thresholds (0.5-4 kHz) >25 decibels. RESULTS: Hearing impairment was associated with greater missingness on all auditory-only tests, including Logical Memory (prevalence ratio [PR] comparing ≥ moderate impairment vs normal hearing:1.68, 95% confidence interval [CI] 1.26, 2.25) and Digits Backwards (PR 1.62; 95% CI 1.21, 2.17); and two non-auditory tests, Boston Naming (PR 1.61; 95% CI 1.21, 2.17) and Trail Making B (PR 1.55; 95% CI 1.29, 1.86). Models that imputed missing cognitive scores showed the strongest hearing-cognition associations. DISCUSSION: Older adults with hearing impairment are less likely to complete cognitive testing, thereby underestimating the hearing impairment-cognition relationship.

Trends in the utilization of a peer-supported youth hotline.

BACKGROUND: Peer-supported youth hotlines have been in operation for many years but studies on the acceptance of this hotline model or on the demographics of the callers are lacking. This study was performed to examine the utilization of a metropolitan peer-supported youth hotline between 2010 and 2016. METHOD: The change in demographics, contact channels, and the reasons for contact were analyzed with standard linear regression analysis in 67,478 contacts over 7 years. RESULTS: The data revealed a significant increase in hotline utilization from 8008 annual contacts in 2010 to 12,409 contacts in 2016 (p = .03). The majority of contacts were made by 15-year-old and 16-year-old girls, but contacts by children aged 13 years old and younger have also increased significantly over the years (p = .003). In 2016, anxiety and stress were among the leading reasons for contact (20.14%), followed by sadness and depression (17.21%), suicidal ideation (14.18%), and self-harm (8.15%). Recommendations for follow-up with outside mental health resources were made in 56.22% of contacts. More than 60% of contacts had found information about the hotline on the Internet. More than 30% used text messaging to reach out to the hotline. CONCLUSIONS: Our data indicate that adolescents increasingly utilize a peer-supported youth hotline to get help for mental health concerns. Therefore, it should be explored whether this hotline model could also be used for prevention and early intervention. KEY PRACTITIONER MESSAGE: Peer-supported youth hotlines are well accepted and frequently utilized by adolescents to get help for mental health issues. Our data indicate that peer-supported youth hotlines could be utilized to identify youth at risk for depression and suicide. Further research should evaluate whether peer-supported youth hotlines could serve in the prevention and in early mental health intervention, and how they could be effectively linked to other mental health resources in the community.

Cognitive Function, Access to Kidney Transplantation, and Waitlist Mortality Among Kidney Transplant Candidates With or Without Diabetes.

RATIONALE & OBJECTIVE: Intact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers. PREDICTORS: Cognitive impairment (3MS score<80). OUTCOMES: Listing, waitlist mortality, and kidney transplantation. ANALYTICAL APPROACH: We estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test. RESULTS: At evaluation, 6.4% of participants had cognitive impairment, which was independently associated with 25% lower chance of listing (adjusted HR, 0.75; 95% CI, 0.61-0.91); this association did not differ by diabetes status (Pinteraction=0.07). There was a nominal difference by diabetes status for the association between cognitive impairment and kidney transplantation rate (Pinteraction=0.05), while the association between cognitive impairment and waitlist mortality differed by diabetes status kidney transplantation rates (Pinteraction=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes. LIMITATIONS: Single measure of cognitive impairment. CONCLUSIONS: Cognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.

Interventions Made to Preserve Cognitive Function Trial (IMPCT) study protocol: a multi-dialysis center 2x2 factorial randomized controlled trial of intradialytic cognitive and exercise training to preserve cognitive function.

BACKGROUND: Kidney disease and dialysis significantly impact cognitive function across the age spectrum. Cognitive training (CT) and/or exercise training (ET) are promising approaches to preserve cognitive function among community-dwelling older adults, but have not been tested for cognition preservation in hemodialysis patients of all ages. In this manuscript, we summarize the protocol for the Interventions Made to Preserve Cognitive Function Trial (IMPCT). METHODS: We will perform a 2 × 2 factorial randomized controlled trial (RCT) of eligible adult (≥18 years) hemodialysis initiates (n = 200) to test whether intradialytic CT (brain games on a tablet PC), ET (foot peddlers) and combined CT + ET while undergoing hemodialysis preserves executive function compared to standard of care (SC). Participants will engage in the interventions to which they are randomized for 6 months. The primary objective is to compare, among interventions, the 3-month change in executive function measured using the Trail Making Test A (TMTA) and B (TMTB); specifically, executive function is calculated as TMTB-TMTA to account for psychomotor speed. This primary outcome was selected based on findings from our pilot study. The secondary objectives are to compare the risk of secondary cognitive outcomes, ESKD-specific clinical outcomes, and patient-centered outcomes at 3-months and 6-months. All data collection and interventions are conducted in the dialysis center. DISCUSSION: We hypothesize that receiving intradialytic CT or ET will better preserve executive function than SC but receiving combined CT + ET, will be the most effective intervention. The current trial will be an important step in understanding how intradialytic interventions might preserve cognitive health. TRIAL REGISTRATION: Clinicaltrials.Gov (Date: 8/6/18): # NCT03616535 . Protocol Version: 10 (April 2020). FUNDING: NIDDK R01DK114074.

Frailty and Changes in Cognitive Function after Kidney Transplantation.

BACKGROUND: Restoration of kidney function after kidney transplant generally improves cognitive function. It is unclear whether frail recipients, with higher susceptibility to surgical stressors, achieve such post-transplant cognitive improvements or whether they experience subsequent cognitive decline as they age with a functioning graft. METHODS: In this two-center cohort study, we assessed pretransplant frailty (Fried physical frailty phenotype) and cognitive function (Modified Mini-Mental State Examination) in adult kidney transplant recipients. To investigate potential short- and medium-term effects of frailty on post-transplant cognitive trajectories, we measured cognitive function up to 4 years post-transplant. Using an adjusted mixed effects model with a random slope (time) and intercept (person), we characterized post-transplant cognitive trajectories by pretransplant frailty, accounting for nonlinear trajectories. RESULTS: Of 665 recipients (mean age 52.0 years) followed for a median of 1.5 years, 15.0% were frail. After adjustment, pretransplant cognitive scores were significantly lower among frail patients compared with nonfrail patients (89.0 versus 90.8 points). By 3 months post-transplant, cognitive performance improved for both frail (slope =0.22 points per week) and nonfrail (slope =0.14 points per week) recipients. Between 1 and 4 years post-transplant, improvements plateaued among nonfrail recipients (slope =0.005 points per week), whereas cognitive function declined among frail recipients (slope =-0.04 points per week). At 4 years post-transplant, cognitive scores were 5.8 points lower for frail recipients compared with nonfrail recipients. CONCLUSIONS: On average, both frail and nonfrail recipients experience short-term cognitive improvement post-transplant. However, frailty is associated with medium-term cognitive decline post-transplant. Interventions to prevent cognitive decline among frail recipients should be identified.

The association of a novel cognitive frailty index and physical functioning in older at-risk adults.

Objectives: Cognitive frailty is a state at the lower end of the continuum of cognitive resilience in which one is at elevated risk for cognitive impairment and dementia. Metrics of a newly developed Cognitive Frailty Index (CFI) were examined for their association with objective functional limitations.Methods: We used baseline data from 607 participants from the Baltimore Experience Corps Trial with measures on the CFI, a computerized Stroop test, and Short Physical Performance Battery (SPPB) score ≤9. Multivariable log-binomial regression models were used to evaluate the associations of CFI metrics (mean reaction time (RT) for total, first-half and second-half trials per condition) with the SPPB. Latent growth models were used to create additional CFI metrics of initial level (intercept) and change (slope) in RT across accurate trials by easy (Color-X) and difficult (Color-Word) conditions. Models were adjusted for race, sex, age, income, major morbidities, depressive symptoms, self-reported health, and Stroop interference (for Color-Word condition only).Results: All CFI RT metrics were associated with SPPB <9, yet latent growth model approaches were most informative. Initial levels of performance on easy (Risk Ratio, [RR] = 1.24; 95% Confidence Interval, [CI]: 1.03, 1.49) and difficult conditions (RR = 1.22; 95% CI: 1.05, 1.41), not rates of learning (slope) (RR = 1.08, 95% CI: 0.81, 1.45 and RR = 1.11, 95% CI: 0.96, 1.27 respectively), were associated with worse physical functioning.Conclusions: The association between the CFI and physical functioning demonstrates the interplay of cognitive frailty and worse objective mobility within a sociodemographic at-risk sample.

Self-reported Lifestyle Activities in Relation to Longitudinal Cognitive Trajectories.

BACKGROUND: Few studies have examined the relationship between lifestyle activity engagement and cognitive trajectories among individuals who were cognitively normal at baseline. OBJECTIVE: To examine the relationship of current engagement in lifestyle activities to previous cognitive performance among individuals who were cognitively normal at baseline, and whether this relationship differed for individuals who subsequently developed mild cognitive impairment (MCI), or by APOE-4 genotype, age, and level of cognitive reserve. METHODS: Participants (N=189) were primarily middle-aged (M=56.6 y) at baseline and have been prospectively followed with annual assessments (M follow-up=14.3 y). Engagement in physical, cognitive, and social activities was measured by the CHAMPS activity questionnaire. Longitudinal cognitive performance was measured by a global composite score. RESULTS: Among individuals who progressed to MCI (n=27), higher lifestyle activity engagement was associated with less decline in prior cognitive performance. In contrast, among individuals who remained cognitively normal, lifestyle activity engagement was not associated with prior cognitive trajectories. These effects were largely independent of APOE-4 genotype, age, and cognitive reserve. CONCLUSIONS: Greater engagement in lifestyle activities may modify the rate of cognitive decline among those who develop symptoms of MCI, but these findings need to be confirmed in prospective studies.

Incidence, Risk Factors, and Sequelae of Post-kidney Transplant Delirium.

Background Frail kidney transplant (KT) recipients may be particularly vulnerable to surgical stressors, resulting in delirium and subsequent adverse outcomes. We sought to identify the incidence, risk factors, and sequelae of post-KT delirium.Methods We studied 125,304 adult KT recipients (1999-2014) to estimate delirium incidence in national registry claims. Additionally, we used a validated chart abstraction algorithm to identify post-KT delirium in 893 adult recipients (2009-2017) from a cohort study of frailty. Delirium sequelae were identified using adjusted logistic regression (length of stay ≥2 weeks and institutional discharge [skilled nursing or rehabilitation facility]) and adjusted Cox regression (death-censored graft loss and mortality).Results Only 0.8% of KT recipients had a delirium claim. In the cohort study, delirium incidence increased with age (18-49 years old: 2.0%; 50-64 years old: 4.6%; 65-75 years old: 9.2%; and ≥75 years old: 13.8%) and frailty (9.0% versus 3.9%); 20.0% of frail recipients aged ≥75 years old experienced delirium. Frailty was independently associated with delirium (odds ratio [OR], 2.05; 95% confidence interval [95% CI], 1.02 to 4.13; P=0.04), but premorbid global cognitive function was not. Recipients with delirium had increased risks of ≥2-week length of stay (OR, 5.42; 95% CI, 2.76 to 10.66; P<0.001), institutional discharge (OR, 22.41; 95% CI, 7.85 to 63.98; P<0.001), graft loss (hazard ratio [HR], 2.73; 95% CI, 1.14 to 6.53; P=0.03), and mortality (HR, 3.12; 95% CI, 1.76 to 5.54; P<0.001).Conclusions Post-KT delirium is a strong risk factor for subsequent adverse outcomes, yet it is a clinical entity that is often missed.

Impact of Experience Corps® Participation on Children's Academic Achievement and School Behavior.

This article reports on the impact of the Experience Corps® (EC) Baltimore program, an intergenerational, school-based program aimed at improving academic achievement and reducing disruptive school behavior in urban, elementary school students in Kindergarten through third grade (K-3). Teams of adult volunteers aged 60 and older were placed in public schools, serving 15 h or more per week, to perform meaningful and important roles to improve the educational outcomes of children and the health and well-being of volunteers. Findings indicate no significant impact of the EC program on standardized reading or mathematical achievement test scores among children in grades 1-3 exposed to the program. K-1st grade students in EC schools had fewer principal office referrals compared to K-1st grade students in matched control schools during their second year in the EC program; second graders in EC schools had fewer suspensions and expulsions than second graders in non-EC schools during their first year in the EC program. In general, both boys and girls appeared to benefit from the EC program in school behavior. The results suggest that a volunteer engagement program for older adults can be modestly effective for improving selective aspects of classroom behavior among elementary school students in under-resourced, urban schools, but there were no significant improvements in academic achievement. More work is needed to identify individual- and school-level factors that may help account for these results.

The Use of Three-Dimensional Printing for Complex Scaphoid Fractures.

Scaphoid fractures are one of the most common fractures treated by hand surgeons. The complex anatomy and size of the scaphoid bone can make the reduction and fixation of these fractures technically challenging. Careful preoperative planning is required to ensure stable fixation is achieved. We report on the use of 3-dimensional printing to improve preoperative planning for a series of complex scaphoid fractures.

Blood amyloid levels and risk of dementia in the Ginkgo Evaluation of Memory Study (GEMS): A longitudinal analysis.

INTRODUCTION: Both high or low plasma amyloid levels have been associated with risk of dementia in nondemented subjects. METHODS: We examined baseline plasma ß-amyloid (Aß) levels in relationship to incident dementia during a period of 8.5 years in 2840 subjects age >75 years; 2381 were cognitively normal (CN) and 450 mild cognitive impairment. RESULTS: Increased plasma Aß1-40 and Aß1-42 levels were associated with gender (women), age, low education, creatinine levels, history of stroke, and hypertension. CN participants who developed dementia had lower levels of Aß1-42 and Aß1-42/Aß1-40 ratio compared with those who did not. Aß levels did not predict dementia in mild cognitive impairment participants. DISCUSSION: There was an inverse association between Aß1-42 and Aß1-42/Aß1-40 ratio to risk of dementia in CN participants. Cerebral and cardiovascular disease and renal function are important determinants of increased Aß levels and must be considered in evaluations of relationship of plasma Aß and subsequent risk of dementia.

Late-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia.

OBJECTIVE: To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution's magnitude. METHODS: Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (N = 2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores ≥8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D. RESULTS: Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12% faster time to MCI/dementia (time ratio [TR]: 0.88; 95% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95% CI: 0.88, 0.97); 64.5% of the total effect was mediated by late-life depressive symptoms. CONCLUSIONS: These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

Discordance between ICD-Coded Myocardial Infarction and Diagnosis according to the Universal Definition of Myocardial Infarction.

BACKGROUND: International Classification of Diseases (ICD) coding is the standard diagnostic tool for healthcare management. At present, type 2 myocardial infarction (T2MI) classification by the Universal Definition of Myocardial Infarction (MI) remains ignored in the ICD system. We determined the concordance for the diagnosis of MI using ICD-9 coding vs the Universal Definition. METHODS: Cardiac troponin I (cTnI) was measured by both contemporary (cTnI) and high-sensitivity (hs-cTnI) assays in 1927 consecutive emergency department (ED) patients [Use of TROPonin In Acute coronary syndromes (UTROPIA) cohort] who had cTnI ordered on clinical indication. All patients were adjudicated using both contemporary and hs-cTnI assays. The Kappa index and McNemar test were used to assess concordance between ICD-9 code 410 and type 1 MI (T1MI) and type 2 MI (T2MI). RESULTS: Among the 249 adjudicated MIs using the contemporary cTnI, only 69 (28%) were ICD-coded MIs. Of 180 patients not ICD coded as MI, 34 (19%) were T1MI and 146 (81%) were T2MI. For the ICD-coded MIs, 79% were T1MI and 21% were T2MI. A fair Kappa index, 0.386, and a McNemar difference of 0.0892 (P < 0.001) were found. Among the 207 adjudicated MIs using the hs-cTnI assay, 67 (32%) were ICD coded as MI. Of the 140 patients not ICD coded as MI, 27 (19%) were T1MI and 113 (81%) were T2MI. For the ICD-coded MIs, 85% were T1MI and 15% T2MI. A moderate Kappa index, 0.439, and a McNemar difference of 0.0674 (P < 0.001) were found. CONCLUSIONS: ICD-9-coded MIs captured only a small proportion of adjudicated MIs, primarily from not coding T2MI. Our findings emphasize the need for an ICD code for T2MI.

Diagnostic Performance of High Sensitivity Compared with Contemporary Cardiac Troponin I for the Diagnosis of Acute Myocardial Infarction.

BACKGROUND: We examined the diagnostic performance of high-sensitivity cardiac troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction (MI) and serial changes (deltas) to rule in MI. METHODS: We included consecutive patients presenting to a US emergency department with serial cTnI onclinical indication. Diagnostic performance for acute MI, including MI subtypes, and 30-day outcomes were examined. RESULTS: Among 1631 patients, MI was diagnosed in 12.9% using the contemporary cTnI assay and in 10.4% using the hs-cTnI assay. For ruling out MI, contemporary cTnI ≤99th percentile at 0, 3, and 6 h and a normal ECG had a negative predictive value (NPV) of 99.5% (95% CI, 98.6-100) and a sensitivity of 99.1% (95% CI, 97.4-100) for diagnostic and safety outcomes. Serial hs-cTnI measurements ≤99th percentile at 0 and 3 h and a normal ECG had an NPV and sensitivity of 100% (95% CI, 100-100) for diagnostic and safety outcomes. For ruling in MI, contemporary cTnI measurements had specificities of 84.4% (95% CI, 82.5-86.3) at presentation and 78.7% (95% CI, 75.4-82.0) with serial testing at 0, 3, and 6 h, improving to 89.2% (95% CI, 87.1-91.3) by using serial cTnI changes (delta, 0 and 6 h) >150%. hs-cTnI had specificities of 86.9% (95% CI, 85.1-88.6) at presentation and 85.7% (95% CI, 83.5-87.9) with serial testing at 0 and 3 h, improving to 89.3% (95% CI, 87.3-91.2) using a delta hs-cTnI (0 and 3 h) >5 ng/L. CONCLUSIONS: hs-cTnI and contemporary cTnI assays are excellent in ruling out MI following recommendations predicated on serial testing and the 99th percentile with a normal ECG. For ruling in MI, deltas improve the specificity. ClinicalTrials.gov Identifier: NCT02060760.