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Delirium is a debilitating medical condition that disproportionately affects hospitalized older adults(1) and is associated with adverse health outcomes, increased mortality, and high medical costs.(2) Efforts to understand delirium risk in hospitalized older adults have focused on examining medical comorbidities, pre-existing cognitive deficits, and other clinical and demographic factors present in the period proximate to the hospitalization.(3,4) The contribution of social determinants of health (SDOH), including social circumstances, environmental characteristics, and early-life exposures, referred as the social exposome,(5) to delirium risk are poorly understood. Increased knowledge about the influence of SDOH will offer a more comprehensive understanding of factors that may increase vulnerability to delirium and poor outcomes. Clinically, these efforts can guide the development and implementation of holistic preventive strategies to improve clinical outcomes. We propose a social determinants of health (SDOH) framework for delirium tailored to older adults. We provide the definition, description, and rationale for the domains and variables in our proposed model.

Background and ObjectivesAndexanet alfa was recently approved as a reversal agent for the factor Xa inhibitors (FXais) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. We aimed to explore potential clinical implications of andexanet alfa in FXai-associated ICH in this simulation study.MethodsWe simulated potential downstream implications of andexanet alfa across a range of possible hemostatic effects using data from a single center that treats FXai-associated ICH with prothrombin complex concentrate (PCC). We determined baseline probabilities of inadequate hemostasis across patients taking FXai and those not taking FXai via multivariable regression models and then determined the probabilities of unfavorable 3-month outcome (modified Rankin Scale score 4–6) using models comprising established predictors and each patient's calculated probability of inadequate hemostasis. We applied bootstrapping with model parameters from this derivation cohort to simulate a range of hemostatic improvements and corresponding outcomes and then calculated absolute risk reduction (relative to PCC) and projected number needed to treat (NNT) to prevent 1 unfavorable outcome.ResultsTraining models using real-world patients (n = 603 total, 55 on FXai) had good accuracy in predicting inadequate hemostasis (area under the curve [AUC] 0.78) and unfavorable outcome (AUC 0.78). Inadequate hemostasis was strongly associated with unfavorable outcome (odds ratio 4.5, 95% confidence interval [CI] 2.0–9.9) and occurred in 11.4% of patients taking FXai. Across simulated patients taking FXai comparable to those in A Study in Participants With Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4) study, predicted absolute risk reduction of unfavorable outcome was 4.9% (95% CI 1.3%–7.8%) when the probability of inadequate hemostasis was reduced by 33% and 7.4% (95% CI 2.0%–11.9%) at 50% reduction, translating to projected NNT of 21 (cumulative cost $519,750) and 14 ($346,500), respectively.DiscussionEven optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered. Placebo-controlled randomized trials are needed before its use can definitively be recommended.

Purpose To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury. Materials and methods We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring 24 h after presentation (“later-onset”). Results Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5–7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1–8.2]), and troponin (OR 3.0 [95% CI 1.2–7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients. Conclusions Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.

Background/objectives Delirium manifests clinically in varying ways across settings. More than 40 instruments currently exist for characterizing the different manifestations of delirium. We evaluated all delirium identification instruments according to their psychometric properties and frequency of citation in published research. Design We conducted the systematic review by searching Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Excerpta Medica Database (Embase), PsycINFO, PubMed, and Web of Science from January 1, 1974, to January 31, 2020, with the keywords "delirium" and "instruments," along with their known synonyms. We selected only systematic reviews, meta-analyses, or narrative literature reviews including multiple delirium identification instruments. Measurements Two reviewers assessed the eligibility of articles and extracted data on all potential delirium identification instruments. Using the original publication on each instrument, the psychometric properties were examined using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) framework. Results Of 2,542 articles identified, 75 met eligibility criteria, yielding 30 different delirium identification instruments. A count of citations was determined using Scopus for the original publication for each instrument. Each instrument underwent methodological quality review of psychometric properties using COSMIN definitions. An expert panel categorized key domains for delirium identification based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III through DSM-5. Four instruments were notable for having at least two of three of the following: citation count of 200 or more, strong validation methodology in their original publication, and fulfillment of DSM-5 criteria. These were, alphabetically, Confusion Assessment Method, Delirium Observation Screening Scale, Delirium Rating Scale-Revised-98, and Memorial Delirium Assessment Scale. Conclusion Four commonly used and well-validated instruments can be recommended for clinical and research use. An important area for future investigation is to harmonize these measures to compare and combine studies on delirium.

Background Evaluating the long-term health consequences of migration requires longitudinal data on migrants and non-migrants to facilitate adjustment for time-varying confounder-mediators of the effect of migration on health. Methods We merged harmonized data on subjects aged 50+ from the US-based Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS). Our exposed group includes MHAS-return migrants (n = 1555) and HRS Mexican-born migrants (n = 924). Our unexposed group includes MHAS-never migrants (n = 16,954). We constructed a lifecourse data set from birth (age 0) until either age at migration to the United States or age at study entry. To account for confounding via inverse probability of treatment weights (IPTW), we modeled the probability of migration at each year of life using time-varying pre-migration characteristics. We then evaluated the effect of migration on mortality hazard estimated with and without IPTW. Results Mexico to the United States migration was predicted by time-varying factors that occurred before migration. Using measured covariates at time of enrollment to account for selective migration, we estimated that, for women, migrating reduces mortality risk by 13%, although this estimate was imprecise and results were compatible with either large protective or deleterious associations (hazard ratio [HR] =0.87, 95% confidence interval [CI]: 0.60, 1.27). When instead using IPTWs, the estimated effect on mortality was similarly imprecise (HR = 0.98, 95% CI: 0.77, 1.25). The relationship among men was similarly uncertain in both models. Conclusions Although time-varying social factors predicted migration, IPTW weighting did not affect our estimates. Larger samples are needed to precisely estimate the health effects of migration.

Rationale: Delirium severity and duration are independently associated with higher mortality and morbidity. No studies to date have described a delirium trajectory by integrating both severity and duration. Objectives: The primary aim was to develop delirium trajectories by integrating symptom severity and duration. The secondary aim was to investigate the association among trajectory membership, clinical characteristics, and 30-day mortality. Methods: A secondary analysis of the PMD (Pharmacologic Management of Delirium) randomized control trial (ClinicalTrials.gov Identifier: NCT00842608; N = 531) was conducted. The presence of delirium and symptom severity were measured at least daily for 7 days using the Confusion Assessment Method for the intensive care unit (CAM-ICU) and CAM-ICU-7 (on a scale of 0–7, with 7 being the most severe). Delirium trajectories were defined using an innovative, data-driven statistical method (group-based trajectory modeling [GBTM]) and SAS v9.4. Results: A total of 531 delirious participants (mean age 60 yr [standard deviation = 16], 55% female, and 46% African American) were analyzed. Five distinct delirium trajectories were described (CAM-ICU-7: mean [standard deviation]); mild-brief (CAM-ICU-7: 0.5 [0.5]), severe-rapid recovers (CAM-ICU-7: 2.1 [1.0]), mild-accelerating (CAM-ICU-7: 2.2 [0.9]), severe-slow recovers (CAM-ICU-7: 3.9 [0.9]), and severe-nonrecovers (CAM-ICU-7: 5.9 [1.0]). Baseline cognition and race were associated with trajectory membership. Trajectory membership independently predicted 30-day mortality while controlling for age, sex, race, cognition, illness severity, and comorbidities. Conclusions: This secondary analysis described five distinct delirium trajectories based on delirium symptom severity and duration using group-based trajectory modeling. Trajectory membership predicted 30-day mortality.

Objectives Compare longitudinal trajectories of youth with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Bipolar Disorder (BD), grouped at baseline by presence/absence of increased energy during their worst lifetime mood episode (required for DSM-5). Methods Participants from the parent Course and Outcome of Bipolar Youth study (N = 446) were assessed utilizing The Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS), KSADS Mania Rating Scale (KMRS), and KSADS Depression Rating Scale (KDRS). Youth were grouped at baseline into those with increased energy (meeting DSM-5 Criteria A for mania) vs. without increased energy (meeting DSM-IV, but not DSM-5, Criteria A for mania), for those who had worst lifetime mood episode recorded (n = 430). Youth with available longitudinal data had the presence/absence of increased energy measured, as well as psychiatric symptomatology/clinical outcomes (evaluated via the Adolescent Longitudinal Interval Follow-Up Evaluation), at each follow-up for 12.5 years (n = 398). Results At baseline, the increased energy group (based on endorsed increased energy during worst lifetime mood episode; 86% of participants) vs. the without increased energy group, were more likely to meet criteria for BD-I and BD Not Otherwise Specified, had higher KMRS/KDRS total scores, and displayed poorer family/global psychosocial functioning. However, frequency of increased energy between groups was comparable after 5 years, and no significant group differences were found on clinical/psychosocial functioning outcomes after 12.5 years. Limitations Secondary data limited study design; groupings were based on one time point. Conclusions Results indicate no clinically relevant longitudinal group differences.

OBJECTIVES We examined the association between delirium severity and outcomes of delirium among persons with and without Alzheimer's disease and related dementias (ADRD). DESIGN Prospective cohort study. SETTING Academic tertiary medical center. PARTICIPANTS A total of 352 medical and surgical patients. MEASUREMENTS Delirium incidence and severity were rated daily using the Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) score during hospitalization. Severe delirium was defined as a CAM-S Short Form score in the highest tertile (3-7 points out of 7). ADRD status was determined by a clinical consensus process. Clinical outcomes included prolonged length of stay (>6 d), discharge to post-acute nursing facility, any decline in activities of daily living (ADLs) at 1 month from prehospital baseline, ongoing nursing facility stay, and mortality. RESULTS Patients with ADRD (n = 85 [24%]) had a significantly higher relative risk (RR) for incident delirium (RR = 2.31; 95% confidence interval [CI] = 1.64-3.28) and higher peak CAM-S scores (mean difference = 1.24 points; CI = .83-1.65; P

Background: Delirium is a common and preventable geriatric syndrome. Moving beyond the binary classification of delirium present/absent, delirium severity represents a potentially important outcome for evaluating preventive and treatment interventions and tracking the course of patients. Although several delirium severity assessment tools currently exist, most have been developed in the absence of advanced measurement methodology and have not been evaluated with rigorous validation studies. Objective: We aimed to report our development of new delirium severity items and the results of item reduction and selection activities guided by psychometric analysis of data derived from a field study. Methods: Building on our literature review of delirium instruments and expert panel process to identify domains of delirium severity, we adapted items from existing delirium severity instruments and generated new items. We then fielded these items among a sample of 352 older hospitalized patients. Results: We used an expert panel process and psychometric data analysis techniques to narrow a set of 303 potential items to 17 items for use in a new delirium severity instrument. The 17-item set demonstrated good internal validity and favorable psychometric characteristics relative to comparator instruments, including the Confusion Assessment Method – Severity (CAM-S) score, the Delirium Rating Scale Revised 98, and the Memorial Delirium Assessment Scale. Conclusion: We more fully conceptualized delirium severity and identified characteristics of an ideal delirium severity instrument. These characteristics include an instrument that is relatively quick to administer, is easy to use by raters with minimal training, and provides a severity rating with good content validity, high internal consistency reliability, and broad domain coverage across delirium symptoms. We anticipate these characteristics to be represented in the subsequent development of our final delirium severity instrument.

Rhythmic neural activity has been proposed to play a fundamental role in cognition. Both healthy and pathological aging are characterized by frequency-specific changes in oscillatory activity. However, the cognitive relevance of these changes across the spectrum from normal to pathological aging remains unknown. We examined electroencephalography (EEG) correlates of cognitive function in healthy aging and 2 of the most prominent and debilitating age-related disorders: type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Relative to healthy controls (HC), patients with AD were impaired on nearly every cognitive measure, whereas patients with T2DM performed worse mainly on learning and memory tests. A continuum of alterations in resting-state EEG was associated with pathological aging, generally characterized by reduced alpha (α) and beta (β) power (ADT2DMHC) and increased delta (δ) and theta (θ) power (ADT2DMHC), with some variations across different brain regions. There were also reductions in the frequency and power density of the posterior dominant rhythm in AD. The ratio of (α + β)/(δ + θ) was specifically associated with cognitive function in a domain- and diagnosis-specific manner. The results thus captured both similarities and differences in the pathophysiology of cerebral oscillations in T2DM and AD. Overall, pathological brain aging is marked by a shift in oscillatory power from higher to lower frequencies, which can be captured by a single cognitively relevant measure of the ratio of (α + β) over (δ + θ) power.

The current study examined the association of patient factors, patient/caregiver relationships, and living arrangements with caregiver burden due to delirium. The sample included a subset ( N = 207) of hospitalized medical and surgical patients (aged >70 years) enrolled in the Better Assessment of Illness Study and their care-givers. The majority of caregivers were female (57%) and married (43%), and 47% reported living with the patient. Delirium occurred in 22% of the sample, and delirium severity, pre-existing cognitive impairment, and impairment of any activities of daily living (ADL) were associated with higher caregiver burden. However, only the ADL impairment of needing assistance with transfers was independently significantly associated with higher burden ( p < 0.01). Child, child-in-law, and other relatives living with or apart from the patient reported significantly higher caregiver burden compared to spouse/partners ( p < 0.01), indicating caregiver relationship and living arrangement are associated with burden. Future studies should examine additional factors contributing to delirium burden. [ Journal of Gerontological Nursing, 47 (9), 32–39.]

Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1-2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample.

Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD.Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors.Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity.iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.

OBJECTIVES To measure the burden of delirium in older adults with or without Alzheimer disease or related disorders (ADRDs). DESIGN Prospective, observational cohort. SETTING Inpatient hospital and study participants' homes. PARTICIPANTS A subset (n = 267) of older medical and surgical patients and their caregivers enrolled in the Better Assessment of Illness study. MEASUREMENTS Delirium burden was measured using the DEL-B instrument (range = 0-40, with higher scores indicating greater burden) in caregivers (DEL-B-C) and patients 1 month after hospitalization. Severity of cognitive impairment (Montreal Cognitive Assessment [MoCA]), delirium presence (Confusion Assessment Method [CAM]), and delirium severity (CAM-Severity [CAM-S]) were measured during hospitalization and at 1-month follow-up. ADRD diagnosis was determined by a clinical consensus process. RESULTS For patients with (n = 56) and without (n = 211) ADRD, both DEL-B instruments had good internal consistency. DEL-B-C scores had a median (interquartile range) among caregivers of patients with and without ADRD of 9 (5-15) and 5 (1-11), respectively (P

Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is NewBackgroundPostoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up.MethodsThis study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months.ResultsOne hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09).ConclusionsDelirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

INTRODUCTION: Many patients with advanced dementia and Parkinson’s disease and related disorders (PDRD) are receiving gastrostomy tube (GT) placement annually, despite its lack of proven benefit for preventing aspiration, enhancing nutrition, or prolonging survival. Given clinical practice variability in the care of people with neurodegenerative disorders, we sought to examine racial and geographic disparities in GT placement for these populations in the United States. METHOD: Data were extracted from a nationally available database using diagnostic and procedural codes from 2006 to 2010. GT placement rates and odds ratios were calculated for two groups: PDRD and non-parkinsonian dementia (NPD). RESULTS: In the PDRD group, odds of GT placement were higher among patients coded as Black (OR 1.69, CI .80-3.56, p=.17) and Asian (OR 2.17, CI 0.70-6.78, p=.18) than Whites; although these tendencies did not reach statistical significance. In the NPD group, GT placement among Black patients was significantly more likely (OR 2.88, CI 1.90-4.36, p

Background: Andexanet alfa was recently approved as a reversal agent for the Factor Xa inhibitors (FXai) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. Methods: We performed a simulation study to determine the potential clinical implications of andexanet alfa across a range of possible hemostatic effects using data from a single-center cohort of ICH patients who did not receive the drug. We used this data to determine the baseline probability of insufficient hemostatic efficacy (IHE) across patients with and without FXai use via k-fold cross-validated multivariable regression models, which we aggregated into an IHE propensity score. We then determined the probability of unfavorable 3-month outcome (modified Rankin Scale 4-6) using a model comprised of established clinical predictors and IHE propensity. We applied model parameters from this derivation cohort to simulate a range of IHE reductions and corresponding outcomes, which we used to calculate absolute risk reduction (ARR) and projected number needed to treat (NNT) to prevent one unfavorable outcome. Results: Training models using a real-world ICH cohort (n=604 total; 55 FXai patients) had good accuracy in predicting IHE (AUC 0.78) and unfavorable outcome (AUC 0.82). IHE was strongly associated with unfavorable outcome (OR 6.7, 95% CI 3.8-11.8) and occurred in 11.4% of FXai patients. Predicted ARR of unfavorable outcome was 5% (95% CI 3-8%) at one-third reduction of IHE and 8% (95% CI = 4-13%) at 50% IHE reduction, translating to a projected NNT of 20 (cumulative treatment cost $495,000) and 13 ($321,750), respectively. Conclusion: Even optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered, and placebo-controlled randomized trials are needed before its use can definitively be recommended.

Purpose Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health. Methods We pooled data from the Mexican Health and Aging Study (N = 17,771) and Mexican-born U.S. Health and Retirement Study (N = 898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration. Results Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95% CI: 0.89, 1.08]) and women (ratio of average symptom-count = 1.00 [95% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood. Conclusions In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms.

Introduction The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity. Methods Participants (n = 59) were free of clinical dementia, age ≥70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme‐linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were A = amyloid beta (Aβ)42 80 pg/mL; and N = t‐tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM‐Severity (CAM‐S) were rated daily post‐operatively for delirium and delirium severity, respectively. Results Aβ42, tau, and p‐tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM‐S [mean difference (95% confidence interval)] was 1.48 points higher (0.29‐2.67), P = 0.02 among the ATN positive. Delirium in the ATN‐positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM‐S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM‐S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM‐S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM‐S scores. Discussion The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre‐clinical phase, in delirium.

Introduction Our goal was to determine if features of surgical patients, easily obtained from the medical chart or brief interview, could be used to predict those likely to experience more rapid cognitive decline following surgery. Methods We analyzed data from an observational study of 560 older adults (≥70 years) without dementia undergoing major elective non‐cardiac surgery. Cognitive decline was measured using change in a global composite over 2 to 36 months following surgery. Predictive features were identified as variables readily obtained from chart review or a brief patient assessment. We developed predictive models for cognitive decline (slope) and predicting dichotomized cognitive decline at a clinically determined cut. Results In a hold‐out testing set, the regularized regression predictive model achieved a root mean squared error (RMSE) of 0.146 and a model r‐square (R2) of .31. Prediction of “rapid” decliners as a group achieved an area under the curve (AUC) of .75. Conclusion Some of our models could predict persons with increased risk for accelerated cognitive decline with greater accuracy than relying upon chance, and this result might be useful for stratification of surgical patients for inclusion in future clinical trials.

Highlights • Rate of gastrostomy tube down trended during the study period. • Thousands of patients are still undergoing gastrostomy tube placement. • Gastrostomy tube is associated with longer hospital stay. • Gastrostomy tube is associated with a higher odds of discharge to nursing facility., Introduction Dysphagia causing aspiration pneumonia is a common complication in the advanced stages of neurodegenerative disorders. Historically, physicians attempted to prevent this complication with gastrostomy tube (GT) placement. Its use is supported in amyotrophic lateral sclerosis (ALS), not supported in Alzheimer’s disease (AD), and without disease-specific guidelines in Parkinson’s disease (PD). Method The rate of GT placement in these three populations over two decades, from 1990 to 2010, was calculated using a binomial regression model with the data extracted using diagnosis and procedural codes from a national database. The median length-of-stay (LOS) and discharge destinations were compared. Results The rate of GT placement was 6.0% lower annually in AD, 3.4% in PD, and 0.2% in ALS (all p ≤ 0.007). The analysis of hospital LOS and discharge destination showed 3.2 to 5.5 days longer LOS with GT placement in all groups (all p ≤ 0.01), and three to four times lower odds of going home with GT placement in AD and PD groups (OR 0.28, 95% CI 0.14–0.55, and OR 0.22, CI 0.11–0.42 respectively), while unchanged in ALS group (OR 1.1, 95% CI 0.6–1.9). Conclusion Despite the downward trend of GT placement over two decades, thousands of AD and PD patients still underwent GT placement annually, and this was associated with longer LOS in all groups and increased likelihood of being discharged to a nursing facility in AD and PD. Further research is necessary to understand the effects of GT on physician practices and patient expectations in advanced AD and PD.

Introduction: Implantable loop recorders (ILR) are widely used for long term arrhythmia monitoring in patients with cryptogenic stroke (CS). Single center study has shown that some patients with incidental arrhythmias found by ILR, aside from atrial fibrillation (AF), resulted in changes in clinical management. Unfortunately, a large portion of the patients had premature ILR explantation before the end of battery life and other studies on incidental arrhythmias are limited. Hypothesis: We sought to determine the rate of occurrence of incidental arrhythmias other than AF on ILR monitoring among patients with CS and to characterize the rate of these incidental arrhythmias that result in a change in clinical management. Methods: All adult patients with ILR for CS at Rhode Island Hospital between 1/2015-1/2019 were included. Demographics, cardiac risk factors and structural features, and ILR tracings were reviewed. Results: Three hundred and twelve patients were identified with a median follow up time of 27.9 months (IQR 18.5-35.8 months). Incidental arrhythmias were identified in 110 patients (35.2%) with a median of 7.8 months (IQR 4.4-16.2 months) at a rate of 20.1 per 100 person-years. AF was detected in 51 patients (16.3%) with a median of 3.9 months (IQR 1.3-12.3 months). Eighteen patients had both AF and incidental arrhythmias and incidental arrhythmias were found after AF in 8 of those patients. Premature explantation occurred in 9.3% of patients with the most common reason being patient preference. Twelve patients with incidental arrhythmias (10.9%) had a resultant change in management; 9 with procedural interventions and 3 with medication adjustments. Overall, the rate of actionable incidental arrhythmias is 2.2 per 100 person-years. Conclusions: Other than AF detection, long term EKG monitoring in patients with CS with ILR allows for detection of other arrhythmias. These incidental findings can result in changes in management and potentially favorable clinical outcomes.

Introduction: Dilated cardiomyopathy (DCM) has a heterogenous aetiology. Precise disease stratification enabling personalised therapy may be key to improving management. Genetic testing and cardiac magnetic resonance (CMR) may help stratify the cause of DCM. Hypothesis: Adding genetic testing and CMR to routine tests will improve confidence and reproducibility in DCM stratification and, in turn, guide management. Methods: Case profiles for 60 consecutive patients with DCM were sent to 4 independent experts. Using routinely available clinical information, they were asked to determine the aetiology of the phenotype, based on the classification in the ESC Position Statement on DCM, and record their confidence (score 1-3) in the diagnosis. This was repeated after the addition of genetic testing and CMR results in a step-wise manner. Clinicians were also asked whether they would make changes to patient management. Results: Overall, 4 physicians reviewed 60 cases, giving 240 responses. Adding genetic testing and CMR resulted in changes to disease stratification ( Table 1 ). The most common change was from idiopathic to genetic DCM, following the identification of pathogenic or likely pathogenic variants in 13 cases. Confidence scores improved with the addition of genetic testing and CMR results (routine 1.69±0.53; routine & genetic 1.93±0.61, pLMNA or DSP variants were identified (n=3, 5.0%), new recommendations for device therapy were made. Adding genetic and CMR data improved interobserver agreement in stratification (routine κ=0.40; routine & genetic κ=0.66; routine, genetic & CMR κ=0.68). Conclusion: Adding genetic testing and CMR to routine tests changed how DCM was stratified, improved confidence and interobserver variability in making this diagnosis, and subsequently, directed management.

BACKGROUND: Our objective was to assess the performance of machine learning methods to predict post-operative delirium using a prospective clinical cohort. METHODS: We analyzed data from an observational cohort study of 560 older adults (≥ 70 years) without dementia undergoing major elective non-cardiac surgery. Post-operative delirium was determined by the Confusion Assessment Method supplemented by a medical chart review (N = 134, 24%). Five machine learning algorithms and a standard stepwise logistic regression model were developed in a training sample (80% of participants) and evaluated in the remaining hold-out testing sample. We evaluated three overlapping feature sets, restricted to variables that are readily available or minimally burdensome to collect in clinical settings, including interview and medical record data. A large feature set included 71 potential predictors. A smaller set of 18 features was selected by an expert panel using a consensus process, and this smaller feature set was considered with and without a measure of pre-operative mental status. RESULTS: The area under the receiver operating characteristic curve (AUC) was higher in the large feature set conditions (range of AUC, 0.62–0.71 across algorithms) versus the selected feature set conditions (AUC range, 0.53–0.57). The restricted feature set with mental status had intermediate AUC values (range, 0.53–0.68). In the full feature set condition, algorithms such as gradient boosting, cross-validated logistic regression, and neural network (AUC = 0.71, 95% CI 0.58–0.83) were comparable with a model developed using traditional stepwise logistic regression (AUC = 0.69, 95% CI 0.57–0.82). Calibration for all models and feature sets was poor. CONCLUSIONS: We developed machine learning prediction models for post-operative delirium that performed better than chance and are comparable with traditional stepwise logistic regression. Delirium proved to be a phenotype that was difficult to predict with appreciable accuracy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-06238-7) contains supplementary material, which is available to authorized users.

Introduction Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults. Methods We used item response theory to derive composite measures for language (ADNI‐Lan) and visuospatial functioning (ADNI‐VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress. Results ADNI‐Lan and ADNI‐VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre‐specified magnetic resonance imaging measures. ADNI‐Lan had strong associations with a cerebrospinal fluid biomarker pattern. Discussion ADNI‐Lan and ADNI‐VS may be useful composites for language and visuospatial functioning in ADNI.

Background/objectives Delirium is a common postoperative complication associated with prolonged length of stay, hospital readmission, and premature mortality. We explored the association between neighborhood-level characteristics and delirium incidence and severity, and compared neighborhood- with individual-level indicators of socioeconomic status in predicting delirium incidence. Design A prospective observational cohort of patients enrolled between June 18, 2010, and August 8, 2013. Baseline interviews were conducted before surgery, and delirium/delirium severity was evaluated daily during hospitalization. Research staff evaluating delirium were blinded to baseline cognitive status. Setting Two academic medical centers in Boston, MA. Participants A total of 560 older adults, aged 70 years or older, undergoing major noncardiac surgery. Intervention The Area Deprivation Index (ADI) was used to characterize each neighborhood's socioeconomic disadvantage. Measurements Delirium was assessed using the Confusion Assessment Method (CAM) long form. Delirium severity was calculated using the highest value of CAM Severity score (CAM-S) occurring during daily hospital assessments (CAM-S Peak). Results Residing in the most disadvantaged neighborhoods (ADI > 44) was associated with a higher risk of incident delirium (12/26; 46%), compared with the least disadvantaged neighborhoods (122/534; 23%) (risk ratio (RR) (95% confidence interval (CI)) = 2.0 (1.3-3.1). The CAM-S Peak score was significantly associated with ADI (Spearman rank correlation, ρ = 0.11; P = .009). Mean CAM-S Peak scores generally rose from 3.7 to 5.3 across levels of increasing neighborhood disadvantage. The RR (95% CI) values associated with individual-level markers of socioeconomic status and cultural background were: 1.2 (0.9-1.7) for education of 12 years or less; 1.3 (0.8-2.1) for non-White race; and 1.7 (1.1-2.6) for annual household income of less than $20,000. None of these individual-level markers exceeded the ADI in terms of effect size or significance for prediction of delirium risk. Conclusions Neighborhood-level makers of social disadvantage are associated with delirium incidence and severity, and demonstrated an exposure-response relationship. Future studies should consider contextual-level metrics, such as the ADI, as risk markers of social disadvantage that can help to guide delirium treatment and prevention.

OBJECTIVE To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance. METHODS Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery type, cognition, and vascular comorbidities. Biomarkers were measured in plasma collected preoperatively (PREOP), and 2 days (POD2) and 30 days postoperatively (PO1MO) using Simoa technology (Quanterix, Lexington, MA). The Confusion Assessment Method (CAM) and CAM-S (Severity) were used to measure delirium and delirium severity, respectively. Cognitive function was measured with General Cognitive Performance (GCP) scores. RESULTS Delirium cases had higher NfL on POD2 and PO1MO (median matched pair difference = 16.2pg/ml and 13.6pg/ml, respectively; p

Background: Delirium occurs frequently in patients with intracerebral hemorrhage (ICH), though its pathogenesis may be multifactorial. Given the potential role of systemic stressors in delirium, we aimed to explore differences in commonly measured markers of physiologic stress between delirious and non-delirious ICH patients. Methods: We performed a single-center cohort study using data from consecutive non-comatose ICH patients over 12 months. ICH and patient characteristics were prospectively collected, and the presence of delirium at any point during hospitalization was diagnosed based on DSM-5 criteria. We retrospectively abstracted admission laboratory values and selected three common markers of physiologic stress for comparison: neutrophil-lymphocyte ratio (NLR), troponin, and glucose. Using multivariable models adjusted for demographics, relevant comorbidities, and ICH severity, we determined associations between delirium and the following: NLR, using linear regression; elevated troponin (>0.05 ng/mL), using binary logistic regression; and elevated glucose (categorized as 130-180 or >180 mg/dL), using ordered logistic regression. Results: Of 284 ICH patients in our cohort, 55% (n=157) had delirium. Patients with delirium were not significantly older than non-delirious patients (mean age 71.7±16.2 vs. 68.3±15.1, p=0.07), but had larger ICH volumes (mean 23.3±24.6 vs. 7.0±10.6 cc, p Conclusions: Delirium after ICH is independently associated with elevated serum markers of physiologic stress, suggesting that systemic factors may be implicated in delirium pathogenesis.

ObjectiveTo determine the impact of delirium on withdrawal of life-sustaining treatment (WLST) after intracerebral hemorrhage (ICH) in the context of established predictors of poor outcome, using data from an institutional ICH registry.MethodsWe performed a single-center cohort study on consecutive patients with ICH admitted over 12 months. ICH features were prospectively adjudicated, and WLST and corresponding hospital day were recorded retrospectively. Patients were categorized using DSM-5 criteria as never delirious, ever delirious (either on admission or later during hospitalization), or persistently comatose. We determined the impact of delirium on WLST using Cox regression models adjusted for demographics and ICH predictors (including Glasgow Coma Scale score), then used logistic regression with receiver operating characteristic curve analysis to compare the accuracy of ICH score–based models with and without delirium category in predicting WLST.ResultsOf 311 patients (mean age 70.6 ± 15.6, median ICH score 1 [interquartile range 1–2]), 50% had delirium. WLST occurred in 26%, and median time to WLST was 1 day (0–6). WLST was more frequent in patients who developed delirium (adjusted hazard ratio 8.9 [95% confidence interval (CI) 2.1–37.6]), with high rates of WLST in both early (occurring ≤24 hours from admission) and later delirium groups. An ICH score-based model was strongly predictive of WLST (area under the curve [AUC] 0.902 [95% CI 0.863–0.941]), and the addition of delirium category further improved the model's accuracy (AUC 0.936 [95% CI 0.909–0.962], p = 0.004).ConclusionDelirium is associated with WLST after ICH regardless of when it occurs. Further study on the impact of delirium on clinician and surrogate decision-making is warranted.

Introduction Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation. Methods We tested whether APOE modifies the established association between C-reactive protein (CRP) and delirium incidence, severity, and duration in 553 noncardiac surgical patients aged 70 and older. High postoperative plasma CRP (≥234.12 mg/L) was defined by the highest sample-based quartile. Delirium was determined using the Confusion Assessment Method and chart review, and severity was determined by the Confusion Assessment Method––Severity score. Results APOE e4 carrier prevalence was 19%, and postoperative delirium occurred in 24%. The relationship between CRP and delirium incidence, severity, and duration differed by e4 status. Among e4 carriers, there was a strong relationship between high CRP (vs. low CRP) and delirium incidence (relative risk [95% confidence interval], 3.0 [1.4–6.7]); however, no significant association was observed among non-e4 carriers (relative risk [95% CI], 1.2 [0.8–1.7]). Discussion Our findings raise the possibility that APOE e4 carrier status may modify the relationship between postoperative day 2 CRP levels and postoperative delirium.

Introduction Understanding the associations among depression, subjective cognitive decline, and prodromal Alzheimer's disease (AD) has important implications for both depression and dementia screening in older adults. The Geriatric Depression Scale (GDS) is a depression screening tool for older adults that queries memory concerns. To determine whether depression symptoms on the GDS (15‐item version), including self‐reported memory problems, differ by levels of brain amyloid beta (Aβ), a pathological hallmark of early stage AD, we investigated potential measurement bias with regard to Aβ level. We also examined measurement bias attributable to level of cognitive functioning and sex as positive controls. Methods We examined 3961 cognitively normal older adults from the A4/LEARN Study. We used the MIMIC (multiple indicators, multiple causes) approach to detect measurement bias. Results We found measurement bias with small‐to‐moderate range effect sizes in several GDS‐15 items with respect to Aβ level, cognitive functioning, and sex. There was negligible impact of measurement bias attributable to Aβ level on overall depressive symptom level. Discussion GDS‐15 item responses are sensitive to Aβ burden, cognitive functioning, and sex over and above what would be expected given the effect of those factors on depressive symptom severity overall. However, these direct effects for GDS item measurement bias are of small magnitude and do not appreciably impact the validity of inferences about depression based on the GDS‐15.

Background: Practice effects (PEs) are improvements in performance after repeated exposure to test materials, and typically viewed as a source of bias in repeated cognitive assessments. We aimed to determine whether characterizing PEs could also provide a useful marker of early cognitive decline. Methods: We conducted a systematic review of the literature, searching PsycInfo (Ebsco) and PubMed databases for articles studying PEs in aging and dementia populations. Articles published between 1920 and 2019 were included. Result: We identified 259 articles, of which 27 studied PEs as markers of cognitive performance. These studies consistently showed that smaller, less-robust PEs were associated with current diagnostic status and/or future cognitive decline. In addition, lower PEs were associated with Alzheimer's disease risk factors and neurodegeneration biomarkers. Conclusion: PEs provide a potentially useful marker of cognitive decline, and could prove valuable as part of a cost-effective strategy to select individuals who are at-risk for dementia for future interventions.

Background and objective Chronic low back pain (CLBP) is highly prevalent, with a substantial psychosocial burden. Pain has both sensory and affective components. The latter component is a significant driver of disability and psychiatric comorbidity but is often inadequately treated. Previously we reported that noninvasive transcranial direct current stimulation (tDCS) may modulate pain-associated affective distress. Here we tested whether 10 daily tDCS sessions aimed to inhibit the left dorsal anterior cingulate cortex (dACC), a region strongly implicated in the affective component of pain, would produce selective reduction in pain-related symptoms. Methods In this multisite, double-blinded, randomized placebo-controlled trial (RCT), 21 CLBP patients received 10 weekday sessions of 2-mA active tDCS or sham (20 minutes/session). A cathodal electrode was placed over FC1 (10-20 electroencephalography coordinates), and an identical anodal return electrode was placed over the contralateral mastoid. Participants rated pain intensity, acceptance, interference, disability, and anxiety, plus general anxiety and depression. Results Regression analysis noted significantly less pain interference (P =0.002), pain disability (P =0.001), and depression symptoms (P =0.003) at six-week follow-up for active tDCS vs sham. Omnibus tests suggested that these improvements were not merely due to baseline (day 1) group differences. Conclusions To our knowledge, this is the first double-blinded RCT of multiple tDCS sessions targeting the left dACC to modulate CLBP's affective symptoms. Results are encouraging, including several possible tDCS-associated improvements. Better-powered RCTs are needed to confirm these effects. Future studies should also consider different stimulation schedules, additional cortical targets, high-density multi-electrode tDCS arrays, and multimodal approaches.

Objectives To reduce the incidence of urinary tract infection, Surgical Care Improvement Project 9 mandates the removal of urinary catheters within 48 hours postoperatively. In patients with thoracic epidural anesthesia, we sought to determine the rate of catheter reinsertion, the complications of reinsertion, and the factors associated with reinsertion. Methods We conducted a prospective observational study of consecutive patients undergoing major pulmonary or esophageal resection with thoracic epidural analgesia over a 2-year period. As per Surgical Care Improvement Project 9, all urinary catheters were removed within 48 hours postoperatively. Excluded were patients with chronic indwelling catheter, patients with urostomy, and patients requiring continued strict urine output monitoring. Multivariable logistic regression analysis was used to identify independent risk factors for urinary catheter reinsertion. Results Thirteen patients met exclusion criteria. Of the 275 patients evaluated, 60 (21.8%) required reinsertion of urinary catheter. There was no difference in the urinary tract infection rate between patients requiring reinsertion (1/60 [1.7%]) versus patients not requiring reinsertion (1/215 [0.5%], P = .389). Urethral trauma during reinsertion was seen in 1 of 60 patients (1.7%). After reinsertion, discharge with urinary catheter was required in 4 of 60 patients (6.7%). Multivariable logistic regression analysis found esophagectomy, lower body mass index, and benign prostatic hypertrophy to be independent risk factors associated with catheter reinsertion after early removal in the presence of thoracic epidural analgesia. Conclusions When applying Surgical Care Improvement Project 9 to patients undergoing thoracic procedures with thoracic epidural analgesia, consideration to delayed removal of urinary catheter may be warranted in patients with multiple risk factors for reinsertion.

Background Many factors may potentially complicate the stroke recovery process, including persistently impaired level of consciousness (LOC)—whether from residual stroke effects or from superimposed delirium. We aimed to determine the degree to which impaired LOC at hospital discharge is associated with outcomes after ischemic stroke. Methods We conducted a single-center retrospective cohort study using prospectively-collected data from 2015 to 2017, collecting total NIHSS-LOC score at discharge as well as subscores for responsiveness (LOC-R), orientation questions (LOC-Q), and command-following (LOC-C). We determined associations between LOC scores and 3-month outcome using logistic regression, with discharge location (skilled nursing facility [SNF] vs. inpatient rehabilitation) representing a pre-specified secondary outcome. Results We identified 1003 consecutive patients with ischemic stroke who survived to discharge, of whom 32% had any LOC score > 0. Total LOC score at discharge was associated with unfavorable 3-month outcome (OR 4.9 [95% CI 2.4–9.8] for LOC = 1; OR 8.0 [2.7–23.9] for LOC = 2–3; OR 6.3 [2.1–18.5] for LOC = 4–5; all patients with LOC = 6–7 had poor outcomes), as were subscores for LOC-R (OR 5.3 [1.3–21.2] for LOC-R = 1; all patients with LOC-R = 2–3 had poor outcomes) and LOC-Q (OR 4.1 [2.1–8.3] for LOC-Q = 1; OR 4.9 [1.8–13.5] for LOC-Q = 2). Total LOC score (OR 2.6 [1.3–5.3] for LOC = 1; OR 3.1 [1.2–8.2] for LOC = 2–3) and LOC-Q (OR 3.3 [1.6–6.6] for LOC-Q = 1; OR 3.4 [1.3–9.0] for LOC-Q = 2) were also associated with discharge to SNF rather than to inpatient rehabilitation. Conclusions The presence of impaired consciousness or disorientation at discharge is associated with markedly worse outcomes after ischemic stroke. Further studies are necessary to determine the separate effects of residual stroke-related LOC changes and those caused by superimposed delirium.

Delirium — an acute disorder of attention and cognition — is a common, life-threatening and costly syndrome occurring frequently in older hospitalized persons. The unexpected, rapid, and volatile nature of delirium can be difficult for family caregivers to experience and may contribute to subjective feelings of distress (i.e. “delirium burden”). The aim of this study was to examine whether pre-admission patient characteristics or patient-caregiver relationship and living arrangements were associated with caregiver burden as measured by the delirium burden scale for caregivers (DEL-B-C; score 0-40, higher score is more burden). Our sample consisted of 208 older adults and their caregivers from the Better Assessment of Illness (BASIL) study, an ongoing prospective, observational study of surgical and medical patients ≥70 years old; 22% of patients experienced delirium by the Confusion Assessment Method (CAM) and the average DEL-B-C score was 7.9, 95% CI(6.95-8.88). Results indicated that neither patient-caregiver relationship and living arrangement or patient factors including pre-admission pain, sleep disturbance, or new onset incontinence were significantly correlated with delirium-related caregiver burden. However, DEL-B-C scores were significantly higher in caregivers of patients with any ADL impairment (mean 8.5 vs. 5.2, p = .016) during hospitalization although none of the individual functional deficits alone were statistically significant. This finding suggests that the association of ADL impairment and DEL-B-C scores is not driven by a single functional domain. Future studies are needed to further understand how caregiver characteristics and patient factors occurring before and during hospitalization contribute to caregiver burden after the occurrence of delirium.

INTRODUCTION: Older adults, including those with mild cognitive impairment (MCI), are increasingly undergoing surgery. METHODS: Relative risks of MCI alone or with delirium on adverse outcomes were estimated in an ongoing prospective, observational cohort study of 560 non-demented adults ≥70 years old. RESULTS: MCI (n=61, 11%) was associated with increased relative risk (RR) of delirium (RR=1.9, p

Background and Purpose: There are limited data to guide intensive care unit (ICU) versus dedicated stroke unit (SU) admission for intracerebral hemorrhage (ICH) patients. We hypothesized select patients can be safely cared for in SU versus ICU at lower costs. Methods: We conducted a retrospective cohort study of consecutive patients with predefined minor ICH (≤20 cm3, supratentorial, no coagulopathy) receiving care in either an ICU or an SU. Multiple linear regression and inverse probability weighting were used to adjust for differences in patient characteristics and nonrandom ICU versus SU assignment. The primary outcome was poor functional status at discharge (modified Rankin score [mRS] ≥3). Secondary outcomes included complications, discharge disposition, hospital length of stay, and direct inpatient costs. Results: The study population included 104 patients (41 admitted to the ICU and 63 admitted to the SU). After controlling for differences in baseline characteristics, there were no differences in poor functional outcome at discharge (93% vs 85%, P = .26) or in mean mRS (2.9 vs 3.0, P = .73). Similarly, there were no differences in the rates of complications (6% vs 10%, P = .44), discharged dead or to a skilled nursing facility (8% vs 13%, P = .59), or direct patient costs (US$7100 vs US$6200, P = .33). Median length of stay was significantly longer in the ICU group (5 vs 4 days, P = .01). Conclusions: This study revealed a shorter length of stay but no large differences in functional outcome, safety, or cost among patients with minor ICH admitted to a dedicated SU compared to an ICU.

Background The nested case-control study (NCC) design within a prospective cohort study is used when outcome data are available for all subjects, but the exposure of interest has not been collected, and is difficult or prohibitively expensive to obtain for all subjects. A NCC analysis with good matching procedures yields estimates that are as efficient and unbiased as estimates from the full cohort study. We present methodological considerations in a matched NCC design and analysis, which include the choice of match algorithms, analysis methods to evaluate the association of exposures of interest with outcomes, and consideration of overmatching. Methods Matched, NCC design within a longitudinal observational prospective cohort study in the setting of two academic hospitals. Study participants are patients aged over 70 years who underwent scheduled major non-cardiac surgery. The primary outcome was postoperative delirium from in-hospital interviews and medical record review. The main exposure was IL-6 concentration (pg/ml) from blood sampled at three time points before delirium occurred. We used nonparametric signed ranked test to test for the median of the paired differences. We used conditional logistic regression to model the risk of IL-6 on delirium incidence. Simulation was used to generate a sample of cohort data on which unconditional multivariable logistic regression was used, and the results were compared to those of the conditional logistic regression. Partial R-square was used to assess the level of overmatching. Results We found that the optimal match algorithm yielded more matched pairs than the greedy algorithm. The choice of analytic strategy—whether to consider measured cytokine levels as the predictor or outcome-- yielded inferences that have different clinical interpretations but similar levels of statistical significance. Estimation results from NCC design using conditional logistic regression, and from simulated cohort design using unconditional logistic regression, were similar. We found minimal evidence for overmatching. Conclusions Using a matched NCC approach introduces methodological challenges into the study design and data analysis. Nonetheless, with careful selection of the match algorithm, match factors, and analysis methods, this design is cost effective and, for our study, yields estimates that are similar to those from a prospective cohort study design.

Hospital and surgeon volume each have an association with postoperative outcomes. The volume of lung cancer surgery at our Veterans Administration Medical Center (VAMC) is lower than at our academic medical center (AMC). We compared the outcomes after lobectomy at VAMC versus AMC to identify specific areas of clinical care requiring quality improvement.To keep surgeon experience constant, data were derived from a prospective database from a single surgeon. Included were all male patients undergoing lobectomy for non-small cell lung cancer. Postoperative morbidity, mortality, and overall survival were compared after propensity score matching.From 2004 to 2013, 419 patients were evaluated (338 AMC, 81 VAMC). Outcomes comparison after propensity score matching of 81 AMC patients with 81 VAMC patients found a higher rate of major complications (12% versus 27%, p = 0.02) and longer hospital stay (median 6.0 versus 7.5 days, p0.001) for VAMC, but no difference in 90-day mortality (AMC 5% versus VAMC 6%, p0.99). Pneumonia was the specific complication found to be higher at VAMC (11% versus AMC 1.2%, p = 0.01). There was no difference in 5-year overall survival for stage I disease (AMC 68% versus VAMC 69%, p = 0.95).Keeping surgeon experience constant, and after adjusting for patient factors, the rate of major complication after lobectomy is higher at VAMC. The difference is largely attributable to a higher rate of postoperative pneumonia at VAMC. Complications after pulmonary resection at VAMC could be reduced by implementing quality improvement initiatives aimed at reducing the rate of postoperative pneumonia.

To describe functional recovery after elective surgery and to determine whether improvements differ among individuals who develop delirium.No large studies of older adults have investigated whether delirium influences the trajectory of functional recovery after elective surgery. The prospective observational study assessed this association among 566 individuals aged 70 years and older.Patients undergoing major elective surgery were assessed daily while in hospital for presence and severity of delirium using the Confusion Assessment Method, and their functional recovery was followed for 18 months thereafter. The Activities of Daily Living and Instrumental Activities of Daily Living Scales and the Physical Component Summary of the Short Form-12 were obtained before surgery and at 1, 2, 6, 12, and 18 months. A composite index (standard deviation 10, minimally clinically significant difference 2) derived from these scales was then analyzed using mixed-effects regression.Mean age was 77 years; 58% of participants were women and 24% developed postoperative delirium. Participants with delirium demonstrated lesser functional recovery than their counterparts without delirium; at 1 month, the covariate-adjusted mean difference on the physical function composite was -1.5 (95% confidence interval -3.3, -0.2). From 2 to 18 months, the corresponding difference was -1.8 (95% confidence interval -3.2, -0.3), an effect comparable with the minimally clinically significant difference.Delirium was associated with persistent and clinically meaningful impairment of functional recovery, to 18 months. Use of multifactorial preventive interventions for patients at high risk for delirium and tailored transitional care planning may help to maximize the functional benefits of elective surgery.

Background Increasing evidence suggests that postoperative delirium may result in long-term cognitive decline among older adults. Risk factors for such cognitive decline are unknown. Methods We studied 126 older participants without delirium or dementia upon entering the Successful AGing After Elective Surgery (SAGES) study, who developed postoperative delirium and completed repeated cognitive assessments (up to 36 months of follow-up). Pre-surgical factors were assessed preoperatively and divided into nine groupings of related factors ("domains"). Delirium was evaluated at baseline and daily during hospitalization using the Confusion Assessment Method diagnostic algorithm, and cognitive function was assessed using a neuropsychological battery and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) at baseline and 6-month intervals over 3 years. Linear regression was used to examine associations between potential risk factors and rate of long-term cognitive decline over time. A domain-specific and then overall selection method based on adjusted R2 values was used to identify explanatory factors for the outcome. Results The General Cognitive Performance (GCP) score (combining all neuropsychological test scores), IQCODE score, and living alone were significantly associated with long-term cognitive decline. GCP score explained the most variation in rate of cognitive decline (13%), and six additional factors-IQCODE score, cognitive independent activities of daily living impairment, living alone, cerebrovascular disease, Charlson comorbidity index score, and exhaustion level-in combination explained 32% of variation in this outcome. Conclusions Global cognitive performance was most strongly associated with long-term cognitive decline following delirium. Pre-surgical factors may substantially predict this outcome.

Delirium is a common problem associated with substantial morbidity and increased mortality. However, the brain dysfunction that leads some individuals to develop delirium in response to stressors is unclear. In this article, we briefly review the neurophysiologic literature characterizing the changes in brain function that occur in delirium, and in other cognitive disorders such as Alzheimer's disease. Based on this literature, we propose a conceptual model for delirium. We propose that delirium results from a breakdown of brain function in individuals with impairments in brain connectivity and brain plasticity exposed to a stressor. The validity of this conceptual model can be tested using Transcranial Magnetic Stimulation in combination with Electroencephalography, and, if accurate, could lead to the development of biomarkers for delirium risk in individual patients. This model could also be used to guide interventions to decrease the risk of cerebral dysfunction in patients preoperatively, and facilitate recovery in patients during or after an episode of delirium.

Background Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation. Methods The Successful Aging after Elective Surgery study enrolled dementia-free adults ≥70 years old undergoing major scheduled noncardiac surgery ( N = 566; 24% delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation–based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium. Results C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the preoperative (median paired difference [MPD] 1.97 mg/L [ p p p p p p p Conclusions Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.