Search

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.

The objective of this study was to determine the clinical features that moderate a later age at ASD diagnosis in females in a large sample of females with ASD. Within two large and independent ASD datasets (> 20,000 females), females were first diagnosed with ASD 14-months later relative to males. This later age at diagnosis was moderated by a mild or atypical presentation, wherein repetitive behaviors were limited, IQ and language were broadly intact, and recognized symptoms emerged later in development. Females are at risk for a later age at ASD diagnosis and treatment implementation, and modification of early childhood ASD screening methods for females may be warranted.

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.

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

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.

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

PURPOSE: Our purpose was to create a content domain framework for delirium severity to inform item development for a new instrument to measure delirium severity. METHODS: We used an established, multi-stage instrument development process during which expert panelists discussed best approaches to measure delirium severity and identified related content domains. We conducted this work as part of the Better Assessment of ILlness (BASIL) study, a prospective, observational study aimed at developing and testing measures of delirium severity. Our interdisciplinary expert panel consisted of twelve national delirium experts and four expert members of the core research group. Over a one month period, experts participated in two rounds of review. RESULTS: Experts recommended that the construct of delirium severity should reflect both the phenomena and the impact of delirium to create an accurate, patient-centered instrument useful to interdisciplinary clinicians and family caregivers. Final content domains were Cognitive, Level of Consciousness, Inattention, Psychiatric-Behavioral, Psychomotor Features, Emotional Dysregulation, and Functional. Themes debated by experts included reconciling clinical geriatrics and psychiatric content, mapping symptoms to one specific domain, and accurate capture of unclear clinical presentations. CONCLUSIONS: We believe this work represents the first application of instrument development science to delirium. The identified content domains are inclusive of various, wide-ranging domains of delirium severity and are reflective of a consistent framework that relates delirium severity to potential clinical outcomes. Our content domain framework provides a foundation for development of delirium severity instruments that can help improve care and quality of life for patients with delirium.

Objectives The objective of this study was to assess the measurement properties of the self-reported Patient Health Questionnaire-9 (PHQ-9) and its 10-item observer version (PHQ-10OV) among nursing home residents. Methods We conducted a retrospective study of Minimum Data Set 3.0 assessments for national cohorts of Medicare Fee-for-Service beneficiaries who were newly admitted or incident long-stay residents in 2014-2015 at US nursing homes (NHs) certified by the Center for Medicare and Medicaid Services. Statistical analyses included examining internal reliability with McDonald's omega, structural validity with confirmatory factor analysis, and hypothesis testing for expected gender differences and criterion validity with descriptive statistics. The Chronic Condition Warehouse depression diagnoses were used as an administrative reference standard. Results Both the PHQ-9 and PHQ-10OV had good internal reliability with omega values above 0.85. The self-reported scale yielded good model fit for a one-factor solution, while the PHQ-10OV had slightly poorer fit and a lower standardized factor loading on the additional irritability item. Both scales appear sufficiently one-dimensional given that somatic items had higher factor loading on a general depression factor than on a somatic subfactor. We were unable to obtain expected gender differences on the PHQ-10OV scale. The PHQ-9 and PHQ-10OV were both highly specific but had poor sensitivity compared with an administrative reference standard. Conclusions The PHQ-9 appears to be a valid and promising measurement instrument for research about depression among NH residents, while the validity of the PHQ-10OV should be examined further with a structured psychiatric interview as a stronger criterion standard.

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

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/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.

Delirium is an acute disorder of attention and cognition. It occurs across the life span, yet it is particularly common among older adults, and is closely linked with underlying neurocognitive disorders. Evidence is mounting that intervening on delirium may represent an important opportunity for delaying the onset or progression of dementia. To accelerate the current understanding of delirium, the Network for Investigation of Delirium: Unifying Scientists (NIDUS) held a conference “Advancing Delirium Research: A Scientific Think Tank” in June 2019. This White Paper encompasses the major knowledge and research gaps identified at the conference: advancing delirium definition and measurement, understanding delirium pathophysiology, and prevention and treatment of delirium. A roadmap of research priorities is proposed to advance the field in a systematic, interdisciplinary, and coordinated fashion. A call is made for an international consortium and biobank targeted to delirium, as well as a public health campaign to advance the field.

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.

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.

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

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.

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.

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.

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.

Objectives (1) To determine the relationship of incident delirium during hospitalization with 90-day mortality; (2) to identify potential in-hospital mediators through which delirium increases 90-day mortality. Design Analysis of data from Project Recovery, a controlled clinical trial of a delirium prevention intervention from 1995 to 1998 with follow-up through 2000. Setting Large academic hospital. Participants Patients ≥70 years old without delirium at hospital admission who were at intermediate-to-high risk of developing delirium and received usual care only. Measurements (1) Incident delirium; (2) potential mediators of delirium on death including use of restraining devices (physical restraints, urinary catheters), development of hospital acquired conditions (HACs) (falls, pressure ulcers), and exposure to other noxious insults (sleep deprivation, acute malnutrition, dehydration, aspiration pneumonia); (3) death within 90 days of admission. Results Among 469 patients, 70 (15%) developed incident delirium. These patients were more likely to experience restraining devices (37% vs 16%, P < .001), HACs (37% vs 12%, P < .001), other noxious insults (63% vs 49%, P = .03), and 90-day mortality (24% vs 6%, P < .001). The inverse probability weighted hazard of death due to delirium was 4.2 (95% CI = 2.8–6.3) in bivariable analyses, increased in a graded manner with additional exposures to restraining devices, HACs, and other noxious insults, and declined by 10.9% after addition of these potential mediator categories, providing evidence of mediation. Conclusion Restraining devices, HACs, and additional noxious insults were more frequent among patients with delirium, increased mortality in a graded manner, and were responsible for a significant percentage of the association of delirium with death. Additional efforts to prevent potential downstream mediators through which delirium increases mortality may help to improve outcomes among hospitalized older adults.

Objectives To examine the effect of hospital readmission on functional recovery after elective surgery in older adults. Design Prospective cohort of individuals aged 70 and older undergoing elective surgery, enrolled from June 2010 to August 2013. Setting Two academic medical centers. Participants Community-dwelling older adults (N = 566; mean age ± standard deviation 77 ± 5) undergoing major elective surgery and expected to be admitted for at least 3 days. Measurements Readmission was assessed in multiple interviews with participants and family members over 18 months and validated against medical record review. Physical function was assessed according to ability to perform instrumental activities of daily living (IADLs) and activities of daily living (ADL), Medical Outcomes Study 12-item Short-Form Survey Physical Component Summary score, and a standardized functional composite. Results Two hundred fifty-five (45%) participants experienced 503 readmissions. Readmissions were associated with delays in functional recovery in all measures of physical function. Having two or more readmissions over 18 months was associated with persistent and significantly greater risk of IADL dependence (relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.5–2.3) and ADL dependence (RR = 3.3, 95% CI = 1.7–6.4). Degree of functional impairment increased progressively with number of readmissions. Readmissions within 2 months resulted in delayed functional recovery to baseline by 18 months, and readmissions between 12 and 18 months after surgery resulted in loss of functional recovery previously achieved. Conclusion Readmission after elective surgery may contribute to delays in functional recovery and persistent functional deficits in older adults.

Objective To assess racial variation in depression risk factors and symptom trajectories among older women. Methods Using Nurses' Health Study data, participants (29,483 non-Hispanic white and 288 black women) aged 60 years or older, free of depression in 2000, were followed until 2012. Data on race and risk factors, selected a priori, were obtained from biennial questionnaires. Incident depression was defined as depression diagnosis, antidepressant use, or presence of severe depressive symptoms. Group-based trajectories of depressive symptoms were determined using latent variable modeling approaches. Results Black participants had lower risk (hazard ratio: 0.76; 95% confidence interval: 0.57–0.99) of incident late-life depression compared with whites. Although blacks had higher prevalence than whites of some risk factors at study baseline, distributions of major contributors to late-life depression risk (low exercise, sleep difficulty, physical/functional limitation, pain) were comparable. There was evidence of effect modification by race for relations of region of birth (Southern birthplace), smoking, and medical comorbidity to depression risk; however, wide confidence intervals occurred among blacks because of smaller sample size. Four trajectories were identified: minimal symptoms-stable (58.3%), mild symptoms-worsening (31.4%), subthreshold symptoms-worsening (4.8%), and subthreshold symptoms-improving (5.5%). Probabilities of trajectory types were similar for blacks and whites. Conclusion Although overall trajectories of late-life depressive symptoms were comparable by race, there was racial variation in depression risk estimates associated with less-studied factors, such as U.S. region of birth. Future work may address unmeasured health and resilience determinants that may underlie observed findings and that could inform clinical assessment of late-life depression risk factors.

OBJECTIVES Poststroke delirium may be underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurologic deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in patients with intracerebral hemorrhage. DESIGN Prospective observational cohort study. SETTING Neurocritical Care and Stroke Units at a university hospital. PATIENTS Consecutive patients with intracerebral hemorrhage from February 2018 to May 2018. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS An attending neurointensivist performed 257 total daily assessments for delirium on 60 patients (mean age 68.0 [SD 18.4], 62% male, median intracerebral hemorrhage score 1.5 [interquartile range 1-2], delirium prevalence 57% [n = 34]). Each assessment included the Confusion Assessment Method for the ICU, Intensive Care Delirium Screening Checklist, a focused bedside cognitive examination, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, then compared performance of the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist against reference-standard expert diagnosis. Symptom fluctuation (61% of all assessments), psychomotor changes (46%), sleep-wake disturbances (46%), and impaired arousal (37%) had the highest prevalence and were never rated "unable to assess," while inattention (36%), disorientation (27%), and disorganized thinking (18%) were also common but were often rated 'unable to assess' (32%, 43%, and 44% of assessments, respectively), most frequently due to aphasia (32% of patients). Including nonverbal assessments of attention decreased the frequency of 'unable to assess' ratings to 11%. Since the Intensive Care Delirium Screening Checklist may be positive without the presence of symptoms that require verbal assessment, it was more accurate (sensitivity = 77%, specificity = 97%, area under the receiver operating characteristic curve, 0.87) than the Confusion Assessment Method for the ICU (sensitivity = 41%, specificity = 88%, area under the receiver operating characteristic curve, 0.64). CONCLUSIONS Delirium is common after intracerebral hemorrhage, but severe neurologic deficits may confound its assessment and lead to underdiagnosis. The Intensive Care Delirium Screening Checklist's inclusion of nonverbal features may make it more accurate than the Confusion Assessment Method for the ICU in patients with neurologic deficits, but novel tools designed for such patients may be warranted.

Purpose To examine associations between fluctuating consciousness and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) assessments in stroke patients compared to non-neurological patients. Materials and methods We linked all recorded CAM-ICU assessments with corresponding Richmond Agitation Sedation Scale (RASS) measurements in patients with stroke or sepsis from a single-center ICU database. Fluctuating consciousness was defined by RASS variability using standard deviations (SD) over 24-h periods; regression analyses were performed to determine associations with RASS variability and CAM-ICU rating. Results We identified 16,509 paired daily summaries of CAM-ICU and RASS measurements in 546 stroke patients and 1586 sepsis patients. Stroke patients had higher odds of positive (OR 4.2, 95% CI 3.3–5.5) and “unable to assess” (UTA; OR 5.2, 95% CI 4.0–6.8) CAM-ICU ratings compared to sepsis patients, and CAM-ICU-positive and UTA assessment-days had higher RASS variability than CAM-ICU-negative assessment-days, especially in stroke patients. Based on model-implied associations of RASS variability (OR 2.0 per semi-IQR-difference in RASS-SD, 95% CI 1.7–2.2) and stroke diagnosis (OR 2.7, 95% CI 2.0–3.7) with CAM-ICU-positive assessments, over one-third of probable delirium cases among stroke patients were potentially missed by the CAM-ICU. Conclusions Post-stroke delirium may frequently go undetected by the CAM-ICU, even in the setting of fluctuating consciousness.

Background To use neuropsychological assessments for studying the underlying disease processes contributing to dementia, it is crucial that they correspond to magnetic resonance imaging (MRI)-based measures of dementia, regardless of educational level. Methods French 3-City Dijon MRI study cohort members (n=1782) with assessments of white matter lesion volume (WMLV), hippocampal volume (HCV), and cerebrospinal fluid volume (CSFV), and 6 waves of neuropsychological assessments over 11 years, including Mini-Mental State Examination (MMSE), plus 5 other tests combined using a Z-score or item-response theory (IRT-cognition) comprised the study cohort. We evaluated, testing interactions, whether education modified associations of MRI markers with intercept or rate of change of MMSE, Z-score composite, or IRT-cognition. Results In linear models, education modified the associations of WMLV and CSFV with MMSE and CSFV and Z-score composite. In mixed models, education modified the associations of WMLV and CSFV with level of MMSE and the association of HCV with slope of MMSE. Education also modified the association with CSFV and slope of Z-score composite decline. There was no evidence that education modified associations between MRI measures and level or slope of IRT-cognition. Conclusions Longitudinal analysis of correctly scaled neuropsychological assessments may provide unbiased proxies for MRI-based measures of dementia risk.

PURPOSE OF REVIEW: In this review I trace the origins, applications, limitations and future prospects for research on measurement item bias, or differential item functioning (DIF) in the context of health research. DIF arises in the context of using multiple item or symptom health instruments to rate the level of a particular condition, and describes the situation where not all persons at the same level at the same level of the underlying condition have the same probability of endorsing one or more symptoms. The presence of DIF can lead to biased assessment of group differences and confound risk factor and outcomes research. RECENT FINDINGS: The epidemiologic literature includes a great many applied, review, and methodological articles focusing on DIF. The preponderance of the literature appears in the areas of health-related quality of life, physical functioning, cognition, and mental health outcomes. SUMMARY: Epidemiologists and other researchers in the health sciences often rely upon multiple item rating scales or questionnaires to assess for the presence of or level of health conditions or states that are otherwise not directly observable. When population subgroups respond differently to a subset of the items, this is referred to as differential item functioning (DIF), and might be a source of bias.

Introduction: Established predictors for outcome after intracerebral hemorrhage (ICH) may be subject to self-fulfilling prophecy, as studies examining their effects on mortality have generally not considered changes in code status leading to withdrawal of life-sustaining treatment (WLST). We aimed to identify factors specifically associated with WLST, and hypothesized that impaired consciousness and delirium would be especially implicated. Methods: We analyzed data from consecutive patients admitted with ICH from February-June 2018. ICH score and other clinical predictors were prospectively adjudicated, and most patients had delirium assessments performed by an expert clinician; for those who did not, we established the presence of probable delirium via chart review. Using logistic regression models that adjusted for ICH severity, we determined the association of impaired consciousness on admission (Glasgow Coma Scale [GCS] Results: Of 106 patients in our cohort (mean age 68.7 [SD 17.8], median ICH score 1.5 [IQR 1-2]), WLST occurred in 29% (22/40 with admission GCS 80; OR 8.4, 95% CI 1.7-40.7 for size >30cc; intraventricular hemorrhage and infratentorial location were not significant). Of 92 patients who survived >24 hours without early WLST, 52% had delirium. We found that delirious patients were significantly more likely than patients without delirium to have subsequent WLST (33% vs. 2%, p Conclusion: Impaired consciousness and delirium likely play a significant role in WLST after ICH. However, whether this phenomenon is due to effects on clinician or surrogate decision-making remains unclear.

Introduction: Post-stroke delirium is associated with worse outcomes, yet is likely underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurological deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in a cohort of patients with intracerebral hemorrhage (ICH). Methods: Consecutive patients admitted with ICH received daily assessments for delirium by an expert clinician, all of which included the Confusion Assessment Method for the ICU (CAM-ICU), Intensive Care Delirium Screening Checklist (ICDSC), a focused bedside cognitive exam, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using DSM-5 criteria, then compared performance of the CAM-ICU and ICDSC with reference-standard diagnosis. Results: We performed 257 assessments on 60 patients (mean age 68.0 [SD 18.4], 62% male, median ICH score 1.5 [IQR 1-2]), of whom 55% had delirium. Symptom fluctuation (61% of all assessments), impaired arousal (37%), psychomotor changes (46%), and sleep-wake disturbances (46%) had a high prevalence and were never rated “unable to assess” (UTA), while inattention (36%), disorganized thinking (18%), and disorientation (27%) were also common but were often UTA (32%, 44%, and 43% of assessments, respectively), most frequently due to aphasia (present in 32% of patients). As the ICDSC may be positive without the presence of symptoms that require verbal assessment, it was more accurate ( Sensitivity= 77%, Specificity= 97%) than the CAM-ICU ( Sensitivity= 41%, Specificity= 88%) relative to the DSM-5-based reference standard. Allowing non-verbal assessments of attention using visual and auditory stimuli decreased the frequency of UTA assessments to 11%. Conclusion: Delirium is common after ICH, but reliance on verbal interaction with patients may confound its assessment and lead to underdiagnosis. The ICDSC’s inclusion of non-verbal features makes it more accurate than the CAM-ICU, but novel tools specifically designed for patients with neurological deficits may be warranted.

Delirium is common among dementia patients and can be distressing to both patients and their caregivers. Distress, the subjective experience of delirium (i.e. “delirium burden”), was measured using newly developed patient and caregiver delirium-burden questionnaires, in a subset of patients and/or caregivers (n=267) from the Better Assessment of Illness (BASIL) study, an ongoing prospective, observational study of surgical and medical patients ≥70 years old. Thirty percent of the cohort had dementia as defined by proxy Informant Questionnaire on Cognitive Decline in the Elderly score ≥3.5 or ICD-9 codes from chart review; 22% experienced delirium by the Confusion Assessment Method (CAM). Delirium-burden instruments were reliable in patients with dementia (Cronbach’s α=0.82) and their caregivers (α=0.77). Delirium resulted in higher caregiver delirium-burden, regardless of dementia status (mean difference [compared to cognitively normal, CN]=6.87, 95% CI [4.02–9.72] with dementia; mean difference=6.03, 95% CI [2.80–9.27] without dementia). Delirium increased patient delirium-burden overall (mean difference [compared to CN]=7.99, 95% CI [5.57–10.42]); this effect was attenuated by dementia (mean difference [compared to CN =2.97, 95% CI [0.34–5.59]). Caregiver delirium-burden correlated with delirium-severity in patients with (r=.21) and without dementia (r=0.30); however, patient delirium-burden correlated with delirium severity only in patients without (r=.43) but not with dementia (r=.06). Instruments for measuring delirium burden are useful for estimating distress in caregivers and in patients without dementia; however, reporting in patients with dementia may be limited. Such measures are important to ultimately lessen the distress of delirium for patients and family caregivers.

Frailty is present in almost half of all older surgical patients. Although frailty has been associated with cognitive decline, this has not been examined in the context of surgery. It is also not known if this relationship is independent of delirium, an established risk factor for postoperative cognitive decline. We probed these questions in the Successful Aging after Elective Surgery cohort of 560 dementia-free older adults (≥70 years old) undergoing elective surgery. Frailty and delirium were measured, respectively, by the Fried Frailty Index and the Confusion Assessment Method supplemented by medical chart review. Postoperative cognitive trajectory was measured as the slope of the General Cognitive Performance (GCP) score, a composite derived from results of a neuropsychological battery administered 2–36 months post-surgery. 64 (12%) of patients were robust, 280 (56%) were pre-frail, and 160 (32%) were frail. Delirium occurred in 134 patients (24%) overall. Compared to the rate of GCP decline among robust patients, decline was steeper by -0.47 points/year (95% CI -0.83, -0.14, p=.005) among pre-frail patients and by -0.48 points/year (95% CI -0.88, -0.07, p=.02) among frail patients. This effect was independent of age, sex, and education. Notably, the known influence of delirium on cognitive decline did not account for the association between frailty and cognitive decline. These results suggest pre-frailty, frailty and delirium are independently associated with accelerated postoperative cognitive decline, with effects of similar magnitude to each other and to mild cognitive impairment. Preoperative frailty screening could identify patients at higher risk of cognitive decline after surgery.

Background Bariatric surgery is currently the most effective strategy for producing significant and durable weight loss. Yet, not all patients achieve initial weight loss success and some degree of weight regain is very common, sometimes as early as 1–2 years post-surgery. Suboptimal weight loss not fully explained by surgical, demographic, and medical factors has led to greater emphasis on patient behaviors evidenced by clinical guidelines for appropriate eating and physical activity. However, research to inform such guidelines has often relied on imprecise measures or not been specific to bariatric surgery. There is also little understanding of what psychosocial factors and environmental contexts impact outcomes. To address research gaps and measurement limitations, we designed a protocol that innovatively integrates multiple measurement tools to determine which behaviors, environmental contexts, and psychosocial factors are related to outcomes and explore how psychosocial factors/environmental contexts influence weight. This paper provides a detailed description of our study protocol with a focus on developing and deploying a multi-sensor assessment tool to meet our study aims. Methods This NIH-funded prospective cohort study evaluates behavioral, psychosocial, and environmental predictors of weight loss after bariatric surgery using a multi-sensor platform that integrates objective sensors and self-report information collected via smartphone in real-time in patients’ natural environment. A target sample of 100 adult, bariatric surgery patients (ages 21–70) use this multi-sensor platform at preoperative baseline, as well as 3, 6, and 12 months postoperatively, to assess recommended behaviors (e.g., meal frequency, physical activity), psychosocial indicators with prior evidence of an association with surgical outcomes (e.g., mood/depression), and key environmental factors (e.g., type/quality of food environment). Weight also is measured at each assessment point. Discussion This project has the potential to build a more sophisticated and valid understanding of behavioral and psychosocial factors contributing to success and risk after bariatric surgery. This new understanding could directly contribute to improved (i.e., specific, consistent, and validated) guidelines for recommended pre- and postoperative behaviors, which could lead to improved surgical outcomes. These data will also inform behavioral, psychosocial, and environmental targets for adjunctive interventions to improve surgical outcomes. Trial registration Registered trial NCT02777177 on 5/19/2016. Electronic supplementary material The online version of this article (10.1186/s40608-018-0204-6) contains supplementary material, which is available to authorized users.

Some caregivers of persons with Alzheimer’s Disease and related dementias (ADRD) are known to be under high levels of burden, which is associated with higher levels of anxiety, depression, and stress. Previous research has established anxiety, depression, and stress are associated with heavy alcohol use, but little research has examined heavy alcohol use among ADRD caregivers. Heavy alcohol use could influence the ability of ADRD caregivers to provide care. The purpose of this study was to explore the prevalence and prevalence correlates of heavy alcohol use among ADRD caregivers using the 2016 Behavior Risk Factor Surveillance Survey (BRFSS). We identified 2,028 persons among the 486,303 BRFSS respondents who were the primary informal caregivers of a person with ADRD. Among them, the prevalence of heavy alcohol use was 6.3 per 100 persons. Adult child caregiver relationship, positive smoking status, and fewer hours of providing care per day were all positively and significantly associated with heavy alcohol use. Notably, sex was not. Future research should examine if heavy alcohol use by ADRD caregivers is related to personally and clinically relevant outcomes of care provided to the persons with ADRD.