A pragmatic tool to screen for pre-transplant cognitive impairment among potential candidates for liver transplant.

INTRODUCTION: Cognitive impairment (CI) among liver transplant (LT) candidates is associated with increased risk of waitlist mortality and inferior outcomes. While formal neurocognitive evaluation is the gold standard for CI diagnosis, the Montreal Cognitive Assessment (MoCA) is often used for first-line cognitive screening. However, MoCA requires specialized training and may be too lengthy for a busy evaluation appointment. An alternate approach may be the Quick Dementia Rating System (QDRS), which is patient- and informant-based and can be administered quickly. We compared potential LT candidates identified by MoCA and QDRS as potentially benefiting from further formal cognitive evaluation. METHODS: We identified 46 potential LT candidates enrolled at a single center of a prospective, observational cohort study who were administered MoCA and QDRS during transplant evaluation (12/2021-12/2022). Scores were dichotomized as (1) normal versus abnormal and (2) normal/mild impairment versus more-than-mild impairment. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of QDRS compared to MoCA. RESULTS: By MoCA, this population had a prevalence of 48% normal cognition, 48% mild, 4% moderate, and 0% severe impairment. This was categorized as 96% normal/mild and 4% more-than-mild impairment. When comparing to MoCA cognitive screening, QDRS had a sensitivity of 61%, specificity of 56%, NPV of 56%, and PPV of 61%. When identifying more-than-mild impairment, QDRS had a sensitivity of 100%, specificity of 73%, NPV of 100%, and PPV of 10%. CONCLUSION: The high sensitivity and NPV of QDRS in identifying more-than-mild impairment suggests it could identify potential LT candidates who would benefit from further formal cognitive evaluation. The ability to administer QDRS quickly and remotely makes it a pragmatic option for pre-transplant screening.

A world-wide study on delirium assessments and presence of protocols.

BACKGROUND: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities. OBJECTIVE: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols. DESIGN: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023. SETTING: Cross-sectional online survey including hospitals, rehabilitation and long-term facilities. METHODS: Participating clinicians reported data on delirium, the presence of protocols, delirium assessments, delirium-awareness interventions, non-pharmacological and pharmacological interventions, and ward/unit-specific barriers. RESULTS: Data from 44 countries, 1664 wards/units and 36 048 patients were analysed. Validated delirium assessments were used in 66.7% (n = 1110) of wards/units, 18.6% (n = 310) used personal judgement or no assessment, and 10% (n = 166) used other assessment methods. A delirium management protocol was reported in 66.8% (n = 1094) of wards/units. The presence of protocols for delirium management varied across continents, ranging from 21.6% (on 21/97 wards/units) in Africa to 90.4% (235/260) in Australia, similar to the use of validated delirium assessments with 29.6% (29/98) in Africa to 93.5% (116/124) in North America. Wards/units with a delirium management protocol [n = 1094/1664, 66.8%] were more likely to use a validated delirium test than those without a protocol [odds ratio 6.97 (95% confidence interval 5.289-9.185)]. The presence of a delirium protocol increased the chances for valid delirium assessment and, likely, evidence-based interventions. CONCLUSION: Wards/units that reported the presence of delirium management protocols had a higher probability of using validated delirium assessments tools to assess for delirium.

Advancing specificity in delirium: The delirium subtyping initiative.

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

Utility of amyloid PET Imaging in a Memory Clinic.

There is greater interest in amyloid biomarker for the diagnosis of Alzheimer disease (AD) with the recent Food and Drug Administration approval of amyloid-targeted therapy. The goal of this study was to assess the clinical utility of amyloid positron emission tomography (PET) in clinically ambiguous cases of cognitive impairment by examining outcomes of patients enrolled in the Imaging Dementia-Evidence of Amyloid Scanning study at 2 academic institutions. Of the 112 patients in the study, 66.1% (n=74) of patients had a positive amyloid PET scan, and 33.96% (n=38) had a negative amyloid PET scan. Lower cognitive test scores were predictive of positive amyloid PET scan ( P =0.001). Eighty-two percent (92/112) of the patients were seen for follow-up. Of the 30 patients with negative amyloid PET scan results, 90% had a diagnosis of non-AD etiology after receiving the negative results, suggesting a negative amyloid scan can be used to rule out AD diagnosis.

Associations between circulating cell-free mitochondrial DNA, inflammatory markers, and cognitive and physical outcomes in community dwelling older adults.

BACKGROUND: Dementia and frailty are common age-related syndromes often linked to chronic inflammation. Identifying the biological factors and pathways that contribute to chronic inflammation is crucial for developing new therapeutic targets. Circulating cell-free mitochondrial DNA (ccf-mtDNA) has been proposed as an immune stimulator and potential predictor of mortality in acute illnesses. Dementia and frailty are both associated with mitochondrial dysfunction, impaired cellular energetics, and cell death. The size and abundance of ccf-mtDNA fragments may indicate the mechanism of cell death: long fragments typically result from necrosis, while short fragments arise from apoptosis. We hypothesize that increased levels of necrosis-associated long ccf-mtDNA fragments and inflammatory markers in serum are linked to declines in cognitive and physical function, as well as increased mortality risk. RESULTS: Our study of 672 community-dwelling older adults revealed that inflammatory markers (C-Reactive Protein, soluble tumor necrosis factor alpha, tumor necrosis factor alpha receptor 1 [sTNFR1], and interleukin-6 [IL-6]) positively correlated with ccf-mtDNA levels in serum. Although cross-sectional analysis revealed no significant associations between short and long ccf-mtDNA fragments, longitudinal analysis demonstrated a connection between higher long ccf-mtDNA fragments (necrosis-associated) and worsening composite gait scores over time. Additionally, increased mortality risk was observed only in individuals with elevated sTNFR1 levels. CONCLUSION: In a community dwelling cohort of older adults, there are cross-sectional and longitudinal associations between ccf-mtDNA and sTNFR1 with impaired physical and cognitive function and increased hazard of death. This work suggests a role for long ccf-mtDNA as a blood-based marker predictive of future physical decline.

The association of hearing loss with frailty among community-dwelling older adults: findings from the National Health and Aging Trends Study.

BACKGROUND: The identification of modifiable risk factors is crucial for the prevention and/or reversal of frailty, which is associated with significant morbidity and mortality. Hearing loss affects two-thirds of older adults in the United States (U.S.) and is associated with physical and cognitive decline which may increase frailty risk. We investigated the association of hearing loss and hearing aid use with frailty and pre-frailty in a nationally representative sample of older adults in the U.S. METHODS: Cross-sectional analysis of the National Health and Aging Trends Study (2021 round). The better-hearing ear pure-tone average (BPTA) at speech-frequencies (0.5-4 kHz) was modeled continuously (per 10 dB) and categorically (no ≤ 25 dB, mild 26-40 dB, moderate or greater > 40 dB hearing loss). Hearing aid use was self-reported. The physical frailty phenotype (frail, pre-frail, robust) was determined based on Fried criteria: unintentional weight loss, exhaustion, low physical activity, weakness, slow walking speed. We used multinomial multivariable regression adjusted for sociodemographic and health characteristics (odds ratios [95% Confidence Intervals]). RESULTS: Among 2,361 participants (mean age = 81 years, 56% female, 19% Black), 860 (36%) had mild and 864 (37%) had moderate or greater hearing loss. Worse hearing was associated with greater odds of being frail versus robust (OR = 1.20 [1.05-1.38] per 10 dB difference). Categorically, moderate or greater hearing loss was associated with greater odds of being frail (OR = 1.84 [1.01-3.08]) and pre-frail (OR = 1.46 [1.01-2.10]) versus robust. Among 1,724 participants with hearing loss, compared to hearing aid users (N = 522), nonusers had greater odds of being frail (OR = 2.54 [1.54-4.18]) and pre-frail (OR = 1.51 [1.05-2.17]) versus robust, and frail versus pre-frail (OR = 1.68 [1.04-2.72]). CONCLUSIONS: In a nationally representative sample of older adults in the U.S., using gold-standard hearing measures and a validated frailty phenotype, hearing loss and lack of hearing aid use was cross-sectionally associated with frailty and pre-frailty. Future longitudinal studies are needed to establish if hearing loss is a risk factor for frailty, which may have significant clinical importance.

Delirium detection methodologies: Implications for outcome measurement in clinical trials in postoperative delirium.

OBJECTIVE: Delirium is a common postoperative complication of hip fracture. Various methods exist to detect delirium as a reference standard. The goal of this study was to characterize the properties of the measures obtained in a randomized controlled trial, to document their relationship to the Diagnostic and Statistical Manual of Mental Disorders:Text Revision based diagnosis of postoperative delirium by a consensus panel, and to describe the method in detail to allow replication by others. METHODS: A secondary analysis of the randomized trial STRIDE (A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients) was conducted. Delirium assessments were performed in 200 consecutive hip fracture repair patients ≥65 years old. Assessors underwent extensive training in delirium assessment and the final delirium diagnosis was adjudicated by a consensus panel of three physicians with expertise in delirium assessment. RESULTS: A total of 680 consensus panel delirium diagnoses were completed. There were only 19 (2.8%, 19/678) evaluations where the delirium adjudication by the consensus panel differed from delirium findings by the Confusion Assessment Method (CAM). In 16 (84%, 16/19) of the cases, CAM was negative but the consensus panel diagnosed the patient as having delirium based on all of the available information including the CAM. CONCLUSION: The consensus panel diagnosis was more sensitive compared to CAM alone, however the magnitude of the difference was not large. When assessors are well trained and delirium assessments are closely supervised throughout the study, CAM may be adequate for delirium diagnosis in a clinical trial. Future studies are needed to test this hypothesis.

Satisfaction With Quality of Health Care Among Medicare Beneficiaries With Functional Hearing Loss.

BACKGROUND/OBJECTIVES: Nearly 38 million Americans have hearing loss. Understanding how sensory deficits such as hearing loss, which limit communication, impact satisfaction has implications for Medicare value-based reimbursement mechanisms. The aim of this study was to characterize the association of functional hearing loss and dissatisfaction with quality of health care over the past year among Medicare beneficiaries. METHODS: Cross-sectional study of satisfaction with quality of health care among Medicare beneficiaries with self-reported trouble hearing from the 2015 Medicare Current Beneficiaries Survey. There were 11,441 Medicare beneficiaries representing a 48.6 million total weighted nationally representative sample. RESULTS: Forty-eight percent of Medicare beneficiaries reported a little or a lot of trouble hearing. Medicare beneficiaries with a little trouble hearing (odds ratio=1.496; 95% confidence interval, 1.079-2.073; P=0.016) and a lot of trouble hearing (odds ratio=1.769; 95% confidence interval, 1.175-2.664; P=0.007) had 49.6% and 76.9% higher odds of being dissatisfied with the quality of their health care over the previous year, respectively. CONCLUSIONS: Medicare beneficiaries with functional hearing loss had higher odds of dissatisfaction with health care over the past year compared to those without functional hearing loss. Given Medicare's reliance on patient satisfaction as a value-based measure for hospital reimbursement, interventions to address hearing loss in the health care system are needed.

Effects of Ramelteon on the Prevention of Postoperative Delirium in Older Patients Undergoing Orthopedic Surgery: The RECOVER Randomized Controlled Trial.

OBJECTIVES: Postoperative delirium, associated with negative consequences including longer hospital stays and worse cognitive and physical outcomes, is frequently accompanied by sleep-wake disturbance. Our objective was to evaluate the efficacy and short-term safety of ramelteon, a melatonin receptor agonist, for the prevention of postoperative delirium in older patients undergoing orthopedic surgery. DESIGN: A quadruple-masked randomized placebo-controlled trial (Clinical Trials.gov NCT02324153) conducted from March 2017 to June 2019. SETTING: Tertiary academic medical center. PARTICIPANTS: Patients aged 65 years or older, undergoing elective primary or revision hip or knee replacement. INTERVENTION: Ramelteon (8 mg) or placebo MEASUREMENTS: Eighty participants were randomized to an oral gel cap of ramelteon or placebo for 3 consecutive nights starting the night before surgery. Trained research staff conducted delirium assessments for 3 consecutive days starting on postoperative day (POD) 0, after recovery from anesthesia, and on to POD2. A delirium diagnosis was based upon DSM-5 criteria determined by expert panel consensus. RESULTS: Of 80 participants, five withdrew consent (one placebo, four ramelteon) and four were excluded (four ramelteon) after randomization. Delirium incidence during the 2 days following surgery was 7% (5 of 71) with no difference between the ramelteon versus placebo: 9% (3 of 33) and 5% (2 of 38), respectively. The adjusted odds ratio for postoperative delirium as a function of assignment to the ramelteon treatment arm was 1.28 (95% confidence interval: 0.21-7.93; z-value 0.27; p-value = 0.79). Adverse events were similar between the two groups. CONCLUSION: In older patients undergoing elective primary or revision hip or knee replacement, ramelteon was not efficacious in preventing postoperative delirium.

Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients.

OBJECTIVES: While there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium. METHODS: Patients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study "A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aß) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)181. RESULTS: For every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02-1.25). Both CSF Aß42/t-tau (ß = -1.52, 95%CI = -2.1 to -0.05) and Aß42/p-tau181 (ß = -0.29, 95%CI = -0.48 to -0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers. CONCLUSIONS: In older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome.

Association of Hearing Loss With Neuropsychiatric Symptoms in Older Adults With Cognitive Impairment.

Neuropsychiatric symptoms (NPS) in persons with dementia (PWD) are common and can lead to poor outcomes, such as institutionalization and mortality, and may be exacerbated by sensory loss. Hearing loss is also highly prevalent among older adults, including PWD. OBJECTIVE: This study investigated the association between hearing loss and NPS among community- dwelling patients from a tertiary memory care center. DESIGN, SETTING, AND PARTICIPANTS: Participants of this cross-sectional study were patients followed at the Johns Hopkins Memory and Alzheimer's Treatment Center who underwent audiometric testing during routine clinical practice between October 2014 and January 2017. OUTCOME MEASUREMENTS: Included measures were scores on the Neuropsychiatric Inventory-Questionnaire and the Cornell Scale for Depression in Dementia. RESULTS: Participants (n = 101) were on average 76 years old, mostly female and white, and had a mean Mini-Mental State Examination score of 23. We observed a positive association between audiometric hearing loss and the number of NPS (b = 0.7 per 10 dB; 95% confidence interval [CI]: 0.2, 1.1; t = 2.86; p = 0.01; df = 85), NPS severity (b = 1.3 per 10 dB; 95% CI: 0.4, 2.5; t = 2.13; p = 0.04; df = 80), and depressive symptom severity (b = 1.5 per 10 dB; 95% CI: 0.4, 2.5; t = 2.83; p = 0.01; df = 89) after adjustment for demographic and clinical characteristics. Additionally, the use of hearing aids was inversely associated with the number of NPS (b = -2.09; 95% CI -3.44, -0.75; t = -3.10; p = 0.003; df = 85), NPS severity (b = -3.82; 95% CI -7.19, -0.45; t = -2.26; p = 0.03; df = 80), and depressive symptom severity (b = -2.94; 95% CI: -5.93, 0.06; t = 1.70; p = 0.05; df = 89). CONCLUSION: Among patients at a memory clinic, increasing severity of hearing loss was associated with a greater number of NPS, more severe NPS, and more severe depressive symptoms, while hearing aid use was associated with fewer NPS, lower severity, and less severe depressive symptoms. Identifying and addressing hearing loss may be a promising, low-risk, non-pharmacological intervention in preventing and treating NPS.

Developing Treatments for Alzheimer's and Related Disorders with Precision Medicine: A Vision.

Precision medicine, also known as personalized medicine, is concerned with finding the right treatment for the right patient at the right time. It is a way of thinking focused on parsing heterogeneity ultimately down to the level of the individual. Its main mission is to identify characteristics of heterogeneous clinical conditions so as to target tailored therapies to individuals. Precision Medicine however is not an agnostic collection of all manner of clinical, genetic and other biologic data in select cohorts. This is an important point. Simply collecting as much information as possible on individuals without applying this way of thinking should not be considered Precision Medicine.

Hearing Loss.

Hearing loss is highly prevalent and may significantly affect how we age. Although the population is aging, relatively few adults receive treatment for hearing loss. Internists are a critical partner to audiologists and otolaryngologists in caring for the adult population with hearing loss. This review provides a primer on diagnosing and managing hearing loss.

Preoperative Evaluation of the Frail Patient.

Perioperative management of older adults is a complex field that is heavily influenced by the clinical heterogeneity of older adults. Frailty-a geriatric syndrome in which a patient is more vulnerable to stressors due to decreases in physical function and reserve-has been indicative of adverse postoperative outcomes. Many tools have been developed to measure frailty that incorporate a variety of factors including physical and cognitive function, comorbidities, self-reported measures of health, and clinical judgment. Most of these frailty assessment tools are able to identify a subset of patients at risk of adverse outcomes including postoperative complications, longer hospital length of stay, discharge to a higher level of care, and mortality. Frailty assessment before surgical interventions can also guide discussions among patients, their families, anesthesiologists, and surgeons to tailor operative plans for patients to mitigate this increased risk. Studies are ongoing to identify interventions in frail patients that can improve postoperative outcomes, but high-quality data in the form of randomized controlled trials are lacking at this time.

Effect of baseline cognitive impairment on association between predicted propofol effect site concentration and Bispectral index or sedation score.

BACKGROUND: This study determined whether the relationship between predicted propofol effect site concentration (Ce) and observer's assessment of alertness/sedation scale (OAA/S) or Bispectral Index (BIS) was similar comparing cognitively intact vs impaired patients undergoing hip fracture repair with spinal anesthesia and sedation. METHODS: Following informed consent baseline mini-mental status exam (MMSE), Clinical Dementia Rating (CDR) and geriatric depression scale (GDS) were obtained. Intraoperatively OAA/S, BIS, and propofol (timing and exact amounts) administered were recorded. Cerebrospinal fluid was collected for Alzheimer's (AD) biomarkers. Mean Ce level (AvgCe) during surgery was calculated using the area under the Ce measurement series from incision to closure, divided by surgical time. Average OAA/S (AvgOAA/S), and BIS (AvgBIS) were similarly calculated. Pearson correlations of AvgCe with AvgOAA/S and AvgBIS were calculated overall and by CDR. Nonparametric locally weighted scatterplot smoothing (LOWESS) fits of AvgOAA/S and AvgBIS on AvgCe were produced, stratified by CDR. Multivariable regression incorporating baseline cognitive measurements or AD biomarkers assessed AvgOAA/S or AvgBIS associations with AvgCe. RESULTS: In 186 participants AvgBIS and AvgOAA/S correlated with AvgCe (Pearson ρ = - 0.72; p < 0.0001 and Pearson ρ = - 0.81; p < 0.0001, respectively), and remained unchanged across CDR levels. Association patterns of AvgOAA/S or AvgBIS on AvgCe guided by LOWESS fits and modeled through regression, were similar when stratified by CDR (p = 0.16). Multivariable modeling found no independent effect on AvgBIS or AvgOAA/S by MMSE, CDR, GDS, or AD biomarkers after accounting for AvgCe. CONCLUSIONS: When administering sedation in conjunction with spinal anesthesia, cognitive impairment does not affect the relationship between predicted propofol AvgCe and AvgOAA/S or AvgBIS.

Dementia.

Alzheimer disease (AD) and other dementia syndromes are becoming more common; an estimated 5.5 million adults aged 65 years or older are living with AD in the United States. It is important for primary care physicians to gain knowledge in this field because most community-dwelling older adults receive their care from them. This article discusses the latest findings in approaches to prevent cognitive decline as well as dementia screening, diagnosis, and treatment. Approaches to address quality of life for persons with dementia and their caregivers are also discussed.

Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review.

Background: Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear. Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults. Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions. Study Selection: Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms. Data Extraction: One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers. Data Synthesis: Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently. Limitations: Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes. Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review.

Background: Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear. Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults. Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up. Study Selection: Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group. Data Extraction: One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias. Data Synthesis: A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use. Limitations: There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes. Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

A roadmap to advance delirium research: Recommendations from the NIDUS Scientific Think Tank.

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.

Depth of sedation as an interventional target to reduce postoperative delirium: mortality and functional outcomes of the Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients randomised clinical trial.

BACKGROUND: The Strategy to Reduce the Incidence of Postoperative Delirium in the Elderly trial tested the hypothesis that limiting sedation during spinal anaesthesia decreases in-hospital postoperative delirium after hip fracture repair. This manuscript reports the secondary outcomes of this trial, including mortality and function. METHODS: Two hundred patients (≥65 yr) undergoing hip fracture repair with spinal anaesthesia were randomised to heavier [modified Observer's Assessment of Alertness/Sedation score (OAA/S) 0-2] or lighter (OAA/S 3-5) sedation, and were assessed for postoperative delirium. Secondary outcomes included mortality and return to pre-fracture ambulation level at 1 yr. Kaplan-Meier analysis, multivariable Cox proportional hazard model, and logistic regression were used to evaluate intervention effects on mortality and odds of ambulation return. RESULTS: One-year mortality was 14% in both groups (log rank P=0.96). Independent risk factors for 1-yr mortality included: Charlson comorbidity index [hazard ratio (HR)=1.23, 95% confidence interval (CI), 1.02-1.49; P=0.03], instrumental activities of daily living [HR=0.74, 95% CI, 0.60-0.91; P=0.005], BMI [HR=0.91, 95% CI 0.84-0.998; P=0.04], and delirium severity [HR=1.20, 95% CI, 1.03-1.41; P=0.02]. Ambulation returned to pre-fracture levels, worsened, or was not obtained in 64%, 30%, and 6% of 1 yr survivors, respectively. Lighter sedation did not improve odds of ambulation return at 1 yr [odds ratio (OR)=0.76, 95% CI, 0.24-2.4; P=0.63]. Independent risk factors for ambulation return included Charlson comorbidity index [OR=0.71, 95% CI, 0.53-0.97; P=0.03] and delirium [OR=0.32, 95% CI, 0.10-0.97; P=0.04]. CONCLUSIONS: This study found that in elderly patients having hip fracture surgery with spinal anaesthesia supplemented with propofol sedation, heavier intraoperative sedation was not associated with significant differences in mortality or return to pre-fracture ambulation up to 1 yr after surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00590707.