Malignant Catatonia: A Review for the Intensivist.

Catatonia is a clinical syndrome characterized by psychomotor, neurological and behavioral changes. The clinical picture of catatonia ranges from akinetic stupor to severe motoric excitement. Catatonia can occur in the setting of a primary psychiatric condition such as bipolar disorder or secondary to a general medical illness like autoimmune encephalitis. Importantly, it can co-occur with delirium or coma. Malignant catatonia describes catatonia that presents with clinically significant autonomic abnormalities including change in temperature, blood pressure, heart rate, and respiratory rate. It is a life-threatening form of acute brain dysfunction that has several motoric manifestations and occurs secondary to a primary psychiatric condition or a medical cause. Many of the established predisposing and precipitating factors for catatonia such as exposure to neuroleptic medications or withdrawal states are common in the setting of critical illness. Catatonia typically improves with benzodiazepines and treatment of its underlying psychiatric or medical conditions, with electroconvulsive therapy reserved for catatonia refractory to benzodiazepines or for malignant catatonia. However, some forms of catatonia, such as catatonia secondary to a general medical condition or catatonia comorbid with delirium, may be less responsive to traditional treatments. Prompt recognition and treatment of catatonia are crucial because malignant catatonia may be fatal without treatment. Given the high morbidity and mortality associated with malignant catatonia, intensivists should familiarize themselves with this important and under-recognized condition.

In-Hospital Depressed Level of Consciousness and Long-Term Functional Outcomes in ICU Survivors.

OBJECTIVES: Among critically ill patients, acutely depressed level of consciousness is associated with mortality, but its relationship to long-term outcomes such as disability and physical function is unknown. We investigated the relationship of level of consciousness during hospitalization with long-term disability and physical function in ICU survivors. DESIGN: Multi-center observational cohort study. SETTING: Medical or surgical ICUs at five U.S. centers. PATIENTS: Adult survivors of respiratory failure or shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Depressed level of consciousness during hospitalization was defined using the Richmond Agitation Sedation Scale (RASS) score (including all negative scores) by calculating the area under the curve using linear interpolation. Sedative-associated level of consciousness was similarly defined for all hospital days that sedation was received. We measured disability in basic activities of daily living (BADLs), instrumental activities of daily living (IADLs), discharge destination, and self-reported physical function. In separate models, we evaluated associations between these measures of level of consciousness and outcomes using multivariable regression, adjusted for age, sex, race, body mass index, education level, comorbidities, baseline frailty, baseline IADLs and BADLs, hospital type (civilian vs veteran), modified mean daily Sequential Organ Failure Assessment score, duration of severe sepsis, duration of mechanical ventilation, and hospital length of stay. Of the 1,040 patients enrolled in the ICU, 781 survived to hospital discharge. We assessed outcomes in 624 patients at 3 months and 527 patients at 12 months. After adjusting for covariates, there was no association between depressed level of consciousness (total or sedation-associated) with BADLs or IADLs at either 3- or 12-month follow-up. There was also no association with self-reported physical function at 3 or 12 months or with discharge destination. CONCLUSIONS: Depressed level of consciousness, as defined by the RASS, was not associated with disability or self-reported physical function. Future studies should investigate additional modifiable in-hospital risk factors for disability and poor physical function following critical illness.

Worse Than Death: Survey of Public Perceptions of Disability Outcomes After Hypothetical Traumatic Brain Injury.

OBJECTIVE: The aim of this study was to determine the health utility states of the most commonly used traumatic brain injury (TBI) clinical trial endpoint, the Extended Glasgow Outcome Scale (GOSE). SUMMARY BACKGROUND DATA: Health utilities represent the strength of one's preferences under conditions of uncertainty. There are insufficient data to indicate how an individual would value levels of disability after a TBI. METHODS: This was a cross-sectional web-based online convenience sampling adaptive survey. Using a standard gamble approach, participants evaluated their preferences for GOSE health states 1 year after a hypothetical TBI. The categorical GOSE was studied from vegetative state (GOSE2) to upper good recovery (GOSE8). Median (25th percentile, 75th percentile) health utility values for different GOSE states after TBI, ranging from -1 (worse than death) to 1 (full health), with 0 as reference (death). RESULTS: Of 3508 eligible participants, 3235 (92.22%) completed the survey. Participants rated lower GOSE states as having lower utility, with some states rated as worse than death, though the relationship was nonlinear and intervals were unequal between health states. Over 75% of participants rated a vegetative state (GOSE2, absence of awareness and bedridden) and about 50% rated lower severe disability (GOSE3, housebound needing all-day assistance) as conditions worse than death. CONCLUSIONS: In the largest investigation of public perceptions about post-TBI disability, we demonstrate unequally rated health states, with some states perceived as worse than death. Although limited by selection bias, these results may guide future comparative-effectiveness research and shared medical decision-making after neurologic injury.

Pseudodelirium: Psychiatric Conditions to Consider on the Differential for Delirium.

OBJECTIVE: The phenotypes of several psychiatric conditions can very closely resemble delirium; the authors describe such presentations as pseudodelirium. However, because the clinical management of these conditions differs markedly from that of delirium, prompt differentiation is essential. The authors provide an educational review to assist clinicians in identifying and managing psychiatric conditions that may be especially challenging to differentiate from delirium. METHODS: Based on clinical experience, the authors identified four psychiatric conditions as among the most difficult to differentiate from delirium: disorganized psychosis, Ganser syndrome, delirious mania, and catatonia. An overview of each condition, description of clinical features, differentiation of specific phenotypes from delirium, and review of clinical management are also provided. RESULTS: The thought and behavioral disorganization in disorganized psychosis can be mistaken for the clouded sensorium and behavioral dysregulation encountered in delirium. The fluctuating alertness and apparent confusion in Ganser syndrome resemble delirium's altered arousal and cognitive features. As its name suggests, delirious mania presents as a mixture of hyperactive delirium and mania; additional features may include psychosis, autonomic activation, and catatonia. Both delirium and catatonia have hypokinetic and hyperkinetic variants, and the two syndromes can also co-occur. CONCLUSIONS: The clinical presentations of several psychiatric conditions can blend with the phenotype of delirium, at times even co-occurring with it. Detailed evaluation is often required to differentiate such instances of pseudodelirium from delirium proper.

Pharmacologic Management of Intensive Care Unit Delirium: Clinical Prescribing Practices and Outcomes in More Than 8500 Patient Encounters.

BACKGROUND: Pharmacologic agents are frequently utilized for management of intensive care unit (ICU) delirium, yet prescribing patterns and impact of medication choices on patient outcomes are poorly described. We sought to describe prescribing practices for management of ICU delirium and investigate the independent association of medication choice on key in-hospital outcomes including delirium resolution, in-hospital mortality, and days alive and free of the ICU or hospital. METHODS: A retrospective study of delirious adult ICU patients at a tertiary academic medical center. Data were obtained regarding daily mental status (normal, delirious, and comatose), pharmacologic treatment, hospital course, and survival via electronic health record. Daily transition models were constructed to assess the independent association of previous day mental status and medication administration on mental status the following day and in-hospital mortality, after adjusting for prespecified covariates. Linear regression models investigated the association of medication administration on days alive and free of the ICU or the hospital during the first 30 days after ICU admission. RESULTS: We identified 8591 encounters of ICU delirium. Half (45.6%) of patients received pharmacologic treatment for delirium, including 45.4% receiving antipsychotics, 2.2% guanfacine, and 0.84% valproic acid. Median highest Richmond Agitation-Sedation Scale (RASS) score was 1 (0, 1) in patients initiated on medications and 0 (-1, 0) for nonrecipients. Haloperidol, olanzapine, and quetiapine comprised >97% of antipsychotics utilized with 48% receiving 2 or more and 20.6% continued on antipsychotic medications at hospital discharge. Haloperidol and olanzapine were associated with greater odds of continued delirium (odds ratio [OR], 1.48; 95% confidence interval [95% CI], 1.30-1.65; P < .001 and OR, 1.37; 95% CI, 1.20-1.56; P = .003, respectively) and increased hazard of in-hospital mortality (hazard ratio [HR], 1.46; 95% CI, 1.10-1.93; P = .01 and HR, 1.67; 95% CI, 1.14-2.45; P = .01, respectively) while quetiapine showed a decreased hazard of in-hospital mortality (HR, 0.58; 95% CI, 0.40-0.84; P = .01). Haloperidol, olanzapine, and quetiapine were associated with fewer days alive and free of hospitalization (all P < .001). There was no significant association of any antipsychotic medication with days alive and free of the ICU. Neither guanfacine nor valproic acid were associated with in-hospital outcomes examined. CONCLUSIONS: Pharmacologic interventions for management of ICU delirium are common, most often with antipsychotics, and frequently continued at hospital discharge. These medications may not portend benefit, may introduce additional harm, and should be used with caution for delirium management. Continuation of these medications through hospitalization and discharge draws into question their safety and role in patient recovery.

Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study.

BACKGROUND: The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year. METHODS: We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium. RESULTS: Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2-7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2-7) days and 1 (1-2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year. CONCLUSIONS: Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.

COVID-19: ICU delirium management during SARS-CoV-2 pandemic.

The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.

Delirium's Arousal Subtypes and Their Relationship with 6-Month Functional Status and Cognition.

OBJECTIVE: We sought to determine how delirium subtyped by arousal affected 6-month function and cognition in acutely ill older patients. METHODS: This was secondary analysis of a prospective cohort study which enrolled hospitalized patients ≥65 years old. Delirium and arousal were ascertained daily in the emergency department and the first 7 days of hospitalization using the modified Brief Confusion Assessment Method and Richmond Agitation Sedation Scale, respectively. For each day, patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Preillness and 6-month functional status were determined using the Older American Resources and Services activities of daily living scale which ranges from 0 (completely dependent) to 28 (completely independent). Preillness and 6-month cognition were determined using the Informant Questionnaire on Cognitive Decline in the Elderly which ranges from 1 (markedly improved cognition) to 5 (severe cognitive impairment). Multiple linear regression was performed adjusted for preillness Older American Resources and Services activities of daily living and Informant Questionnaire on Cognitive Decline in the Elderly and other relevant confounders. RESULTS: In 228 older patients, delirium with normal arousal was the only subtype independently associated with poorer 6-month function and cognition. For every day spent in this subtype, the 6-month Older American Resources and Services activities of daily living decreased by 0.84 points (95% confidence interval: -1.59 to -0.09) and the patient's 6-month Informant Questionnaire on Cognitive Decline in the Elderly significantly increased by 0.14 points (95% confidence interval: 0.06-0.23). CONCLUSIONS: Delirium with normal arousal, as opposed to delirium with decreased or increased arousal, was the only arousal subtype significantly associated with worsening 6-month function and cognition. Subtyping delirium by arousal may have important prognostic value.

Deficits in Self-Reported Initiation Are AssociatedWith Subsequent Disability in ICU Survivors.

OBJECTIVE: To determine whether deficits in a key aspect of executive functioning, namely, initiation, were associated with current and future functional disabilities in intensive care unit survivors. METHODS: A nested substudy within a 2-center prospective observational cohort. We used 3 tests of initiation at 3 and 12 months: the Ruff Total Unique Design, Controlled Oral Word Association, and Behavior Rating Inventory of Executive Function initiation. Disability in instrumental activities of daily living (IADL) was measured with the Functional Activities Questionnaire. We used a proportional odds logistic regression model to evaluate the association between initiation and disability. Covariates in the model included age, education, baseline Functional Activities Questionnaire, pre-existing cognitive impairment, comorbidities, admission severity of illness, episodes of hypoxia, and days of severe sepsis. RESULTS: In 195 patients, after adjusting for covariates, only the Behavior Rating Inventory of Executive Function initiation was associated with disability at any time point. Comparing the 25th vs the 75th percentile scores (95% confidence interval) of the Behavior Rating Inventory of Executive Function initiation at 3 months, patients with worse initiation scores had 5.062 times the odds (95% confidence interval: 2.539, 10.092) of disability according to the Functional Activities Questionnaire at 3 months, with similar odds at 12 months (odds ratio: 3.476, 95% confidence interval: 1.943, 6.216). Worse Behavior Rating Inventory of Executive Function initiation scores at 3 months were associated with future disability at 12 months odds ratio (95% confidence interval) 5.079 (2.579, 10.000). CONCLUSIONS: Executive function deficits acquired after a critical illness in the domain of initiation are common in intensive care unit survivors, and when they are identified via self-report tools, they are associated with current and future disability in instrumental activities of daily living.

Use of the brief Confusion Assessment Method in a veteran palliative care population: A pilot validation study.

OBJECTIVE: Many patients with advanced serious illness or at the end of life experience delirium, a potentially reversible form of acute brain dysfunction, which may impair ability to participate in medical decision-making and to engage with their loved ones. Screening for delirium provides an opportunity to address modifiable causes. Unfortunately, delirium remains underrecognized. The main objective of this pilot was to validate the brief Confusion Assessment Method (bCAM), a two-minute delirium-screening tool, in a veteran palliative care sample. METHOD: This was a pilot prospective, observational study that included hospitalized patients evaluated by the palliative care service at a single Veterans' Administration Medical Center. The bCAM was compared against the reference standard, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Both assessments were blinded and conducted within 30 minutes of each other. RESULT: We enrolled 36 patients who were a median of 67 years (interquartile range 63-73). The primary reasons for admission to the hospital were sepsis or severe infection (33%), severe cardiac disease (including heart failure, cardiogenic shock, and myocardial infarction) (17%), or gastrointestinal/liver disease (17%). The bCAM performed well against the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, for detecting delirium, with a sensitivity (95% confidence interval) of 0.80 (0.4, 0.96) and specificity of 0.87 (0.67, 0.96). SIGNIFICANCE OF RESULTS: Delirium was present in 27% of patients enrolled and never recognized by the palliative care service in routine clinical care. The bCAM provided good sensitivity and specificity in a pilot of palliative care patients, providing a method for nonpsychiatrically trained personnel to detect delirium.

Exploring Delirium's Heterogeneity: Association Between Arousal Subtypes at Initial Presentation and 6-Month Mortality in Older Emergency Department Patients.

OBJECTIVES: To determine how delirium subtyped by level of arousal at initial presentation affects 6-month mortality. DESIGN: This was a preplanned secondary analysis of two prospective cohort studies. SETTING: Academic tertiary care emergency department (ED). PARTICIPANTS: 1,084 ED patients who were 65 years old or older. MEASUREMENTS: At the time of enrollment, trained research personnel performed the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation Sedation Score to determine delirium and level of arousal, respectively. Patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Death was ascertained by medical record review and the Social Security Death Index. Cox proportional hazard regression was used to analyze the association between delirium arousal subtypes and 6-month mortality. RESULTS: Delirium with normal arousal was the only subtype that was significantly associated with increased 6-month mortality (hazard ratio [HR]: 3.1, 95% confidence interval [CI]: 1.3-7.4) compared with the no delirium group after adjusting for confounders. The HRs for delirium with decreased and increased arousal were 1.4 (95% CI: 0.9-2.1) and 1.3 (95% CI: 0.3-5.4), respectively. CONCLUSIONS: Delirious ED patients with normal arousal at initial presentation had a threefold increased hazard of death within 6 months compared with patients without delirium. There was a trend towards increased hazard of death in delirious ED patients with decreased arousal, but this relationship did not reach statistical significance. These data suggest that subtyping delirium by arousal may have prognostic value but requires confirmation with a larger study.

Identifying and Addressing the Hidden Reasons Why Patients Refuse Discharge From the Hospital.

BACKGROUND: Consultation-liaison psychiatrists are often asked to evaluate patients who refuse discharge from a medical facility. Literature to guide clinicians on the management of these patients is very limited. OBJECTIVE: This article seeks to explain this phenomenon through a case series, provide a differential diagnosis of patients who request to stay in the hospital, as well as provide clinicians with direction in the management of these difficult situations. METHODS: We discuss a case series of 3 patients treated at a large academic medical center, who refused discharge, discuss potential differential diagnoses, and provide management recommendations to guide clinicians. DISCUSSION: Providing care for a patient who refuses discharge can present several dilemmas for the treatment provider. Additionally, patients who refuse discharge may face emotional, physical, and financial costs secondary to continued unnecessary medical hospitalization. A variety of psychiatric conditions may contribute to a patient׳s desire to stay in the hospital. CONCLUSIONS: Patients who refuse medical discharge can present unique challenges for hospital-based medical providers as well as consultation psychiatrists who care for these patients. Careful consideration of diagnostic etiologies as well as coordination of care across the treatment team may be required to manage these unique and challenging cases.

The schizoaffective disorder diagnosis: a conundrum in the clinical setting.

The term schizoaffective was introduced to describe the co-occurrence of both psychotic and affective symptoms. Overtime, as the diagnosis schizoaffective disorder was added to diagnostic manuals, significant concerns were raised as to the reliability and clinical utility of the diagnosis. We recruited 134 psychiatrically hospitalized subjects who had received a diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features by their treating clinician. The subjects were also diagnosed by trained research personnel with the Structured Clinical Interview of the DSM-IV-TR, employing an explicit time threshold for criterion C of the schizoaffective disorder diagnosis. We found significant differences between the clinical and research diagnoses. Clinicians diagnosed 48 patients (36%) with schizophrenia, 50 patients (37%) with schizoaffective disorder and 36 patients (27%) with psychotic bipolar disorder. In contrast, researchers diagnosed 64 patients (48%) with schizophrenia, 38 patients (28%) with schizoaffective disorder and 32 patients (24%) with psychotic bipolar disorder. This was a statistically significant disagreement between the research and clinical diagnoses (p = 0.003) and indicates that clinicians choose the less severe diagnosis for psychotic patients. We conclude that a more stringent criterion C for the schizoaffective disorder diagnosis will address an implicit bias in clinical practice and will affect the prevalence of the psychotic disorder diagnoses.

Exploring genetic risk for catatonia in a genome wide association study and polygenic risk score analysis.

BACKGROUND: Catatonia is an under-recognized disorder characterized by psychomotor (increased, decreased, or abnormal) changes, affective symptoms, and disturbance of volition, which may arise in the setting of decompensated psychiatric or non-psychiatric medical disorders. Genetic studies of catatonia are limited, and to the best of our knowledge no prior genome wide association studies of catatonia have been performed to date. METHODS: First we performed a genome wide association study of catatonia regardless of etiology (psychiatric or non-psychiatric). Secondarily we evaluated whether there was an elevated genetic risk profile for predisposing psychiatric disorders (schizophrenia spectrum disorder, bipolar affective disorder, etc.) in patients with catatonia. We used a matched case control design and applied polygenic risk scores to evaluate for a shared polygenetic contribution to catatonia from common psychiatric phenotypes that show a high prevalence of catatonia in their decompensated states. RESULTS: Anxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorder polygenic risk scores were significantly associated with catatonia case status in both unadjusted and adjusted logistic regression models for the European Ancestry set even after correcting for multiple comparisons. Depression, Alzheimer's, Autism Spectrum Disorder and Obsessive Disorder polygenic risk scores were not significantly associated with catatonia status in participants of European Ancestry. In the African Ancestry set, no psychiatric polygenic risk scores were significantly associated with catatonia status in either the unadjusted or adjusted regression models. CONCLUSIONS: Even after controlling for relevant covariates, anxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorders were significantly associated with catatonia status suggesting that there might be a shared genetic risk for those disorders amongst patients with catatonia.

In-hospital catatonia, delirium, and coma and mortality: Results from the delirium and catatonia prospective cohort investigation.

BACKGROUND: Catatonia, a form of acute brain dysfunction typically linked with severe affective and psychotic disorders, occurs in critical illness with delirium and coma. Delirium and coma are associated with mortality, though catatonia's relationship with mortality is unclear. We aim to describe whether catatonia, delirium, and coma are associated with mortality. METHODS: We enrolled a convenience cohort of critically ill adults (N = 378) at an academic medical center. We assessed catatonia, delirium, and coma using the Bush-Francis Catatonia Rating Scale, the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively. We tested the associations between previous day brain dysfunction state occurrence with in-hospital and one-year mortality using multivariable time-dependent risk models. Additionally, we tested the association between brain dysfunction duration and one-year mortality. RESULTS: Catatonia was not associated with death on the day after diagnosis during hospitalization, and neither previous catatonia occurrence nor duration was associated with one-year mortality. Delirium was not associated with death on any day following diagnosis during hospitalization, and neither previous delirium occurrence nor duration was associated with one-year mortality. The occurrence of coma was associated with death on any day after diagnosis during hospitalization (HR 2.30,CI 1.19-4.44,p = 0.014), as well as through one year following hospital discharge (HR 1.68,CI 1.09-2.59,p = 0.02). CONCLUSIONS: Coma, but neither catatonia nor delirium, was associated with future day in-hospital and one-year mortality. More research is needed to understand catatonia's clinical impact. Delirium results differ from existing literature likely due to cohort demographics and size. Coma results highlight the prognostic significance of suppressed arousal while critically ill.

Sex, racial, and APOE-ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

INTRODUCTION: The effects of sex, race, and Apolipoprotein E (APOE) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. METHODS: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. RESULTS: Sex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.

Why We Must Prevent and Appropriately Manage Delirium.

Delirium is common and increases in prevalence with age and medical complexity. A form of acute brain dysfunction, its presence is associated with significant morbidity, such as cognitive impairment, decreased mobility, depression, and institutionalization, as well as mortality. Many organizations have developed clinical protocols to prevent and treat delirium and what are called "cognitive-friendly" policies to care for elderly patients.

Thinking Clearly: The History of Brain Dysfunction in Critical Illness.

Brain dysfunction during critical illness (ie, delirium and coma) is extremely common, and its lasting effect has only become increasingly understood in the last two decades. Brain dysfunction in the intensive care unit (ICU) is an independent predictor of both increased mortality and long-term impairments in cognition among survivors. As critical care medicine has grown, important insights regarding brain dysfunction in the ICU have shaped our practice including the importance of light sedation and the avoidance of deliriogenic drugs such as benzodiazepines. Best practices are now strategically incorporated in targeted bundles of care like the ICU Liberation Campaign's ABCDEF Bundle.