Preliminary Validation of the Acute Care Mobility Assessment as a Measure of Hospital Mobility.

BACKGROUND: Despite heighted interest, measurement of hospital mobility remains challenging. Available assessment tools lack patient input regarding level and frequency of hospital mobility. The purpose of this study was to validate a brief self-reported mobility assessment to measure out-of-bed activity during hospitalization. METHODS: We recruited cognitively intact hospitalized adults (age ≥65 years) who walked prior to admission, to wear an accelerometer for 24 hours and to complete the Acute Care Mobility Assessment (ACMA), a self-report of mobility that ranges from bed rest to walking off the hospital unit in the prior 24 hours. For each mobility level from sitting in a chair to walking off the unit, patients reported frequency of the activity and need for help from another person or equipment. Spearman correlation coefficients were calculated using several scoring algorithms to compare ACMA to accelerometer data. RESULTS: Fifty-one patients (mean age 74.3 (SD 6.2) years, 63% female, 39% Black) had complete data. Steps taken in 24 hours ranged from 10 - 2831. Correlation analyses identified strong associations between ACMA scores and total steps, and moderate correlations with total time walking using all algorithms. However, the unweighted frequency count using the three ambulation levels only (walking in room, in hall and off ward) had the highest correlation with total steps (r=0.84; p<0.001) and total time walking (r=0.66; p<0.001). CONCLUSION: ACMA is a valid measure of mobility among cognitively intact hospitalized older adults. The ACMA may add value to our current armamentarium of tools by adding patient report of hospital mobility.

Delirium Due to Potentially Avoidable Hospitalizations Among Older Adults.

BACKGROUND: Delirium is a common complication during acute care hospitalizations in older adults. A substantial percentage of admissions are for ambulatory care-sensitive conditions (ACSCs) or potentially avoidable hospitalizations-conditions that might be treated early in the outpatient setting to prevent hospitalization and hospital complications. METHODS: This retrospective cross-sectional study examined rates of delirium among older adults hospitalized for ACSCs. Participants were 39 933 older adults ≥65 years of age admitted from January 1, 2015 to December 31, 2019 to general inpatient units and ICUs of a large Southeastern academic medical center. Delirium was defined as a score ≥ 2 on the Nursing Delirium Screening Scale or positive on the Confusion Assessment Method for the Intensive Care Unit during admission, and ACSCs were identified from the primary admission diagnosis using standardized definitions. Generalized linear mixed models were used to examine the association between ACSCs and delirium, compared with admissions for non-ACSC diagnoses, adjusting for covariates and repeated observations for individuals with multiple admissions. RESULTS: Delirium occurred in 15.6% of admissions for older adults. Rates were lower for ACSC admissions versus admissions for other conditions (13.9% vs 15.8%, p < .001). Older age and higher comorbidity were significant predictors of the development of delirium. CONCLUSIONS: Rates of delirium among older adults hospitalized for ACSCs were lower than rates for non-ACSC hospitalization but still substantial. Optimizing the treatment of ACSCs in the outpatient setting is an important goal not only for reducing hospitalizations but also for reducing risks for hospital-associated complications such as delirium.

Life-Space Mobility: Normative Values From a National Cohort of U.S. Older Adults.

BACKGROUND: Life-space mobility, which measures the distance, frequency, and independence achieved as individuals move through their community, is one of the most important contributors to healthy aging. The University of Alabama at Birmingham Life-Space Assessment (LSA) is the most commonly used measure of life-space mobility in older adults, yet U.S. national norms for LSA have not previously been reported. This study reports such norms based on age and sex among community-dwelling older adults. METHODS: A cross-sectional analysis using data from the national REasons for Geographic and Racial Disparities in Stroke cohort study. LSA data were available for 10 118 Black and White participants over age 50, which were grouped by age (in 5-year increments) and sex, weighted for the U.S. national population. Correlations were calculated between LSA and measures of functional and cognitive impairment and physical performance. RESULTS: The weighted mean LSA ranged from 102.9 for 50-54-year-old males to 69.5 for males aged 85 and older, and from 102.1 for 50-54-year-old females to 60.1 for females aged 85 and older. LSA was strongly correlated with measures of timed walking, activities of daily living, cognition, depressive symptoms, and quality of life (all p < .001). CONCLUSIONS: We report U.S. national norms for LSA among community-dwelling Black and White older adults. These norms can serve as a reference tool for determining if clinical and research samples have greater or lesser life-space mobility than typical older adults in the United States for their age and sex.

Changes in Life-Space Mobility With Loss of Relatives and Friends Among Older Adults: Results From the UAB Study of Aging.

BACKGROUND AND OBJECTIVES: Increasing age brings a greater risk of death of friends and family (hereafter referred to as loss) potentially impacting individuals' life-space mobility (LSM) trajectory. RESEARCH DESIGN AND METHODS: Using the UAB study of aging, we examined differences in LSM trajectories of 1,000 community-dwelling older Alabamians (65 + years) with and without loss over 8.5 years. We measured LSM using UAB's Life-Space Assessment (LSA), a validated instrument assessing movement through zones ranging from their bedroom to out of town. We assessed loss every 6 months using a standard bereavement questionnaire capturing spousal, other relative, or friend loss. We used piecewise linear mixed-effects models to compare LSA trajectories. RESULTS: At baseline, those who later experienced loss, compared with those who did not were younger, more likely to be female, and overall in better health. Those without loss had a baseline mean LSA score of 49.5 and a decline of 0.08 points per year (p < .001). Those with loss had a baseline LSA score of 60 and declined by 1.0 point per year before loss (p < .001), accelerating to 1.8 points per year after loss (p < .001). DISCUSSION AND IMPLICATIONS: Those with loss do not experience acute decline postloss but do have an acceleration of the preexisting decline. Although additional research may explain the impact of loss on LSM; this finding suggests that more interventions such as social, mental, or health care services, may be needed for those who experience loss. Specifically, bereaved individuals may benefit from it.

Specialist Availability and Drug Adherence in Older Adults with Dementia Across Regions of the United States.

BACKGROUND: Access to specialists facilitates appropriate Alzheimer's disease and related dementia (ADRD) medication use and adherence. However, there is little information on the impact of specialists' availability on ADRD medication adherence, especially in regions of the United States (US) where specialists are scarce, e.g., the Deep South (DS). OBJECTIVE: To ascertain whether the availability of specialty physicians in the DS and other US regions predicts ADRD medication adherence among community-dwelling older adultsMethods:We conducted secondary analyses of claims data for 54,194 Medicare beneficiaries with ADRD in 2013-2015. Medication adherence was measured using the proportion of days covered (PDC). Multivariable-adjusted Modified Poisson regression was used to examine associations of adherence with physicians' availability by region. RESULTS: The race/ethnicity distribution was 81.44% white, 9.17% black, 6.24% Hispanic, 2.25% Asian, and 1% other; 71.81% were female, and 42.36% were older than 85 years. Beneficiaries across regions differed in all individual and contextual characteristics except sex and comorbidities. Neurologists and psychiatrists' availability was not significantly associated with adherence (DS = 1.00, 0.97-1.03 & non-DS = 1.01, 1.00-1.01). Race and having ≥1 specialist visits were associated with a lower risk of adherence in both regions (p < 0.0001). Advanced age, dual Medicare/Medicaid eligibility, and living in non-large metropolitan areas, were associated with adherence in the non-DS region. CONCLUSION: Among older Americans with ADRD, a context defined by specialist availability does not affect adherence, but other context characteristics related to socioeconomic status may. Research should further examine the influence of individual and contextual factors on ADRD treatment among older adults.

Delirium Mediates Incidence of Hospital-Associated Disability Among Older Adults.

OBJECTIVE: To examine whether delirium predicts occurrence of hospital-associated disability (HAD), or functional decline after admission, among hospitalized older adults. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: General inpatient (non-ICU) units of a large regional Southeastern US academic medical center, involving 33,111 older adults ≥65 years of age admitted from January 1, 2015, to December 31, 2019. METHODS: Delirium was defined as a score ≥2 on the Nursing Delirium Screening Scale (NuDESC) during hospital admission. HAD was defined as a decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. Generalized linear mixed models were used to examine the association between delirium and HAD, adjusting for covariates and repeated observations with multiple admissions. We performed multivariate and mediation analyses to examine strength and direction of association between delirium and HAD. RESULTS: One-fifth (21.6%) of older adults developed HAD during hospitalization and experienced higher delirium rates compared to those not developing HAD (24.3% vs 14.3%, P < .001). Age, presence of delirium, Elixhauser Comorbidity Score, admission cognitive status, admission ADL function, and length of stay were associated (all P < .001) with incident HAD. Mediational analyses found 46.7% of the effect of dementia and 16.7% of the effect of comorbidity was due to delirium (P < .001). CONCLUSIONS AND IMPLICATIONS: Delirium significantly increased the likelihood of HAD within a multivariate predictor model that included comorbidity, demographics, and length of stay. For dementia and comorbidity, mediation analysis showed a significant portion of their effect attributable to delirium. Overall, these findings suggest that reducing delirium rates may diminish HAD rates.

National Norms for Hospitalizations Due to Ambulatory Care Sensitive Conditions among Adults in the US.

BACKGROUND: Ambulatory care sensitive conditions (ACSCs) are acute or chronic health issues that lead to potentially preventable hospitalizations when not treated in the outpatient primary care setting. OBJECTIVE: To describe national hospitalization rates due to ACSCs among adult inpatients in the US. DESIGN: A retrospective cross-sectional analysis of the 2018 US National Inpatient Sample (NIS) dataset from the Healthcare Cost and Utilization Project at the Agency of Healthcare Research and Quality was completed in the year 2022. PARTICIPANTS: Participants were adult inpatients from community hospitals in 48 states of the US and District of Columbia. MAIN MEASURES: ACSC admission rates were calculated using ICD-10 codes and the Purdy ACSC definition. The admission rates were weighted to the US inpatient population and stratified by age, sex, and race. KEY RESULTS: ACSC hospitalization rates varied considerably across age and average number of hospitalizations varied across sex and race. ACSC hospitalization rates increased with age, male sex, and Native American and Black race. The most common ACSCs were pneumonia, diabetes, and congestive heart failure. CONCLUSIONS: Previous studies have emphasized the importance of preventable hospitalizations, however, the national rates for ACSC hospitalizations across all ages in the US have not been reported. The national rates presented will facilitate comparisons to identify hospitals and health care systems with higher-than-expected rates of ACSC admissions that may suggest a need for improved primary care services.

Hospital-associated disability due to avoidable hospitalizations among older adults.

BACKGROUND: Hospital-associated disability (HAD) is a common complication during the course of acute care hospitalizations in older adults. Many admissions are for ambulatory care sensitive conditions (ACSCs), considered potentially avoidable hospitalizations-conditions that might be treated in outpatient settings to prevent hospitalization and HAD. We compared the incidence of HAD between older adults hospitalized for ACSCs versus those hospitalized for other diagnoses. METHODS: We conducted a retrospective cohort study in inpatient (non-ICU) medical and surgical units of a large southeastern regional academic medical center. Participants were 38,960 older adults ≥ 65 years of age admitted from January 1, 2015, to December 31, 2019. The primary outcome was HAD, defined as decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. We used generalized linear mixed models to examine differences in HAD between hospitalizations with a primary diagnosis for an ACSC using standard definitions versus primary diagnosis for other conditions, adjusting for covariates and repeated observations for individuals with multiple hospitalizations. RESULTS: We found that 10% of older adults were admitted for an ACSC, with rates of HAD in those admitted for ACSCs lower than those admitted for other conditions (16% vs. 20.7%, p < 0.001). Age, comorbidity, admission functional status, and admission cognitive impairment were significant predictors for development of HAD. ACSC admissions to medical and medical/surgical services had lower odds of HAD compared with admissions for other conditions, with no significant differences between ACSC and non-ACSC admissions to surgical services. CONCLUSIONS: Rates of HAD among older adults hospitalized for ACSCs are substantial, though lower than rates of HAD with hospitalization for other conditions, reflecting that acute care hospitalization is not a benign event in this population. Treatment of ACSCs in the outpatient setting could be an important component of efforts to reduce HAD.

A systematic review and meta-analysis: Assessment of hospital walking programs among older patients.

AIM: The aim of this study is to assess effect of hospital walking programs on outcomes for older inpatients and to characterize hospital walking dose reported across studies. DESIGN: A systematic review and meta-analysis examining impact of hospital walking and/or reported walking dose among medical-surgical inpatients. For inclusion, studies were observational or experimental, published in English, enrolled inpatients aged ≥ 65 yrs hospitalized for medical or surgical reasons. METHODS: Searches of PubMed, CINAHL, Embase, Scopus, NICHSR, OneSearch, ClinicalTrials.gov, and PsycINFO were completed in December 2020. Two reviewers screened sources, extracted data, and performed quality bias appraisal. RESULTS: Hospital walking dose was reported in 6 studies and commonly as steps/24 hr. Length of stay (LOS) was a common outcome reported. Difference in combined mean LOS between walking and control groups was -5.89 days. Heterogeneity across studies was considerable (I2  = 96%) suggesting poor precision of estimates. Additional, high-quality trials examining hospital walking and patient outcomes of older patients is needed.

National Norms for the Elixhauser and Charlson Comorbidity Indexes Among Hospitalized Adults.

BACKGROUND: Comorbidity burden is commonly measured among hospitalized adults, yet the U.S. national norms for 2 commonly used comorbidity indexes have not yet been reported. Thus, this study reports U.S. national norms for both Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) among hospitalized adults based on age, biological sex, and race. METHODS: A retrospective observational cohort study using data from the Agency of Healthcare Research and Quality U.S. National Inpatient Sample database for 2017. Patient data were extracted from 7 159 694 inpatient adults, and analyses were focused on individuals older than 45 years, yielding 4 370 225 patients. International Classification of Diseases, 10th Edition, diagnostic codes were used to calculate CCI and ECI scores. These scores were then weighted for the U.S. national population. RESULTS: The weighted mean CCI was 1.22 (95% confidence interval [CI]: 1.22, 1.22), and the weighted mean ECI was 2.76 (95% CI: 2.76, 2.76). Both indexes had increasing average scores with increasing age, independent of sex and race (all p values < .001). CONCLUSION: For the first time, U.S. national norms for the CCI and ECI are reported for adult inpatients. The norms can serve as a reference tool for determining if clinical and research populations have greater or lesser comorbidity burden than typical hospitalized adults in the United States for their age, sex, and race.

Preserving independence among under-resourced older adults in the Southeastern United States: existing barriers and potential strategies for research.

Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as "the Deep South", is an economically and culturally unique region ravaged by pervasive health disparities - thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region.

Association of Performance on the Financial Capacity Instrument-Short Form With Brain Amyloid Load and Cortical Thickness in Older Adults.

Background and Objectives: To investigate the association of the Financial Capacity Instrument-Short Form (FCI-SF) performance and timing total scores with brain ß-amyloid and cortical thickness in cognitively unimpaired (CU) (at baseline) older adults. Methods: A total of 309 participants (aged 70 years or older) of the Mayo Clinic Study of Aging underwent 11C-Pittsburgh compound B PET amyloid imaging and MRI, and completed the FCI-SF. Abnormal amyloid PET was defined as standardized uptake value ratio ≥1.48 in an Alzheimer disease (AD)-related region of interest and reduced AD signature cortical thickness as ≤2.68 mm (neurodegeneration). A cohort of 218 (of the 309) participants had follow-up visits (every 15 months) with FCI-SF data for longitudinal analysis (number of visits including baseline, median [range]: 2 [2-4]). In the analysis, we used linear regression and mixed-effects models adjusted for age, sex, education, apolipoprotein E ε4 allele status, global cognitive z score, and previous FCI-SF testing. Results: Participants' mean age (SD) was 80.2 (4.8) years (56.3% male individuals). In cross-sectional analysis, abnormal amyloid PET (vs normal) was associated with a lower FCI-SF total score and slower total composite time. In longitudinal analysis, FCI-SF total score declined faster (difference in annualized rate of change, beta coefficient [ß] [95% confidence interval (CI)] = -1.123 [-2.086 to -0.161]) and FCI-SF total composite time increased faster (difference in annualized rate of change, ß [95% CI] = 16.274 [5.951 to 26.597]) for participants with neurodegeneration at baseline (vs those without). Participants who exhibited both abnormal amyloid PET and neurodegeneration at baseline had a greater increase in total composite time when compared with the group without abnormal amyloid and without neurodegeneration (difference in annualized rate of change, ß [95% CI] = 16.750 [3.193 to 30.307]). Discussion: Performance and processing speed on the FCI-SF were associated with imaging biomarkers of AD pathophysiology in CU (at baseline) older adults. Higher burdens of imaging biomarkers were associated with longitudinal worsening on FCI-SF performance. Additional research is needed to delineate further these associations and their predictive utility at the individual person level.

The Relationship Between Prior Cancer Diagnosis and All-Cause Dementia Progression Among US Adults.

BACKGROUND: Cancer-related cognitive impairment (CRCI), a frequent effect of cancer and its treatments, shares common cognitive symptoms with dementia syndromes. Cross-sectional studies demonstrate an inverse relationship between cancer and dementia. However, the longitudinal relationship between dementia decline and cancer has not been investigated. OBJECTIVE: To evaluate the association between cancer and longitudinal progression of dementia. METHODS: We extracted electronic health record data from July 2003 to February 2020 from a single academic medical center. We identified dementia and cancer history prior to dementia using ICD-9/10 codes. We measured cognitive decline with the Alabama Brief Cognitive Screener (ABCs). We used adjusted linear mixed models to estimate baseline cognition and rate of progression by cancer history, including differences by race. RESULTS: The study included 3,809 participants with dementia, of which 672 (17.6%) had cancer history. Those with cancer history had higher baseline cognition (ß: 1.07, 95% CI: 0.45, 1.69), but similar rate of decline. Non-Hispanic Blacks had lower cognitive scores at baseline and throughout follow-up regardless of cancer status compared to non-Hispanic Whites and other races/ethnicities with and without cancer history. CONCLUSION: In this longitudinal retrospective study, participants with cancer history demonstrate better cognition at dementia diagnosis and no difference in cognitive decline than those without cancer history. Smoking and comorbidities attenuate this association and results indicate non-Hispanic Blacks have worse cognitive outcomes in dementia regardless of cancer history than other race/ethnicity groups. Further exploration of the role of smoking, comorbidities, and race/ethnicity on cancer and dementia-related cognitive decline is needed.

Image Quantification for TSPO PET with a Novel Image-Derived Input Function Method.

There is a growing interest in using 18F-DPA-714 PET to study neuroinflammation and microglial activation through imaging the 18-kDa translocator protein (TSPO). Although quantification of 18F-DPA-714 binding can be achieved through kinetic modeling analysis with an arterial input function (AIF) measured with blood sampling procedures, the invasiveness of such procedures has been an obstacle for wide application. To address these challenges, we developed an image-derived input function (IDIF) that noninvasively estimates the arterial input function from the images acquired for 18F-DPA-714 quantification. Methods: The method entails three fully automatic steps to extract the IDIF, including a segmentation of voxels with highest likelihood of being the arterial blood over the carotid artery, a model-based matrix factorization to extract the arterial blood signal, and a scaling optimization procedure to scale the extracted arterial blood signal into the activity concentration unit. Two cohorts of human subjects were used to evaluate the extracted IDIF. In the first cohort of five subjects, arterial blood sampling was performed, and the calculated IDIF was validated against the measured AIF through the comparison of distribution volumes from AIF (VT,AIF) and IDIF (VT,IDIF). In the second cohort, PET studies from twenty-eight healthy controls without arterial blood sampling were used to compare VT,IDIF with VT,REF measured using a reference region-based analysis to evaluate whether it can distinguish high-affinity (HAB) and mixed-affinity (MAB) binders. Results: In the arterial blood-sampling cohort, VT derived from IDIF was found to be an accurate surrogate of the VT from AIF. The bias of VT, IDIF was −5.8 ± 7.8% when compared to VT,AIF, and the linear mixed effect model showed a high correlation between VT,AIF and VT, IDIF (p < 0.001). In the nonblood-sampling cohort, VT, IDIF showed a significance difference between the HAB and MAB healthy controls. VT, IDIF and standard uptake values (SUV) showed superior results in distinguishing HAB from MAB subjects than VT,REF. Conclusions: A novel IDIF method for 18F-DPA-714 PET quantification was developed and evaluated in this study. This IDIF provides a noninvasive alternative measurement of VT to quantify the TSPO binding of 18F-DPA-714 in the human brain through dynamic PET scans.

Proportional constrained longitudinal data analysis models for clinical trials in sporadic Alzheimer's disease.

Introduction: Clinical trials for sporadic Alzheimer's disease generally use mixed models for repeated measures (MMRM) or, to a lesser degree, constrained longitudinal data analysis models (cLDA) as the analysis model with time since baseline as a categorical variable. Inferences using MMRM/cLDA focus on the between-group contrast at the pre-determined, end-of-study assessments, thus are less efficient (eg, less power). Methods: The proportional cLDA (PcLDA) and proportional MMRM (pMMRM) with time as a categorical variable are proposed to use all the post-baseline data without the linearity assumption on disease progression. Results: Compared with the traditional cLDA/MMRM models, PcLDA or pMMRM lead to greater gain in power (up to 20% to 30%) while maintaining type I error control. Discussion: The PcLDA framework offers a variety of possibilities to model longitudinal data such as proportional MMRM (pMMRM) and two-part pMMRM which can model heterogeneous cohorts more efficiently and model co-primary endpoints simultaneously.

Influence of Subject-Specific Effects in Longitudinal Modelling of Cognitive Decline in Alzheimer's Disease.

BACKGROUND: Accurate longitudinal modelling of cognitive decline is a major goal of Alzheimer's disease and related dementia (ADRD) research. However, the impact of subject-specific effects is not well characterized and may have implications for data generation and prediction. OBJECTIVE: This study seeks to address the impact of subject-specific effects, which are a less well-characterized aspect of ADRD cognitive decline, as measured by the Alzheimer's Disease Assessment Scale's Cognitive Subscale (ADAS-Cog). METHODS: Prediction errors and biases for the ADAS-Cog subscale were evaluated when using only population-level effects, robust imputation of subject-specific effects using model covariances, and directly known individual-level effects fit during modelling as a natural control. Evaluated models included pre-specified parameterizations for clinical trial simulation, analogous mixed-effects regression models parameterized directly, and random forest ensemble models. Assessment used a meta-database of Alzheimer's disease studies with validation in simulated synthetic cohorts. RESULTS: All models observed increases in variance under imputation leading to increased prediction error. Bias decreased with imputation except under the pre-specified parameterization, which increased in the meta-database, but was attenuated under simulation. Known fitted subject effects gave the best prediction results. CONCLUSION: Subject-specific effects were found to have a profound impact on predicting ADAS-Cog. Reductions in bias suggest imputing random effects assists in calculating results on average, as when simulating clinical trials. However, reduction in error emphasizes population-level effects when attempting to predict outcomes for individuals. Forecasting future observations greatly benefits from using known subject-specific effects.

Gut- and oral-dysbiosis differentially impact spinal- and bulbar-onset ALS, predicting ALS severity and potentially determining the location of disease onset.

BACKGROUND: Prior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field. METHODS: ALS patients diagnosed within 12 months and their spouses as healthy controls (n = 150 couples) were screened. For eligible sALS and bALS patients (n = 36) and healthy controls (n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R). RESULTS: sALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes-ratio (F/B-ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B-ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B-ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.8006, P < 0.0001) and more severe symptoms (r = 0.9470, P < 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B-ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.9860, P < 0.0001) and greater disease severity (r = 0.9842, P < 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P < 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS. CONCLUSIONS: We found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.

Inpatient Diagnosis of Delirium and Encephalopathy: Coding Trends in 2011-2018.

BACKGROUND: Ten medical societies have called for scientific literature to integrate research on delirium and encephalopathy, while physicians continually debate how to accurately document diagnoses of acute confusional states. OBJECTIVE: To promote this integration, we evaluated trends in diagnoses of delirium and encephalopathy among hospitalized adults and physician specialties, incorporating transitions to the Diagnostic and Statistical Manual of Mental Disorders-5 and the International Classification of Disease, tenth edition. METHODS: Using the 2011-2018 IBM MarketScan datasets, we identified delirium/encephalopathy patients aged ≥18 years using International Classification of Disease 9/10 codes among hospitalized patients. We identified physician specialties associated with the hospitalization and comorbidities within one year before the diagnosis of delirium or encephalopathy. Log-binomial models were used to evaluate diagnostic trends, adjusting for age, gender, insurance, and comorbidities. RESULTS: We identified 10,509 hospitalized patients with a diagnosis of delirium and 94,438 with encephalopathy between 2011 and 2018. Although the number of patients with either diagnosis increased over time, the use of delirium diagnosis was less than it was for encephalopathy compared with 2011 after adjusting for covariates (adjusted risk ratio 0.45; 95% confidence interval 0.43 to 0.48). During the 8 years, neurologists and internists increased their use of both diagnoses, whereas only psychiatrists increased their use of delirium. Family practice physicians and nurse practitioners presented no significant change in either diagnosis for this timeframe. CONCLUSIONS: Our results suggest that refined diagnostic codes and criteria may alter trends among clinicians in diagnosing delirium and/or encephalopathy. Additional diagnostic clarity may be necessary to support refined diagnoses among family practice physicians and nurse practitioners.

Dynamic Amyloid PET: Relationships to 18F-Flortaucipir Tau PET Measures.

Measuring amyloid and predicting tau status using a single amyloid PET study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are determined primarily by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: The study included 120 participants (63 amyloid-positive and 57 amyloid-negative) with dynamic 18F-florbetapir PET and static 18F-flortaucipir PET scans obtained within 6 mo of each other. These subjects were predominantly cognitively intact in both the amyloid-positive (63%) and the amyloid-negative (93%) groups. Parameters for efAP quantification were optimized for stratification of tau PET positivity, assessed by either a tauopathy score or Braak regions. The ability of efAP to stratify tau positivity was measured using receiver-operating-characteristic analysis of area under the curve (AUC). Pearson r and Spearman ρ were used for parametric and nonparametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in using efAP as an additional copredictor over hippocampal volume in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 min of brain activity after injection showed the strongest discriminative ability to stratify for tau positivity (AUC, 0.67-0.89 across tau PET Braak regions) in amyloid-positive individuals. Hippocampal efAP correlated significantly with a global tau PET tauopathy score in amyloid-positive participants (r = -0.57, P < 0.0001). Compared with hippocampal volume, hippocampal efAP showed a stronger association with tau PET Braak stage (ρ = -0.58 vs. -0.37) and superior stratification of tau PET tauopathy score (AUC, 0.86 vs. 0.66; P = 0.002). Conclusion: Hippocampal efAP can provide additional information to conventional amyloid PET, including estimation of the likelihood of tau positivity in amyloid-positive individuals.