Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

The Confusion Assessment Method in action: Implementation of a protocol to increase delirium screening and diagnosis.

The use of the Confusion Assessment Method (CAM) for delirium assessment in real-life can be inconsistent. We examined the impact of a protocol on delirium screening and detection in hospitalized older adults using the CAM. We analyzed data from 32,338 admissions to a quaternary hospital between 2018 and 2022. We assessed the percentage of admissions screened for delirium, adherence to daily screening, positive screening, and overlap with ICD-10 coding. The percentage of admissions screened for delirium increased from 74% in 2018 to 98.7% in 2022. Adherence to daily screening was achieved in 24.5% of admissions, and the percentage of positive screenings fluctuated between 8.4% and 11.5%. Among the admissions with a delirium-related ICD-10 code, 32% had a positive screening, 62% were negative, and 6% remained unscreened. While implementing a protocol increased the proportion of admissions screened for delirium, adherence to daily screening and consistency of positive delirium screenings remain areas for improvement.

The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70.

BACKGROUND: This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. METHODS: Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. RESULTS: Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. CONCLUSIONS: Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

Patient-Centered Outcomes Following COVID-19: Frailty and Disability Transitions in Critical Care Survivors.

OBJECTIVES: As the pandemic advances, the interest in the long-lasting consequences of COVID-19 increases. However, a few studies have explored patient-centered outcomes in critical care survivors. We aimed to investigate frailty and disability transitions in COVID-19 patients admitted to ICUs. DESIGN: Prospective cohort study. SETTING: University hospital in Sao Paulo. PATIENTS: Survivors of COVID-19 ICU admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed frailty using the Clinical Frailty Scale (CFS). We also evaluated 15 basic, instrumental, and mobility activities. Baseline frailty and disability were defined by clinical conditions 2-4 weeks before COVID-19, and post-COVID-19 was characterized 90 days (day 90) after hospital discharge. We used alluvial flow diagrams to visualize transitions in frailty status, Venn diagrams to describe the overlap between frailty and disabilities in activities of daily living, and linear mixed models to explore the occurrence of new disabilities following critical care in COVID-19. We included 428 participants with a mean age of 64 years, 57% males, and a median Simplified Acute Physiology Score-3 score of 59. Overall, 14% were frail at baseline. We found that 124/394 participants (31%) were frail at day 90, 70% of whom were previously non-frail. The number of disabilities also increased (mean difference, 2.46; 95% CI, 2.06-2.86), mainly in participants who were non-frail before COVID-19. Higher pre-COVID-19 CFS scores were independently associated with new-onset disabilities. At day 90, 135 patients (34%) were either frail or disabled. CONCLUSIONS: Frailty and disability were more frequent 90 days after hospital discharge compared with baseline in COVID-19 patients admitted to the ICU. Our results show that most COVID-19 critical care survivors transition to poorer health status, highlighting the importance of long-term medical follow-up for this population.

Prospective GERiatric Observational (ProGERO) study: cohort design and preliminary results.

BACKGROUND: The demographic changes in Brazil as a result of population aging is one of the fastest in the world. The far-reaching new challenges that come with a large older population are particularly disquieting in low- and middle-income countries (LMICs). Longitudinal studies must be completed in LMICs to investigate the social and biological determinants of aging and the consequences of such demographic changes in their context. Therefore, we designed the Prospective GERiatric Observational (ProGERO) study, a longitudinal study of outpatient older adults in São Paulo, Brazil, to collect data both on aging and chronic diseases, and investigate characteristics associated with adverse outcomes in this population. METHODS: The ProGERO study takes place in a geriatric outpatient clinic in the largest academic medical center in Latin America. We performed baseline health examinations in 2017 and will complete subsequent in-person visits every 3 years when new participants will also be recruited. We will use periodic telephone interviews to collect information on the outcomes of interest between in-person visits. The baseline evaluation included data on demographics, medical history, physical examination, and comprehensive geriatric assessment (CGA; including multimorbidity, medications, social support, functional status, cognition, depressive symptoms, nutritional status, pain assessment, frailty, gait speed, handgrip strength, and chair-stands test). We used a previously validated CGA-based model to rank participants according to mortality risk (low, medium, high). Our selected outcomes were falls, disability, health services utilization (emergency room visits and hospital admissions), institutionalization, and death. We will follow participants for at least 10 years. RESULTS: We included 1336 participants with a mean age of 82 ± 8 years old. Overall, 70% were women, 31% were frail, and 43% had a Charlson comorbidity index score ≥ 3. According to our CGA-based model, the incidence of death in 1 year varied significantly across categories (low-risk = 0.6%; medium-risk = 7.4%; high-risk = 17.5%; P < 0.001). CONCLUSION: The ProGERO study will provide detailed clinical data and explore the late-life trajectories of outpatient older patients during a follow-up period of at least 10 years. Moreover, the study will substantially contribute to new information on the predictors of aging, senescence, and senility, particularly in frail and pre-frail outpatients from an LMIC city.

Delirium and post-discharge dementia: results from a cohort of older adults without baseline cognitive impairment.

OBJECTIVES: to investigate the association between delirium occurrence in acutely ill older adults and incident dementia after hospital discharge. METHODS: retrospective cohort study examining acutely ill older adults aged +60 years and consecutively admitted to the geriatric ward of a tertiary university hospital from 2010 to 2016. Inclusion criteria were absence of baseline cognitive decline on admission and documented clinical follow-up of +12 months after discharge. Admission data were collected from our local database, including results from a standardized comprehensive geriatric assessment completed for every patient. Pre-existing cognitive decline was identified based on clinical history, CDR and IQCODE-16. Delirium was diagnosed using short-CAM criteria, while post-discharge dementia after 12 months was identified based on medical records' review. We used competing-risk proportional-hazard models to explore the association between delirium and post-discharge dementia. RESULTS: we included 309 patients. Mean age was 78 years, and 186 (60%) were women. Delirium was detected in 66 (21%) cases. After a median follow-up of 24 months, 21 (32%) patients who had experienced delirium progressed with dementia, while only 38 (16%) of those without delirium had the same outcome (P = 0.003). After adjusting for possible confounders, delirium was independently associated with post-discharge dementia with a sub-hazard ratio of 1.94 (95%CI = 1.10-3.44; P = 0.022). CONCLUSION: one in three acutely ill older adults who experienced delirium in the hospital developed post-discharge dementia during follow-up. Further understanding of delirium as an independent and potentially preventable risk factor for cognitive decline emphasizes the importance of systematic initiatives to fight it.

Fairness: from the guts to the brain - a critical examination by Atlantic fellows of the Global Brain Health Institute.

In January 2023, the Global Brain Health Institute (GBHI) at UCSF hosted an online salon to discuss the relationship between fairness and brain health equity. We aimed to address two primary questions: first, how is fairness perceived by the public, and how does it manifest in societal constructs like equity and justice? Second, what are the neurobiological foundations of fairness, and how do they impact brain health? Drawing from interdisciplinary fields such as philosophy, psychology, and neuroscience, the salon served as a platform for participants to share diverse perspectives on fairness. Fairness is a multifaceted concept encompassing equity, justice, empathy, opportunity, non-discrimination, and the Golden Rule, but by delving into its evolutionary origins, we can verify its deep-rooted presence in both human and animal behaviors. Real-world experiments, such as Frans de Waal's capuchin monkey study, have proven enlightening, elucidating many mechanisms that have shaped our neurobiological responses to fairness. Contemporary cognitive neuroscience research further emphasizes the role of neuroanatomical areas and neurotransmitters in encoding fairness-related processes. We also discussed the critical interconnection between fairness and healthcare equity, particularly its implications for brain health. These values are instrumental in promoting social justice and improving health outcomes. In our polarized social landscape, there are rising concerns about a potential decrease in fairness and prosocial behaviors due to isolated social bubbles. We stress the urgency for interventions that enhance perspective-taking, reasoning, and empathy. Overall, fairness is vital to fostering an equitable society and its subsequent influence on brain health outcomes.

Transforming the invisible into the visible: disparities in the access to health in LGBT+ older people.

OBJECTIVES: To compare variables of access to healthcare between the LGBT+ population aged 50 and over and those non-LGBT+. METHODS: A cross-sectional study was carried out in Brazil through a confidential online questionnaire. The use of the health system was characterized by the number of preventive tests performed and measured by the PCATool-Brasil scale (a 10-point scale in which higher scores were associated with better assistance in healthcare). The association between being LGBT+ and access to health was analyzed in Poisson regression models. RESULTS: 6693 participants (1332 LGBT+ and 5361 non-LGBT+) with a median age of 60 years were included. In the univariate analysis, it was observed not only lower scores on the PCATool scale (5.13 against 5.82, p < 0.001), but a greater proportion of individuals among those classified with the worst quintile of access to healthcare (< 4 points), 31% against 18% (p < 0.001). Being LGBT+ was an independent factor associated with worse access to health (PR = 2.5, 95% CI 2.04‒3.06). The rate of screening cancer, for breast, colon, and cervical cancer was also found to be lower in the LGBT+ population. CONCLUSION: Healthcare access and health service experiences were worse in the LGBT+ group than in their non-LGBT peers. Inclusive and effective healthcare public policies are essential to promote healthy aging for all.

Acute Muscle Mass Loss Predicts Long-Term Fatigue, Myalgia, and Health Care Costs in COVID-19 Survivors.

OBJECTIVE: We examined the impact of loss of skeletal muscle mass in post-acute sequelae of SARS-CoV-2 infection, hospital readmission rate, self-perception of health, and health care costs in a cohort of COVID-19 survivors. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Tertiary Clinical Hospital. Eighty COVID-19 survivors age 59 ± 14 years were prospectively assessed. METHODS: Handgrip strength and vastus lateralis muscle cross-sectional area were evaluated at hospital admission, discharge, and 6 months after discharge. Post-acute sequelae of SARS-CoV-2 were evaluated 6 months after discharge (main outcome). Also, health care costs, hospital readmission rate, and self-perception of health were evaluated 2 and 6 months after hospital discharge. To examine whether the magnitude of muscle mass loss impacts the outcomes, we ranked patients according to relative vastus lateralis muscle cross-sectional area reduction during hospital stay into either "high muscle loss" (-18 ± 11%) or "low muscle loss" (-4 ± 2%) group, based on median values. RESULTS: High muscle loss group showed greater prevalence of fatigue (76% vs 46%, P = .0337) and myalgia (66% vs 36%, P = .0388), and lower muscle mass (-8% vs 3%, P < .0001) than low muscle loss group 6 months after discharge. No between-group difference was observed for hospital readmission and self-perceived health (P > .05). High muscle loss group demonstrated greater total COVID-19-related health care costs 2 ($77,283.87 vs. $3057.14, P = .0223, respectively) and 6 months ($90,001.35 vs $12, 913.27, P = .0210, respectively) after discharge vs low muscle loss group. Muscle mass loss was shown to be a predictor of total COVID-19-related health care costs at 2 (adjusted ß = $10, 070.81, P < .0001) and 6 months after discharge (adjusted ß = $9885.63, P < .0001). CONCLUSIONS AND IMPLICATIONS: COVID-19 survivors experiencing high muscle mass loss during hospital stay fail to fully recover muscle health. In addition, greater muscle loss was associated with a higher frequency of post-acute sequelae of SARS-CoV-2 and greater total COVID-19-related health care costs 2 and 6 months after discharge. Altogether, these data suggest that the loss of muscle mass resulting from COVID-19 hospitalization may incur in an economical burden to health care systems.

Association Between Gut Microbiota and Delirium in Acutely Ill Older Adults.

Our aim was to investigate the association between gut microbiota and delirium occurrence in acutely ill older adults. We included 133 participants 65+ years consecutively admitted to the emergency department of a tertiary university hospital, between September 2019 and March 2020. We excluded candidates with ≥24-hour antibiotic utilization on admission, recent prebiotic or probiotic utilization, artificial nutrition, acute gastrointestinal disorders, severe traumatic brain injury, recent hospitalization, institutionalization, expected discharge ≤48 hours, or admission for end-of-life care. A trained research team followed a standardized interview protocol to collect sociodemographic, clinical, and laboratory data on admission and throughout the hospital stay. Our exposure measures were gut microbiota alpha and beta diversities, taxa relative abundance, and core microbiome. Our primary outcome was delirium, assessed twice daily using the Confusion Assessment Method. Delirium was detected in 38 participants (29%). We analyzed 257 swab samples. After adjusting for potential confounders, we observed that a greater alpha diversity (higher abundance and richness of microorganisms) was associated with a lower risk of delirium, as measured by the Shannon (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.60-0.99; p = .042) and Pielou indexes (OR = 0.69; 95% CI = 0.51-0.87; p = .005). Bacterial taxa associated with pro-inflammatory pathways (Enterobacteriaceae) and modulation of relevant neurotransmitters (Serratia: dopamine; Bacteroides, Parabacteroides: GABA) were more common in participants with delirium. Gut microbiota diversity and composition were significantly different in acutely ill hospitalized older adults who experienced delirium. Our work is an original proof-of-concept investigation that lays a foundation for future biomarker studies and potential therapeutic targets for delirium prevention and treatment.

Brain injury biomarkers do not predict delirium in acutely ill older patients: a prospective cohort study.

Delirium is a common, serious, and often preventable neuropsychiatric emergency mostly characterized by a disturbance in attention and awareness. Systemic insult and inflammation causing blood-brain-barrier (BBB) damage and glial and neuronal activation leading to more inflammation and cell death is the most accepted theory behind delirium's pathophysiology. This study aims to evaluate the relationship between brain injury biomarkers on admission and delirium in acutely ill older patients. We performed a prospective cohort study which analyzed plasma S100B levels at admission in elderly patients. Our primary outcome was delirium diagnosis. Secondary outcomes were association between S100B, NSE and Tau protein and delirium diagnosis and patients' outcomes (admissions to intensive care, length of hospital stay, and in-hospital mortality). We analyzed 194 patients, and 46 (24%) developed delirium, 25 on admission and 21 during hospital stay. Median of S100B at admission in patients who developed delirium was 0.16 and median was 0.16 in patients who didn't develop delirium (p: 0.69). Levels S100B on admission did not predict delirium in acutely ill elderly patients.Trial registration: The study was approved by the local institutional review board (CAPPESq, no. 77169716.2.0000.0068, October 11, 2017) and registered in Brazilian Clinical Trials Registry (ReBEC, no. RBR-233bct).

COVID-19 outcomes in people living with HIV: Peering through the waves.

OBJECTIVE: To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. METHODS: This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. RESULTS: Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). CONCLUSIONS: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group.

Association of Frailty, Organ Support, and Long-Term Survival in Critically Ill Patients With COVID-19.

Few studies have explored the effect of frailty on the long-term survival of COVID-19 patients after ICU admission. Furthermore, the Clinical Frailty Scale (CFS) validity in critical care patients remains debated. We investigated the association between frailty and 6-month survival in critically ill COVID-19 patients. We also explored whether ICU resource utilization varied according to frailty status and examined the concurrent validity of the CFS in this setting. DESIGN: Ancillary study of a longitudinal prospective cohort. SETTING: University hospital in São Paulo. PATIENTS: Patients with severe COVID-19 admitted to ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed baseline frailty using the CFS (1-9; frail ≥ 5) and used validated procedures to compute a Frailty Index (0-1; frail > 0.25). We used Cox models to estimate associations of frailty status with 6-month survival after ICU admission and area under the receiver operating characteristic curves (AUCs) to estimate CFS's accuracy in identifying frailty according to Frailty Index. We included 1,028 patients (mean age, 66 yr; male, 61%). Overall, 224 (22%) patients were frail (CFS ≥ 5), and 608 (59%) died over the 6-month follow-up. Frailty was independently associated with lower 6-month survival and further stratified mortality in patients with similar age and Sequential Organ Failure Assessment scores. We additionally verified that the CFS was highly accurate in identifying frailty as defined by the Frailty Index (AUC, 0.91; 95% CI, 0.89-0.93). Although treatment modalities did not diverge according to frailty status, higher CFS scores were associated with withholding organ support due to refractory organ failure. CONCLUSIONS: One in five COVID-19 patients admitted to the ICU was frail. CFS scores greater than or equal to 5 were associated with lower long-term survival and decisions on withholding further escalation of invasive support for multiple organ failure in the ICU. Clinicians should consider frailty alongside sociodemographic and clinical measures to have a fuller picture of COVID-19 prognosis in critical care.

Characteristics and Outcomes of Patients With Frailty Admitted to ICU With Coronavirus Disease 2019: An Individual Patient Data Meta-Analysis.

Frailty is often used in clinical decision-making for patients with coronavirus disease 2019, yet studies have found a variable influence of frailty on outcomes in those admitted to the ICU. In this individual patient data meta-analysis, we evaluated the characteristics and outcomes across the range of frailty in patients admitted to ICU with coronavirus disease 2019. DATA SOURCES: We contacted the corresponding authors of 16 eligible studies published between December 1, 2019, and February 28, 2021, reporting on patients with confirmed coronavirus disease 2019 admitted to ICU with a documented Clinical Frailty Scale. STUDY SELECTION: Individual patient data were obtained from seven studies with documented Clinical Frailty Scale were included. We classified patients as nonfrail (Clinical Frailty Scale = 1-4) or frail (Clinical Frailty Scale = 5-8). DATA EXTRACTION: We collected patient demographics, Clinical Frailty Scale score, ICU organ supports, and clinically relevant outcomes (ICU and hospital mortality, ICU and hospital length of stays, and discharge destination). The primary outcome was hospital mortality. DATA SYNTHESIS: Of the 2,001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and Sequential Organ Failure Assessment score, Clinical Frailty Scale score greater than or equal to 4, use of mechanical ventilation, vasopressors, renal replacement therapy, and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in patients with frailty (65.2% vs 41.8%; p < 0.001), with adjusted mortality increasing with a rising Clinical Frailty Scale score beyond 3. Younger and nonfrail patients were more likely to receive mechanical ventilation. Patients with frailty spent less time on mechanical ventilation (median days [interquartile range], 9 [5-16] vs 11 d [6-18 d]; p = 0.012) and accounted for only 12.3% of total ICU bed days. CONCLUSIONS: Patients with frailty with coronavirus disease 2019 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with nonfrail patients. Patients with frailty receiving mechanical ventilation were at greater risk of death than patients without frailty.

Muscle strength and muscle mass as predictors of hospital length of stay in patients with moderate to severe COVID-19: a prospective observational study.

BACKGROUND: Strength and muscle mass are predictors of relevant clinical outcomes in critically ill patients, but in hospitalized patients with COVID-19, it remains to be determined. In this prospective observational study, we investigated whether muscle strength or muscle mass are predictive of hospital length of stay (LOS) in patients with moderate to severe COVID-19 patients. METHODS: We evaluated prospectively 196 patients at hospital admission for muscle mass and strength. Ten patients did not test positive for SARS-CoV-2 during hospitalization and were excluded from the analyses. RESULTS: The sample comprised patients of both sexes (50% male) with a mean age (SD) of 59 (±15) years, body mass index of 29.5 (±6.9) kg/m2 . The prevalence of current smoking patients was 24.7%, and more prevalent coexisting conditions were hypertension (67.7%), obesity (40.9%), and type 2 diabetes (36.0%). Mean (SD) LOS was 8.6 days (7.7); 17.0% of the patients required intensive care; 3.8% used invasive mechanical ventilation; and 6.6% died during the hospitalization period. The crude hazard ratio (HR) for LOS was greatest for handgrip strength comparing the strongest versus other patients (1.47 [95% CI: 1.07-2.03; P = 0.019]). Evidence of an association between increased handgrip strength and shorter hospital stay was also identified when handgrip strength was standardized according to the sex-specific mean and standard deviation (1.23 [95% CI: 1.06-1.43; P = 0.007]). Mean LOS was shorter for the strongest patients (7.5 ± 6.1 days) versus others (9.2 ± 8.4 days). Evidence of associations were also present for vastus lateralis cross-sectional area. The crude HR identified shorter hospital stay for patients with greater sex-specific standardized values (1.20 [95% CI: 1.03-1.39; P = 0.016]). Evidence was also obtained associating longer hospital stays for patients with the lowest values for vastus lateralis cross-sectional area (0.63 [95% CI: 0.46-0.88; P = 0.006). Mean LOS for the patients with the lowest muscle cross-sectional area was longer (10.8 ± 8.8 days) versus others (7.7 ± 7.2 days). The magnitude of associations for handgrip strength and vastus lateralis cross-sectional area remained consistent and statistically significant after adjusting for other covariates. CONCLUSIONS: Muscle strength and mass assessed upon hospital admission are predictors of LOS in patients with moderate to severe COVID-19, which stresses the value of muscle health in prognosis of this disease.

Divergent: Age, Frailty, and Atypical Presentations of COVID-19 in Hospitalized Patients.

BACKGROUND: Although frailty has been associated with atypical manifestations of infections, little is known about COVID-19 presentations in hospitalized frail patients. We aimed to investigate the association between age, frailty, and clinical characteristics of COVID-19 in hospitalized middle-aged and older adults. METHOD: Longitudinal observational study comprising 711 patients aged ≥50 years consecutively admitted to a university hospital dedicated to COVID-19 severe cases, between March and May 2020. We reviewed electronic medical records to collect data on demographics, comorbidities, COVID-19 signs/symptoms, and laboratory findings on admission. We defined frailty using the Clinical Frailty Scale (CFS = 1-9; frail ≥5). We also documented in-hospital mortality. We used logistic regressions to explore associations between age, frailty, and COVID-19 signs/symptoms; and between typical symptoms (fever, cough, dyspnea) and mortality. RESULTS: Participants had a mean age of 66 ± 11 years, and 43% were female. Overall, 25% were frail, and 37% died. The most common COVID-19 presentations were dyspnea (79%), cough (74%), and fever (62%), but patients aged ≥65 years were less likely to have a co-occurrence of typical symptoms, both in the absence (OR = 0.56; 95% CI = 0.39-0.79) and in the presence of frailty (OR = 0.52; 95% CI = 0.34-0.81). In contrast, older age and frailty were associated with unspecific presentations, including functional decline, acute mental change, and hypotension. After adjusting for age, sex, and frailty, reporting fever was associated with lower odds of mortality (OR = 0.70; 95% CI = 0.50-0.97). CONCLUSIONS: Atypical COVID-19 presentations are common in frail and older hospitalized patients. Providers should be aware of unspecific disease manifestations during the management and follow-up of this population.

Diagnostic discrepancies between emergency department admissions and hospital discharges among older adults: secondary analysis on a population-based survey.

BACKGROUND: Older adults frequently experience nonspecific clinical features. However, there is limited evidence on how often admission diagnoses for hospitalized older patients are incorrect, potentially leading to treatment delays. OBJECTIVES: To determine the consistency between hospital admission and discharge diagnoses, and identify factors associated with diagnostic discrepancies in older adults. DESIGN AND SETTING: Population-based cohort study in the United States. We included adults aged ≥ 18 years who were admitted from emergency departments (EDs) to hospitals, identified using the 2005-2010 National Hospital Ambulatory Medical Survey, a nationally representative survey. METHODS: Three admission diagnoses and the principal discharge diagnosis were captured and classified as discrepant if they involved considerably different conditions within the same organ system, or different organ systems altogether. RESULTS: Each year, 12 million adults were hospitalized following ED visits in the United States; 45% were aged ≥ 65 years. These patients' mean age was 79 years and 58% were women. Diagnostic discrepancies between admission and discharge were more common among adults ≥ 65 years (12.5 versus 8.3%; P < 0.001). Certain admission diagnoses had particularly high rates of diagnostic discrepancies: 26-27% of patients presenting with mental disorders or with endocrine and metabolic diseases had substantial diagnostic discrepancies between admission and discharge. Substantial diagnostic discrepancy was independently associated with longer hospitalization and higher in-hospital mortality. CONCLUSION: One out of eight older adults hospitalized from EDs was discharged with a principal diagnosis differing considerably from the admission diagnosis. Given that missed or delayed diagnoses are a critical safety problem, clinicians should be vigilant and frequently cogitate alternative diagnostic possibilities.

Association Between Level of Arousal and 30-Day Survival in Acutely Ill Older Adults.

OBJECTIVE: To investigate the association between impaired arousal on admission and 30-day mortality in acutely ill older adults. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients age +65 years admitted to the geriatric ward of a tertiary university hospital from 2010 to 2018 in Sao Paulo, Brazil. METHODS: Participants were evaluated on admission according to a standardized comprehensive geriatric assessment model. Delirium was detected using the short version of the Confusion Assessment Method (Short-CAM). We used 2 alternative criteria to define impaired arousal: lethargy, stupor, or coma according to the Short-CAM; and a Glasgow Coma Scale (GCS) score of ≤13. Our primary outcome was time-to-death in 30 days, and we used Cox proportional hazards models to explore the association between impaired arousal and decreased survival. RESULTS: We included 1554 admissions with a mean age of 81 years and of whom 61% were women. Overall, prevalent delirium was observed in 28% of the cases. We found that in 33% of admissions, patients were lethargic, stuporous, or comatose, and that in 23%, they had GCS scores of ≤13. General 30-day mortality was 19% but reached 32% in patients with GCS scores of ≤13. Impaired arousal was independently associated with lower survival in 30 days, both when defined using Short-CAM criteria [lethargy + stupor + coma: hazard ratio (HR) 2.33, 95% confidence interval (CI) 1.66‒3.27] and GCS scores (GCS 12‒13: HR 1.62, 95% CI 1.13‒2.33; GCS ≤ 11: HR 2.53, 95% CI 1.68‒3.80). In interaction analyses, we confirmed our results in patients who had impaired arousal but were neither delirious (lethargy + stupor + coma: HR 2.16, 95% CI 1.44‒3.24; GCS ≤ 11: HR 3.07; 95% CI 1.50‒6.29) nor demented (lethargy + stupor + coma: HR 1.95, 95% CI 1.15‒3.28). CONCLUSIONS AND IMPLICATIONS: Level of arousal on admission was an independent predictor of 30-day survival in acutely ill older adults, regardless of delirium or baseline dementia. Clinicians should be aware that even if unsure of whether a patient has delirium, arousal assessment can provide crucial clinical and prognostic insight.

Prognostic effects of delirium motor subtypes in hospitalized older adults: A prospective cohort study.

OBJECTIVES: To investigate the association between delirium motor subtypes and hospital mortality and 12-month mortality in hospitalized older adults. DESIGN: Prospective cohort study conducted from 2009 to 2015. SETTING: Geriatric ward of a university hospital in Sao Paulo, Brazil. PARTICIPANTS: We included 1,409 consecutive admissions of acutely ill patients aged 60 years and over. We excluded admissions for end-of-life care, with missing data on the main variables, length of stay shorter than 48 hours, or when consent to participate was not given. MAIN OUTCOMES AND MEASURES: Delirium was detected using the Confusion Assessment Method and categorized in hypoactive, hyperactive, or mixed delirium. Primary outcomes were time to death in the hospital, and time to death in 12 months (for the discharged sample). Comprehensive geriatric assessment was performed at admission and included socio-demographic, clinical, functional, cognitive, and laboratory variables. Further clinical data were documented upon death or discharge. Multivariate analyses used Cox proportional hazards models adjusted for possible confounders. RESULTS: We included 1,409 admissions, with a mean age of 80 years. The proportion of in-hospital deaths was 19%, with a cumulative mortality of 38% in 12 months. Delirium occurred in 47% of the admissions. Hypoactive delirium was the predominant motor subtype (53%), followed by mixed delirium (30%) and hyperactive delirium (17%). Hospital mortality rates were respectively 33%, 34% and 15%. We verified that hypoactive and mixed delirium were independently associated with hospital mortality, with respective hazard ratios of 2.43 (95%CI = 1.64-3.59) and 2.31 (95%CI = 1.53-3.50). Delirium motor subtypes were not independently predictive of 12-month mortality. CONCLUSIONS: One in three acutely ill hospitalized older adults who suffered hypoactive or mixed delirium died in the hospital. Clinicians should be aware that hypoactive symptoms of delirium, whether shown exclusively or in alternation with hyperactive symptoms, are indicative of a worse prognosis in this population.