Delirium symptoms duration and mortality in SARS-COV2 elderly: results of a multicenter retrospective cohort study.

BACKGROUND: Since the occurrence of the SARS-COV2 pandemic, there has been an increasing interest in investigating the epidemiology of delirium. Delirium is frequent in SARS-COV2 patients and it is associated with increased mortality; however, no information is available on the association between delirium duration in SARS-COV2 patients and related outcomes. AIMS: The aim of this study is to investigate the association between the duration of delirium symptoms and in-hospital mortality in older patients with SARS-COV2 infection. METHODS: Retrospective cohort study of patients 65 years of age and older with SARS-CoV 2 infection admitted to two acute geriatric wards and one rehabilitation ward. Delirium symptoms duration was assessed retrospectively with a chart-based validated method. In-hospital mortality was ascertained via medical records. RESULTS: A total of 241 patients were included. The prevalence of delirium on admission was 16%. The median number of days with delirium symptoms was 4 (IQR 2-6.5) vs. 0 (IQR 0-2) in patients with and without delirium on admission. In the multivariable Cox regression model, each day with a delirium symptom in a patient with the same length of stay was associated with a 10% increase in in-hospital mortality (Hazard ratio 1.1, 95% Confidence interval 1.01-1.2; p = 0.03). Other variables associated with increased risk of in-hospital death were age, comorbidity, CPAP, CRP levels and total number of drugs on admission. CONCLUSIONS: The study supports the necessity to establish protocols for the monitoring and management of delirium during emergency conditions to allow an appropriate care for older patients.

The 4-DSD: A New Tool to Assess Delirium Superimposed on Moderate to Severe Dementia.

OBJECTIVES: The purpose of this study was to create, standardize, and validate a new instrument, named 4-DSD, and determine its diagnostic accuracy in the diagnosis of delirium in subjects with moderate to severe dementia. DESIGN: Multicenter cross-sectional observational study. SETTING AND PARTICIPANTS: Older patients consecutively admitted to acute and rehabilitation hospital wards. MEASURES: The DSM-5 was used as the reference standard delirium assessment. The presence and severity of dementia was defined using the AD8 and the Global Deterioration Scale (GDS). The 4-DSD is a 4-item tool that ranges from 0 to 12. Item 1 measures alertness, item 2 altered function, item 3 attention, and item 4 acute change or fluctuation in mental status. RESULTS: A total of 134 patients were included in the study. Most of the patients were enrolled in acute hospital wards (60%), with 40% in rehabilitation settings. A minority of the patients were categorized with moderate dementia, with a GDS score of 5 (4%). Most of the patients were in the moderate-severe stage with a GDS score ≤6 (77%); 19% were classed as severe, with a GDS score of 7. A 4-DSD cutoff score ≥5 had a sensitivity of 80% and specificity of 80% with a positive predictive value (PPV) of 67% and a negative predictive value (NPV) of 89%. In the subgroup with moderate-severe dementia (n = 108), the sensitivity and the specificity were 79% and 82%, respectively, with a PPV and NPV of 62% and 92%. In the subgroup with severe dementia (n = 26) the sensitivity was 82% and the specificity 56% with a PPV of 78% and a NPV of 63%. CONCLUSIONS AND IMPLICATIONS: The availability of a specific tool to detect delirium in patients with moderate-severe dementia has important clinical and research implications, allowing all health care providers to improve their ability to identify it.

Delirium in Patients with SARS-CoV-2 Infection: A Multicenter Study.

OBJECTIVES: The aims of this study are to report the prevalence of delirium on admission to the unit in patients hospitalized with SARS-CoV-2 infection, to identify the factors associated with delirium, and to evaluate the association between delirium and in-hospital mortality. DESIGN: Multicenter observational cohort study. SETTINGS: Acute medical units in four Italian hospitals. PARTICIPANTS: A total of 516 patients (median age 78 years) admitted to the participating centers with SARS-CoV-2 infection from February 22 to May 17, 2020. MEASUREMENTS: Comprehensive medical assessment with detailed history, physical examinations, functional status, laboratory and imaging procedures. On admission, delirium was determined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria, 4AT, m-Richmond Agitation Sedation Scale, or clinical impression depending on the site. The primary outcomes were delirium rates and in-hospital mortality. RESULTS: Overall, 73 (14.1%, 95% confidence interval (CI) = 11.0-17.3%) patients presented delirium on admission. Factors significantly associated with delirium were dementia (odds ratio, OR = 4.66, 95% CI = 2.03-10.69), the number of chronic diseases (OR = 1.20, 95% CI = 1.03; 1.40), and chest X-ray or CT opacity (OR = 3.29, 95% CI = 1.12-9.64 and 3.35, 95% CI = 1.07-10.47, for multiple or bilateral opacities and single opacity vs no opacity, respectively). There were 148 (33.4%) in-hospital deaths in the no-delirium group and 43 (58.9%) in the delirium group (P-value assessed using the Gray test <.001). As assessed by a multivariable Cox model, patients with delirium on admission showed an almost twofold increased hazard ratio for in-hospital mortality with respect to patients without delirium (hazard ratio = 1.88, 95% CI = 1.25-2.83). CONCLUSION: Delirium is prevalent and associated with in-hospital mortality among older patients hospitalized with SARS-CoV-2 infection.

Denosumab Inhibition of RANKL and Insulin Resistance in Postmenopausal Women with Osteoporosis.

The tumor necrosis factor-related cytokine receptor activator of nuclear factor kappa B ligand (RANKL) has been proposed as predictor of incident type 2 diabetes mellitus, and experimental blockade of RANKL resulted in a marked improvement of glucose tolerance. Denosumab is a fully human monoclonal antibody that binds to RANKL and prevents osteoclast formation, function and survival, leading to fracture risk reduction. The aim of our study was to investigate glucometabolic parameters, insulin resistance, and lipid profile in non-diabetic women receiving denosumab. Forty-eight women with postmenopausal osteoporosis were enrolled and treated with a subcutaneous dose (60 mg) of denosumab. At baseline and after 4, 12, ad 24 weeks, insulin resistance was computed by homeostasis model assessment of insulin resistance (HOMA-IR) and total cholesterol, triglycerides and HDL cholesterol were also measured. At baseline and after 24 weeks, bone turn-over markers were also evaluated. After denosumab administration, with the exception of a slight reduction of insulin and HOMA-IR values after 4 weeks (p < 0.05), neither fasting plasma glucose nor insulin and insulin resistance were significantly changed. Lipid parameters remained unchanged at each time-points of this study. A reduction of C-telopeptide of type 1 collagen (-63%, p < 0.0001) and osteocalcin (-45%, p < 0.0001), as bone resorption and formation markers, respectively, were observed after 24 weeks. Baseline levels of bone biomarkers were not predictive of HOMA-IR, and changes of osteocalcin were not associated to markers of glucose control. In osteoporotic otherwise healthy postmenopausal women, denosumab was not associated with relevant modification of insulin resistance and lipid profile.