Is lipoprotein(a) measurement important for cardiovascular risk stratification in children and adolescents?

BACKGROUND: Elevated lipoprotein (Lp(a)) levels are associated with increased risk of atherosclerotic processes and cardiovascular events in adults. The amount of Lp(a) is mainly genetically determined. Therefore, it is important to identify individuals with elevated Lp(a) as early as possible, particularly if other cardiovascular risk factors are present. The purpose of the study was to investigate whether, in a population of children and adolescents already followed for the presence of one or more cardiovascular risk factors (elevated blood pressure (BP), and/or excess body weight, and/or dyslipidemia), the measurement of Lp(a) can be useful for better stratifying their risk profile. METHODS: In a sample of 195 children and adolescents, height, body weight, waist circumference and systolic (SBP) and diastolic (DBP) BP were measured. Body Mass Index (BMI) and SBP and DBP z-scores were calculated. Plasma Lp(a), total cholesterol, high-density lipoprotein (HDL), triglycerides, glucose, insulin, uric acid and creatinine were assessed. Low-density lipoprotein (LDL) cholesterol was calculated with the Friedewald formula. High Lp(a) was defined as ≥ 75 nmol/L and high LDL cholesterol as ≥ 3.37 mmol/L. RESULTS: Our sample of children and adolescents (54.4% males, mean age 11.5 years) had median LDL cholesterol and Lp(a) values equal to 2.54 (interquartile range, IQR: 2.07-3.06) mmol/L and 22 (IQR: 7.8-68.6) nmol/L respectively. 13.8% of children had LDL cholesterol ≥ 3.37 mmol/L and 22.6 Lp(a) values ≥ 75 nmol/L. Lp(a) values were higher in children of normal weight than in those with excess weight (p = 0.007), but the difference disappeared if normal weight children referred for dyslipidemia only were excluded from the analysis (p = 0.210). 69.4% of children had normal Lp(a) and LDL cholesterol values and only 6.2% showed both elevated Lp(a) and LDL cholesterol levels. However, 16.6% of the sample, despite having normal LDL cholesterol, had elevated Lp(a) values. Multivariable analyses showed a significant association of LDL cholesterol both with Lp(a) values, and with the presence of elevated Lp(a) levels. For each mmol/L increase in LDL cholesterol the risk of having an elevated Lp(a) value increased by 73%. There was an inverse correlation between BMI z-score and Lp(a). Neither BP z-scores, nor other biochemical parameters were associated with Lp(a). CONCLUSIONS: In our population more than one out of five children had elevated Lp(a) values, and in about 17% of children elevated Lp(a) values were present in the absence of increased LDL cholesterol. Our results suggest that Lp(a) measurement can be useful to better define the cardiovascular risk profile in children and adolescents already followed for the presence of other cardiovascular risk factors such as elevated BP, excess body weight and high LDL cholesterol.

Adverse events in single-arm clinical trials with non-fatal time-to-event efficacy endpoint: from clinical questions to methods for statistical analysis.

BACKGROUND: In any single-arm trial on novel treatments, assessment of toxicity plays an important role as occurrence of adverse events (AEs) is relevant for application in clinical practice. In the presence of a non-fatal time-to-event(s) efficacy endpoint, the analysis should be broadened to consider AEs occurrence in time. The AEs analysis could be tackled with two approaches, depending on the clinical question of interest. Approach 1 focuses on the occurrence of AE as first event. Treatment ability to protect from the efficacy endpoint event(s) has an impact on the chance of observing AEs due to competing risks action. Approach 2 considers how treatment affects the occurrence of AEs in the potential framework where the efficacy endpoint event(s) could not occur. METHODS: In the first part of the work we review the strategy of analysis for these two approaches. We identify theoretical quantities and estimators consistent with the following features: (a) estimators should address for the presence of right censoring; (b) theoretical quantities and estimators should be functions of time. In the second part of the work we propose the use of alternative methods (regression models, stratified Kaplan-Meier curves, inverse probability of censoring weighting) to relax the assumption of independence between the potential times to AE and to event(s) in the efficacy endpoint for addressing Approach 2. RESULTS: We show through simulations that the proposed methods overcome the bias due to the dependence between the two potential times and related to the use of standard estimators. CONCLUSIONS: We demonstrated through simulations that one can handle patients selection in the risk sets due to the competing event, and thus obtain conditional independence between the two potential times, adjusting for all the observed covariates that induce dependence.

Two-year cardio-pulmonary follow-up after severe COVID-19: a prospective study.

Short- and medium-term cardio-pulmonary sequelae after COVID-19 have been extensively studied. However, studies with longer follow-ups are required. This study aims to identify and characterise cardio-pulmonary sequelae, in patients hospitalised for SARS-CoV-2 pneumonia, at 24 months follow-up. This is a prospective, observational cohort study conducted on consecutive patients hospitalised for COVID-19 and acute respiratory failure. Patients were followed up at 24 months with complete pulmonary function tests (PFTs), 6-min walking test and a dyspnoea score (Modified Medical Research Council scale). A subgroup of patients with at least one clinical or functional sign suggestive of increased pulmonary pressures also underwent transthoracic echocardiography (TTE) to evaluate the presence of direct or indirect signs of pulmonary hypertension (PH). Ninety consecutive patients (74% men, median age 59.1 years) were enrolled in the study. In regard to PFTs, carbon monoxide diffusion capacity (DLCO) impairment was observed in 23 cases (26%), in all cases of mild entity. When considering the dyspnoea, 30 (34%) patients showed some degree of breathlessness. Forty patients underwent TTE. No patients had overt PH or chronic thromboembolic PH. However, all patients showed a hyperdynamic state of the right ventricle, and 8 (20%) patients had a decreased acceleration time on pulmonary valve, signs of increased pulmonary vasculature resistances and afterload elevation. At 24-month follow-up after severe COVID-19, DLCO and TTE prove to be the most sensitive tool to detect cardio-pulmonary sequelae. Dyspnoea is still present in about one-third of patients and requires a multidisciplinary approach.

Wall Properties of Elastic and Muscular Arteries in Children and Adolescents at Increased Cardiovascular Risk.

BACKGROUND: Pulse wave velocity (PWV) assessment represents a simple method to estimate arterial distensibility. At present, carotid-femoral PWV (cf-PWV) is considered the gold standard method in the non-invasive evaluation of the elastic properties of the aorta. On the other hand, the mechanical properties of muscular arteries can be evaluated on the axillo-brachial-radia axis by estimating the carotid-radial PWV (cr-PWV). While a number of studies have addressed these issues in adults, limited information is available on the respective features of cf-PWV and cr-PWV and on their modulating factors in children and adolescents at increased cardiovascular risk. METHODS: The mechanical properties of the predominantly elastic (aorta) and muscular (axillo-brachial-radial axis) arteries were evaluated in a pediatric population characterized by either elevated blood pressure (BP) or excess body weight, and the main factors affecting cf-PWV and cr-PWV values in these individuals were investigated. RESULTS: 443 children and adolescents (median age 11.5 years, 43.3% females) were enrolled; 25% had BP values >90th percentile and 81% were excess weight. The cf-PWV values were significantly lower than the cr-PWV values: median (Q1-Q3) = 4.8 m/s (4.3-5.5) and 5.8 m/s (5.0-6.5), respectively (p < 0.001). The pubertal development (p < 0.03), systolic BP and diastolic BP z-scores (p = 0.002), heart rate (p < 0.001), and waist-to-height ratio (p < 0.005) were significantly associated with cf-PWV values. No significant association was found between BMI z-score and cf-PWV. Predictors of high cf-PWV (>95th percentile) were the heart rate (OR 1.07, 95%CI 1.04-1.10, p < 0.001) and waist-to-height ratio (OR 1.06, 95%CI 1.0-1.13, p = 0.04). The variables significantly related with cr-PWV values were diastolic BP z-score (p = 0.001), heart rate (p < 0.01), and HOMA index (p < 0.02). No significant association was found between the cr-PWV and BMI z-score or waist-to-height ratio. CONCLUSIONS: Systolic and diastolic BP values and central obesity are associated with aortic stiffness in a population of children and adolescents at increased cardiovascular risk. In contrast, diastolic BP, heart rate, and levels of insulin resistance appear to be related to distensibility of the upper limb vascular district.

Frailty and post-operative delirium influence on functional status in patients with hip fracture: the GIOG 2.0 study.

BACKGROUND: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF). METHODS: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT. A 26-item Frailty Index (FI) was created using data collected on admission. The outcome measures were Cumulated Ambulation Score (CAS) ≤ 2 at discharge and a telephone-administered CAS ≤ 2 after 4 months. Poisson regression models were used to assess the effect of frailty and POD on outcomes. RESULTS: 984 patients (median age 84 years, IQR = 79-89) were recruited: 480 (48.7%) were frail at admission, 311 (31.6%) developed POD, and 158 (15.6%) had both frailty and POD. In a robust Poisson regression, frailty alone (Relative Risk, RR = 1.56, 95% Confidence Intervals, CI 1.19-2.04, p = 0.001) and its combination with POD (RR = 2.57, 95% CI 2.02-3.26, p < 0.001) were associated with poor functional status at discharge. At 4-month follow-up, the combination of frailty with POD (RR 3.65, 95% CI 1.85-7.2, p < 0.001) increased the risk of poor outcome more than frailty alone (RR 2.38, 95% CI 1.21-4.66, p < 0.001). CONCLUSIONS: POD development exacerbates the negative effect that frailty exerts on functional outcomes in HF patients.

Association between lifestyle modifications and improvement of early cardiac damage in children and adolescents with excess weight and/or high blood pressure.

BACKGROUND: It is not known whether, in children and adolescents with alterations in weight and/or blood pressure (BP), lifestyle modifications are associated with an improvement of early cardiac damage. METHODS: In a pediatric population referred for excess weight, high BP, or both (n = 278, 10.6 (2.3) years), echocardiography was performed at enrollment and after 15 months of follow-up, during which participants received nonpharmacological treatment, based on correcting unhealthy lifestyles and improving dietary habits. Left ventricular mass was indexed for height (g/m2.7, LVMI), and an LVMI value higher than or equal to age- and gender-specific 95th percentile was the criterion for defining left ventricular hypertrophy (LVH). Multiple linear and logistic regression analyses were carried out to determine associations between changes in BMI and BP z-scores and changes of LVMI values and LVH prevalence, from baseline to follow-up. RESULTS: At baseline, 33.1% of study participants were hypertensive, 52.9% obese, and 36.3% had LVH. At follow-up, the prevalence of hypertension, obesity, and LVH was 18.7%, 30.2%, and 22.3%, respectively (p < 0.001 for all). A decrease in LVMI from 37.1 to 35.2 g/m2.7 (p < 0.001) was observed. Only delta BMI z-score positively related to an improvement of LVMI. Reductions of BMI (OR = 0.22, 95% CI 0.07-0.64) and diastolic BP (OR = 0.64, 95% CI 0.42-0.93) z-scores from baseline to follow-up and family history of hypertension (OR = 0.36, 95% CI 0.16-0.78) were associated with a lower prevalence of LVH. CONCLUSIONS: In a pediatric population at cardiovascular risk, changing incorrect lifestyle and dietary habits is associated with both reduction of BMI and BP values and regression of early cardiac damage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study.

BACKGROUND: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated. METHODS: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy. RESULTS: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P=0.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05-1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95-1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60-1.02). CONCLUSIONS: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events. CLINICAL TRIAL REGISTRATION: NCT03616054.

The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease.

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1-KO mice. WT mice transplanted with an allogeneic graft from Cmklr1-KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1-KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium-induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD.

Frailty and long-COVID: is COVID-19 responsible for a transition in frailty status among older adults who survived hospitalization for COVID-19?

BACKGROUND: There is a paucity of knowledge about the effects of COronaVIrus Disease-19 (COVID-19) on long-term frailty development or progression over time. AIM: This study aims to assess transitions in frailty status in older adults who survived hospitalization for COVID-19. METHODS: This is a longitudinal panel study. A multidisciplinary outpatient follow-up service was established since summer 2020, for the evaluation of individuals discharged alive, after hospitalization due to COVID-19. Frailty status was assessed in-hospital and at follow-up using the clinical frailty scale (CFS). Main patients' characteristics, including health, functional, cognitive, and psychological status were collected. RESULTS: A total of 177 patients aged 65 years and older were evaluated until June 2022. They were predominantly male, with a median age of 70 (Q1-Q3 67-75) years and a median body mass index of 27.5 (Q1-Q3 24.9-30.6) kg/m2 at hospital admission. The median follow-up time was 6.3 (Q1-Q3 3.7-10.9) months. Sixty-one patients (34.5%) scored worse at CFS follow-up compared to hospital admission, and twenty-two patients (12.4%) became frail. DISCUSSION AND CONCLUSION: This study shows that one out of three older patients previously hospitalized for COVID-19 had an unfavorable transition in CFS score during a median follow-up of nearly 6 months. Specific interventions to prevent frailty development or progression should be considered for patients at risk. Further studies are required to confirm our findings.

Association of obesity phenotypes with left ventricular mass index and left ventricular hypertrophy in children and adolescents.

It has been argued that metabolically healthy obesity (MHO) does not increase the risk of cardiovascular disease. The aim of this study is to evaluate whether, in a population of obese children/adolescents, the metabolically unhealthy obesity (MUO) phenotype is associated with higher left ventricular mass index and/or higher prevalence of left ventricular hypertrophy than the MHO phenotype. We also tested whether the addition of an insulin resistance index (HOMA-index >90th percentile by sex and age) and the presence of hyperuricemia (serum uric acid >90th percentile by sex and age) to the definition of MUO better identified obese children with early cardiac damage. Left ventricular hypertrophy was defined as the presence of left ventricular mass index greater than or equal to the age- and sex-specific 95th percentile. The study population included 459 obese children (males 53.2%, mean age 10.6 [standard deviation, 2.6] years), of whom 268 (58.4%) were MUO. The left ventricular mass index was higher in MUO children than in MHO children (37.8 vs 36.3 g/m2.7, p=0.015), whereas the percentage of MUO children presenting left ventricular hypertrophy was only slightly higher in MUO children (31.1 vs 40%, p=0.06). Multiple linear regression analyses showed that the variables significantly associated with higher left ventricular mass index were male gender (p<0.01), Body Mass Index z-score (p<0.001) and Waist-to-Height-ratio (p<0.001). Multiple logistic regression analyses showed that the presence of left ventricular hypertrophy was only significantly associated with higher Body Mass Index z-score (p<0.05) and Waist-to-Height-ratio (p<0.05). In spite of the higher left ventricular mass index of MUO as compared to MHO children, the MUO phenotype was not a significant predictor of either higher left ventricular mass index or higher left ventricular hypertrophy prevalence. The MUO phenotype had a low predictive ability on the presence of left ventricular hypertrophy. The area under the receiver operating characteristic curve was 0.57 (sensitivity 0.64, 1-specificity 0.55). The addition of insulin resistance and hyperuricemia to the definition of MUO did not change the results observed with the standard definition of MUO at multivariable analysis. The MUO phenotype appears to be of little usefulness in identifying the early presence of cardiac damage in a large population of obese children and adolescents. Excess weight and abdominal obesity are confirmed as an important determinant of early organ damage in obese children.

Peri-intubation Cardiovascular Collapse in Patients Who Are Critically Ill: Insights from the INTUBE Study.

Rationale: Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. Objectives: To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e., systolic arterial pressure <65 mm Hg [once] or <90 mm Hg for >30 minutes; new/increased vasopressor requirement; fluid bolus >15 ml/kg, or cardiac arrest). Methods: INTUBE (International Observational Study to Understand the Impact and Best Practices of Airway Management In Critically Ill Patients) was a multicenter prospective cohort study of patients who were critically ill and undergoing tracheal intubation in a convenience sample of 197 sites from 29 countries across five continents from October 1, 2018, to July 31, 2019. Measurements and Main Results: A total of 2,760 patients were included in this analysis. Peri-intubation cardiovascular instability/collapse occurred in 1,199 out of 2,760 patients (43.4%). Variables associated with this event were older age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.03), higher heart rate (OR, 1.008; 95% CI, 1.004-1.012), lower systolic blood pressure (OR, 0.98; 95% CI, 0.98-0.99), lower oxygen saturation as measured by pulse oximetry/FiO2 before induction (OR, 0.998; 95% CI, 0.997-0.999), and the use of propofol as an induction agent (OR, 1.28; 95% CI, 1.05-1.57). Patients with peri-intubation cardiovascular instability/collapse were at a higher risk of ICU mortality with an adjusted OR of 2.47 (95% CI, 1.72-3.55), P < 0.001. The inverse probability of treatment weighting method identified the use of propofol as the only factor independently associated with cardiovascular instability/collapse (OR, 1.23; 95% CI, 1.02-1.49). When administered before induction, vasopressors (OR, 1.33; 95% CI, 0.84-2.11) or fluid boluses (OR, 1.17; 95% CI, 0.96-1.44) did not reduce the incidence of cardiovascular instability/collapse. Conclusions: Peri-intubation cardiovascular instability/collapse was associated with an increased risk of both ICU and 28-day mortality. The use of propofol for induction was identified as a modifiable intervention significantly associated with cardiovascular instability/collapse.Clinical trial registered with clinicaltrials.gov (NCT03616054).

Prevalence and features of delirium in older patients admitted to rehabilitation facilities: a multicenter study.

BACKGROUND: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. AIM: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the "Delirium Day project". METHODS: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the "Delirium Day project" (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. RESULTS: Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17-1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08-2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62-2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10-1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02-1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68-3.36, p value < 0.0001). CONCLUSION: This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

Impact of Lifestyle Modifications on Alterations in Lipid and Glycemic Profiles and Uric Acid Values in a Pediatric Population.

Cardiometabolic risk factors are frequent in children and adolescents with excess weight. The aim of this study was to evaluate the effects of lifestyle modifications on alterations in lipid and glycemic profiles and uric acid values in a pediatric population at increased cardiovascular risk. The study involved 276 subjects with a mean age of 10.6 (2.3) years. Body mass index (BMI) z-score and biochemical parameters (serum low-density lipoprotein (LDL) cholesterol, triglycerides and uric acid and homeostasis model assessment to quantify insulin resistance (HOMA index)) were assessed at baseline and at the end of a median follow-up of 14.7 (12.4, 19.3) months. Throughout follow-up, all children received a non-pharmacological treatment based on increased physical activity, reduced sedentary activity and administration of a personalized, healthy and balanced diet. All children attended periodic quarterly control visits during follow-up. Multivariable statistical analyses showed that each BMI z-score point reduction at follow-up was associated with an 8.9 (95% CI −14.2; −3.6) mg/dL decrease in LDL cholesterol (p = 0.001), 20.4 (95% CI −30.0; −10.7) mg/dL in triglycerides (p < 0.001), 1.6 (95% CI −2.2; −1.0) in HOMA index (p < 0.001), and 0.42 (95% CI −0.66; −0.18) mg/dL in uric acid (p = 0.001) values. At each reduction of the BMI z-score by one point, the odds of presenting with insulin resistance and hyperuricemia at follow-up significantly decreased (OR 0.23, 95% CI 0.10−0.50, and OR 0.32, 95% CI 0.10−0.95, p < 0.001 and p < 0.05, respectively). Improvement of dietary habits and lifestyles may improve lipid and glycemic profiles and serum uric acid values in a pediatric population.

The relationship between frailty and delirium: insights from the 2017 Delirium Day study.

BACKGROUND: although frailty and delirium are among the most frequent and burdensome geriatric syndromes, little is known about their association and impact on short-term mortality. OBJECTIVE: to examine, in hospitalized older persons, whether frailty is associated with delirium, and whether these two conditions, alone or in combination, affect these patients' 30-day survival. DESIGN: observational study nested in the Delirium Day project, with 30-day follow-up. SETTING: acute medical wards (n = 118) and rehabilitation wards (n = 46) in Italy. SUBJECTS: a total of 2,065 individuals aged 65+ years hospitalized in acute medical (1,484 patients, 71.9%) or rehabilitation (581 patients, 28.1%) wards. METHODS: a 25-item Frailty Index (FI) was created. Delirium was assessed using the 4AT test. Vital status was ascertained at 30 days. RESULTS: overall, 469 (22.7%) patients experienced delirium on the index day and 82 (4.0%) died during follow-up. After adjustment for potential confounders, each FI score increase of 0.1 significantly increased the odds of delirium (odds ratio, OR: 1.66 [95% CI: 1.45-1.90]), with no difference between the acute (OR: 1.65 [95% CI: 1.41-1.93]) and rehabilitation ward patients (OR: 1.71 [95% CI: 1.27-2.30]). The risk of dying during follow-up also increased significantly for every FI increase of 0.1 in the overall population (OR: 1.65 [95% CI: 1.33-2.05]) and in the acute medical ward patients (OR: 1.61 [95% CI: 1.28-2.04]), but not in the rehabilitation patients. Delirium was not significantly associated with 30-day mortality in either hospital setting. CONCLUSIONS: in hospitalized older patients, frailty is associated with delirium and with an increased risk of short-term mortality.

Uric acid in chronic coronary syndromes: Relationship with coronary artery disease severity and left ventricular diastolic parameter.

BACKGROUND AND AIMS: Uric Acid (UA) has been related to the development of Cardio-Vascular (CV) events in patients affected by Chronic Coronary Syndromes (CCS). Among various hypothesis, two arise: UA may negatively act on coronary artery determining a higher degree of atherosclerotic disease, and/or on heart determining a higher prevalence of diastolic dysfunction. Both the above hypothesized effects are object of our investigation. METHODS AND RESULTS: 231 patients who were admitted to the cardiological department of the Niguarda Hospital (Milan, Italy) for CCS from January 2017 to June 2018 were enrolled. Coronary atherosclerotic burden was evaluated from coronary angiography as the number and type of involved vessels, as well as with both Gensini and Syntax scores. All subjects underwent a complete echocardiogram. At unadjusted and adjusted/multivariable analysis, UA levels were not significantly associated with variables analysed from the coronary angiography (number and type of vessels involved, neither the Gensini and Syntax scores) as well as with echocardiographic parameters regarding systolic and diastolic function. CONCLUSIONS: In conclusion, the main finding of our work is the absence of a role for UA in determining coronary arteries disease as well as LV diastolic dysfunction in CCS subjects. Taking together the results of previous studies with ours, we hypothesize that UA could act on heart (both on coronary arteries and on LV function) in an early phase of the disease, whereas while in the advanced stages other factors (previous myocardial infarction, previous myocardial revascularization and so on) may overshadow its effects.

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events-in particular cardiovascular instability-were observed frequently.

Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study.

OBJECTIVE: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. DESIGN: Cross-sectional study nested in the 2017 "Delirium Day" project. SETTING AND PARTICIPANTS: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. METHODS: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). RESULTS: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). CONCLUSIONS AND IMPLICATIONS: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Blood Pressure and Body Weight Have Different Effects on Pulse Wave Velocity and Cardiac Mass in Children.

BACKGROUND: High blood pressure (BP) and excess weight can lead to early cardiovascular organ damage already in children. Carotid-femoral pulse wave velocity (cf-PWV) is the non-invasive gold standard method for assessing aortic stiffness, while carotid-radial PWV (cr-PWV) provides information on the distensibility of the upper limb arteries. The aim of this study was to evaluate the relationship of BP and BMI z-scores with arterial stiffness and left ventricular mass index (LVMI) in a pediatric population. METHODS: In 343 children (57.7% males; age ± SD 11.7 ± 2.9 years), systolic (SBP) and diastolic (DBP) BP, BMI, cf-PWV, cr-PWV and LVMI were measured. A multiple linear regression model was used to assess the impact of BMI and SBP (or DBP) z-scores on cf-PWV, cr-PWV and LVMI. RESULTS: About 21% of children were normal weight, 34% were overweight and 45% obese. Adjusted for possible confounders, SBP and DBP z-scores were significantly associated with cf-PWV (p < 0.001), while only DBP z-scores were related to cr-PWV (p < 0.01). BMI was neither associated with cf-PWV nor with cr-PWV values but was a strong predictor of LVMI (<0.001), whereas cardiac mass and BP z-scores were not related. CONCLUSIONS: Our study suggests that, in children, elevated BP values and excess weight may have different effects on the heart and the vessels in causing early cardiovascular alterations.

Three-year National report from the Gruppo Italiano di Ortogeriatria (GIOG) in the management of hip-fractured patients.

BACKGROUND: Hip fractures (HF) are a major issue worldwide. We aimed at evaluating the practices in delivering care to patients with HF among several Italian Orthogeriatric centers. METHODS: The study took place from February 2016 to July 2018. Seven performance indicators (pre-surgical cognitive assessment, surgery performed ≤ 48 h from fracture, removal of urinary catheter/absence of delirium/start of physiotherapy on the first post-operative day, prescription of bone protection at discharge, and discharge toward rehabilitation) were collected. RESULTS: The 14 participating hospitals totally recruited 3.017 patients. Patients were old (median age 86 years; Inter Quartile Range [IQR] 80-90), mostly females (77%). Nearly 55% of them were already impaired in mobility and about 10% were nursing home residents. Median time-to-surgery was 41 h (IQR 23-62). Models of care greatly varied among centers, only 49.3% of patients being co-managed by geriatricians and orthopedics. There was high variability across centers in four indicators ("pre-surgical cognitive assessment", "bone protection prescription", "use of urinary catheter" and "start of physiotherapy"), moderate in two indicators ("surgery performed ≤ 48 h from fracture" and "discharge toward rehabilitation" and low in one ("absence of delirium on day following surgery"). Comparison with international studies suggests very different ways of providing care to HF Italian patients. CONCLUSIONS: The study results suggest high inter-center variability in the key-performance indicators, and different approaches in providing care to our HF patients in comparison to other countries. A National debate on the topic is required in Italy to harmonize practices of orthogeriatric care.

Modeling the hazard of transition into the absorbing state in the illness-death model.

The illness-death model is the simplest multistate model where the transition from the initial state 0 to the absorbing state 2 may involve an intermediate state 1 (e.g., disease relapse). The impact of the transition into state 1 on the subsequent transition hazard to state 2 enables insight to be gained into the disease evolution. The standard approach of analysis is modeling the transition hazards from 0 to 2 and from 1 to 2, including time to illness as a time-varying covariate and measuring time from origin even after transition into state 1. The hazard from 1 to 2 can be also modeled separately using only patients in state 1, measuring time from illness and including time to illness as a fixed covariate. A recently proposed approach is a model where time after the transition into state 1 is measured in both scales and time to illness is included as a time-varying covariate. Another possibility is a model where time after transition into state 1 is measured only from illness and time to illness is included as a fixed covariate. Through theoretical reasoning and simulation protocols, we discuss the use of these models and we develop a practical strategy aiming to (a) validate the properties of the illness-death process, (b) estimate the impact of time to illness on the hazard from state 1 to 2, and (c) quantify the impact that the transition into state 1 has on the hazard of the absorbing state. The strategy is also applied to a literature dataset on diabetes.