Sustainability in Internal Medicine: A Year-Long Ward-Wide Observational Study.

Population aging and multimorbidity challenge health system sustainability, but the role of assistance-related variables rather than individual pathophysiological factors in determining patient outcomes is unclear. To identify assistance-related determinants of sustainable hospital healthcare, all patients hospitalised in an Internal Medicine Unit (n = 1073) were enrolled in a prospective year-long observational study and split 2:1 into a training (n = 726) and a validation subset (n = 347). Demographics, comorbidities, provenance setting, estimates of complexity (cumulative illness rating scale, CIRS: total, comorbidity, CIRS-CI, and severity, CIRS-SI subscores) and intensity of care (nine equivalents of manpower score, NEMS) were analysed at individual and Unit levels along with variations in healthcare personnel as determinants of in-hospital mortality, length of stay and nosocomial infections. Advanced age, higher CIRS-SI, end-stage cancer, and the absence of immune-mediated diseases were correlated with higher mortality. Admission from nursing homes or intensive care units, dependency on activity of daily living, community- or hospital-acquired infections, oxygen support and the number of exits from the Unit along with patient/physician ratios were associated with prolonged hospitalisations. Upper gastrointestinal tract disorders, advanced age and higher CIRS-SI were associated with nosocomial infections. In addition to demographic variables and multimorbidity, physician number and assistance context affect hospitalisation outcomes and healthcare sustainability.

Exploring the Association between Delirium and Malnutrition in COVID-19 Survivors: A Geriatric Perspective.

Older individuals face an elevated risk of developing geriatric syndromes when confronted with acute stressors like COVID-19. We assessed the connection between in-hospital delirium, malnutrition, and frailty in a cohort of COVID-19 survivors. Patients aged ≥65, hospitalized in a tertiary hospital in Milan for SARS-CoV-2 pneumonia, were enrolled and screened for in-hospital delirium with the 4 'A's Test (4AT) performed twice daily (morning and evening) during hospital stay. Malnutrition was assessed with the malnutrition universal screening tool (MUST) at hospital admission and with the mini-nutritional assessment short-form (MNA-SF) one month after hospital discharge. Frailty was computed with the frailty index one month after hospital discharge. Fifty patients (median age 78.5, 56% male) were enrolled. At hospital admission, 10% were malnourished. The 13 patients (26%) who developed delirium were frailer (7 vs. 4), experienced a higher in-hospital mortality (5 vs. 3), and were more malnourished one month after discharge (3 of the 4 patients with delirium vs. 6 of the 28 patients without delirium who presented at follow up). The 4AT scores correlated with the MNA-SF scores (r = -0.55, p = 0.006) and frailty (r = 0.35, p = 0.001). Frailty also correlated with MUST (r = 0.3, p = 0.04), MNA-SF (r = -0.42, p = 0.02), and hospitalization length (r = 0.44, p = 0.001). Delirium, malnutrition, and frailty are correlated in COVID-19 survivors. Screening for these geriatric syndromes should be incorporated in routine clinical practice.

Edoxaban and/or colchicine in outpatients with COVID-19: rationale and design of the CONVINCE trial.

BACKGROUND: An excessive inflammatory response and a hypercoagulable state are not infrequent in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse clinical outcomes. However, the optimal treatment strategy for COVID-19 patients managed in the out-of-hospital setting is still uncertain. DESIGN: The CONVINCE (NCT04516941) is an investigator-initiated, open-label, blinded-endpoint, 2 × 2 factorial design randomized trial aimed at assessing two independently tested hypotheses (anticoagulation and anti-inflammatory ones) in COVID-19 patients. Adult symptomatic patients (≥18 years of age) within 7 days from reverse transcription-PCR (RT-PCR) diagnosis of SARS-CoV-2 infection managed at home or in nursery settings were considered for eligibility. Eligible patients fulfilling all inclusion and no exclusion criteria were randomized to edoxaban versus no treatment (anticoagulation hypothesis) and colchicine versus no treatment (anti-inflammatory hypothesis) in a 1 : 1:1 : 1 ratio. The study had two co-primary endpoints (one for each randomization), including the composite of major vascular thrombotic events at 25 ±â€Š3 days for the anticoagulation hypothesis and the composite of SARS-CoV-2 detection rates at 14 ±â€Š3 days by RT-PCR or freedom from death or hospitalizations (anti-inflammatory hypothesis). Study endpoints will be adjudicated by a blinded Clinical Events Committee. With a final sample size of 420 patients, this study projects an 80% power for each of the two primary endpoints appraised separately. CONCLUSION: The CONVINCE trial aims at determining whether targeting anticoagulation and/or anti-inflammatory pathways may confer benefit in COVID-19 patients managed in the out-of-hospital setting. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04516941.

Effect of a quality improvement program on compliance to the sepsis bundle in non-ICU patients: a multicenter prospective before and after cohort study.

Objective: Sepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a "simplified 1-h bundle" (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU). Methods: Emergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort). Measurements and main results: The effect of QIP on bundle compliance and hospital mortality was evaluated in a before-after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the "simplified rapid (1 h) intervention bundle" (the Sepsis 6 bundle - S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p < 0.001). We then analyzed compliance with S6 and hospital mortality in the before- and after-QIP periods, stratifying the two patients' cohorts by admission characteristics. Adherence to the S6 bundle was increased in patients with severe sepsis in the absence of shock, in patients with serum lactate <4.0 mmol/L, and in patients with hypotension at the time of enrollment, regardless of the type of admission (from EDs or MWs). Subsequently, in an observational analysis, we also investigated the relation between bundle compliance and hospital mortality by logistic regression. In the after-QIP cohort, we observed a lower in-hospital mortality than that observed in the before-QIP cohort. This finding was reported in subgroups where a higher adherence to the S6 bundle in the after-QIP period was found. After adjustment for confounders, the QIP appeared to be independently associated with a significant improvement in hospital mortality. Among the single S6 procedures applied within the first hour of sepsis diagnosis, compliance with blood culture and antibiotic therapy appeared significantly associated with reduced in-hospital mortality. Conclusion: A multi-faceted QIP aimed at promoting an early simplified bundle of care for the management of septic patients out of the ICU was associated with improved compliance with sepsis bundles and lower in-hospital mortality.

Is SARS-CoV-2-induced disease a decisive factor influencing testosterone in males? Findings from a case-control ex post facto study.

BACKGROUND: Whether the observed lower total testosterone (tT) levels in male patients with COVID-19 are caused by a direct impact of SARS-CoV-2 infection or are collateral phenomena shared by other systemic inflammatory conditions has not yet been clarified. OBJECTIVES: To investigate the independent role of COVID-19 in reducing circulating tT levels in men. MATERIALS AND METHODS: We compared demographic, clinical, and hormonal values of patients with laboratory confirmed COVID-19 admitted during the first wave of the pandemic with a cohort of consecutive male patients admitted to the intensive care unit (ICU) of the same academic center because of severe acute respiratory distress syndrome (ARDS) but without SARS-CoV-2 infection and no previous history of COVID-19. Linear regression model tested the independent impact of COVID-19 on circulating tT levels. Logistic regression model was used to test predictors of death in the entire cohort. RESULTS: Of 286 patients with COVID-19, 70 men had been admitted to the ICU ( = cases) and were compared to 79 patients equally admitted to ICU because of severe ARDS but negative for SARS-CoV-2 infection and without previous history of COVID-19 ( = controls). Controls were further grouped into noninfective (n = 49) and infective-ARDS (n = 30) patients. At baseline, controls were older (p = 0.01) and had more comorbidities (p < 0.0001). Overall, cases admitted to ICU had significantly lower circulating tT levels compared to controls (0.9 nmol/L vs. 2.1 nmol/L; vs. 1.2 nmol/L; p = 0.03). At linear regression, being negative for COVID-19 was associated with higher tT levels (Coeff: 2.13; 95% confidence interval - CI 0.71-3.56; p = 0.004) after adjusting for age, BMI, comorbidities and IL-6 levels. Only age and IL-6 levels emerged to be associated with higher risk of death regardless of COVID-19 status. CONCLUSIONS: This case-control ex post facto study showed lower tT levels in men with COVID-19 compared to those without COVID-19 despite both groups have been equally admitted to ICU for severe ARDS, thus suggesting a possible direct impact of SARS-CoV-2 infection toward circulating tT levels and a consequent more severe clinical outcome.

Baseline Characteristics and 3-Year Outcome of Nonvalvular Atrial Fibrillation Patients Treated with the Four Direct Oral Anticoagulants (DOACs).

Direct oral anticoagulants (DOACs) represent the cornerstone therapy for cardioembolic events prevention in patients with nonvalvular atrial fibrillation (NVAF). In practice, the choice of one DOAC over another is guided by the decision-making process of the physician, which considers specific patient and drug characteristics. This study aimed to evaluate the clinical features and long-term outcomes of a real-world population treated with DOACs, where the use of the 4 different DOACs is quite equal. We conducted a retrospective observational, single-center, multidisciplinary study enrolling consecutive NVAF patients treated with one of the 4 DOACs. From an initial number of 753 patients, we excluded 72 patients because of loss to follow-up, at the end we enrolled 681:174 (23%) treated with dabigatran, 175 (23%) with apixaban, 190 (25%) with rivaroxaban, and 214 (29%) with edoxaban. Patients treated with apixaban were significantly older, more women represented (p <0.001), and with a higher cardioembolic and bleeding risk (p <0.001). Dabigatran was preferred in patients with liver failure (p = 0.008), whereas Apixaban and Edoxaban were chosen in chronic kidney disease (p = 0.002). At 3-year follow-up, 20 patients (2.7%) experienced a systemic thromboembolic event without significant differences in the 4 DOACs. In the same period, an International Society of Thrombosis and Hemostasis classification major bleeding event occurred in 26 patients (3.6%), more statistically correlated to edoxaban (6.1%) (p = 0.038). Thromboembolic events or major bleeding were higher in the edoxaban group (10%) compared with the others (p = 0.014). In our single-center real-world experience, the choice of the DOAC for a patient with NVAF was tailored to specific clinical features and drug pharmacokinetics of the patient. As a result, a small number of adverse events were observed.

Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

BACKGROUND: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV). METHODS: Patients with COVID-19 pneumonia admitted up to May 28th, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan. RESULTS: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes. CONCLUSIONS: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Microvascular lung vessels obstructive thromboinflammatory syndrome in patients with COVID-19: Insights from lung intravascular optical coherence tomography.

Background: Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo, probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome. Methods: The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients. Results: A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 ± 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 ± 4.6 mm2, with stenosis of 60.9 ± 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 ± 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 ± 2.6, and the mean thrombus-containing lesion length was 14.1 ± 13.9 mm. No peri-procedural complications occurred in any of the 13 patients. Conclusion: OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis. Clinical trial registration: ClinicalTrial.gov, identifier NCT04410549.

Antibiotic appropriateness for Gram-negative bloodstream infections: impact of infectious disease consultation.

BACKGROUND: We investigated the role of infectious disease consultation (IDC) on therapeutic appropriateness in Gram-negative bloodstream infections (GNBSIs) in a setting with a high proportion of antibiotic resistance. Secondary outcomes were in-hospital mortality and the impact of rapid diagnostic tests (RDTs). METHODS: Retrospective study on hospitalised patients with GNBSIs. Therapy was deemed appropriate if it had the narrowest spectrum considering infection and patients' characteristics. Interventional-IDC (I-IDC) group included patients with IDC-advised first appropriate or last non-appropriate therapy. Time to first appropriate therapy and survival were evaluated by Kaplan-Meier curves. Factors associated with therapy appropriateness were assessed by multivariate Cox proportional-hazard models. RESULTS: 471 patients were included. High antibiotic resistance rates were detected: quinolones 45.5%, third-generation cephalosporins 37.4%, carbapenems 7.9%. I-IDC was performed in 31.6% of patients (149/471), RDTs in 70.7% (333/471). The 7-day probability of appropriate treatment was 91.9% (95% confidence interval [95%CI]: 86.4-95.8%) vs. 75.8% (95%CI: 70.9-80.4%) with and without I-IDC, respectively (p-value = 0.0495); 85.5% (95%CI: 81.3-89.1%) vs. 69.4% (95%CI: 61.3-77.2%) with and without RDTs, respectively (p-value = 0.0023). Compared to RDTs alone, the combination with I-IDC was associated with a higher proportion of appropriate therapies at day 7: 81.9% (95%CI: 76.4-86.7%) vs. 92.6% (95%CI: 86.3-96.7%). At multivariate analysis, I-IDC and RDTs were associated with time to first appropriate therapy [adjusted hazard-ratio 1.292 (95%CI: 1.014-1.647) and 1.383 (95%CI: 1.080-1.771), respectively], with no impact on mortality. CONCLUSIONS: In a setting with a high proportion of antibiotic resistance, IDC and RDTs were associated with earlier prescription of appropriate therapy in GNBSIs, without impact on mortality.

Predictors and outcomes of delirium in the emergency department during the first wave of the COVID-19 pandemic in Milan.

BACKGROUND: Respiratory infections can be complicated by acute brain failure. We assessed delirium prevalence, predictors and outcomes in COVID-19 ED patients. METHODS: This was a retrospective observational study conducted at the San Raffaele ED (Italy). Patients age >18 years attending the ED between 26 February 2020 and 30 May 2020 and who had a positive molecular nasopharyngeal swab for SARS-CoV-2 were included. The Chart-Based Delirium Identification Instrument (CHART-DEL) was used to retrospectively assess delirium. Univariable and multivariable logistic regression analyses were used to evaluate delirium predictors. Univariable binary logistic regression analyses, linear regression analyses and Cox regression analyses were used to assess the association between delirium and clinical outcomes. Age-adjusted and sex-adjusted models were then run for the significant predictors of the univariable models. RESULTS: Among the 826 included patients, 123 cases (14.9%) of delirium were retrospectively detected through the CHART-DEL method. Patients with delirium were older (76.9±13.15 vs 61.3±14.27 years, p<0.001) and more frequently living in a long-term health facility (32 (26%) vs 22 (3.1%), p<0.001). Age (OR 1.06, 95% CI 1.04 to 1.09, p<0.001), dementia (OR 17.5, 95% CI 7.27 to 42.16, p<0.001), epilepsy (OR 6.96, 95% CI 2.48 to 19.51, p<0.001) and the number of chronic medications (OR 1.09, 95% CI 1.01 to 1.17, p=0.03) were significant predictors of delirium in multivariable analyses. Delirium was associated with increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.55 to 3.03, p<0.001) and with a reduced probability of being discharged home compared with being institutionalised (adjusted OR 0.39, 95% CI 0.25 to 0.61, p<0.001). CONCLUSIONS: Chart review frequently identified ED delirium in patients with COVID-19. Age, dementia, epilepsy and polypharmacy were significant predictors of ED delirium. Delirium was associated with an increased in-hospital mortality and with a reduced probability of being discharged home after hospitalisation. The findings of this single-centre retrospective study require validation in future studies.

Testosterone in males with COVID-19: a 12-month cohort study.

BACKGROUND: Male patients with COVID-19 have been found with reduced serum total testosterone (tT) levels and with more severe clinical outcomes. OBJECTIVES: To assess total testosterone (tT) levels and the probability of recovering eugonadal tT levels during a minimum 12-month timespan in a cohort of men who have been followed over time after the recovery from laboratory-confirmed COVID-19. MATERIALS AND METHODS: Demographic, clinical and hormonal values were collected for the overall cohort. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index was used to score health-significant comorbidities. Descriptive statistics was used to compare hormonal levels at baseline versus 7-month (FU1) versus 12-month (FU2) follow-up, respectively. Multivariate cox proportional hazards regression model was used to identify the potential predictors of eugonadism recovery over time among patients with hypogonadism at the time of infection. RESULTS: Of the original cohort of 286 patients, follow-up data were available for 121 (42.3%) at FU1 and 63 (22%) patients at FU2, respectively. Higher median interquartile range (IQR) tT levels were detected at FU2 (13.8 (12.3-15.3) nmol/L) versus FU1 (10.2 [9.3-10.9] nmol/L) and versus baseline (3.6 [3.02-4.02] nmol/L) (all p < 0.0001), whilst both LH and E2 levels significantly decreased over the same time frame (all p ≤ 0.01). Circulating IL-6 levels further decreased at FU2 compared to FU1 levels (19.3 vs. 72.8 pg/ml) (p = 0.02). At multivariable cox regression analyses, baseline tT level (HR 1.19; p = 0.03 [1.02-1.4]) was independently associated with the probability of tT level normalization over time, after adjusting for potential confounders. CONCLUSIONS: Circulating tT levels keep increasing over time in men after COVID-19. Still, almost 30% of men who recovered from COVID-19 had low circulating T levels suggestive for a condition of hypogonadism at a minimum 12-month follow-up.

Combined plasma levels of IL-10 and testosterone, but not soluble HLA-G5, predict the risk of death in COVID-19 patients.

BACKGROUND: The identification of biomarkers correlated with coronavirus disease 2019 (COVID-19) outcomes is a relevant need for clinical management. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by elevated interleukin (IL)-6, IL-10, HLA-G, and impaired testosterone production. OBJECTIVES: We aimed at defining the combined impact of sex hormones, interleukin-10, and HLA-G on COVID-19 pathophysiology and their relationship in male patients. MATERIALS AND METHODS: We measured by chemiluminescence immunoassay, electrochemiluminescent assays, and enzyme-linked immunosorbent assay circulating total testosterone, 17ß-estradiol (E2 ), IL-10, and -HLAG5 as well as SARS-CoV-2 S1/S2 Immunoglobulin G from 292 healthy controls and 111 COVID-19 patients with different disease severity at hospital admission, and in 53 COVID-19 patients at 7-month follow-up. RESULTS AND DISCUSSION: We found significantly higher levels of IL-10, HLA-G, and E2 in COVID-19 patients compared to healthy controls and an inverse correlation between IL-10 and testosterone, with IL-10, progressively increasing and testosterone progressively decreasing with disease severity. This correlation was lost at the 7-month follow-up. The risk of death in COVID-19 patients with low testosterone increased in the presence of high IL-10. A negative correlation between SARS-CoV-2 Immunoglobulin G and HLA-G or IL-10 at hospitalization was observed. At the 7-month follow-up, IL-10 and testosterone normalized, and  HLA-G decreased. CONCLUSION: Our findings indicate that combined evaluation of IL-10 and testosterone predicts the risk of death in men with COVID-19 and support the hypothesis that IL-10 fails to suppress excessive inflammation by promoting viral spreading.

Safety and efficacy of direct oral anticoagulants (DOACs) in very elderly patients (≥85 years old) with non-valvular atrial fibrillation.

BACKGROUND: Limited real-world data are available regarding the comparison about safety and efficacy of DOACs prescription in very elderly patients (≥85 years) with non-valvular atrial fibrillation (NVAF). Concern about the risk of bleeding with anticoagulation in very older patients still represents an important challenge for clinicians. The aim of this study was to evaluate the different prevalence of major bleeding and thromboembolic events between very elderly NVAF patients (≥85 years) compared to those non very elderly (<85 years). METHODS: Single center multidisciplinary registry including NVAF patients treated with DOACs. Primary safety endpoint was 2-year rate of major bleeding. Primary efficacy endpoint was 2-year rate of thromboembolic events. Event-free survival curves among groups were compared using Cox-Mantel Test. RESULTS: 908 NVAF consecutive patients were included, of these, 805 patients were <85 years (89%) and 103 patients were very elderly patients with ≥85 years (11%). Compared to patients <85 years, those very elderly have higher CHA2DS2-VASc Score (P=0.001), higher rate of hypertension (P=0.001), diabetes mellitus (P=0.030), previous bleeding events (P<0.001), previous stroke/TIA/SE (P≤0.001), heart failure (P≤0.001), and lower creatinine clearance (P<0.001). In terms of safety endpoints (overall ISTH-major bleeding) no significative difference between two groups (P=0.952) were observed up to 2-year follow-up. Systemic thromboembolic event (primary efficacy endpoint) was significantly higher in patients with ≥85 years (P=0.027). The incidence of all-cause death was significantly higher in very elderly patients (P<0.001). CONCLUSIONS: This single center registry, showed that the use of DOACs in very elderly NVAF was safe and is a therapeutic option to be pursued for stroke prevention especially for those who are at high risk of ischemic events.

Impact of Remdesivir on SARS-CoV-2 Clearance in a Real-Life Setting: A Matched-Cohort Study.

Background: Evidence regarding the impact of remdesivir (RDV) on SARS-CoV-2 viral clearance (VC) is scarce. The aim of this study was to compare VC timing in hospitalized COVID-19 patients who did or did not receive RDV. Methods: This was a matched-cohort study of patients hospitalized with pneumonia, a SARS-CoV-2-positive nasopharyngeal swab (NPS) at admission, and at least one NPS during follow-up. Patients who received RDV (cases) and those who did not (controls) were matched in a 1:2 ratio by age, sex, and PaO2/FiO2 (P/F) values at admission. NPSs were analyzed using real-time polymerase chain reaction. Time to VC (within 30 days after hospital discharge) was estimated using the Kaplan-Meier curve. A multivariable Cox proportional hazard model was fitted to determine factors associated with VC. Results: There were 648 patients enrolled in the study (216 cases and 432 controls). VC was observed in 490 patients (75.6%), with a median time of 25 (IQR 16-34) days. Overall, time to VC was similar between cases and controls (p = 0.519). However, time to VC was different when considering both RDV treatment status and age (p = 0.007). A significant finding was also observed when considering both RDV treatment status and P/F values at admission (p = 0.007). A multivariate analysis showed that VC was associated with a younger age (aHR = 0.990, 95% CI 0.983-0.998 per every 10-year increase in age; p = 0.009) and a higher baseline P/F ratio (aHR=1.275, 95% CI 1.029-1.579; p=0.026), but not with RDV treatment status. Conclusion: Time to VC was similar in cases and controls. However, there was a benefit associated with using RDV in regard to time to VC in younger patients and in those with a P/F ratio ≤200 mmHg at hospital admission.

Z-drugs and falls in nursing home patients: data from the INCUR study.

BACKGROUND: Z-drugs are the most prescribed treatment for insomnia, but their negative effect on the body sway can increase the risk of falls. AIMS: Evaluating the association between Z-drugs and falls in a resident cohort. METHODS: Prospective observational study using the data collected in the Incidence of pNeumonia and related ConseqUences in nursing home Residents (INCUR) study. RESULTS: During the one-year follow-up, among the 800 participants (median age 87), 93 individuals fell (64 fracturing and 29 without fracturing). Lower calf circumference (adjusted OR 0.92, 95% CI 0.86-0.97, p = 0.006) and the use of selective serotonin reuptake inhibitors (adjusted OR 1.86, 95% CI 1.1-3.05, p = 0.01) predicted falls, whereas the use of Z-drugs (adjusted OR 2.37, 95% CI 1.13-4.94, p = 0.02) and lower body mass index (adjusted OR 0.9, 95% CI 0.84-0.97, p = 0.005) were associated with falls without fractures. CONCLUSIONS: Z-drugs predicted falls without fractures in residents. Alternative strategies to promote sleep in residents should be pursued.

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19.

Background: This study's primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods: This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray's method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results: Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8-11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7-21.0) and 9.3 (95% CI, 7.9-11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018-3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions: In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections.

Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients.

Background: A motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals. Methods: This was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia. Results: A total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23-1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B -5.63, 95% CI -8.39 to -2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10-15.13, p = 0.003), impaired muscle performance (SPPB: B -3.47, 95% CI -6.33 to -0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52-619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37-813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87-1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32-8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17-12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44-1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009). Conclusion: The precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.

Hypereosinophilia management in patients with type 2 chronic rhinosinusitis treated with dupilumab: preliminary results.

PURPOSE: Biological therapies are gaining relevance in the management of CRSwNP with few adverse events reported. Among these, dupilumab, an anti-IL4-Ra monoclonal antibody, is frequently associated with hypereosinophilia (HE) which usually remains silent and progressively resolves, although some cases of systemic involvement occurs. The aim of this paper is to describe our experience and propose a management flowchart for HE during therapy with dupilumab. METHODS: Patients with CRSwNP who satisfied EPOS2020 criteria for biological therapies were included in this prospective study. Each case was discussed in a multidisciplinary meeting with subsequent prescription of dupilumab; all patients were candidates to follow-up bi-monthly for 6 months, while additional blood tests were scheduled in the event of HE. RESULTS: A total of 21 patients with a mean age of 48.4 years were enrolled. Of these, 15 of 21 presented an asthma comorbidity and 9 of 21 ASA sensitivity. Four patients (19%) developed HE with AEC > 1.5 × 109/L, whereas it occurred in 9.5% (two patients) if considered AEC > 3 × 109/L. No cases of hypereosinophilic syndrome were recorded. Following our decision-making flowchart, two patients received short-term corticosteroid therapy, whereas the other two were only eligible for closer follow-up. CONCLUSIONS: During dupilumab therapy, HE may occur and should be considered benign when < 3 × 109/L in the absence of organ involvement. Conversely, in case of HE ≥ 3 × 109/L, an empirical approach with short-term corticosteroid therapy should be considered to debulk the blood from eosinophils and prevent potential organ involvement.