The LiberAction Project: Implementation of a Pediatric Liberation Bundle to Screen Delirium, Reduce Benzodiazepine Sedation, and Provide Early Mobilization in a Human Resource-Limited Pediatric Intensive Care Unit

Background: Delirium, bed immobilization, and heavy sedation are among the major contributors of pediatric post-intensive care syndrome. Recently, the Society of Critical Care Medicine has proposed the implementation of daily interventions to minimize the incidence of these morbidities and optimize children functional outcomes and quality of life. Unfortunately, these interventions require important clinical and economical efforts which prevent their use in many pediatric intensive care units (PICU). Aim: First, to evaluate the feasibility and safety of a PICU bundle implementation prioritizing delirium screening and treatment, early mobilization (<72 h from PICU admission) and benzodiazepine-limited sedation in a human resource-limited PICU. Second, to evaluate the incidence of delirium and describe the early mobilization practices and sedative drugs used during the pre- and post-implementation periods. Third, to describe the barriers and adverse events encountered during early mobilization. Methods: This observational study was structured in a pre- (15th November 2019-30th June 2020) and post-implementation period (1st July 2020-31st December 2020). All patients admitted in PICU for more than 72 h during the pre and post-implementation period were included in the study. Patients were excluded if early mobilization was contraindicated. During the pre-implementation period, a rehabilitation program including delirium screening and treatment, early mobilization and benzodiazepine-sparing sedation guidelines was developed and all PICU staff trained. During the post-implementation period, delirium screening with the Connell Assessment of Pediatric Delirium scale was implemented at bedside. Early mobilization was performed using a structured tiered protocol and a new sedation protocol, limiting the use of benzodiazepine, was adopted. Results: Two hundred and twenty-five children were enrolled in the study, 137 in the pre-implementation period and 88 in the post-implementation period. Adherence to delirium screening, benzodiazepine-limited sedation and early mobilization was 90.9, 81.1, and 70.4%, respectively. Incidence of delirium was 23% in the post-implementation period. The median cumulative dose of benzodiazepines corrected for the total number of sedation days (mg/kg/sedation days) was significantly lower in the post-implementation period compared with the pre-implementation period: [0.83 (IQR: 0.53-1.31) vs. 0.74 (IQR: 0.55-1.16), p = 0.0001]. The median cumulative doses of fentanyl, remifentanil, and morphine corrected for the total number of sedation days were lower in the post-implementation period, but these differences were not significant. The median number of mobilizations per patient and the duration of each mobilization significantly increased in the post-implementation period [3.00 (IQR: 2.0-4.0) vs. 7.00 (IQR: 3.0-12.0); p = 0.004 and 4 min (IQR: 3.50-4.50) vs. 5.50 min (IQR: 5.25-6.5); p < 0.0001, respectively]. Barriers to early mobilization were: disease severity and bed rest orders (55%), lack of physicians' order (20%), lack of human resources (20%), and lack of adequate devices for patient mobilization (5%). No adverse events related to early mobilization were reported in both periods. Duration of mechanical ventilation and PICU length of stay was significantly lower in the post-implementation period as well as the occurrence of iatrogenic withdrawal syndrome. Conclusion: This study showed that the implementation of a PICU liberation bundle prioritizing delirium screening and treatment, benzodiazepine-limited sedation and early mobilization was feasible and safe even in a human resource-limited PICU. Further pediatric studies are needed to evaluate the clinical impact of delirium, benzodiazepine-limited sedation and early mobilization protocols on patients' long-term functional outcomes and on hospital finances

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5–11 December, to 17.5% (25/143 samples) in the week 12–18, to 65.9% (89/135 samples) in the week 19–25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased fromone in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

Italian RED Study Sub-Analysis: 30-Day Post-Discharge BNP Levels Predict 6-Month All-Cause Mortality and Cardiac Events

Introduction:Rehospitalization of patients after acute decompensated heart failure (ADHF) is a major medical problem. B-type natriuretic peptide (BNP) levels are very prognostic at discharge, but their role in the weeks after discharge have not been elucidated. Hypothesis:Our aim was to determine if BNP levels after discharge for ADHF had significant prognostic ability. Methods: This was a 8 center Italian observational study. 287 patients with ADHF were studied with physical exams, lab tests, CXR, ECGs and BNP values at admission, 24 hours, discharge, and 30/90/180-day post-discharge. In this analysis, 104 patients were included whom were all recruited at the main study site. This population had more hypertension, coronary artery disease, and beta-blocker use in the hospital. Logistic regression and receiver operating characteristic (ROC) curves were used to assess the ability of BNP levels at 30 days post-discharge to predict future events up to 6 months. Results: Of the 104 patients, 15 had events (all-cause mortality, re-hospiatlization, or cardiac events) within 6 months of discharge from the hospital. Logistic regression demonstrated that BNP levels 30 days post-discharge were significantly predictive of future events (OR=12.2, p=0.03)..Discharge levels were not predictive of future events. On ROC analysis, BNP values above 400 pg/mL at 30 days had the maximum area under curve at 0.780. Conclusion: Our analysis demonstrates that 30-day BNP levels post-discharge also have significant prognostic value. Patients with BNP levels greater than 400 pg/mL 1 month after discharge should be considered high risk for hospitalization and death, and considered to optimize therapeutic and preventative strategie

Adhesion of Enterococcus faecalis in the Nonculturable State to Plankton Is the Main Mechanism Responsible for Persistence of This Bacterium in both Lake and Seawater

The presence of enterococci in lake and seawater in an 18-month survey comparing molecular (PCR and quantitative PCR) and culture methods was evaluated, as well as the possibility that zooplankton could act as reservoirs for enterococci. Samples of both water and zooplankton were collected monthly from a Lake Garda site and an Adriatic Sea site. In lake water, the positive samples numbered 13 of 54 (24%) by culture and 32 of 54 (59%) when PCR was applied. In seawater, they numbered 0 of 51 by culture and 18 of 51 (35%) by PCR. Enterococci were found either totally bound to plankton or totally in water, depending on the presence or absence of plankton, respectively. These results clearly indicate that the PCR assay is a powerful tool for detecting fecal indicators and pathogens in the environment, thus providing a much more sensitive method than culture

Drug self-poisoning in adolescents: A report of 267 cases

Introduction: The current study aims at describing a sample of adolescents admitted to a tertiary referral pediatric hospital for drug self-poisoning and to identify variables that could explain and predict a higher severity of intoxication. Methods: We retrospectively reviewed the cases of drug self-poisoning in adolescents admitted to the Bambino Gesù Children’s Hospital between January 2014 and June 2022 requiring consultation by the local Pediatric Poison Control Center (PPCC). We reported the type and class of drug ingested and correlated the clinical characteristics of the patients with their Poison Severity Score. Results: The data of 267 patients were reported. Most patients were female (85.8 %), with a median age of 15.8 years at presentation. Half of the patients were symptomatic at admission (44.2 %), and most had at least one psychiatric comorbidity (71.1 %). Most patients were hospitalized (79.6 %), 16.6 % of cases required antidote administration and a minority required intensive care. Most patients received a PSS score of 0 (59.6 %). The most frequently ingested drug was acetaminophen (28.1 %) followed by ibuprofen (10.1 %) and aripiprazole (10.1 %). Antipsychotics as a class were the most abused drugs (33.1 %). The correlation of clinical variables with the PSS showed that older and male patients were more prone to be severely intoxicated. Conclusions: This single-center study identifies the most commonly ingested drugs in a large sample of adolescents with voluntary drug self-poisoning, also showing that older and male patients are more susceptible to severe intoxication

Casetta Rossa: studio ed evoluzione di una Casa del Popolo bolognese

La mostra raccoglie gli esiti del progetto di riqualificazione della Casetta Rossa, Casa del Popolo bolognese. L'esposizione della proposta progettuale, sviluppata nell'ambito del Dottorato di Ricerca in Architettura dell'Università di Bologna, è accompagnata da una anteprima della rassegna fotografica curata da Lucio Rossi

Usefulness of Combining Galectin-3 and BIVA Assessments in Predicting Short- and Long-Term Events in Patients Admitted for Acute Heart Failure

Introduction:. Acute heart failure (AHF) is associated with a higher risk for the occurrence of rehospitalization and death. Galectin-3 (GAL3) is elevated in AHF patients and is an indicator in predicting short-term mortality. The total body water using bioimpedance vector analysis (BIVA) is able to identify mortality within AHF patients. The aim of this study was to evaluate the short- and long-term predictive value of GAL3, BIVA, and the combination of both in AHF patients in Emergency Department (ED). Methods:. 205 ED patients with AHF were evaluated by testing for B type natriuretic peptide (BNP) and GAL3. The primary endpoint was death and rehospitalization at 30, 60, 90, and 180 days and 12 and 18 months. AHF patients were evaluated at the moment of ED arrival with clinical judgment and GAL3 and BIVA measurement. Results:. GAL3 level was significantly higher in patients >71 years old, and with eGFR 17.8 ng/mL shows significant survival difference. At multivariate Cox regression analysis GAL3 is an independent variable to predict death + rehospitalization with a value of 32.24 ng/mL at 30 days (P < 0.005). Conclusion:. In patients admitted for AHF an early assessment of GAL3 and BIVA seems to be useful in identifying patients at high risk for death and rehospitalization at short and long term. Combining the biomarker and the device could be of great utility since they monitor the severity of two pathophysiological different mechanisms: heart fibrosis and fluid overload

Safety outcomes and long-term effectiveness of ex vivo autologous cultured limbal epithelial transplantation for limbal stem cell deficiency

PURPOSE: To evaluate the safety and effectiveness of ex vivo autologous cultured limbal stem cell transplantation (CLET). METHODS: We reviewed the clinical records of 59 consecutive patients treated with 65 CLETs. Efficacy was graded 1 year after surgery as successful, partially successful or failed. A safety analysis was performed considering side effects and complications that were recorded during the first year after CLET and those reported later than 1 year, including the events related to subsequent treatments. RESULTS: The mean post-CLET follow-up was 6.0\ub14.1 years. 69% of CLETs had either one or more adverse events (AEs), or adverse drug reactions (ADRs), within 1 year of surgery, with inflammation being the most common (42%), followed by corneal epithelium defects/disepithelialisation (31%), and blood coagula under the fibrin (24%). One year after surgery, 41% of the 59 primary CLET procedures were successful, 39% partially successful and 20% failed. The most common ADRs recorded for the primary unsuccessful CLETs were ulcerative keratitis, melting/perforation, and epithelial defects/disepithelialisation. Six failed CLETs required reconstructive penetrating keratoplasty (PK). Among CLETs with a favourable outcome, 13 underwent corrective PK (mean 4.8\ub13.4 years), and thereafter seven eyes maintained integrity of the corneal epithelium, five showed corneal surface failure, and one had recurrent epithelial defects. Corneal graft rejection episodes were reported in 71% and 58% of patients following corrective or reconstructive PK, respectively. Seven primary CLETs with a favourable outcome worsened thereafter, and the overall 3-year long-term effectiveness was 68%. CONCLUSIONS: This study addresses important issues regarding possible risks associated with disarray of the ocular surface homeostasis following autologous CLET in patients with limbal stem cell deficiency, despite the fact that the majority of patients experienced a favourable long-term benefit