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Background: Antibiotics are the most prescribed drugs for children worldwide, but overuse and misuse have led to an increase in antibiotic resistance. Antimicrobial stewardship programmes (ASPs) have proven feasible in reducing inappropriate antimicrobial use. The study aimed at evaluating the impact and sustainability of an ASP with multiple interventions over 8 years., Methods: This quasi-experimental study was conducted between 2014 and 2022 in the paediatric acute care unit of Padua University Hospital. Demographic and clinical data were retrieved from the electronic clinical records. Daily prescriptions were collected and analysed based on the AWaRe classification and using days of therapy (DOT) out of 1000 patient days (DOT/1000PDs). The primary outcome was to assess the change in overall antibiotic consumption and of access and watch antibiotics, stratifying patients with and without comorbidities. Trends in antibiotic consumption (DOTs/1000PD) were assessed using joinpoint regression analysis., Findings: A total of 3118 children were included. Total antibiotic consumption remained stable and low in patients without comorbidities, ∼300 DOT/1000PDs, whereas a statistically significant constant reduction was observed in children with comorbidities, from almost 500 DOT/1000PPDs to <400 DOT/1000PDs. Access consumption increased in both groups of patients, whereas watch consumption constantly decreased, although statistically significant only in children with comorbidities., Interpretation: Implementing a multistep ASP has proven feasible and sustainable in improving antibiotic prescriptions for previously healthy and fragile children. All the implemented interventions were low cost, and with efficient use of resources, ensuring an ASP that was effective, practical, and easily replicable and implementable in various healthcare settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Urinary tract infections (UTIs) are the most common bacterial infections in children. The high variability in pathogen susceptibility rates leads to the lack of clear guidelines for empiric and targeted therapies. In this view, local microbiological surveillance and locally adapted stewardship interventions need to be implemented., Objective: The study aims to describe the results of a pediatric antimicrobial stewardship program on antibiotic prescriptions for UTIs over 8 years in a pediatric general ward of a tertiary center., Design: This quasi-experimental study was conducted between 2015 and 2022, with two different implementations, one in 2018 and one in 2021., Methods: Demographic, clinical, microbiological, and therapeutic data were retrieved from the electronic clinical records of included patients. The primary outcomes were adherence to local guidelines for empiric therapies and the adequacy of targeted therapy. Secondary outcomes were evaluating antibiotic prescription patterns stratified by antibiotics during hospital stay and at discharge, and assessing the microbiological characteristics of UTI episodes., Results: During the study period, 7038 patients were admitted to the pediatric acute care unit (PACU), and 264 (3.7%) were included in this study. Adherence to local guidelines was highest immediately after the interventions, and it slightly decreased thereafter. Use of cephalosporins remained high throughout the 8 years but the changing microbiological scenario observed led to changing recommendations within the study period. An increase in E. coli strains resistant to co-amoxiclav was observed in the last years. Oral second-line agent consumption remained high but was adequate considering the prevalence of resistant bacteria., Conclusion: The variability of antimicrobial consumption reflects the changing resistance patterns for UTIs pathogens, underlying the importance of locally adapted, persevering antimicrobial stewardship interventions., (© The Author(s), 2024.)

Importance: Point prevalence surveys (PPSs) are used globally to collect data on antibiotic prescriptions. However, the optimal frequency for data collection to ensure comprehensive understanding of antibiotic use and to target and monitor stewardship interventions remains unknown., Objective: To identify the optimal frequency for collecting data on antibiotic use among the pediatric population through PPSs leveraging administrative data., Design, Setting, and Participants: This prognostic study used a cross-sectional validation approach and was conducted in pediatric outpatient and inpatient settings in the Veneto region of Italy. Antibiotics were classified according to the World Health Organization Access, Watch and Reserve criteria. Prescribing rates of access antibiotics were analyzed for pediatric inpatients with records dated between October 1, 2014, and December 31, 2022, and outpatients with records dated between January 1, 2010, and December 31, 2022. The study included children younger than 15 years with an antibiotic prescription who were admitted to the pediatric acute care unit or evaluated by a primary care pediatrician. Data analysis was performed from October 2023 to January 2024., Main Outcomes and Measures: An algorithm was developed to identify optimal time frames for conducting PPSs. This approach sought to minimize the discrepancy between quarterly and yearly PPS results, aiming to accurately estimate annual antibiotic prescribing rates in both inpatient and outpatient settings (primary outcome). External validity of the optimal PPS time frames derived from outpatient data when applied to the inpatient setting was also investigated. Validation involved assessing the effectiveness of administrative data in identifying strategic PPS periods for capturing inpatient antibiotic use patterns (secondary outcome)., Results: This analysis included 106 309 children: 3124 were inpatients (1773 males [56.8%]) and 103 185 were outpatients (53 651 males [52.0%]). A total of 5099 and 474 867 antibiotic prescriptions from inpatients and outpatients were analyzed, respectively. Outpatients tended to be older than inpatients, with a median age of 3.2 (IQR, 1.3-6.3) years vs 2.6 (IQR, 0.6-6.6) years, respectively, and with a lower burden of clinical comorbidities (≥1 comorbidity: 6618 [6.4%] vs 1141 [36.5%], respectively). The algorithm successfully identified distinct time frames within the calendar year from inpatient and outpatient records optimized for PPS data collection. Rates obtained from the quarterly PPS during these identified periods exhibited greater agreement with annual antibiotic prescribing rates (inpatient: r = 0.17, P < .001; and outpatient: r = 0.42, P < .001) than those derived from the yearly PPS (inpatient: r = 0.04, P = .58; and outpatient: r = 0.05, P = .34), with a Δ reduction of up to 89.8% (where Δ represents the percentage point change in antibiotic prescribing rates). Furthermore, the optimal PPS time frames gleaned from the outpatient data demonstrated robust applicability to the inpatient setting, yielding comparable results in both scenarios., Conclusions and Relevance: This study evaluated the potential of administrative data in determining the optimal timing of PPS implementation. The quarterly PPS balanced precision and sustainability, especially when implemented during strategically selected periods across different seasons. Further studies are needed to validate the algorithm used in this study, especially in post-COVID-19 pandemic years and different settings.

The migration of helical particles in viscous shear flows plays a crucial role in chiral particle sorting. Attaching a nonchiral head to a helical particle leads to a rheotactic torque inducing particle reorientation. This phenomenon is responsible for bacterial rheotaxis observed for flagellated bacteria as Escherichia coli in shear flows. Here, we use a high-resolution microprinting technique to fabricate microparticles with controlled and tunable chiral shape consisting of a spherical head and helical tails of various pitch and handedness. By observing the fully time-resolved dynamics of these microparticles in microfluidic channel flow, we gain valuable insights into chirality-induced orientation dynamics. Our experimental model system allows us to examine the effects of particle elongation, chirality, and head heaviness for different flow rates on the orientation dynamics, while minimizing the influence of Brownian noise. Through our model experiments, we demonstrate the existence of asymmetric bistability of the particle orientation perpendicular to the flow direction. We quantitatively explain the particle equilibrium orientations as a function of particle properties, initial conditions and flow rates, as well as the time-dependence of the reorientation dynamics through a theoretical model. The model parameters are determined using boundary element simulations, and excellent agreement with experiments is obtained without any adjustable parameters. Our findings lead to a better understanding of chiral particle transport and bacterial rheotaxis and might allow the development of targeted delivery applications.

The Fontan operation is a palliative procedure that leads to increased survival of patients with a functional single ventricle (SV). Starting from 1967 when the first operation was performed by Francis Fontan, more and more patients have reached adulthood. Furthermore, it is expected that in the next 20 years, the population with Fontan circulation will reach 150,000 subjects. The absence of right ventricular propulsion and the inability to improve cardiac output because of the low cardiac reserve are the main issues with the Fontan circulation; however, potential complications may also involve multiple organ systems, such as the liver, lungs, brain, bones, and the lymphatic system. As these patients were initially managed mainly by pediatric cardiologists, it was important to assure the appropriate transition to adult care with the involvement of a multidisciplinary team, including adult congenital cardiologists and multiple subspecialists, many of whom are neither yet familiar with the pathophysiology nor the end-organ consequences of the Fontan circulation. Therefore, the aim of our work was to collect all the best available evidence on Fontan's complications management to provide "simple and immediate" information sources for practitioners looking for state of the art evidence to guide their decision-making and work practices. Moreover, we suggest a model of follow-up of patients with Fontan based on a patient-centered multidisciplinary approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martino, Rizzardi, Vigezzi, Guariento, Sturniolo, Tesser and Salvo.)

Background: The novel coronavirus disease of 2019 (COVID-19) outbreak provoked a profound healthcare system reorganization. This study aimed to compare the reasons for requesting a non-deferrable neurological evaluation before the COVID-19 pandemic and during the lockdown., Methods: Retrospective observational study including non-deferrable neurological outpatients before the pandemic (pre-COVID-19 group, n = 223) and during the Italian second wave of the COVID-19 pandemic (LOCKDOWN group, n = 318)., Results: The number of patients sent for cerebrovascular disorders, headache, and vertigo significantly dropped between the pre-COVID-19 era and the lockdown period. While in the pre-COVID-19 group, the most frequent diagnosis was cerebrovascular disorder; neuropsychiatric disorders ranked first in the LOCKDOWN group. Moreover, the percentage of appropriate non-deferrable neurological evaluations significantly increased in the LOCKDOWN group compared with the pre-COVID-19 group., Discussion: Our study shows a significant increase of neuropsychiatric disorders in non-deferrable neurologic evaluations during the Italian second wave of the COVID-19. Overall, cases were more severe and required a more complex management during the lockdown compared with the pre-COVID era. These findings confirm that a careful approach to prevent the psychological consequences of the pandemic is needed, and long-term rearrangements of the healthcare system are desirable to guarantee appropriate management.

The dynamics of a population expanding into unoccupied habitat has been primarily studied for situations in which growth and dispersal parameters are uniform in space or vary in one dimension. Here, we study the influence of finite-sized individual inhomogeneities and their collective effect on front speed if randomly placed in a two-dimensional habitat. We use an individual-based model to investigate the front dynamics for a region in which dispersal or growth of individuals is reduced to zero (obstacles) or increased above the background (hotspots), respectively. In a regime where front dynamics is determined by a local front speed only, a principle of least time can be employed to predict front speed and shape. The resulting analytical solutions motivate an event-based algorithm illustrating the effects of several obstacles or hotspots. We finally apply the principle of least time to large heterogeneous environments by solving the Eikonal equation numerically. Obstacles lead to a slow-down that is dominated by the number density and width of obstacles, but not by their precise shape. Hotspots result in a speed-up, which we characterize as function of hotspot strength and density. Our findings emphasize the importance of taking the dimensionality of the environment into account.

Aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSD) are rare idiopathic autoimmune diseases, presenting with optic neuritis (ON), longitudinally extensive transverse myelitis (LETM), and brainstem syndromes and a prevalence range between 0.5 and 4/100,000. Only 3% to 25% of NMOSD have been described as a paraneoplastic (PN) syndrome (PNNMOSD). Both idiopathic NMOSD (INMOSD) and PNNMOSD cases mostly affect females, but PNNMOSD usually presents with a spinal cord or brainstem involvement in elderly patients. Few cases of both malignancies (for the majority breast or lung cancer) and benign tumors (monoclonal gammopathy) were previously reported. Currently, there is no consensus on treatment approach for PNNMOSD (only surgical removal or surgery combined with chronic immunosuppression). Here, we present a series of three newly diagnosed PNNMOSD cases, who differ from each other for demographic and clinical features, tumor association, long-term treatment, and outcome. We propose that a PN etiology should be considered always whenever a new diagnosis of NMOSD is made, not only in patients over 50 years old or in spinal cord/brainstem lesions presentations. Our findings add to existing evidence and raise awareness on PNNMOSD. We enhance the importance for the clinicians of recognizing tumor symptoms and signs whenever a NMOSD is newly diagnosed.

(1) Background: To limit the COVID-19 outbreak, the Italian government implemented social restrictions that may have had psychological and cognitive repercussions on people with dementia. We aimed to analyze cognitive decline during the pandemic year in people evaluated in a memory clinic in northern Italy, the epicenter of COVID-19 spread. (2) Methods: A single-center retrospective study was carried out, including individuals with annual follow-up evaluated in three different years (2020-GROUP, 2019-GROUP, 2018-GROUP). We performed an intergroup comparison of cognitive decline over a one-year follow-up, and an intragroup comparison in the 2020-GROUP to analyze the five-year cognitive decline trajectory, as measured by the MMSE. (3) Results: The 2020-GROUP showed a significant loss of MMSE points per year in the considered follow-up period compared with the 2019-GROUP and 2018-GROUP ( p = 0.021). Demographics, clinical features, and the other analyzed variables, including rate of diagnosis, therapy, and comorbidities, did not significantly differ between groups. The five-year cognitive decline trajectory confirmed a significant worsening of cognitive decline between 2019 and 2020 ( p < 0.001), while the decrease in MMSE scores was not statistically significant between previous time points. (4) Conclusions: COVID-19 pandemic measures have induced a significant worsening of cognitive decline in people with dementia, needing more careful assistance to minimize the adverse effects of social isolation in case of future lockdowns.

The expansion of biological species in natural environments is usually described as the combined effect of individual spatial dispersal and growth. In the case of aquatic ecosystems flow transport can also be extremely relevant as an extra, advection induced, dispersal factor. We designed and assembled a dedicated microfluidic device to control and quantify the expansion of populations of E. coli bacteria under both co-flowing and counter-flowing conditions, measuring the front speed at varying intensity of the imposed flow. At variance with respect to the case of classic advective-reactive-diffusive chemical fronts, we measure that almost irrespective of the counter-flow velocity, the front speed remains finite at a constant positive value. A simple model incorporating growth, dispersion and drift on finite-size hard beads allows to explain this finding as due to a finite volume effect of the bacteria. This indicates that models based on the Fisher-Kolmogorov-Petrovsky-Piscounov equation (FKPP) that ignore the finite size of organisms may be inaccurate to describe the physics of spatial growth dynamics of bacteria.

Objective: To prospectively evaluate predictors of incomplete recovery after the first attacks in a cohort of patients with clinically isolated syndrome or relapsing-remitting multiple sclerosis., Methods: Seventy-two consecutive patients recruited from January 2001 to December 2003, evaluated every six months or at any relapse up to 31 July 2005. Relapse intervals were calculated from the date of onset, nadir, onset of improvement and maximum improvement. Predictive factors analysed were relapse-related (age at relapse onset, season and severity of the relapse, type of symptoms, speed of onset, plateau and total duration, number of affected Functional systems, preceding infections) and individual-related (gender, age at first attack, season of birth and first attack, characteristics of first brain MRI and cerebrospinal fluid oligoclonal bands, Link Index, IgG)., Results: We counted 209 attacks: 44 (21%) left mild sequelae, and 27 (13%) severe. The highest probability of sequelae was associated with sphincteric symptoms (9/20; 45%), followed by sensitive (38/113; 34%), motor (20/84; 24%), visual (13/61; 21%), cerebellar (4/24; 17%), brainstem (5/44; 11%) and others (0/6) ( P 0.005). Four variables were still relevant to predict sequelae after multivariate analysis: mild, moderate or severe relapses versus very mild (Odds ratio = 17.2, 95% confidence limits = 2.2-136.4), intermediate or long relapses versus short (3.2, 1.5-6.9), age >or= 30 at relapse onset (2.9, 1.5-5.7) and bi-polysymptomatic versus monosymptomatic (2.2, 1.1-4.3)., Conclusions: Factors predicting incomplete recovery are more closely linked to the characteristics of the single relapse (extension and duration of tissue damage) than to the patient's genetic and environmental background.

Human ICOS is a T cell costimulatory molecule supporting IL10 secretion. A pilot study investigating variations of the ICOS gene 3'UTR detected 8 polymorphisms forming three haplotypes (A, B, C). Haplotype-A and -C displayed the highest difference. Activated T cells from healthy AA homozygotes expressed significantly less ICOS and secreted more IL10 than AC heterozygotes, whereas AB heterozygotes displayed intermediate levels. Analysis of 441 multiple sclerosis patients and 793 controls showed that frequency of AA homozygosity was significantly lower in MS patients with relapsing-remitting onset (N=416) than in controls (OR=0.70). Moreover, AA patients with relapsing-remitting onset had lower relapse rate and multiple sclerosis severity score than non-AA patients.