Impact of SARS-CoV-2 Pandemic and Strategies for Resumption of Activities During the Second Wave of the Pandemic : A Report From Eight Paediatric Hospitals From the ECHO Network

The Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) pandemic impacted the organization of paediatric hospitals. This study aimed to evaluate the preparedness for the pandemic among a European network of children's hospitals and to explore the strategies to restart health care services. A cross-sectional, web-based survey was distributed in May 2020 to the 13 children's tertiary care hospitals belonging to the European Children's Hospitals Organisation. Responses were obtained from eight hospitals (62%). Significant reductions were observed in accesses to the emergency departments (41.7%), outpatient visits (35.7%), intensive and non-intensive care unit inpatient admissions (16.4 and 13%, respectively) between February 1 and April 30, 2020 as compared with the same period of 2019. Overall, 93 children with SARS CoV-2 infection were admitted to inpatient wards. All the hospitals created SARS-CoV-2 preparedness plans for the diagnosis and management of infected patients. Routine activities were re-scheduled. Four hospitals shared their own staff with adult units, two designated bed spaces for adults and only one admitted adults to inpatient wards. The three main components for the resumption of clinical activities were testing, source control, and reorganization of spaces and flows. Telemedicine and telehealth services were used before the SARS-CoV-2 pandemic by three hospitals and by all the hospitals during it. Conclusion: The present study provides a perspective on preparedness to SARS-CoV-2 pandemic among eight large European children's hospitals, on the impact of the pandemic on the hospital activities and on the strategies adopted to restart clinical activities.Peer reviewe

Fetal programming and systemic sclerosis

Objective This study investigated whether birthweight is linked to an increased risk of the development of systemic sclerosis. Study Design This was a multicenter case-control study with perinatal data that were obtained from 332 cases with systemic sclerosis and 243 control subjects. Birthweight was treated as a dichotomous variable (<2500 g vs 652500 g); low birthweight was defined as a weight <2500 g; small for gestational age was defined as birthweight <10th percentile for gestational age adjusted for sex. The relationship between systemic sclerosis and both low birthweight and small for gestational age was expressed with the crude (univariate analysis) and adjusted (multivariate analysis) odds ratio (OR). Results Significantly increased ORs were observed in the univariate analysis for low birthweight (OR, 2.59; 95% confidence interval [CI], 1.39-5.05) and small for gestational age (OR, 2.60; 95% CI, 1.34-5.32) subjects. Similarly increased risks were confirmed for both conditions in the multivariate analysis (OR, 3.93; 95% CI, 1.92-8.07; and OR, 2.58; 95% CI, 1.28-5.19), respectively. Conclusion Low birthweight and small for gestational age at birth are risk factors for the adult onset of systemic sclerosis

Efficacy of ketamine in refractory convulsive status epilepticus in children: A protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

Introduction: Status epilepticus (SE) is a lifethreatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-D-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/ hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences

Ear Reconstruction Simulation: From Handcrafting to 3D Printing

Microtia is a congenital malformation affecting one in 5000 individuals and is characterized by physical deformity or absence of the outer ear. Nowadays, surgical reconstruction with autologous tissue is the most common clinical practice. The procedure requires a high level of manual and artistic techniques of a surgeon in carving and sculpting of harvested costal cartilage of the patient to recreate an auricular framework to insert within a skin pocket obtained at the malformed ear region. The aesthetic outcomes of the surgery are highly dependent on the experience of the surgeon performing the surgery. For this reason, surgeons need simulators to acquire adequate technical skills out of the surgery room without compromising the aesthetic appearance of the patient. The current paper aims to describe and analyze the different materials and methods adopted during the history of autologous ear reconstruction (AER) simulation to train surgeons by practice on geometrically and mechanically accurate physical replicas. Recent advances in 3D modelling software and manufacturing technologies to increase the effectiveness of AER simulators are particularly described to provide more recent outcomes

3D printing-based pediatric trainer for ultrasound-guided peripheral venous access

Peripheral venous access is an extremely common procedure, crucial in delivering drugs and collecting blood samples. It is associated to high failure rates, especial-ly when pediatric subjects are involved, due to reduced limb size and low cooper-ation. Ultrasound can sensibly increase success rates and reduce the time required to perform the procedure, though a specific training is necessary to acquire ade-quate hand-eye coordination and simultaneously handle needle and probe. Com-mercially available simulators lack of realistic devices that reproduce anatomy and kinematics of pediatric patients. In this work, an echogenic simulator integrating direct 3D printing and silicone casting is proposed. More specifically, it replicates a five years old upper limb\u2019s anatomy comprising an articulated skeleton, muscle tissues, skin and an integrated blood circuit. The devised simulator shows its ef-fectiveness in terms of acoustic properties, articular kinematics reproduction and haptic feedback. Furthermore, the simulator can be easily customized according to specific training needs thanks to a highly flexible manufacturing process

A CAD-based Procedure for Designing 3D Printable Arm-wrist-hand Cast

Wrist injuries are one of the most common fractures, specifically around 25% of fractures among the pediatric population and up to 18% in the elderly age group are distal radius fractures. To date, the standard treatment entails the use of a tailor-made plaster Paris cast. Although it is a simple and reliable treatment, it presents several disadvantages: its weight generally causes discomfort, it cannot be taken off without breaking it, it can cause skin rashes and prevents ventilation of the treated area. To overcome the limitations of the above mentioned treatment, 3D printed orthopaedic casts based on reverse engineering (RE) and additive manufacturing (AM) techniques have been proposed in literature. Despite these solutions prove to be a valid alternative to the standard treatment, the clinical use of AM-based devices is not trivial due to the need of expert CAD modelers to design the 3D model of the orthosis starting from the patient\u2019s anatomy 3D acquisition. In this work, the authors identify a systematic procedure to create an orthosis model, compliant with medical guidelines, using common CAD tools: the CAD-modeling steps are grouped into five main blocks in view of a future automatization of the process, which can eliminate the necessity of designing expertise to model the orthosis. The produced device is composed of two halves, to ease the application, locked through a zip tie-based mechanism. A preliminary ventilation pattern is proposed and tested with a FEM analysis to ensure structural resistance. The procedure has been tested on six case studies: all the orthoses models were correctly generated without major complications and positive user feedbacks were generally obtained throughout the tests

A practical methodology for computer-aided design of custom 3D printable casts for wrist fractures

In recent years, breakthroughs in the fields of reverse engineering and additive manufacturing techniques have led to the development of innovative solutions for personalized medicine. 3D technologies are quickly becoming a new treatment concept that hinges on the ability to shape patient-specific devices. Among the wide spectrum of medical applications, the orthopaedic sector is experiencing the most benefits. Several studies proposed modelling procedures for patient-specific 3D-printed casts for wrist orthoses, for example. Unfortunately, the proposed approaches are not ready to be used directly in clinical practice since the design of these devices requires significant interaction among medical staff, reverse engineering experts, additive manufacturing specialists and CAD designers. This paper proposes a new practical methodology to produce 3D printable casts for wrist immobilization with the aim of overcoming these drawbacks. In particular, the idea is to realize an exhaustive system that can be used within a paediatric environment. It should provide both a fast and accurate dedicated scanning of the hand-wrist-arm district, along with a series of easy-to-use semi-automatic tools for the modelling of the medical device. The system was designed to be used directly by the clinical staff after a brief training. It was tested on a set of five case studies with the aim of proving its general reliability and identifying possible major flaws. Casts obtained using the proposed system were manufactured using a commercial 3D printer, and the device\u2019s compliance with medical requirements was tested. Results showed that the designed casts were correctly generated by the medical staff without the need of involving engineers. Moreover, positive feedback was provided by the users involved in the experiment

Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta-analysis

Objective: To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years). Methods: Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or â\u89¥50% seizure reduction. Results: We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies. Significance: This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria

Protein–Protein Docking with HADDOCK

Advances in biophysics and biochemistry have pushed back the limits of the structural characterization of biomolecular assemblies. Mixing even a limited amount of experimental and/or bioinformatics data with modeling methods such as macromolecular docking represents a valuable strategy to predict the three-dimensional structures of complexes. In this chapter, we discuss the HADDOCK data-driven approach to the modeling of complexes. The program supports a wide range of NMR and other experimental data as well as bioinformatics predictions. It is also available as a user-friendly web server, facilitating the modeling of biomolecular complexes for a wide community