Nanostructured Medical Devices: Regulatory Perspective and Current Applications.

Nanomaterials (NMs) are having a huge impact in several domains, including the fabrication of medical devices (MDs). Hence, nanostructured MDs are becoming quite common; nevertheless, the associated risks must be carefully considered in order to demonstrate safety prior to their immission on the market. The biological effect of NMs requires the consideration of methodological issues since already established methods for, e.g., cytotoxicity can be subject to a loss of accuracy in the presence of certain NMs. The need for oversight of MDs containing NMs is reflected by the European Regulation 2017/745 on MDs, which states that MDs incorporating or consisting of NMs are in class III, at highest risk, unless the NM is encapsulated or bound in such a manner that the potential for its internal exposure is low or negligible (Rule 19). This study addresses the role of NMs in medical devices, highlighting the current applications and considering the regulatory requirements of such products.

Under the Tech Umbrella: Assessing the Landscape of Telemedicine Innovations (Telemechron Study).

The expanding role of technology assessment in telemedicine is the focus of this study. An umbrella review has been proposed to delve into emerging themes within telemedicine technology assessment by scrutinizing systematic reviews gathered from PubMed and Scopus. The proposed approach was based on a standard narrative checklist and a qualification process. The selection process identified 20 systematic reviews. The main findings underscore the transformative potential of telemedicine, emphasizing technology assessments focused on systematic evaluations, stakeholder engagement, societal impact recognition, targeted interventions, and structured frameworks. While offering valuable insights, the current studies highlight certain limitations that require attention. There is a need for the following: (I) First of all, a more focused approach, primarily centered on a process-centric, multidomain, and generalizable technology assessment (TA). (II) A deeper analysis in specific healthcare areas, including a comprehensive examination of the cost-benefit ratio, peer-to-peer interactions, and a broader inclusion of diagnostic technologies. (III) Greater emphasis on the involved stakeholders, ranging from patients to stakeholders. In conclusion, this study contributes to a comprehensive and nuanced understanding of the continually evolving landscape in telemedicine technology assessment, offering valuable insights for practitioners, researchers, and policymakers alike. Researchers are encouraged to further explore both the established and emerging themes identified in this study.

Adapting the World Health Organization rapid Assistive Technology Assessment (rATA) to the Italian context: implementation of a TRAPD-based approach.

BACKGROUND: Measuring access to assistive technology (AT) has become a global priority. Recently, the World Health Organization (WHO) has developed the rapid assistive technology assessment (rATA), a population-based household survey that measures the use, need, unmet need, and barriers to accessing AT. OBJECTIVE: The aim of this paper is to report on the translation and adaptation process undertaken to implement the rATA survey in the Italian context. METHOD: The Translate, Review, Adjudicate, Pretest, and Document (TRAPD) approach was used to translate and adapt the rATA from English to Italian. Eleven independent reviewers and 23 AT users were involved to validate the Italian translation of the rATA and pilot the survey, respectively. RESULTS: The feedback provided by the first users of the rATA indicate that the data collected are reliable and well reflect the state of AT provision in Italy. CONCLUSION: This study confirmed the applicability of the rATA survey to the Italian context. The Italian version of the rATA can be used to support the government, the health system as well as the civil society to monitor the current state of AT access (and abandonment) in the country.

State of the art and challenges for the classification of studies on electromechanical and robotic devices in neurorehabilitation: a scoping review.

INTRODUCTION: The rapid development of electromechanical and robotic devices has profoundly influenced neurorehabilitation. Growth in the scientific and technological aspects thereof is crucial for increasing the number of newly developed devices, and clinicians have welcomed such growth with enthusiasm. Nevertheless, improving the standard for the reporting clinical, technical, and normative aspects of such electromechanical and robotic devices remains an unmet need in neurorehabilitation. Accordingly, this study aimed to analyze the existing literature on electromechanical and robotic devices used in neurorehabilitation, considering the current clinical, technical, and regulatory classification systems. EVIDENCE ACQUISITION: Within the CICERONE Consensus Conference framework, studies on electromechanical and robotic devices used for upper- and lower-limb rehabilitation in persons with neurological disabilities in adulthood and childhood were reviewed. We have conducted a literature search using the following databases: MEDLINE, Cochrane Library, PeDro, Institute of Electrical and Electronics Engineers, Science Direct, and Google Scholar. Clinical, technical, and regulatory classification systems were applied to collect information on the electromechanical and robotic devices. The study designs and populations were investigated. EVIDENCE SYNTHESIS: Overall, 316 studies were included in the analysis. More than half (52%) of the studies were randomised controlled trials (RCTs). The population investigated the most suffered from strokes, followed by spinal cord injuries, multiple sclerosis, cerebral palsy, and traumatic brain injuries. In total, 100 devices were described; of these, 19% were certified with the CE mark. Overall, the main type of device was an exoskeleton. However, end-effector devices were primarily used for the upper limbs, whereas exoskeletons were used for the lower limbs (for both children and adults). CONCLUSIONS: The current literature on robotic neurorehabilitation lacks detailed information regarding the technical characteristics of the devices used. This affects the understanding of the possible mechanisms underlying recovery. Unfortunately, many electromechanical and robotic devices are not provided with CE marks, strongly hindering the research on the clinical outcomes of rehabilitation treatments based on these devices. A more significant effort is needed to improve the description of the robotic devices used in neurorehabilitation in terms of the technical and functional details, along with high-quality RCT studies.

A mathematical description of blood spiral flow in vessels: application to a numerical study of flow in arterial bending.

Local arterial haemodynamics has been associated with the pathophysiology of several cardiovascular diseases. The stable spiral blood-flows that were observed in vivo in several vessels, may play a dual role in vascular haemodynamics, beneficial since it induces stability, reducing turbulence in the arterial tree, and accounts for normal organ perfusion, but detrimental in view of the imparted tangential velocities that are involved in plaque formation and development. Being a spiral flow considered representative of the local blood dynamics in certain vessels, a method is proposed to quantify the spiral structure of blood flow. The proposed function, computed along a cluster of particle trajectories, has been tested for the quantitative determination of the spiral blood flow in a three-dimensional, s-shaped femoral artery numerical model in which three degrees of stenosis were simulated in a site prone to atherosclerotic development. Our results confirm the efficacy of the Lagrangian analysis as a tool for vascular blood dynamics investigation. The proposed method quantified spiral motion, and revealed the progression in the degree of stenosis, in the presented case study. In the future, it could be used as a synthetic tool to approach specific clinical complications.

Three-dimensional numeric simulation of flow through an aortic bileaflet valve in a realistic model of aortic root.

A three-dimensional, realistic model of an aortic mechanical heart valve and Valsalva sinuses was developed to predict, by means of a numerical time dependent simulation, the flow field during a fraction of the systolic period. The numeric simulation was performed upon a model of valve similar to a Carbomedics 27 mm placed in a physiologic aortic root shaped model, in which no symmetry planes were exploited to reach a more realistic level. Input data for the simulation have been acquired during an experimental session on the same valve, according to the guidelines of testing protocol for prosthetic heart valves. Flow was assumed to be Newtonian and laminar at low regime and the leaflets fixed in the fully open position. The forward flow of the systolic phase was investigated, and a comparison with experimental results was performed at peak systole, the most representative point of the cardiac cycle. The results of this simulation furnished a reasonable indication (in terms of fluid dynamics) parameters downstream of the prosthetic device, especially in Valsalva sinuses, the role of which is proven to affect the valve's performance.

3D velocity field characterization of prosthetic heart valve with two different valve testers by means of stereo-PIV.

BACKGROUND: Prosthetic heart valves can be associated to mechanical loading of blood, potentially linked to complications (hemolysis and thrombogenicity) which can be clinically relevant. In order to test such devices in pulsatile mode, pulse duplicators (PDs) have been designed and built according to different concepts. This study was carried out to compare anemometric measurements made on the same prosthetic device, with two widely used PDs. METHODS: The valve (a 27-mm bileaflet valve) was mounted in the aortic section of the PD. The Sheffield University PD and the RWTH Aachen PD were selected as physical models of the circulation. These two PDs differ mainly in the vertical vs horizontal realization, and in the ventricular section, which in the RWTH PD allows for storage of potential energy in the elastic walls of the ventricle. A glassblown aorta, realized according to the geometric data of the same anatomical district in healthy individuals, was positioned downstream of the valve, obtaining 1:1 geometric similarity conditions. A NaI-glycerol-water solution of suitable kinematic viscosity and, at the same time, the proper refractive index, was selected. The flow field downstream of the valve was measured by means of the stereo-PIV (Particle Image Velocimetry) technique, capable of providing the complete 3D velocity field as well as the entire Reynolds stress tensor. The measurements were carried out at the plane intersecting the valve axis. RESULTS: A three-jet profile was clearly found in the plane crossing the leaflets, with both PDs. The extent of the typical recirculation zone in the Valsalva sinus was much larger in the RWTH PD, on account of the different duration of the swirling motion in the ventricular chamber, caused by the elasticity of the ventricle and its geometry. CONCLUSION: The comparison of the hemodynamical behaviour of the same bileaflet valve tested in two PDs demonstrated the role of the mock loop in affecting the valve performance.

The beneficial vortex and best spatial arrangement in total extracardiac cavopulmonary connection.

OBJECTIVE: Total extracardiac cavopulmonary connection is an established procedure, but the best spatial arrangement remains controversial. On the basis of our clinical experience with total extracardiac cavopulmonary connection, we performed quantitative and qualitative flow analysis on total extracardiac cavopulmonary connection models simulating the two most frequent arrangements applied to our patients to determine the most favorable hydrodynamic pattern. METHODS: We selected two main groups among 110 patients who underwent total extracardiac cavopulmonary connection, those with left-sided inferior vena cava anastomosis (type 1) and those with facing superior and inferior vena cava anastomoses (type 2). Blown-glass total extracardiac cavopulmonary connection phantom models were constructed on the basis of nuclear magnetic resonance and angiographic images. Flow measurements were performed with a Nd:YAG Q-switched laser and a particle imaging velocimetry system. A power dissipation study and a finite-element numeric simulation were also carried out. RESULTS: When applying superior and inferior vena caval flow proportions of total systemic venous return of 40% and 60%, respectively, a vortex was visualized in the type 1 phantom that rotated counterclockwise at the junction of the caval streams. This apparent vortex was not a true vortex; rather, it represented a weakly dissipative recirculating zone modulating the flow distribution into the pulmonary arteries. The power dissipation and finite-element numeric stimulation confirmed the beneficial nature of the apparent vortex and a more energy-saving pattern in the type 1 phantom than in the type 2 phantom. CONCLUSION: Total extracardiac cavopulmonary connection with left-sided diversion of the inferior vena caval conduit anastomosis is characterized by a central vortex that regulates the caval flow partitioning and provides a more favorable energy-saving pattern than is seen with the total extracardiac cavopulmonary connection with directly opposed cavopulmonary anastomoses.

Evaluation of the surface-averaged load exerted on a blood element by the Reynolds shear stress field provided by artificial cardiovascular devices.

Implantable prosthetic devices can often affect the recipient's hemostasis, with possible hemolysis and thrombus formation. Since such devices can produce turbulent flow, it is important to characterize it as accurately as possible, by means of the Reynolds stress tensor. Some parameters related to the latter have been often used to provide a quantity related to the possible damage to blood constituents: the TSS(max), for instance, has been associated with hemolysis. It can be expressed as TSS(max)=(sigma(1)-sigma(3))/2, sigma(1) and sigma(3) being the highest and lowest principal normal stresses (PNSs) in each point of the flow. In the present work, the average value of the shear stress over a spherical surface, representative of a blood component, is derived. All three PNSs (sigma(1), sigma(2) and sigma(3)) are found to have an equal role in the determination of this parameter, since the relative formula shows a marked symmetry with respect to the PNSs. The average shear stress level, for a given (sigma(1), sigma(3)) pair (hence, for a given TSS(max)), has a minimum and maximum value, depending on the particular sigma(2) value yielded by the local structure of the turbulent flow field. A numerical investigation on more complex geometries shows similar results. The role of the intermediate PNS is thus shown for the first time to have a physical relevance. The presented results can be useful whenever a spatial averaging of the shear field is important to be assessed, such as in the case of platelet activation. A new parameter is thus proposed, which can be correlated with prosthetic devices complications.

Monodimensional estimation of maximum Reynolds shear stress in the downstream flow field of bileaflet valves.

BACKGROUND AND AIM OF THE STUDY: Turbulent flow generated by prosthetic devices at the bloodstream level may cause mechanical stress on blood particles. Measurement of the Reynolds stress tensor and/or some of its components is a mandatory step to evaluate the mechanical load on blood components exerted by fluid stresses, as well as possible consequent blood damage (hemolysis or platelet activation). Because of the three-dimensional nature of turbulence, in general, a three-component anemometer should be used to measure all components of the Reynolds stress tensor, but this is difficult, especially in vivo. The present study aimed to derive the maximum Reynolds shear stress (RSS) in three commercially available prosthetic heart valves (PHVs) of wide diffusion, starting with monodimensional data provided in vivo by echo Doppler. METHODS: Accurate measurement of PHV flow field was made using laser Doppler anemometry; this provided the principal turbulence quantities (mean velocity, root-mean-square value of velocity fluctuations, average value of cross-product of velocity fluctuations in orthogonal directions) needed to quantify the maximum turbulence-related shear stress. RESULTS: The recorded data enabled determination of the relationship, the Reynolds stresses ratio (RSR) between maximum RSS and Reynolds normal stress in the main flow direction. The RSR was found to be dependent upon the local structure of the flow field. CONCLUSION: The reported RSR profiles, which permit a simple calculation of maximum RSS, may prove valuable during the post-implantation phase, when an assessment of valve function is made echocardiographically. Hence, the risk of damage to blood constituents associated with bileaflet valve implantation may be accurately quantified in vivo.

Innovative technologies for the assessment of cardiovascular medical devices: state-of-the-art techniques for artificial heart valve testing.

Prosthetic heart valves (PHVs) are engineered devices used for replacing diseased natural cardiac valves. This article presents several investigational techniques for the evaluation of the performance of these clinical devices, whose implantation is not completely free of drawbacks. The state-of-the-art in the technological approach for PHV testing is addressed. As the fluid dynamics of PHVs are particularly complex, the main focus will be on experimental velocimetric techniques and computational analysis. A methodology for the analysis of the valve's signature, in terms of its characteristic sound in the opening and closing phases, is also presented. The aforementioned techniques are necessary to guarantee an operational life of the implanted device as free as possible from clinical complications. It can be realistically expected that this characterization will help designers in improving PHV performance.

Evolutive algorithms for beat-by-beat estimation of left ventricular mechanics.

Traditional methods to evaluate the ventricular mechanics need intraventricular pressure and volume recordings for multiple variably loaded beats. To do this, a complex and invasive procedure must be applied, that may decrease the clinical use. To overcome this limitation, a method to estimate the ventricular mechanics beat-by-beat is presented, modeling the ventricular pressure-volume relationship with a time-varying elastance function. The ability of the genetic algorithms (GAs) as identification technique is exploited. Applying GAs on surrogated data simulating variably loading conditions, the parameters of the time-varying elastance function, considered a measure of the contractility of the myocardial fibers are identified. These single-beat estimates are highly correlated with the end systolic pressure-volume relationship slope obtained by conventional multiple-beat analysis. The main advantage in using GAs for single beat analysis may lie, in the perspective of an use for in vivo investigations, both in their stochastic nature, and in the guaranteed better performance with respect to other search techniques on problems involving noisy signals. Future studies will approach the reduction in GAs computational costs, for a real time in vivo application.

Oxygen permeability measurements of contact lenses: a proposal for accuracy improvement.

Contact lens are a widespread medical device. In view of the importance of a proper oxygenation of the cornea, new materials are continuously being tested, with a high permeability to oxygen. Taking into account the limitations of the methods for testing soft contact lenses, as presented in the relevant international standards, this paper focuses on the polarographic method and on the approach of measuring oxygen permeability of stacked contact lenses. The effect of the interspersed saline solution layers on the measurable permeability of the stack is considered, using Fick's law of diffusive flux, and a proposal for accuracy improvement in oxygen permeability measurements is presented.

Fluid dynamics studies of cardiovascular medical devices and blood damage prediction.

The implantation of cardiovascular devices such as prosthetic heart valves, even though very common in the clinical domain, is still not free from complications. Thromboembolic events and hemolysis are the major clinical problems that can occur, upon implantation. In this paper, we analyze the role of the particular fluid dynamics associated to such devices, in relation to the clinical outcome. A major issue, still debated, is the way to correlate the experimental findings with blood damage. The availability of advanced techniques such as LDA or PIV is necessary to evaluate the hemodynamical performance of a given implantable device at the local level and to draw reliable conclusions about potentially adverse clinical effects.

The power-law mathematical model for blood damage prediction: analytical developments and physical inconsistencies.

Blood trauma caused by medical devices is a major concern. Complications following the implantation/application of devices such as prosthetic heart valves, cannulae, blood pumps, tubing, and throttles lead to sublethal and lethal damage to platelets and erythrocytes. This damage is provided by the alterations in fluid dynamics, providing a mechanical load on the blood corpuscle's membrane by means of the shear stress. An appropriate quantification of the shear-induced hemolysis of artificial organs is thought to be useful in the design and development of such devices in order to minimize device-induced blood trauma. To date, a power-law mathematical relationship using the time of exposure of a blood corpuscle to a certain mechanical load and the shear stress itself (derived under the peculiar condition of uniform shear stress) has served as a basic model for the estimation of the damage to blood, investigated by means of numerical and/or experimental fluid dynamical techniques. The aim of the present article is to highlight the effect of a time-varying mechanical loading acting on blood cells based on the usual power-law model; furthermore, the effect of the loading history of a blood particle is discussed, showing how the past history of the shear acting on a blood corpuscle is not taken into account, as researchers have done until now. The need for a reassessment of the power-law model for potential blood trauma assessment is discussed by using a mathematical formulation based on the hypotheses of the existence of damage accumulation for blood with respect to time and with respect to shear stress, to be applied in complex flow fields such as the ones established in the presence of artificial organs.