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.

UNet and MobileNet CNN-based model observers for CT protocol optimization: comparative performance evaluation by means of phantom CT images.

Purpose: The aim of this work is the development and characterization of a model observer (MO) based on convolutional neural networks (CNNs), trained to mimic human observers in image evaluation in terms of detection and localization of low-contrast objects in CT scans acquired on a reference phantom. The final goal is automatic image quality evaluation and CT protocol optimization to fulfill the ALARA principle. Approach: Preliminary work was carried out to collect localization confidence ratings of human observers for signal presence/absence from a dataset of 30,000 CT images acquired on a PolyMethyl MethAcrylate phantom containing inserts filled with iodinated contrast media at different concentrations. The collected data were used to generate the labels for the training of the artificial neural networks. We developed and compared two CNN architectures based respectively on Unet and MobileNetV2, specifically adapted to achieve the double tasks of classification and localization. The CNN evaluation was performed by computing the area under localization-ROC curve (LAUC) and accuracy metrics on the test dataset. Results: The mean of absolute percentage error between the LAUC of the human observer and MO was found to be below 5% for the most significative test data subsets. An elevated inter-rater agreement was achieved in terms of S-statistics and other common statistical indices. Conclusions: Very good agreement was measured between the human observer and MO, as well as between the performance of the two algorithms. Therefore, this work is highly supportive of the feasibility of employing CNN-MO combined with a specifically designed phantom for CT protocol optimization programs.

Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. METHODS: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. RESULTS: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of -0.62 (95%CI - 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (ß = -1.019, 95% CI - 1.827; -0.210, p-value = 0.0135). CONCLUSIONS: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy.

Effectiveness of robot-assisted arm therapy in stroke rehabilitation: An overview of systematic reviews.

BACKGROUND: Robot-assisted arm therapy (RAT) has been used mainly in stroke rehabilitation in the last 20 years with rising expectations and growing evidence summarized in systematic reviews (SRs). OBJECTIVE: The aim of this study is to provide an overview of SRs about the effectiveness, within the ICF domains, and safety of RAT in the rehabilitation of adult with stroke compared to other treatments. METHODS: The search strategy was conducted using search strings adapted explicitly for each database. A screening base on title and abstract was realized to find all the potentially relevant studies. The methodological quality of the included SRs was assessed using AMSTAR-2. A pre-determined standardized form was used to realize the data extraction. RESULTS: 18 SRs were included in this overview. Generally, positive effects from the RAT were found for motor function and muscle strength, whereas there is no agreement for muscle tone effects. No effect was found for pain, and only a SR reported the positive impact of RAT in daily living activity. CONCLUSION: RAT can be considered a valuable option to increase motor function and muscle strength after stroke. However, the poor quality of most of the included SRs could limit the certainty around the results.

Robot-assisted rehabilitation for children with neurological disabilities: Results of the Italian consensus conference CICERONE.

BACKGROUND: The use of robotic technologies in pediatric rehabilitation has seen a large increase, but with a lack of a comprehensive framework about their effectiveness. OBJECTIVE: An Italian Consensus Conference has been promoted to develop recommendations on these technologies: definitions and classification criteria of devices, indications and limits of their use in neurological diseases, theoretical models, ethical and legal implications. In this paper, we present the results for the pediatric age. METHODS: A systematic search on Cochrane Library, PEDro and PubMed was performed. Papers published up to March 1st, 2020, in English, were included and analyzed using the methodology of the Centre for Evidence-Based Medicine in Oxford, AMSTAR2 and PEDro scales for systematic reviews and RCT, respectively. RESULTS: Some positives aspects emerged in the area of gait: an increased number of children reaching the stance, an improvement in walking distance, speed and endurance. Critical aspects include the heterogeneity of the studied cases, measurements and training protocols. CONCLUSION: Many studies demonstrate the benefits of robotic training in developmental age. However, it is necessary to increase the number of trials to achieve greater homogeneity between protocols and to confirm the effectiveness of pediatric robotic rehabilitation.

Reference theories and future perspectives on robot-assisted rehabilitation in people with neurological conditions: A scoping review and recommendations from the Italian Consensus Conference on Robotics in Neurorehabilitation (CICERONE).

BACKGROUND: Robot-based treatments are developing in neurorehabilitation settings. Recently, the Italian National Health Systems recognized robot-based rehabilitation as a refundable service. Thus, the Italian neurorehabilitation community promoted a national consensus on this topic. OBJECTIVE: To conceptualize undisclosed perspectives for research and applications of robotics for neurorehabilitation, based on a qualitative synthesis of reference theoretical models. METHODS: A scoping review was carried out based on a specific question from the consensus Jury. A foreground search strategy was developed on theoretical models (context) of robot-based rehabilitation (exposure), in neurological patients (population). PubMed and EMBASE® databases were searched and studies on theoretical models of motor control, neurobiology of recovery, human-robot interaction and economic sustainability were included, while experimental studies not aimed to investigate theoretical frameworks, or considering prosthetics, were excluded. RESULTS: Overall, 3699 records were screened and finally 9 papers included according to inclusion and exclusion criteria. According to the population investigated, structured information on theoretical models and indications for future research was summarized in a synoptic table. CONCLUSION: The main indication from the Italian consensus on robotics in neurorehabilitation is the priority to design research studies aimed to investigate the role of robotic and electromechanical devices in promoting neuroplasticity.

Effects of robotic upper limb treatment after stroke on cognitive patterns: A systematic review.

BACKGROUND: Robotic therapy (RT) has been internationally recognized for the motor rehabilitation of the upper limb. Although it seems that RT can stimulate and promote neuroplasticity, the effectiveness of robotics in restoring cognitive deficits has been considered only in a few recent studies. OBJECTIVE: To verify whether, in the current state of the literature, cognitive measures are used as inclusion or exclusion criteria and/or outcomes measures in robotic upper limb rehabilitation in stroke patients. METHODS: The systematic review was conducted according to PRISMA guidelines. Studies eligible were identified through PubMed/MEDLINE and Web of Science from inception to March 2021. RESULTS: Eighty-one studies were considered in this systematic review. Seventy-three studies have at least a cognitive inclusion or exclusion criteria, while only seven studies assessed cognitive outcomes. CONCLUSION: Despite the high presence of cognitive instruments used for inclusion/exclusion criteria their heterogeneity did not allow the identification of a guideline for the evaluation of patients in different stroke stages. Therefore, although the heterogeneity and the low percentage of studies that included cognitive outcomes, seemed that the latter were positively influenced by RT in post-stroke rehabilitation. Future larger RCTs are needed to outline which cognitive scales are most suitable and their cut-off, as well as what cognitive outcome measures to use in the various stages of post-stroke rehabilitation.

Evidence-based improvement of gait in post-stroke patients following robot-assisted training: A systematic review.

BACKGROUND: The recovery of walking after stroke is a priority goal for recovering autonomy. In the last years robotic systems employed for Robotic Assisted Gait Training (RAGT) were developed. However, literature and clinical practice did not offer standardized RAGT protocol or pattern of evaluation scales. OBJECTIVE: This systematic review aimed to summarize the available evidence on the use of RAGT in post-stroke, following the CICERONE Consensus indications. METHODS: The literature search was conducted on PubMed, Cochrane Library and PEDro, including studies with the following criteria: 1) adult post-stroke survivors with gait disability in acute/subacute/chronic phase; 2) RAGT as intervention; 3) any comparators; 4) outcome regarding impairment, activity, and participation; 5) both primary studies and reviews. RESULTS: Sixty-one articles were selected. Data about characteristics of patients, level of disability, robotic devices used, RAGT protocols, outcome measures, and level of evidence were extracted. CONCLUSION: It is possible to identify robotic devices that are more suitable for specific phase disease and level of disability, but we identified significant variability in dose and protocols. RAGT as an add-on treatment seemed to be prevalent. Further studies are needed to investigate the outcomes achieved as a function of RAGT doses delivered.

Gait robot-assisted rehabilitation in persons with spinal cord injury: A scoping review.

BACKGROUND: Many robots are available for gait rehabilitation (BWSTRT and ORET) and their application in persons with SCI allowed an improvement of walking function. OBJECTIVE: The aim of the study is to compare the effects of different robotic exoskeletons gait training in persons with different SCI level and severity. METHODS: Sixty-two studies were included in this systematic review; the study quality was assessed according to GRADE and PEDro's scale. RESULTS: Quality assessment of included studies (n = 62) demonstrated a prevalence of evidence level 2; the quality of the studies was higher for BWSTRT (excellent and good) than for ORET (fair and good). Almost all persons recruited for BWSTRT had an incomplete SCI; both complete and incomplete SCI were recruited for ORET. The SCI lesion level in the persons recruited for BWSTRT are from cervical to sacral; mainly from thoracic to sacral for ORET; a high representation of AIS D lesion resulted both for BWSTRT (30%) and for ORET (45%). The walking performance, tested with 10MWT, 6MWT, TUG and WISCI, improved after exoskeleton training in persons with incomplete SCI lesions, when at least 20 sessions were applied. Persons with complete SCI lesions improved the dexterity in walking with exoskeleton, but did not recover independent walking function; symptoms such as spasticity, pain and cardiovascular endurance improved. CONCLUSION: Different exoskeletons are available for walking rehabilitation in persons with SCI. The choice about the kind of robotic gait training should be addressed on the basis of the lesion severity and the possible comorbidities.

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.

Robot-assisted gait training in patients with Parkinson's disease: Implications for clinical practice. A systematic review.

BACKGROUND: Gait impairments are common disabling symptoms of Parkinson's disease (PD). Among the approaches for gait rehabilitation, interest in robotic devices has grown in recent years. However, the effectiveness compared to other interventions, the optimum amount of training, the type of device, and which patients might benefit most remains unclear. OBJECTIVE: To conduct a systematic review about the effects on gait of robot-assisted gait training (RAGT) in PD patients and to provide advice for clinical practice. METHODS: A search was performed on PubMed, Scopus, PEDro, Cochrane library, Web of science, and guideline databases, following PRISMA guidelines. We included English articles if they used a robotic system with details about the intervention, the parameters, and the outcome measures. We evaluated the level and quality of evidence. RESULTS: We included twenty papers out of 230 results: two systematic reviews, 9 randomized controlled trials, 4 uncontrolled studies, and 5 descriptive reports. Nine studies used an exoskeleton device and the remainders end-effector robots, with large variability in terms of subjects' disease-related disability. CONCLUSIONS: RAGT showed benefits on gait and no adverse events were recorded. However, it does not seem superior to other interventions, except in patients with more severe symptoms and advanced disease.

Technologies to Support Frailty, Disability, and Rare Diseases: Towards a Monitoring Experience during the COVID-19 Pandemic Emergency.

This report illustrates the design and results of an activity of surveillance proposed by the National Centre for Innovative Technologies in Public Health and the National Centre for Rare Diseases of the Istituto Superiore di Sanità with the aim of monitoring the state-of-use of technologies by people with frailty, disabilities, and rare diseases. The results of the surveillance activity reported in this report are as follows: (a) An international Webinar; (b) A Full report published by the Istituto Superiore di Sanità (ISS); (c) an electronic survey tool, for periodic monitoring; (d) an initial summary of the survey (15 September-30 November 2020), giving an overall picture relating to the state-of-use of technologies by the interviewed; (e) an understanding of the needs that emerged, causing reflection on the current state-of-the-art and offering important stimuli for all the stakeholders involved.

Welcoming teleretinography into diabetes integrated care.

Integrated Care (IC) is a perfect fit for people with diabetes. Fundus examination (FE) is a disease marker for diabetologists and identifies potentially blinding complications (Diabetic Retinopathy, DR). In our Diabetes Clinic (DC) in Pescara, Italy, FE is possibly provided with telemedicine in same day as other exams, avoiding it to be a standalone clinical one; images taken with a retinal digital camera are graded by a remote ophthalmologist within a shared Electronic Health Record (EHR), immediately readable by other stakeholders; a dedicated care path to the Eye Clinic, University of Chieti-Pescara is provided for urgent cases. Personnel's worktime shortening allows gaining time for ophthalmologists' eye examinations in outpatient settings and other stakeholders' work in the DC. The need for a DR digital screening system is growing worldwide: our experience confirms the ease of implementation, and the advantage of sharing clinical data with all stakeholders when working within an EHR, aiming to optimize an IC effective system.

Upper Limb Robotic Rehabilitation for Patients with Cervical Spinal Cord Injury: A Comprehensive Review.

The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on "Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin" (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The five-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results. Therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury.

Label-free cell based impedance measurements of ZnO nanoparticles-human lung cell interaction: a comparison with MTT, NR, Trypan blue and cloning efficiency assays.

BACKGROUND: There is a huge body of literature data on ZnOnanoparticles (ZnO NPs) toxicity. However, the reported results are seen to be increasingly discrepant, and deep comprehension of the ZnO NPs behaviour in relation to the different experimental conditions is still lacking. A recent literature overview emphasizes the screening of the ZnO NPs toxicity with more than one assay, checking the experimental reproducibility also versus time, which is a key factor for the robustness of the results. In this paper we compared high-throughput real-time measurements through Electric Cell-substrate Impedance-Sensing (ECIS®) with endpoint measurements of multiple independent assays. RESULTS: ECIS-measurements were compared with traditional cytotoxicity tests such as MTT, Neutral red, Trypan blue, and cloning efficiency assays. ECIS could follow the cell behavior continuously and noninvasively for days, so that certain long-term characteristics of cell proliferation under treatment with ZnO NPs were accessible. This was particularly important in the case of pro-mitogenic activity exerted by low-dose ZnO NPs, an effect not revealed by endpoint independent assays. This result opens new worrisome questions about the potential mitogenic activity exerted by ZnO NPs, or more generally by NPs, on transformed cells. Of importance, impedance curve trends (morphology) allowed to discriminate between different cell death mechanisms (apoptosis vs autophagy) in the absence of specific reagents, as confirmed by cell structural and functional studies by high-resolution microscopy. This could be advantageous in terms of costs and time spent. ZnO NPs-exposed A549 cells showed an unusual pattern of actin and tubulin distribution which might trigger mitotic aberrations leading to genomic instability. CONCLUSIONS: ZnO NPs toxicity can be determined not only by the intrinsic NPs characteristics, but also by the external conditions like the experimental setting, and this could account for discrepant data from different assays. ECIS has the potential to recapitulate the needs required in the evaluation of nanomaterials by contributing to the reliability of cytotoxicity tests. Moreover, it can overcome some false results and discrepancies in the results obtained by endpoint measurements. Finally, we strongly recommend the comparison of cytotoxicity tests (ECIS, MTT, Trypan Blue, Cloning efficiency) with the ultrastructural cell pathology studies.

What does evidence tell us about the use of gait robotic devices in patients with multiple sclerosis? A comprehensive systematic review on functional outcomes and clinical recommendations.

INTRODUCTION: There is growing evidence on the efficacy of gait robotic rehabilitation in patients with multiple sclerosis (MS), but most of the studies have focused on gait parameters. Moreover, clear indications on the clinical use of robotics still lack. As part of the CICERONE Italian Consensus on Robotic Rehabilitation, the aim of this systematic review was to investigate the existing evidence concerning the role of lower limb robotic rehabilitation in improving functional recovery in patients with MS. EVIDENCE ACQUISITION: We searched for and systematically reviewed evidence-based studies on gait robotic rehabilitation in MS, between January 1st, 2010 and December 31st, 2020, in the following databases: Cochrane Library, PEDro, PubMed and Google Scholar. The study quality was assessed by the 16-item assessment of multiple systematic reviews 2 (AMSTAR 2) and the 10-item PEDro scale for the other research studies. EVIDENCE SYNTHESIS: After an accurate screening, only 17 papers were included in the review, and most of them (13 RCT) had a level II evidence. Most of the studies used the Lokomat as a grounded robotic device, two investigated the efficacy of end-effectors and two powered exoskeletons. Generally speaking, robotic treatment has beneficial effects on gait speed, endurance and balance with comparable outcomes to those of conventional treatments. However, in more severe patients (EDSS >6), robotics leads to better functional outcomes. Notably, after gait training with robotics (especially when coupled to virtual reality) MS patients also reach better non-motor outcomes, including spasticity, fatigue, pain, psychological well-being and quality of life. Unfortunately, no clinical indications emerge on the treatment protocols. CONCLUSIONS: The present comprehensive systematic review highlights the potential beneficial role on functional outcomes of the lower limb robotic devices in people with MS. Future studies are warranted to evaluate the role of robotics not only for walking and balance outcomes, but also for other gait-training-related benefits, to identify appropriate outcome measures related to a specific subgroup of MS subjects' disease severity.

Controlled Release of 18-ß-Glycyrrhetinic Acid from Core-Shell Nanoparticles: Effects on Cytotoxicity and Intracellular Concentration in HepG2 Cell Line.

18ß-glycyrrhetinic acid (GA) is a pentacyclic triterpene with promising hepatoprotective and anti-Hepatocellular carcinoma effects. GA low water solubility however reduces its biodistribution and bioavailability, limiting its applications in biomedicine. In this work we used core-shell NPs made of PolyD-L-lactide-co-glycolide (PLGA) coated with chitosan (CS), prepared through an osmosis-based methodology, to efficiently entrap GA. NPs morphology was investigated with SEM and TEM and their GA payload was evaluated with a spectrophotometric method. GA-loaded NPs were administered to HepG2 cells and their efficiency in reducing cell viability was compared with that induced by the free drug in in vitro tests. Cell viability was evaluated by the MTT assay, as well as with Electric Cells-Substrate Impedance Sensing (ECIS), that provided a real-time continuous monitoring. It was possible to correlate the toxic effect of the different forms of GA with the bioavailability of the drug, evidencing the importance of real-time tests for studying the effects of bioactive substances on cell cultures.

Robot-assisted arm therapy in neurological health conditions: rationale and methodology for the evidence synthesis in the CICERONE Italian Consensus Conference.

BACKGROUND: Robot-assisted Arm Therapy (RAT) has been increasingly applied in the last years for promoting functional recovery in patients with disabilities related to neurological health conditions. Evidence of a knowledge-to-action gap for applying robot-assisted technologies in the rehabilitation of patients with neurological health conditions and the difficulty to apply and tailor the knowledge to the local contexts solicited the need for a national consensus conference on these interventions. AIM: The aim of this paper was to explain the methodology used by the working group dedicated to synthesizing evidence on the effectiveness of RAT in neurological health conditions in the context of the CICERONE Italian Consensus Conference. DESIGN: The methodological approach of the working group. SETTING: All rehabilitation settings. POPULATION: Patients with disability following a neurological health condition. METHODS: Following the indications proposed by the Methodological Manual published by the Italian National Institute of Health, a Promoting Committee and a Technical Scientific Committee have been set up. Six working groups (WGs) have been composed to collect evidence on different questions, among which WG2.2 was focused on the effectiveness of RAT in neurological health conditions. RESULTS: WG2.2 started its work defining the specific research questions. It was decided to adopt the ICF as the reference framework for the reporting of all outcomes. Literature search, data extraction and qualitative assessment, evidence analysis and synthesis have been performed. CONCLUSIONS: This paper summarized the methodological approaches used by the WG2.2 of the CICERONE Italian Consensus Conference to define the effectiveness of RAT in the management of patients with neurological health conditions. CLINICAL REHABILITATION IMPACT: WG2.2 synthesis might help clinicians, researchers, and all rehabilitation stakeholders to address the use of RAT in the Individualized Rehabilitation Plan, to guide the allocation of resources and define clinical protocols and indications for the management of patients with different neurological health conditions.

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.