Preclinical evaluation of performance, safety and usability of VAX-ID®, a novel intradermal injection device.

The recent SARS-Cov2 pandemic and mpox health emergency have led to renewed interest in intradermal vaccination due to its dose sparing potential. Indeed, intradermal vaccination is particularly of interest for use in mass vaccination campaigns, pandemic preparedness programs, and/or for vaccines that are expensive or in short supply. Moreover, the rich immune network in the skin makes it an attractive target not only for prophylactic vaccination, but also for therapeutic vaccination, like immunotherapy and (dendritic) cell-based therapies. The aim of the current paper was to provide an overview of preclinical data generated with VAX-ID®, a novel intradermal drug delivery device, to allow assessing it performance, safety and usability. The device can overcome challenges seen with the Mantoux technique whereby the needle needs to be inserted under a shallow angle. Various parameters of VAX-ID® were evaluated, including dead-space volume, dose accuracy, penetration depth & liquid deposit in piglets, as well as usability by healthcare professionals. The device has shown to have a low dead volume and a high dose accuracy. Importantly, the device performed successful injections at a predefined depth into the dermis with a high safety profile as confirmed by visual and histological evaluation in piglets. Moreover, the device was rated as easy to use by healthcare professionals. The combined preclinical performance and usability findings indicate that VAX-ID® can provide reliable, standardized and accurate drug delivery in the dermal layer of the skin with a high ease of use. The device offers a solution for injection of various prophylactic as well as therapeutic vaccines.

Risk Identification and Analysis in the Development of Medical Devices Among Start-Ups: Towards a Broader Risk Management Framework.

Introduction: Whilst risk management has become fundamental in the development of medical devices, enforced by regulations and international standards, there is still no comprehensive model that explains how risk management in medical devices' development should be tackled, especially with regard to the type of risks that should be addressed. Risk management in the medical devices' development field is currently focused on technical risks, comprising product, usability, and development process risks, in alignment with standards' requirements and regulations, without giving enough attention to non-technical risks, which include business and project risks. Start-ups within this heavily regulated domain have a key role in the innovation process, yet they suffer a structural lack of tangible, such as financial capacity, and intangible resources such as development, risk management, and regulations' compliance. Nonetheless, they can still optimize their risk identification coverage beyond the enforced requirements to increase their products' chances of success. Methods: A set of qualitative interviews, serving the adopted grounded theory building research method, with seven start-ups who are involved in the development, commercialization, and quality control of medical devices was accomplished. The purpose was to determine the applied risk management practices and most importantly identify the risk types covered by them. Since every start-up is a project by itself, a sample of project risks, as identified by the project management institute, was utilized to scope the risk coverage and flag missing non-technical risks by the participating start-ups. Results: Un-identified risk types, lack of involvement of the right teams, and other related loopholes were presented. Discussion: A list of requirements was developed and sketched in a user-friendly risk management framework, which is believed to be crucial in helping start-ups attain successful, safe, and regulatory compliant medical devices production, is shared in the discussion and proposed framework section of this paper.

Evaluating Filtering Facepiece Respirator Wearing-Comfort of Lebanese Red Cross Healthcare Providers.

Introduction: The COVID-19 pandemic significantly increased the usage of various types of face masks. In addition, it triggered the rapid manufacture of new production lines of masks to cope with the unprecedented demand to overcome worldwide shortages. Such masks, which were previously used mostly by the health care personnel, became a daily necessity to the greater mainstream population. This rapid and sudden increase in their usage and the fact that new masks' innovations are progressively emerging to meet the growing global shortage requires an ongoing analysis on the factors associated with the fit and comfort while using these masks. Methods: This paper presents the first translation and validation of the R-COMFI questionnaire to evaluate the comfort of a newly developed filtering face-piece respirator by the research team at the University of Antwerp. The questionnaire, which consists of 3 sections: Discomfort, General wearing experience, and Function, was translated from English to Arabic and involved 43 participants in the Lebanese Red Cross healthcare field based in Lebanon. Results: The results showed discomfort factors that are mostly related to breathability and sweating caused by mask usage. Additionally, the results revealed that female respondents found the mask significantly less comfortable than male respondents (p-value with the two-tailed test is 0.0319), which confirmed that future validations should consider the concerns of both genders, and validated the R-COMFI translation exercise detailed in this paper. Discussion: The contribution of this paper can be pinned down into three findings. The first finding is related to the discomfort issues. The second finding highlighted a significant difference in comfort experience between females and males. The last finding is the translation validation of the R-COMFI instrument, which confirmed that the questionnaire can be applied among wider geographical locations.

Efficient Quality Management in MedTech Start-Ups (Based on ISO 13485).

Start-ups that are involved in the development of medical devices play a key role in innovation, yet among the several limitations they encounter, they suffer a lack of knowledge in quality management. This lack may create a challenge that could hinder or limit their success. This paper seeks to present an overview and act as a guideline for the required documentation to establish a quality management system for start-ups in medical devices development, based on a case-studied start-up, in accordance with ISO 13485. Using this case study along with the actual ISO 13485 standard document, can support medical devices start-ups in their ISO compliance and certification journey.

Measuring Spatiotemporal Parameters on Treadmill Walking Using Wearable Inertial System.

This study aims to measure and compare spatiotemporal gait parameters in nineteen subjects using a full wearable inertial mocap system Xsens (MVN Awinda, Netherlands) and a photoelectronic system one-meter OptoGaitTM (Microgait, Italy) on a treadmill imposing a walking speed of 5 km/h. A total of eleven steps were considered for each subject constituting a dataset of 209 samples from which spatiotemporal parameters (SPT) were calculated. The step length measurement was determined using two methods. The first one considers the calculation of step length based on the inverted pendulum model, while the second considers an anthropometric approach that correlates the stature with an anthropometric coefficient. Although the absolute agreement and consistency were found for the calculation of the stance phase, cadence and gait cycle, from our study, differences in SPT were found between the two systems. Mean square error (MSE) calculation of their speed (m/s) with respect to the imposed speed on a treadmill reveals a smaller error (MSE = 0.0008) using the OptoGaitTM. Overall, our results indicate that the accurate detection of heel strike and toe-off have an influence on phases and sub-phases for the entire acquisition. Future study in this domain should investigate how to design and integrate better products and algorithms aiming to solve the problematic issues already identified in this study without limiting the user's need and performance in a different environment.

Case study into the successful emergency production and certification of a filtering facepiece respirator for Belgian hospitals during the COVID-19 pandemic.

The SARS-CoV-2 pandemic presented European hospitals with chronic shortages of personal protective equipment (PPE) such as surgical masks and respirator masks. Demand outstripped the production capacity of certified European manufacturers of these devices. Hospitals perceived emergency local manufacturing of PPE as an approach to reduce dependence on foreign supply. The fact of a pandemic does not circumvent the hospital's responsibility to provide appropriate protective equipment to their staff, so the emergency production needed to result in devices that were certified by testing agencies. This paper is a case study of the emergency manufacturing of respirator masks during the first month of the first wave of SARS-CoV-2 pandemic and is separated into two distinct phases. Phase A describes the three-panel folding facepiece respirator design, material sourcing, performance testing, and an analysis of the folding facepiece respirator assembly process. Phase B describes the redevelopment of individual steps in the assembly process.

Vibrotactile feedback for correcting aerodynamic position of a cyclist.

Guidance to maintain an optimal aerodynamic position is currently unavailable during cycling. This study used real-time vibrotactile feedback to guide cyclists to a reference position with minimal projected frontal area as an indicator of aerodynamic drag, by optimizing torso, shoulder, head and elbow position without compromising comfort when sitting still on the bike. The difference in recapturing the aerodynamic reference position during cycling after predefined deviations from the reference position at different intensities was analysed for 14 participants between three interventions, consisting of 1) vibrotactile feedback with a margin of error of 1.5% above the calibrated reference projected frontal area, 2) vibrotactile feedback with a margin of 3%, and 3) no feedback. The reference position is significantly more accurately achieved using vibrotactile feedback compared to no feedback (p < 0.001), but there is no significant difference between the 1.5% and 3% margin (p = 0.11) in terms of relative projected frontal area during cycling compared to the calibrated reference position (1.5% margin -0.46 ± 1.76%, 3% margin -0.01 ± 2.01%, no feedback 2.59 ± 3.29%). The results demonstrate that vibrotactile feedback can have an added value in assisting and correcting cyclists in recapturing their aerodynamic reference position.

Vibrotactile Feedback During Physical Exercise: Perception of Vibrotactile Cues in Cycling.

The aim of this study was to investigate the perception of vibrotactile signals during physical exercise by comparing differences in recognition between stationary and cycling positions. The impact of physical exercise on the ability to perceive vibrotactile cues is unknown, whereas the recognition in stationary position has been shown previously. Vibrating elements were positioned at 3 locations on the thighs and spine of 9 athletes to apply various vibrotactile cues. Subjects performed at 0, 50, 70 and 90% of their maximal cycling power output and denoted the interpretation of the vibration signals on a touchscreen. The results show a similarity in correct recognition between stationary position and physical exercise for the thighs and spine (p>0.1) and demonstrate a decrease in response time for 70 and 90% levels of physical exercise compared to 0 and 50% (p<0.001). Furthermore, vibrotactile signals at the spine are noticed more accurately and more rapidly compared to the thighs (p<0.01). These results suggest that vibrotactile feedback also has potential in applications during physical exercise. The potential use of vibrotactile feedback can be in cycling for, among other, correcting the aerodynamic position. Applications in other sports and health-related domains are feasible as well.

Sensory information and the perception of verticality in post-stroke patients. Another point of view in sensory reweighting strategies.

INTRODUCTION: Perception of verticality is highly related to balance control in human. Head-on-body tilt <60° results in the E-effect, meaning that a tilt of the perceived vertical is observed contralateral to the head tilt in the frontal plane. Furthermore, somatosensory loss also impacts the accuracy of verticality perception. However, when several input sources are absent or biased, less options for sensory weighting and balance control occur. Therefore, this study aims to identify the E-effect and assess the effect of somatosensory loss on the extent of the E-effect. METHODS: All patients with a first stroke admitted to a Belgian rehabilitation hospital were eligible for inclusion. Patients aged above 80 with other neurological and orthopaedic impairments as well as brainstem, cerebellar or multiple lesions were excluded. In addition, patients with visuospatial neglect and pusher behaviour were also excluded as this can affect verticality perception. The Rivermead Assessment of Somatosensory Performance (RASP), the Subjective Visual (SVV) and Subjective Postural (SPV) Vertical Test were administered. RESULTS: In total, 37 patients were included in the analysis of which 24 patients completed both SVV and SPV assessment. Results show that the E-effect occurred in our sample of stroke survivors for both SVV and SPV. In addition, the presence of somatosensory loss will increase the E-effect in both SVV as SPV assessment. A significant difference in verticality perception was noted for both SVV and SPV between the group with no (SVV: 5.13°(6.92); SPV: 0.30°(1.85)) and highly severe (SVV: 10.54°(13.19); SPV: 5.96°(9.27)) sensory loss. CONCLUSIONS: The E-effect occurs in stroke subjects and increases when patients experience somatosensory loss. This suggests that the lack of available afferent information impede estimation of verticality. Therefore, stroke survivors have fewer alternative input sources as a result of impairments, leading to fewer options about sensory reweighting strategies and balance recovery after perturbations.

Assessment of Forces in Intradermal Injection Devices: Hydrodynamic Versus Human Factors.

PURPOSE: The force that has to be exerted on the plunger for administering a given amount of fluid in a given time, has an important influence on comfort for the subject and usability for the administrator in intradermal drug delivery. The purpose of this study is to model those forces that are subject-independent, by linking needle and syringe geometry to the force required for ejecting a given fluid at a given ejection rate. MATERIAL AND METHODS: We extend the well-known Hagen-Poiseuille formula to predict pressure drop induced by a fluid passing through a cylindrical body. The model investigates the relation between the pressure drop in needles and the theoretic Hagen-Poiseuille prediction and is validated in fifteen needles from 26G up to 33G suited for intradermal drug delivery. We also provide a method to assess forces exerted by operators in real world conditions. RESULTS: The model is highly linear in each individual needle with R-square values ranging from 75% up to 99.9%. Ten out of fifteen needles exhibit R-square values above 99%. A proof-of-concept for force assessment is provided by logging forces in operators in real life conditions. CONCLUSIONS: The force assessment method and the model can be used to pinpoint needle geometry for intradermal injection devices, tuning comfort for subjects and usability for operators.

Vibrotactile feedback as a tool to improve motor learning and sports performance: a systematic review.

BACKGROUND: Evidence concerning the use of vibrotactile feedback for acquiring and learning new motor skills is limited. Although various concepts and applications for tactile feedback have been proposed, little is known about the suitability of this feedback mechanism in sports training. AIM: The goal of this systematic review was to gather knowledge on the efficacy of the use of vibrotactile feedback in improving sports performance skills. DESIGN: Systematic review. METHODS: Comprehensively searched databases were: PubMed, Cochrane and Web of Science. Studies investigating the effects of using vibrotactile feedback in sports training in healthy subjects were included in this review. RESULTS: No consensus was found regarding the positive effectiveness on performance using vibrotactile feedback in a sports context. No evidence was found that the addition of tactile feedback is effective for acquiring new motor skills. None of the studies show a significant learning effect.

Ergonomic design of an EEG headset using 3D anthropometry.

Although EEG experiments over the past decades have shown numerous applications for brain-computer interfacing (BCI), there is a need for user-friendly BCI devices that can be used in real-world situations. 3D anthropometry and statistical shape modeling have been shown to improve the fit of devices such as helmets and respirators, and thus they might also be suitable to design BCI headgear that better fits the size and shape variation of the human head. In this paper, a new design method for BCI devices is proposed and evaluated. A one-size-fits-all BCI headset frame is designed on the basis of three digital mannequins derived from a shape model of the human head. To verify the design, the geometric fit, stability and repeatability of the prototype were compared to an EEG cap and a commercial BCI headset in a preliminary experiment. Most design specifications were met, and all the results were found to be similar to those of the commercial headset. Therefore, the suggested design method is a feasible alternative to traditional anthropometric design for BCI headsets and similar headgear.

Evaluation of an anthropometric shape model of the human scalp.

This paper presents the evaluation a 3D shape model of the human head. A statistical shape model of the head is created from a set of 100 MRI scans. The ability of the shape model to predict new head shapes is evaluated by considering the prediction error distributions. The effect of using intuitive anthropometric measurements as parameters is examined and the sensitivity to measurement errors is determined. Using all anthropometric measurements, the average prediction error is 1.60 ± 0.36 mm, which shows the feasibility of the new parameters. The most sensitive measurement is the ear height, the least sensitive is the arc length. Finally, two applications of the anthropometric shape model are considered: the study of the male and female population and the design of a brain-computer interface headset. The results show that an anthropometric shape model can be a valuable tool for both research and design.

Assessment of acceptability and usability of new delivery prototype device for intradermal vaccination in healthy subjects.

The objectives of this study were to assess the acceptability and usability of a newly developed intradermal prototype device, VAX-ID™, in healthy subjects. In April 2012 an investigational study was conducted in healthy subjects aged 18 to 65 y. To compare injection site and route of administration, subjects were allocated to 4 subgroups, either receiving subsequently 2 intradermal (ID) injections (one in the forearm and one in the deltoid) or an ID (forearm) and an intramuscular (IM) (deltoid) injection. All injections contained saline solution. Acceptability was assessed with a subjects' questionnaire and a daily electronic diary for 5 d. Usability was assessed with a vaccinators' questionnaire and an expert panel. A 10-point Visual Analog Scale was used to score several statements on usability and acceptability. A total of 102 healthy subjects were enrolled in the study (age: 19-63). No statistically significant differences were seen in demographic characteristics between the ID and IM groups. Anxiety before injection, pain during injection and duration of injection were rated significantly lower for ID compared to IM. One day after the injections, redness was reported more often after ID injection in the forearm versus ID in the deltoid; pain at injection site was reported significantly more often after IM vs. ID injection. The new VAX-ID prototype device was found easy to handle, easy to use and safe. The new VAX-ID prototype device was shown to have a high degree of acceptability as well as usability. Further studies with VAX-ID will be conducted using vaccine antigen allowing assessment of immunogenicity and safety. Additionally, these studies will help to further improve VAX-ID in terms of accuracy of delivered dose and feedback to the vaccinator. (NCT01963338).