The design, development and evaluation of an array-based FES system with automated setup for the correction of drop foot

Functional electrical stimulation has been shown to be a safe and effective means of correcting drop foot of central neurological origin. However, despite recent technological advances, the set-up of surface stimulators remains a challenge for many users with drop foot. The automation of the setup process through the use of electrode arrays has been proposed as a way to address this problem. This paper describes a series of research and clinical studies which have led to the first demonstration of unsupervised automated setup of an electrode-array based drop foot stimulator. Finally, future research plans are discussed

Modelling and analysis of electrical impedance myography of the lateral tongue

Objective: Electrical impedance myography (EIM) performed on the centre of the tongue shows promise in detecting amyotrophic lateral sclerosis (ALS). Lateral recordings may improve diagnostic performance and provide pathophysiological insights through the assessment of asymmetry. However, it is not known if electrode proximity to the muscle edge, or electrode rotation, distort spectra. We evaluated this using finite element-based modelling. Approach: Nine thousand EIM from patients and healthy volunteers were used to develop a finite element model for phase and magnitude. Simulations varied electrode proximity to the muscle edge and electrode rotation. LT-Spice simulations assessed disease effects. Patient data were assessed for reliability, agreement and classification performance. Main results: No effect on phase spectra was seen if all electrodes remained in contact with the tissue. Small effects on magnitude were observed. Cole-Cole circuit simulations indicated capacitance reduced with disease severity. Lateral tongue muscle recordings in both patients and healthy volunteers were reproducible and symmetrical. Combined lateral/central tongue EIM improved disease classification compared to either placement alone. Significance: Lateral EIM tongue measurements using phase angle are feasible. Such measurements are reliable, find no evidence of tongue muscle asymmetry in ALS and improve disease classification. Lateral measurements enhance tongue EIM in ALS

A review of the design and clinical evaluation of the ShefStim array-based functional electrical stimulation system

Functional electrical stimulation has been shown to be a safe and effective means of correcting foot 12 drop of central neurological origin. Current surface-based devices typically consist of a single channel stimulator, 13 a sensor for determining gait phase and a cuff, within which is housed the anode and cathode. The cuff-mounted 14 electrode design reduces the likelihood of large errors in electrode placement, but the user is still fully responsible 15 for selecting the correct stimulation level each time the system is donned. Researchers have investigated different 16 approaches to automating aspects of setup and/or use, including recent promising work based on iterative learning 17 techniques. This paper reports on the design and clinical evaluation of an electrode array-based FES system for 18 the correction of drop foot, ShefStim. The paper reviews the design process from proof of concept lab-based study, 19 through modelling of the array geometry and interface layer to array search algorithm development. Finally, the 20 paper summarises two clinical studies involving patients with drop foot. The results suggest that the ShefStim 21 system with automated setup produces results which are comparable with clinician setup of conventional systems. 22 Further, the final study demonstrated that patients can use the system without clinical supervision. When used 23 unsupervised, setup time was 14 minutes (9 minutes for automated search plus 5 minutes for donning the 24 equipment), although this figure could be reduced significantly with relatively minor changes to the design

Cortical Representation of Lateralized Grasping in Chimpanzees (Pan troglodytes): A Combined MRI and PET Study

Functional imaging studies in humans have localized the motor-hand region to a neuroanatomical landmark call the KNOB within the precentral gyrus. It has also been reported that the KNOB is larger in the hemisphere contralateral to an individual's preferred hand, and therefore may represent the neural substrate for handedness. The KNOB has also been neuronatomically described in chimpanzees and other great apes and is similarly associated with handedness. However, whether the chimpanzee KNOB represents the hand region is unclear from the extant literature. Here, we used PET to quantify neural metabolic activity in chimpanzees when engaged in unilateral reach-and-grasping responses and found significantly lateralized activation of the KNOB region in the hemisphere contralateral to the hand used by the chimpanzees. We subsequently constructed a probabilistic map of the KNOB region in chimpanzees in order to assess the overlap in consistency in the anatomical landmarks of the KNOB with the functional maps generated from the PET analysis. We found significant overlap in the anatomical and functional voxels comprising the KNOB region, suggesting that the KNOB does correspond to the hand region in chimpanzees. Lastly, from the probabilistic maps, we compared right- and left-handed chimpanzees on lateralization in grey and white matter within the KNOB region and found that asymmetries in white matter of the KNOB region were larger in the hemisphere contralateral to the preferred hand. These results suggest that neuroanatomical asymmetries in the KNOB likely reflect changes in connectivity in primary motor cortex that are experience dependent in chimpanzees and possibly humans

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Usability Engineering in Practice: Developing an intervention for post-stroke therapy during a global pandemic

This paper provides an overview of the usability engineering process and relevant standards informing the development of medical devices, together with adaptations to accommodate situations such as global pandemics where use of traditional face-to-face methods is restricted. To highlight some of those adaptations, a case study of a project developing a novel electronic rehabilitation device is referenced, which commenced in November 2020 amidst the COVID-19 pandemic. The Sheffield Adaptive Patterned Electrical Stimulation (SHAPES) project, led by Sheffield Teaching Hospitals NHS Foundation Trust (STH), aimed to design, manufacture and trial an intervention for use to treat upper arm spasticity after stroke. Presented is an outline and discussion of the challenges experienced in developing the SHAPES health technology intended for at-home use by stroke survivors and in implementing usability engineering approaches. Also highlighted, are the benefits that arose, which can offer easier involvement of vulnerable users and add flexibility in the ways that user feedback is sought. Challenges included: restricted travel; access to usual prototyping facilities; social distancing; infection prevention and control; availability of components; and changing work pressures and demands. Whereas benefits include: less travel; less time commitment; and greater scope for participants with restricted mobility to participate in the process. The paper advocates a more flexible approach to usability engineering and outlines the onward path for development and trialling of the SHAPES technology

Automated setup of functional electrical stimulation for drop foot using a novel 64 channel prototype stimulator and electrode array : results from a gait-lab based study

Functional electrical stimulation is commonly used to correct drop foot following stroke or multiple sclerosis. This technique is successful for many patients, but previous studies have shown that a significant minority have difficulty identifying correct sites to place the electrodes in order to produce acceptable foot movement. Recently there has been some interest in the use of ‘virtual electrodes’, the process of stimulating a subset of electrodes chosen from an array, thus allowing the site of stimulation to be moved electronically rather than physically. We have developed an algorithm for automatically determining the best site of stimulation and tested it on a computer linked to a small, battery-powered prototype stimulator with 64 individual output channels. Stimulation was delivered via an 8 × 8 array adhered to the leg by high-resistivity self-adhesive hydrogel. Ten participants with stroke (ages 53–71 years) and 11 with MS (ages 40–80 years) were recruited onto the study and performed two walks of 10 m for each of the following conditions: own setup (PS), clinician setup (CS), automated setup (AS) and no stimulation (NS). The PS and CS conditions used the participant's own stimulator with two conventional electrodes; the AS condition used the new stimulator and algorithm. Outcome measures were walking speed, foot angle at initial contact and the Borg Rating of Perceived Exertion. Mean walking speed with no stimulation was 0.61 m/s; all FES setups significantly increased speed relative to this (AS p 0.05) and less dorsiflexed than CS (6.0°, p < 0.05). This proof of principle study has demonstrated that automated setup of an array stimulator produces results broadly comparable to clinician setup. Slower walking speed for automated and clinician setups compared to the participants’ own setup may be due to the participants’ lack of familiarity with responses different to their usual setups. Automated setup using the method described here seems sufficiently reliable for future longer-term investigation outside the laboratory and may lead to FES becoming more viable for patients who, at present, have difficulty setting up conventional stimulators

Genetic association at the 9p21 glaucoma locus contributes to sex bias in normal-tension glaucoma

Purpose. Many genome-wide association studies have identified common single nucleotide polymorphisms (SNPs) at the 9p21 glaucoma locus (CDKN2B/CDKN2B-AS1) to be significantly associated with primary open-angle glaucoma (POAG), with association being stronger in normal tension glaucoma (NTG) and advanced glaucoma. We aimed to determine whether any observed differences in genetic association at the 9p21 locus are influenced by sex. Methods. Sex was assessed as a risk factor for POAG for 2241 glaucoma participants from the Australian and New Zealand Registry of Advanced Glaucoma, the Glaucoma Inheritance Study in Tasmania, and the Flinders Medical Centre. A total of 3176 controls were drawn from the Blue Mountains Eye Study and South Australia: 1523 advanced POAG and 718 nonadvanced POAG cases were genotyped along with 3176 controls. We selected 13 SNPs at the 9p21 locus, and association results were subanalyszd by sex for high-tension glaucoma (HTG) and NTG. Odds ratios (ORs) between sexes were compared. Results. A sex bias was present within advanced NTG cases (57.1% female versus 42.9% male, P = 0.0026). In all POAG cases, the strongest associated SNP at 9p21 was rs1063192 (OR, 1.43; P = 4 × 10⁻¹⁸). This association was stronger in females (OR, 1.5; P = 5 × 10⁻¹³) than inmales (OR, 1.35; P = 7 × 10⁻⁷), with a statistically significant difference in female to male OR comparison (P = 1.0 × 10⁻²). An NTG to HTG subanalysis yielded statistically significant results only in females (OR, 1.63; P = 1.5 × 10⁻⁴) but not in males (OR, 1.15; P = 2.8 × 10⁻¹), with a statistically significant difference in female to male OR comparison (P = 1.4 × 10⁻⁴). Conclusions. This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG.6 page(s