Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

Background: Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective: To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods: A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results: All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions: In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Modulation of Spinal Dorsal Horn Long-term Potentiation by Non-ionotropic NMDA Receptor Activity

Pathological pain is characterized by enhanced synaptic strength within nociceptive pathways of the spinal dorsal horn that arises in the absence of any obvious trigger. Unfortunately, current treatment options often fail to provide adequate and lasting pain relief as they do not address the underlying mechanisms of persistent pain. The enhancement of synaptic transmission between nociceptive afferents and dorsal horn neurons (long-term potentiation; LTP) is associated with sensitization. This project aims to investigate the role of non-ionotropic NMDA receptor (NI-NMDAR) signalling in the plasticity of nociceptive neurons and to induce synaptic depotentiation through a combination of electrophysiological recordings and pharmacological interventions. These data indicate that NI-NMDAR activity could reverse dorsal horn LTP with 7CK, a NMDA receptor glycine site antagonist and was dependent on downstream protein phosphatase-1 activity. Overall, this project will provide essential new insights into the mechanisms by which synaptic depotentiation can be exploited to erase pathological pain.M.Sc.2021-11-30 00:00:0

Video-Based Pairwise Comparison: Enabling the Development of Automated Rating of Motor Dysfunction in Multiple Sclerosis.

OBJECTIVES To examine the feasibility, reliability, granularity, and convergent validity of a video-based pairwise comparison technique that uses algorithmic support to enable automated rating of motor dysfunction in patients with multiple sclerosis (MS). DESIGN Feasibility and larger cross-sectional cohort study. SETTING The outpatient clinic of 2 specialist university medical centers. PARTICIPANTS Selected sample from a cohort of patients with MS participating in the Assess MS study (N=42). Videos were randomly drawn from each strata of the ataxia severity-degrees as defined in the Expanded Disability Status Scale (EDSS). In Basel: 19 videos of 17 patients (mean age, 43.4±11.6y; 10 women). In Amsterdam: 50 videos of 25 patients (mean age, 50.0±10.0y; 15 women). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES In each center, neurologists (n=13; n=10) viewed pairs of videos of patients performing standardized movements (eg, finger-to-nose test) to assess relative performance. A comparative assessment score was calculated for each video using the TrueSkill algorithm and analyzed for intrarater (test-retest; ratio of agreement) and interrater reliability (intraclass correlation coefficient [ICC] for absolute agreement) and convergent validity (Spearman ρ). Granularity was estimated from the average difference in comparative assessment scores at which 80% of neurologists considered performance to be different. RESULTS Intrarater reliability was excellent (median ratio of agreement≥0.87). The comparative assessment scores calculated from individual neurologists demonstrated good-excellent ICCs for interrater reliability (0.89; 0.71). The comparative assessment scores correlated (very) highly with their Neurostatus-EDSS equivalent (ρ=0.78, P<.001; ρ=0.91, P<.05), suggesting a more fine-grained rating. CONCLUSIONS Video-based pairwise comparison of motor dysfunction allows for reliable and fine-grained capturing of clinical judgment about neurologic performance, which can contribute to the development of a consistent quantified metric of motor ability in MS

Setwise comparison: efficient fine-grained rating of movement videos using algorithmic support - a proof of concept study.

PURPOSE Clinical ordinal rating scales of movements, e.g., the Expanded Disability Status Scale, have poor intra- and interrater reliability, are insensitive to subtle differences and result in coarse-grained ratings compared to relative comparative rating methods. We therefore established video-based setwise comparison as a fine-grained, reliable and efficient rating method of motor dysfunction using algorithmic support. MATERIALS AND METHODS Eight neurologists rated a set of 40 multiple sclerosis patient videos of the Finger-to-Nose-Test using both the newly developed setwise comparison and the established pairwise comparison techniques, which result in a continuous rating scale. Reliability was assessed by the intra-class correlation coefficient. Construct validity was estimated as Pearson's correlation between the continuous scale and severity ratings according to the Neurostatus scale for upper-extremity tremor/dysmetria and the Nine-hole-peg-test. Comparing the time needed for ratings assessed efficiency. RESULTS Intra-class correlation coefficient was 0.83 for setwise and 0.7 for pairwise comparison. Correlation to the tremor/dysmetria score of the Neurostatus was 0.86 for both rating procedures and correlation to the Nine-hole-peg-test was 0.64 (setwise) and 0.66 (pairwise). The time needed to rate 40 videos was 22.9 ± 6.9 minutes (setwise) and 77.8 ± 14.5 minutes (pairwise). CONCLUSIONS Setwise comparison is an efficient, valid and reliable method for fine-grained rating of motor dysfunction that can be applied to larger datasets. It is substantially more efficient than pairwise comparison. Implications for rehabilitation Disability rating is crucial in clinical neurorehabilitation and in clinical trials. Humans are naturally inconsistent in rating items on ordinal scales leading to poor intra- and interrater reliability, insensitivity to subtle differences and coarse-grained ratings. Video-based setwise comparison is a new rating method enabling fine-grained, reliable and efficient ratings of motor dysfunction using algorithmic support

Setwise Comparison: Consistent, Scalable, Continuum Labels for Computer Vision

A growing number of domains, including affect recognition and movement analysis, require a single, real number ground truth label capturing some property of a video clip. We term this the provision of continuum labels. Unfortunately, there is often an uncacceptable trade-off between label consistency and the efficiency of the labelling process with current tools. We present a novel interaction technique, ‘setwise’ comparison, which leverages the intrinsic human capability for consistent relative judgements and the TrueSkill algorithm to solve this problem. We describe SorTable, a system demonstrating this technique. We conducted a real-world study where clinicians labelled videos of patients with multiple sclerosis for the ASSESS MS computer vision system. In assessing the efficiency-consistency trade-off of setwise versus pairwise comparison, we demonstrated that not only is setwise comparison more efficient, but it also elicits more consistent labels. We further consider how our findings relate to the interactive machine learning literature

Evidence for Highly Variable, Region-Specific Patterns of T-Cell Epitope Mutations Accumulating in Mycobacterium tuberculosis Strains

Vaccines that confer protection through induction of adaptive T-cell immunity rely on understanding T-cell epitope (TCE) evolution induced by immune escape. This is poorly understood in tuberculosis (TB), an ancient, chronic disease, where CD4 T-cell immunity is of recognized importance. We probed 905 functionally validated, curated human CD4 T cell epitopes in 79 Mycobacterium tuberculosis (Mtb) whole genomes from India. This screen resulted in identifying 64 mutated epitopes in these strains initially using a computational pipeline and subsequently verified by single nucleotide polymorphism (SNP) analysis. SNP based phylogeny revealed the 79 Mtb strains to cluster to East African Indian (EAI), Central Asian Strain (CAS), and Beijing (BEI) lineages. Eighty-nine percent of the mutated T-cell epitopes (mTCEs) identified in the 79 Mtb strains from India has not previously been reported. These mTCEs were encoded by genes with high nucleotide diversity scores including seven mTCEs encoded by six antigens in the top 10% of rapidly divergent Mtb genes encoded by these strains. Using a T cell functional assay readout, we demonstrate 62% of mTCEs tested to significantly alter CD4 T-cell IFN gamma and/or IL2 secretion with associated changes in predicted HLA-DR binding affinity: the gain of function mutations displayed higher predicted HLA-DR binding affinity and conversely mutations resulting in loss of function displayed lower predicted HLA-DR binding affinity. Most mutated antigens belonged to the cell wall/cell processes, and, intermediary metabolism and respiration families though all known Mtb proteins encoded mutations. Analysis of the mTCEs in an SNP database of 5,310 global Mtb strains identified 82% mTCEs to be significantly more prevalent in Mtb strains isolated from India, including 36 mTCEs identified exclusively in strains from India. These epitopes had a significantly higher predicted binding affinity to HLA-DR alleles that were highly prevalent in India compared to HLA-DR alleles rare in India, highlighting HLA-DR maybe an important driver of these mutations. This first evidence of region-specific TCE mutations potentially employed by Mtb to escape host immunity has important implications for TB vaccine design