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.

Tensor electrical impedance myography identifies bulbar disease progression in amyotrophic lateral sclerosis

OBJECTIVE: Electrical impedance myography (EIM) is a promising biomarker for amyotrophic lateral sclerosis (ALS). A key issue is how best to utilise the complex high dimensional, multi-frequency data output by EIM to fully characterise the progression of disease. METHODS: Muscle volume conduction properties were obtained from EIM recordings of the tongue across three electrode configurations and 14 input frequencies (76 Hz-625 kHz). Analyses of individual frequencies, averaged EIM spectra and non-negative tensor factorisation were undertaken. Longitudinal data were collected from 28 patients and 17 healthy volunteers at 3-monthly intervals for a maximum of 9 months. EIM was evaluated against the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) bulbar sub-score, tongue strength and an overall bulbar disease burden score. RESULTS: Longitudinal changes to individual patient EIM spectra demonstrated complex shifts in the spectral shape. At a group level, a clear pattern emerged over time, characterised by an increase in centre frequency and general shift to the right of the spectral shape. Tensor factorisation reduced the spectral data from a total of 168 data points per participant per recording to a single value which captured the complexity of the longitudinal data and which we call tensor EIM (T-EIM). The absolute change in tensor EIM significantly increased within 3 months and continued to do so over the 9-month study duration. In a hypothetical clinical trial scenario tensor EIM required fewer participants (n = 64 at 50% treatment effect), than single frequency measures (n range 87-802) or ALSFRS-R bulbar subscore (n = 298). CONCLUSIONS: Changes to tongue EIM spectra over time in ALS are complex. Tensor EIM captured and quantified disease progression and was more sensitive to changes than single frequency EIM measures and other biomarkers of bulbar disease. SIGNIFICANCE: Objective biomarkers for the assessment of bulbar disease in ALS are lacking. Tensor EIM enhances the biomarker potential of EIM data and can improve bulbar symptom monitoring in clinical trials.

Tensor electrical impedance myography identifies clinically relevant features in amyotrophic lateral sclerosis.

Objective.Electrical impedance myography (EIM) shows promise as an effective biomarker in amyotrophic lateral sclerosis (ALS). EIM applies multiple input frequencies to characterise muscle properties, often via multiple electrode configurations. Herein, we assess if non-negative tensor factorisation (NTF) can provide a framework for identifying clinically relevant features within a high dimensional EIM dataset.Approach.EIM data were recorded from the tongue of healthy and ALS diseased individuals. Resistivity and reactivity measurements were made for 14 frequencies, in three electrode configurations. This gives 84 (2 × 14 × 3) distinct data points per participant. NTF was applied to the dataset for dimensionality reduction, termed tensor EIM. Significance tests, symptom correlation and classification approaches were explored to compare NTF to using all raw data and feature selection.Main Results.Tensor EIM provides highly significant differentiation between healthy and ALS patients (p< 0.001, AUROC = 0.78). Similarly tensor EIM differentiates between mild and severe disease states (p< 0.001, AUROC = 0.75) and significantly correlates with symptoms (ρ= 0.7,p< 0.001). A trend of centre frequency shifting to the right was identified in diseased spectra, which is in line with the electrical changes expected following muscle atrophy.Significance.Tensor EIM provides clinically relevant metrics for identifying ALS-related muscle disease. This procedure has the advantage of using the whole spectral dataset, with reduced risk of overfitting. The process identifies spectral shapes specific to disease allowing for a deeper clinical interpretation.

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.

Multi-dimensional electrical impedance myography of the tongue as a potential biomarker for amyotrophic lateral sclerosis.

OBJECTIVE: In amyotrophic lateral sclerosis (ALS) bulbar disease biomarkers are lacking. We evaluated a novel tongue electrical impedance myography (EIM) system, utilising both 2D and 3D electrode configurations for detection of tongue pathology. METHODS: Longitudinal multi-frequency phase angle spectra were recorded from 41 patients with ALS (baseline, 3 and 6 months) and 30 healthy volunteers (baseline and 6 months). ALS functional rating scale-revised (ALSFRS-R) data and quantitative tongue strength measurements were collected. EIM data were analysed for reliability (intra-class correlation coefficient; ICC) and differences between patients and volunteers ascertained using both univariate (Mann-Whitney U test) and multivariate techniques (feature selection and L2 norm). RESULTS: The device produced highly reliable data (pooled ICC: 0.836). Significant EIM differences were apparent between ALS patients and healthy volunteers (P < 0.001). EIM data demonstrated a significant relationship to tongue strength and bulbar ALSFRS-R scores (P < 0.015). The EIM recordings revealed a group level longitudinal change over 6 months and consistently identified patients in whom symptoms or tongue strength changed. CONCLUSIONS: The novel EIM tongue system produces reliable data and can differentiate between healthy muscle and ALS-related disease. SIGNIFICANCE: Tongue EIM utilising multiple frequencies and electrode configurations has potential as a bulbar disease biomarker in ALS.

Influence of high risk HPV genotype on colposcopic performance: A large prospective study demonstrates improved detection of disease with ZedScan I, particularly in non-HPV 16 patients.

OBJECTIVE: To assess the influence of high-risk Human Papilloma Virus (hrHPV) genotyping on the detection of high-grade disease (CIN2+) using colposcopic impression both with and without electrical impedance spectroscopy (ZedScan I) as an adjunct. STUDY DESIGN: A prospective cohort of women with a known hrHPV genotype referred to a single colposcopy service. RESULTS: 839 women underwent colposcopy and ZedScan I examination. 613 women were referred with abnormal cytology; 411 (67%) with low-grade dyskaryosis (67%) and 202 (33%) with high-grade dyskaryosis. 187 were referred with persistent hrHPV but negative cytology. 35 were attended for follow up and 4 for a clinical indication. 159 (19%) women were positive for HPV16 only; 54 (6%) with HPV18 only, 443 (53%) women were positive for hrHPV other types (HPV O). 183 (22%) were positive for multiple hrHPV genotypes. CIN2+ was present in 170 (84.2%) of high-grade and 69 (16.7%) of low-grade cytology referrals. Colposcopy was better at detecting HPV16 associated CIN2+ than that associated with HPV18 or HPV O (86.9% vs 79.7%, p=0.0191). ZedScan I increased the detection of CIN2+ from 85.6% to 96% irrespective of hrHPV genotype status (p<0.0001). CONCLUSION: The use of an electrical impedance spectroscopic device (ZedScan I) increases detection of CIN2+ irrespective of hrHPV genotype.

Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions.

The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool.

Accuracy of detection of high-grade cervical intraepithelial neoplasia using electrical impedance spectroscopy with colposcopy.

OBJECTIVE: To determine if electrical impedance spectroscopy (EIS) improves the diagnostic accuracy of colposcopy when used as an adjunct. DESIGN: Prospective, comparative, multi-centre clinical study. SETTING: Three colposcopy clinics: two in England and one in Ireland. POPULATION: Women referred with abnormal cytology. METHODS: In phase 1, EIS was assessed against colposcopic impression and histopathology of the biopsies taken. In phase 2, a probability index and cut-off value for the detection of high-grade cervical intraepithelial neoplasia (HG-CIN, i.e. grade CIN2+) was derived to indicate sites for biopsy. EIS data collection and analyses were performed in real time and blinded to the clinician. The phase-2 data were analysed using different cut-off values to assess performance of EIS as an adjunct. MAIN OUTCOME MEASURE: Histologically confirmed HG-CIN (CIN2+). RESULTS: A total of 474 women were recruited: 214 were eligible for analysis in phase 1, and 215 were eligible in phase 2. The average age was 33.2 years (median age 30.3 years, range 20-64 years) and 48.5% (208/429) had high-grade cytology. Using the cut-off from phase 1 the accuracy of colposcopic impression to detect HG-CIN when using EIS as an adjunct at the time of examination improved the positive predictive value (PPV) from 78.1% (95% CI 67.5-86.4) to 91.5%. Specificity was also increased from 83.5% (95% CI 75.2-89.9) to 95.4%, but sensitivity was significantly reduced from 73.6% (95% CI 63.0-82.5) to 62.1%, and the negative predictive value (NPV) was unchanged. The positive likelihood ratio for colposcopic impression alone was 4.46. This increased to 13.5 when EIS was used as an adjunct. The overall accuracy of colposcopy when used with EIS as an adjunct was assessed by varying the cut-off applied to a combined test index. Using a cut-off set to give the same sensitivity as colposcopy in phase 2, EIS increased the PPV to detect HG-CIN from 53.5% (95% CI 45.0-61.8) to 67%, and specificity increased from 38.5% (95% CI 29.4-48.3) to 65.1%. NPV was not significantly increased. Alternatively, applying a cut-off to give the same specificity as colposcopy alone increased EIS sensitivity from 88.5% (95% CI 79.9-94.4) to 96.6%, and NPV from 80.8% (95% CI 67.5-90.4) to 93.3%. PPV was not significantly increased. The receiver operator characteristic (ROC) to detect HG-CIN had an area under the curve (AUC) of 0.887 (95% CI 0.840-0.934). CONCLUSIONS: EIS used as an adjunct to colposcopy improves colposcopic performance. The addition of EIS could lead to more appropriate patient management with lower intervention rates.

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, PS p<0.01, CS p<0.01). Speed for PS (0.72 m/s) was faster than both AS (0.65 m/s, p<0.01) and CS (0.68 m/s, p<0.05). Frontal plane foot orientation at heel-strike was more neutral for AS (0.3° everted) than in the NS (11.2° inverted, p<0.01), PS (4.5° inverted, p<0.05) and CS (3.1° inverted, p<0.05) conditions. Dorsiflexion angles for AS (4.2°) were larger than NS (-3.0°, p<0.01), not different to PS (4.3°, 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.

Feasibility of detecting pulmonary embolism using noncontrast MRI.

Purpose. The purpose of this study was to evaluate the feasibility of detecting pulmonary emboli utilizing noncontrast magnetic resonance imaging techniques in patients with known pulmonary embolism. Materials and Methods. Eleven patients were enrolled in a study to evaluate right ventricular function by cardiac MRI in patients diagnosed with acute pulmonary embolism on CT pulmonary angiogram. Cardiac MRI was performed as soon as possible following pulmonary embolism detection. Two independent observers reviewed the precontrast portion of each MRI, scoring right, left, and lobar arteries as positive or negative for PE. The CTs were reviewed and interpreted in the same manner. Results. MRI was obtained on average of 40 hours after the CT. Forty-eight vessels were affected by PE on CT, 69% of which were identified on MRI. All eight pulmonary emboli located in the right or left pulmonary arteries were detected on MRI. Of the 15 pulmonary emboli that were not detected on MRI, 7 were subsegmental, 6 were segmental, and 2 were located in a branch not included in the MRI field of view. Conclusions. Most pulmonary emboli detected on CT were identified on noncontrast MRI, even though our MRI protocol was not optimized for pulmonary artery visualization.

Tissue levels, histologic changes and plasma pharmacokinetics of meta-Tetra (hydroxyphenyl) chlorin (mTHPC) in the cat.

The biodistribution and pharmacokinetics of meta-tetra(hydroxyphenyl)chlorin (mTHPC)(1) have been documented in humans, rats, dogs and rabbits. It has been demonstrated to be an effective photodynamic therapy agent for treatment of squamous cell carcinoma. Squamous cell carcinoma is a common feline neoplasm, causing significant morbidity and mortality in the feline population. The association between ultraviolet radiation exposure and occurrence of this neoplasm in the cat provides a useful model for the study of human cutaneous squamous cell carcinoma. In this study, we document the biodistribution, pharmacokinetics and toxicity of mTHPC in a group of normal cats. Four groups of cats were given the drug intravenously at dosages of 0, 0.15, 0.30 and 0.60 mg/kg. mTHPC levels were measured in plasma and tissues at 0, 24, 48, 72, 96 and 336 h after drug administration. Additionally, plasma samples were collected at 1 and 6 h post-injection and analysed. Biodistribution and pharmacokinetics of mTHPC in cats mirrors that in other animal species. There were no clinical or pathological changes associated with administration of the drug. The biodistribution and pharmacokinetics of mTHPC in cats mirrors that in other species studied. There were no clinical or pathological changes attributable to administration of the drug at the doses administered. mTHPC may be a useful photodynamic therapy drug in cats.

Retrospective review of febrile neutropenia in the Royal Darwin Hospital, 1994-99.

BACKGROUND: Febrile neutropenia is a life-threatening complication of cytotoxic chemotherapy. Empirical antibiotic treatment should be based on predominant pathogens and epidemiological characteristics of the treated community. The aim of the present study was to review cases of febrile neutropenia at the Royal Darwin Hospital (RDH) in order to assess the appropriateness of empirical antibiotic therapy. METHODS: A retrospective review of cases of febrile neutropenia secondary to malignancy or chemotherapy occurring at the RDH over the period 1994-99. In order to compare infections in this group with those in the wider hospital community, all positive blood cultures in the medical and intensive care units were reviewed for the same time period. RESULTS: Thirty-six episodes of febrile neutropenia were reviewed. Staphylococcus aureus (predominantly methicillin resistant), Pseudomonas aeruginosa and Escherichia coli were the most common organisms identified. Nine patients died of their infection, four with methicillin-resistant S. aureus bacteraemia. S. aureus, E. coli, Streptococcus pneumoniae and Burkholderia pseudomallei (melioid) were the most frequently isolated organisms from blood cultures taken in the medical and intensive care units. CONCLUSIONS: Gram-positive organisms are the predominant pathogens in febrile neutropenic episodes at the RDH. Standard empirical therapy with an extended-spectrum penicillin and an aminoglycoside remains appropriate, with the addition of vancomycin when clinical status fails to improve. When practising in the Top End, particular consideration should be given to skin integrity and scabies and testing for Strongyloides in Aboriginal patients.

Evaluation of carbon dioxide laser and conventional incisional techniques for resection of soft palates in brachycephalic dogs.

OBJECTIVE: To compare clinical outcome, healing, and effect of tracheostomy in conventional incisional and carbon dioxide (CO2) laser techniques for resection of soft palates in brachycephalic dogs. DESIGN: Prospective randomized trial. ANIMALS: 20 adult brachycephalic dogs. METHODS: Dogs were randomly allocated into 4 groups, and 1 of the following was performed: palate resection by use of a CO2 laser; incisional palate resection and closure with suture; and palate resection by use of a C02 laser or incision with tracheostomy. A clinical score for respiratory function was assigned to each dog at 0, 2, 8, 16, and 24 hours. Biopsy specimens of incision sites obtained at days 0, 3, 7, and 14 were examined. Data were analyzed to determine the effects of technique on clinical and histologic outcome. RESULTS: Mean surgical time for laser (309 seconds) was significantly shorter than for sharp dissection (744 seconds). Surgical technique significantly affected clinical scores at 3 of the 5 postoperative time points, but differences were not clinically apparent. Tracheostomy significantly affected clinical scores at 3 of 5 postoperative time points. After tracheostomy tube removal, clinical scores were similar to those of dogs without tracheostomies. Inflammation, necrosis, and ulceration were evident in all groups at day 3; these lesions had almost resolved by day 14. Most complications were associated with tracheostomy. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical outcomes appear to be similar with the laser and incisional techniques. Regarding surgical time and ease, laser resection of the soft palate appears advantageous. Tracheostomy is not warranted in dogs that have uncomplicated surgeries and recoveries.

A report on the Council on Certification 1996 Professional Practice Analysis.

The purpose of this article is to provide an overview of the Council on Certification of Nurse Anesthetists 1996 Professional Practice Analysis. This analysis was used to update the previous content validation studies. Surveys were mailed to a select group and a practitioner group of 2,859 Certified Registered Nurse Anesthetists with a response rate of 63.7%. Respondents were asked survey questions related to demographics, practice settings, education, and fundamental knowledge related to nurse anesthesia practice. Respondents were asked for the frequency and level of expertise related to patient conditions, procedures, anesthesia agents and techniques, equipment, instrumentation, and technology of anesthesia practice. The results for both groups were consistent with the previous studies. The Rasch rating scale model was used to transform the results from ordinal data onto a linear, equal-interval scale. Members of the Council on Certification of Nurse Anesthetists carefully reviewed all of the Professional Practice Analysis results and voted to maintain the current test blueprint and percentage of test items in each area.

A two-year follow-up of neonates with presumed sepsis treated with recombinant human granulocyte colony-stimulating factor during the first week of life.

We have previously reported that recombinant human granulocyte colony-stimulating factor was well tolerated and resulted in sustained neutrophilia and improvement of neutrophil functions in newborn infants with presumed sepsis. We now report a 2-year follow-up on 21 of the initial cohort of 28 patients. Treatment with recombinant human granulocyte colony-stimulating factor in neonates with presumed sepsis was not associated with any long-term adverse hematologic, immunologic, or developmental effects.

The psychological impact of implant-retained mandibular prostheses: a cross-sectional study.

Investigation of the psychological impact of implant-retained overdentures has demonstrated some positive benefits over traditional prosthetic treatment (ie, conventional complete dentures). The aim of the present study was to determine whether treatment response could be understood by controlling the degree of alveolar ridge resorption present. In a cross-sectional single-wave study by means of a questionnaire, patients who had received implant-retained mandibular dentures were compared with patients who had conventional mandibular dentures. For purposes of comparison, all patients in both groups wore conventional maxillary dentures. From the 87 patients who were invited to complete a postal questionnaire, 76 replies were received (85% response rate). The implant (n = 41) and denture (n = 35) patients were assessed on self-rated symptoms, denture satisfaction, psychological distress, body satisfaction, and self-esteem using standardized scales. All patients had the extent of alveolar bone loss classified according to Cawood and Howell's (1991) system during a clinical examination. The results indicated that the response of patients to implants or dentures was influenced by the degree of bone loss. Patients with extensive resorption who received implants appeared, from a psychological perspective, to receive more benefit than their nonimplant counterparts. Hence, there is some evidence to support the inclusion of clinical measures of alveolar bone loss when considering the psychological impact accruing from implant-based treatments.

The price of anesthesia care.

The focus on the cost of health care presents a paradox. Although society demands lower cost healthcare, few want to cut health services or the quality of the care received. There continues to be strong consumer pressure to improve the quality of health care and to increase the scope of services, while keeping cost increases to a minimum. Obviously, there is no single answer to the complex issues facing the health care industry. The nurse anesthetist, must however, begin answering these demands with an analysis of our own practice. Our role in the health care system of the future will be determined, not just on our clinical competency, but also on how we respond to the system as a whole. "Cost effectiveness" will need to be redefined as CRNAs provide a "value added" service.