Telerehabilitation for people with physical disabilities and movement impairment: development and evaluation of an online toolkit for practitioners and patients.

PURPOSE: Telerehabilitation has increasingly been used since the COVID-19 pandemic but with limited guidance available on undertaking physical assessments using remote methods. We aimed to provide such guidance by developing a Telerehab Toolkit, an online information and training resource for practitioners, patients, and carers on telerehabilitation for people with physical disabilities and movement impairment. MATERIALS AND METHODS: Development and evaluation of the toolkit were informed by the Knowledge to Action framework and took place iteratively in two phases-knowledge creation and action. Information was collated from various sources including literature review, online survey, service evaluation, and focus group discussions. The toolkit has been evaluated using think-aloud interviews, e-mail and social media feedback from users, and analytics data on user engagement with the website. RESULTS: The Telerehab Toolkit focuses on remote physical assessments, and contains information on technology, digital skills, remote assessment tools, information governance, and safety for telerehabilitation. Resources include top tips from practitioners and patients, how-to guides, checklists, videos, and links to evidence. CONCLUSIONS: The Telerehab Toolkit has been well-received by practitioners, healthcare students, patients, and carers, is being disseminated widely, and is freely available (www.plymouth.ac.uk/research/telerehab). IMPLICATIONS FOR REHABILITATIONTelerehabilitation has been increasingly used since the COVID-19 pandemic, but with limited guidance and training for practitioners on undertaking safe and effective remote physical assessments.The Telerehab Toolkit has been developed iteratively using the Knowledge to Action framework; it is a free online resource for practitioners and patients with specific guidance on telerehabilitation for physical disabilities and movement impairment.It is anticipated that the resource will help to improve the knowledge, skills, and confidence of the current and future rehabilitation workforce.

E-nursing homes: transforming access to nurses in nursing homes in response to the staffing crisis.

The UK is facing a nationwide staffing crisis within adult social care, due to difficulties in recruiting and retaining registered nurses. Current interpretation of legislation means nursing homes must always have the physical presence of a registered nurse on duty within the home. With the shortage of registered nurses increasing, reliance on agency workers is commonplace, a practice impacting service cost and continuity of care. Lack of innovation to tackle this issue means the question of how to transform service delivery to combat staffing shortages is open for debate. The potential for technology to augment the provision of care was highlighted during the COVID-19 pandemic. In this article the authors present one possible solution focused on the provision of digital nursing care within nursing homes. Anticipated benefits include enhanced accessibility of nursing roles, reduced risk of viral spread and opportunities for upskilling staff. However, challenges include the current interpretation of legislation.

Covid-19 vaccine (covishield) heralding Moyamoya angiopathy

Indroduction: Thrombotic complications leading to cerebrovascular events occuring in conjunction with Covid-19 vaccination though rare, is well-documented. Moyamoya Angiopathy is a progressive intracranial vasculopathy leading to recurrent strokes. Case presentation: We present two index cases of young patient presenting with stroke and TIA following Covid-19 vaccination (COVISHIELD) leading to unmasking of Moyamoya Angiopathy. Conclusion(s): Arterial stroke following Covid-19 vaccination is documented, but uncommon. However, in the background of a vasculopathy, it may not be so rare. Moyamoya Angiopathy has been closely studied in the model of inflammatory pathophysiology in genetically predisposed patients leading to progressive vaso-occlusive disease. Few reports of Covid-19 infection potentiating Moyamoya Angiopathy symptoms are also documented. Thus, as an extrapolation of the inflammatory etiopathogenesis of Moyamoya Angiopathy, Covid-19 vaccination can similarly affect the Moyamoya symptomatology. These two index cases open new lines of enquiry regarding the interplay of Covid-19 vaccination and neurological destabilization in patients with underlying vasculopathy of inflammatory pathophysiology.Copyright © 2022

Association of Angiotensin Converting Enzyme 2 (ACE2) Gene Polymorphisms with Disease Severity in Indian Covid-19 Patients: A Next-gen Sequencing Approach

The clinical picture of COVID-19 ranges from asymptomatic to mild, moderate or severe disease sometimes leading to death. Differences in the interaction between SARS-CoV-2 Spike (S) protein and angiotensin converting enzyme 2 (ACE2) protein may lead to differences in disease severity. We studied whether ACE2 polymorphisms are associated with disease severity and outcome. We recruited 114 patients between July 2020 - March 2022 confirmed positive by RTPCR for COVID-19 with different degrees of severity (21 mild, 29 moderate, 34 severe, 30 death) and 30 controls (10 non-vaccinated+ 20 vaccinated) who were RT-PCR negative inspite of high-risk contact. Next-gen sequencing was done on MiSeq (Illumina) using amplicon-based targeted sequencing approach using a custom-designed panel to sequence all the exons of ACE2 gene. SPSS ver.26 was used for analysis. The following ACE2 variants were identified on the Local Run Manager (LRM) software from Illumina: (i) rs2285666 (c.439+4G>A) splice region variant, in controls (60%) and Patients (45.8%), (ii) rs4646140 (c.802+24G>A) intronic variant in 4/114 patients and 1/30 controls, (iii) rs41303171 ( c.2158A>G) missense variant in 2/114 patients, (iv) rs536749578 (c.2114+9T>C) intron variant, (v) rs763994205 (c.868A>C) missense variant and (vi) rs7595907 (c.656G>A) missense variant in 1/114 patient each only. rs2285666 was observed in equal frequency ( 60%) in vaccinated and non-vaccinated controls. rs2285666 was observed amongst different severity groups: Mild (80.95%), Moderate (37.93%), Severe (44.11%), and Death (56.67%) revealing association with disease severity, probably having a protective effect. However, these results need to be confirmed on larger sample sizes.

PRIMARY LUNG MALIGNANCY PRESENTING AS RARE CUTANEOUS METASTASIS TO EYELID

SESSION TITLE: Unusual Cancer Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Cutaneous lesions may present as a clue to an internal malignancy and provide an easily accessible site for tissue confirmation. We present a case of an eyelid metastatic lesion presenting as an initial sign of primary pulmonary malignancy. CASE PRESENTATION: A 67-year-old woman with past medical history of SARS-COVID-2 pneumonia six months ago and reformed smoker (26 pack year) who quit 27 years ago, presented to the primary care physician's office with a chief complaint of a small right upper eyelid margin (base of eyelashes) lesion (Figure 1A), and ongoing nonproductive cough and fatigue since diagnosis of SARS-COVID-2 pneumonia. The eyelid lesion appeared two weeks prior and had quickly grown in size. The lesion was associated with mild itching, but without any associated pain, discharge, or bleeding. She also complained of left elbow and foot pain but denied fever, chills, rigors, hemoptysis, pleurisy, and weight loss. Physical examination was negative for lymphadenopathy. Chest x-ray revealed a hazy left upper lobe opacity. Urine antigen for blastomycoses and histoplasma were negative. Rheumatoid factor, erythrocyte sedimentation rate, C reactive protein, QuantiFERON TB gold and anti-nuclear and cyclic citrullinated peptide antibodies were negative. Computed tomography of chest revealed a left upper lobe 3.7 x 5.4 x 5.6 cm mass, numerous bilateral ground glass opacities, and scattered (less than 5 mm) nodules (Figure 1B). Simultaneously, the patient was evaluated by an ophthalmologist for excision of the eyelid lesion. Histopathological evaluation revealed malignancy compatible with metastatic lung adenocarcinoma (Figure 1C) DISCUSSION: While an uncommon presentation, this case highlights the importance of a through history and examination in a patient presenting with pulmonary symptoms with risk factors for a lung malignancy. While she did have imaging that demonstrated lung masses, the diagnosis of lung cancer came not from invasive sampling of these masses, but rather from excision and histopathological evaluation of an eyelid soft tissue mass. Lung cancer is prone to metastasis, however cutaneous manifestations of lung cancer are relatively rare and are more common in the advanced stages of disease, making cutaneous metastasis a poor prognostic factor. In terms of cutaneous metastases, ocular metastases are one of the rarest locations making this a unique presentation. In a patient presenting with pulmonary masses, any concurrent development of new and/or growing skin lesions should be evaluated to rule out metastasis and potentially yield diagnosis. CONCLUSIONS: In patients presenting with concern for a malignant lung process, a skin exam should be completed, and suspicious skin lesions should be biopsied. Although rare, lung malignancies do metastasize to ocular cutaneous tissues and are a marker of more advanced stage of the malignancy. Reference #1: Hidaka T, Ishii Y, Kitamura S. Clinical features of skin metastasis from lung cancer. Intern Med. 1996;35:459-462. Reference #2: Marcoval J, Penin RM, Llatjos R, Martinez-Ballarin, I. Cutaneous metastasis from lung cancer: retrospective analysis of 30 patients. Australas J Dermatol. 2012;53(4):288-290. Reference #3: Abdeen Y, Amireh S, Patel A, Al-Halawani M, Shaaban H, Miller R. Cutaneous metastasis as a first presentation for lung adenocarcinoma. N Am J Med Sci. 2016;8(5): 222-225. DISCLOSURES: No relevant relationships by Gregory Griepentrog No relevant relationships by Chinmay Jani No relevant relationships by Bailey Ray No relevant relationships by Harpreet Singh No relevant relationships by Amit Taneja No relevant relationships by Kara Young

Safety, Feasibility, and Outcome of Percutaneous Dilatational Tracheostomy in Critically Ill COVID-19 Patients ABS0009)

Aim and background: Percutaneous dilatational tracheostomy (PDT) may improve outcomes in critically ill COVID-19 patients on mechanical ventilation. However, the timing of performing tracheostomy may be controversial and it is an aerosol-generating procedure with potential risk for viral exposure to the healthcare workers. Materials and methods: An operational protocol for performing PDT was made and subsequently followed in a designated COVID-19 ICU. Critically ill adult patients on a mechanical ventilator who underwent PDT were included in this retrospective cohort study. Case files were retrospectively reviewed and patient characteristics, clinical outcome, and procedure-related details were noted. Results: Forty-one patients were included in the analysis. The median age was 49 years, and 41.5% of patients were females. The median duration of mechanical ventilation before tracheostomy was 10 (8-16) days and the median (IQR) PaO2/FiO2 ratio on the day of PDT was 155 [125-180] mm Hg. 48.8% of patients had transient desaturation to SpO2 <90%. 41.5% survived ICU discharge. None of the health care providers involved developed any symptoms of COVID-19. Conclusion: Early PDT may improve outcomes in critically ill COVID-19 patients and should be considered safe for health care providers. .

Prognostic Role of Different Severity Indexes in COVID-19 Pneumonia: A Retrospective Study

Aim and background: Approximately 50% of the COVID-19 patients require intensive care due to pneumonia and respiratory failure. The CURB-65,3 CRB-654, A-DROP5 score, and Pneumonia Severity Index (PSI) scoring systems are established prognostic tools for community-acquired pneumonia (CAP). Similarly, the qSOFA score is a prognostic tool for critically ill patients. However, the utility of these scoring systems in the context of COVID-19 is yet to be established as a predictive tool for triage by means of rapid decision-making and preventive measures to combat the ongoing pandemic. Materials and methods: This observational, retrospective cohort study was conducted AIIMS, New Delhi during May to June, 2021 after obtaining institutional ethical committee approval (IEC-860/4.9.2020). Only the RT-PCR-proven patients >18 years among the institutionalized patients with severe acute respiratory infections (SARI) were included. Results: Out of the 235 included patients, 27.2% of patients required mechanical ventilation, and the overall period of hospital stay was 9 (5-13) days. While the SMART COP score with an AUC of 0.812 (95% CI 0.752-0.871), the PSI score with an AUC of 0.819 (95% CI 0.762- 0.877) obtained significant results for mortality, the A drop score with an AUC of 0.92 (0.897-0.954), and both the PSI (AUC of 0.964;95% CI 0.928-1.000), and the SMART COP (AUC of 0.925;95% CI 0.887-0.962) acquired the best result for intubation and thereby requirement of mechanical ventilation. Conclusion: Although the outcome of COVID-19 depends upon multiple factors the SMART COP, PSI, and A-drop scoring systems seem to be promising predictive tools for morbidity and mortality.

Implementing Affordable Socially Assistive Pet Robots in Care Homes Before and During the COVID-19 Pandemic: Stratified Cluster Randomized Controlled Trial and Mixed Methods Study.

BACKGROUND: Robot pets may assist in the challenges of supporting an aging population with growing dementia prevalence. Prior work has focused on the impacts of the robot seal Paro on older adult well-being, but recent studies have suggested the good acceptability and implementation feasibility of more affordable devices (Joy for All [JfA] cats and dogs). OBJECTIVE: We aimed to address the limited effectiveness research on JfA devices. METHODS: We conducted an 8-month, stratified, cluster randomized controlled trial in 8 care homes in Cornwall, United Kingdom. Over 4 months, 4 care homes each received 2 JfA devices (1 cat and 1 dog; intervention group), and 4 homes received care as usual (control group). Psychometrics were collected before and after the intervention to compare the change from baseline to follow-up between the groups. In the final 4 months, all 8 care homes received devices, but only qualitative data were collected owing to COVID-19 and reduced capacity. The primary outcome was neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI] Nursing Home version). Care provider burden was a secondary outcome (occupational disruptiveness NPI subscale), alongside the Challenging Behavior scale, the Holden communication scale, the Campaign to End Loneliness questionnaire, and medication use. Qualitative data were collected through care staff observation calendars and end-of-study interviews to understand use, experience, and impact. We also collected demographic data and assessed dementia severity. In total, 253 residents had robot interaction opportunities, and 83 were consented for direct data collection. RESULTS: There was a significant difference in the total change from baseline to follow-up between the intervention and control groups for NPI (P<.001) and occupational disruptiveness (P=.03). Neuropsychiatric symptoms increased in the control group and decreased in the intervention group. No significant difference was seen for communication issues or challenging behavior. For NPI subdomains, there were significant differences from baseline to follow-up in delusions (P=.03), depression (P=.01), anxiety (P=.001), elation (P=.02), and apathy (P=.009), all of which decreased in the intervention group and increased slightly in the control group. The summative impact results suggested that most residents (46/54, 85%) who interacted with robots experienced a positive impact. Those who interacted had significantly higher dementia severity scores (P=.001). The qualitative results suggested good adoption, acceptability, and suitability for subjectively lonely individuals and lack of a novelty effect through sustained use, and demonstrated that the reasons for use were entertainment, anxiety, and agitation. CONCLUSIONS: Affordable robot pets hold potential for improving the well-being of care home residents and people with dementia, including reducing neuropsychiatric symptoms and occupational disruptiveness. This work suggests no novelty effect and contributes toward understanding robot pet suitability. Moreover, interactions were more common among residents with more moderate/severe dementia and those subjectively lonely. TRIAL REGISTRATION: ClinicalTrials.gov NCT04168463; https://www.clinicaltrials.gov/ct2/show/NCT04168463.

A Scoping Review of Digital Twins in the Context of the Covid-19 Pandemic.

Background: Digital Twins (DTs), virtual copies of physical entities, are a promising tool to help manage and predict outbreaks of Covid-19. By providing a detailed model of each patient, DTs can be used to determine what method of care will be most effective for that individual. The improvement in patient experience and care delivery will help to reduce demand on healthcare services and to improve hospital management. Objectives: The aim of this study is to address 2 research questions: (1) How effective are DTs in predicting and managing infectious diseases such as Covid-19? and (2) What are the prospects and challenges associated with the use of DTs in healthcare? Methods: The review was structured according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework. Titles and abstracts of references in PubMed, IEEE Xplore, Scopus, ScienceDirect and Google Scholar were searched using selected keywords (relating to digital twins, healthcare and Covid-19). The papers were screened in accordance with the inclusion and exclusion criteria so that all papers published in English relating to the use of digital twins in healthcare were included. A narrative synthesis was used to analyse the included papers. Results: Eighteen papers met the inclusion criteria and were included in the review. None of the included papers examined the use of DTs in the context of Covid-19, or infectious disease outbreaks in general. Academic research about the applications, opportunities and challenges of DT technology in healthcare in general was found to be in early stages. Conclusions: The review identifies a need for further research into the use of DTs in healthcare, particularly in the context of infectious disease outbreaks. Based on frameworks identified during the review, this paper presents a preliminary conceptual framework for the use of DTs for hospital management during the Covid-19 outbreak to address this research gap.

Scope, context and quality of telerehabilitation guidelines for physical disabilities: a scoping review

ObjectiveTo identify the available guidance and training to implement telerehabilitation movement assessments for people (adults and children) with a physical disability, including those recovering from COVID-19.DesignRapid scoping review.Included sources and articlesPubMed, CINAHL, PsychInfo, Cochrane, Embase, Web of Science, PEDro, UK Health Forum, WHO, National Archives and NHS England were searched using the participant–concept–context framework from 2015 to August 2020. Primary studies that recruited individuals with physical disabilities and guidance documents aimed at providers to implement movement-related telerehabilitation were included.Results23 articles (11 primary research studies, 3 systematic reviews and 9 guidance documents) were included out of 7857 that were identified from the literature search. Two main issues were found: (1) telerehabilitation guidance (from both research studies and guidance documents) was not specific to movement-related assessment and (2) most primary research studies provided neither guidance nor training of movement-specific assessment to practitioners. Of the COVID-19 related guidance, two articles reported COVID-19 management that only referred to identifying COVID-19 status without references to specific movement-related guidance.ConclusionsTelerehabilitation guidance and training have existed pre-COVID-19, yet the lack of specific movement-related information and provider support is surprising. This gap must be addressed to optimise effective implementation of remote assessments for those with physical disabilities.Review registrationOpen Science Framework: osf.io/vm6sp.

Telerehabilitation for physical disabilities and movement impairment: A service evaluation in South West England.

RATIONALE, AIMS AND OBJECTIVES: Telerehabilitation was used to ensure continued provision of care during the COVID-19 pandemic, but there was a lack of guidance on how to use it safely and effectively for people with physical disabilities and movement impairment. In this service evaluation, we aimed to collate information on practitioner and patient experiences, challenges and facilitators, and examples of best practice to inform the development of an online toolkit and training package. METHODS: Guided discussions were carried out with 44 practitioners, 7 patients and 2 carers from five health and social care organisations in South West England, and analysed thematically. RESULTS: Practitioners and patients had positive experiences of telerehabilitation and were optimistic about its future use. Recognized benefits for people with physical disabilities included greater flexibility, reduced travel and fatigue, having appointments in a familiar environment and ease of involving family members. Challenges encountered were: technological (usability issues, access to technology and digital skills); difficulties seeing or hearing patients; the lack of 'hands-on' care; and safety concerns. Facilitators were supported by colleagues or digital champions, and family members or carers who could assist patients during their appointments. Key themes in best practice were: person-centred and tailored care; clear and open communication and observation and preparation and planning. Practitioners shared tips for remote physical assessments; for example, making use of patient-reported outcomes, and asking patients to wear bright and contrasting coloured clothing to make it easier to see movement. CONCLUSION: Telerehabilitation holds promise in health and social care, but it is necessary to share good practice to ensure it is safe, effective and accessible. We collated information and recommendations that informed the content of the Telerehab Toolkit (https://www.plymouth.ac.uk/research/telerehab), a practical resource for practitioners, patients and carers, with a focus on remote assessment and management of physical disabilities and movement impairment.

Exploring Patient and Staff Experiences With Video Consultations During COVID-19 in an English Outpatient Care Setting: Secondary Data Analysis of Routinely Collected Feedback Data.

BACKGROUND: Video consultations (VCs) were rapidly implemented in response to COVID-19 despite modest progress before. OBJECTIVE: We aim to explore staff and patient experiences with VCs implemented during COVID-19 and use feedback insights to support quality improvement and service development. METHODS: Secondary data analysis was conducted on 955 patient and 521 staff responses (from 4234 consultations; 955/4234, 22.6% and 521/4234, 12.3%, respectively) routinely collected following a VC between June and July 2020 in a rural, older adult, and outpatient care setting at a National Health Service Trust. Responses were summarized using descriptive statistics and inductive thematic analysis and presented to Trust stakeholders. RESULTS: Most patients (890/955, 93.2%) reported having good (210/955, 22%) or very good (680/955, 71.2%) experience with VCs and felt listened to and understood (904/955, 94.7%). Most patients accessed their VC alone (806/955, 84.4%) except for those aged ≥71 years (23/58, 40%), with ease of joining VCs negatively associated with age (P<.001). Despite more difficulties joining, older adults were most likely to be satisfied with the technology (46/58, 79%). Patients and staff generally felt that patients' needs had been met (860/955, 90.1% and 453/521, 86.9%, respectively), although staff appeared to overestimate patient dissatisfaction with VC outcomes (P=.02). Patients (848/955, 88.8%) and staff (419/521, 80.5%) felt able to communicate everything they wanted, although patients were significantly more positive than staff (P<.001). Patient satisfaction with communication was positively associated with technical performance satisfaction (P<.001). Most staff members (466/521, 89.4%) reported positive (185/521, 35.5%) or very positive (281/521, 53.9%) experiences with joining and managing VCs. Staff reported reductions in carbon footprint (380/521, 72.9%) and time (373/521, 71.6%). Most patients (880/955, 92.1%) would choose VCs again. We identified three themes in responses: barriers, including technological difficulties, patient information, and suitability concerns; potential benefits, including reduced stress, enhanced accessibility, cost, and time savings; and suggested improvements, including trial calls, turning music off, photo uploads, expanding written character limit, supporting other internet browsers, and shared online screens. This routine feedback, including evidence to suggest that patients were more satisfied than clinicians had anticipated, was presented to relevant Trust stakeholders, allowing for improved processes and supporting the development of a business case to inform the Trust decision on continuing VCs beyond COVID-19 restrictions. CONCLUSIONS: The findings highlight the importance of regularly reviewing and responding to routine feedback following digital service implementation. The feedback helped the Trust improve the VC service, challenge clinician-held assumptions about patient experience, and inform future use of VCs. It has focused improvement efforts on patient information; technological improvements such as blurred backgrounds and interactive whiteboards; and responding to the needs of patients with dementia, communication or cognitive impairment, or lack of appropriate technology. These findings have implications for other health care providers.

Use and usability of GP online services: a mixed-methods sequential study, before and during the COVID-19 pandemic, based on qualitative interviews, analysis of routine eConsult usage and feedback data, and assessment of GP websites in Devon and Cornwall, England.

OBJECTIVES: We explored use and usability of general practitioner (GP) online services. SETTING: Devon and Cornwall, England. DESIGN: Mixed-methods sequential study based on qualitative interviews, analysis of routine eConsult usage and feedback data, and assessment of GP websites. METHODS: First, we interviewed 32 staff and 18 patients from seven practices in June 2018. Second, we used routinely collected consultation meta-data and, third, patient feedback data for all practices using eConsult from June 2018 to March 2021. Lastly, we examined GP websites' usability in January 2020 and September 2021. RESULTS: Interviews suggested practices infrequently involved patients in eConsult implementation. Some patients 'gamed' the system to achieve what they wanted. Usage data showed a major increase in eConsult resulting from COVID-19. Women used eConsult twice as much as men. Older had similar eConsult consultation rates to younger patients. Patient feedback forms were completed for fewer than 3% of consultations. Patients were mostly satisfied with eConsult but some had concerns about its length and repetitiveness, lack of continuity over time and between eConsult and medical records. We did not find clear evidence that patients' suggested improvements were acted on. Finally, few GP websites met accessibility guidelines and may hinder access to online national services such as eConsult. CONCLUSION: Given that, face to face, older people consult more, usage data suggest that older people have reduced online access. That the female-to-male ratio of eConsult use use was even greater than 'traditional' face-to-face ratio was unexpected and needs further research. Although eConsult collects and uses routine patient feedback to improve the system, more open systems for patient feedback, such as Care Opinion, may be more effective in helping online systems evolve. Lastly, we question the need for GP websites and suggest that national or regional services are better placed to maintain accessible services.

Changing practice in the management of non-palpable breast lesion during pandemic;Early experience using Magseed markers

Background: The Covid Pandemic has influenced how cancer surgeries are performed and their pre-operative management to allow appropriate social distancing and self-isolation prior to Surgery. With the requirement of wire localisation of non-palpable breast cancers/ lesions on the day of surgery and non-availability of mammogram and ultrasound machine in an isolated zone, we embarked on localisation of non-palpable breast lesions using MagseedR markers and SentimagR localisation system. We describe our initial experience in the management of these cancers and diagnostic excision biopsies using Magseed. Materials and Methods: Forty consecutive female patients, median age 61 (range 36-84) years underwent Magseed insertion for diagnostic excision biopsy (n=4) and breast conservation surgery (WLE;n= 36). Check mammograms were performed following Magseed insertion to confirm appropriate localisation. During the initial audit of 16 patients, one Magseed guided WLE and sentinel node biopsy was abandoned due to erratic signal strength on the day of surgery and underwent surgery with wire localisation on a later date. Subsequently all cases had Magseed signals confirmed following insertion in the radiology department along with check mammograms. Results: Thirty-nine patients underwent successful breast surgery (Magseed in intra-operative specimen X-ray) with standard axillary procedures (29 sentinel node biopsy, 2 axillary node clearance). The median time from magseed insertion to surgery was 13 (range 3-38) days. The lesions were invasive neoplasm +/- insitu (DCIS) disease (n= 32), DCIS (n=5), and papilloma (n=3). The median overall tumour size was 20 (range 3-38) mm and on postop histology was 17 (2-50) mm. Six patients required further re-excision for margin positivity with DCIS;margins were clear after single cavity shave(n=4) and two patients underwent mastectomy subsequently. Conclusions: Magseed localisation have given us significant flexibility in the management of non-palpable breast cancer and indeterminate lesions requiring diagnostic biopsy during the Covid pandemic. Initial audit suggests usefulness of confirming adequate Magseed signal in the radiology department along with check mammogram during the early learning curve.

Face to face versus virtual assessment - A survey on Indian medical students' perception during COVID-19 pandemic: A cross-sectional study

Background: Assessment has a very important role in curricular development by motivating students and target setting, providing appropriate feedback and quality assurance. During COVID-19 pandemic-induced lockdown, most of the medical schools throughout the world including India had to undergo a paradigm shift from face to face to online mode in medical education and assessment. This study was planned to assess and analyze the perception and opinion of 1 st -year medical students from all over the country regarding the online assessment (OA) process that emerged during the COVID 19 pandemic. We also tried to find out the preferred resources that the students wanted to access via online mode and any major hindrance they faced. Methodology: It was a cross-sectional, Internet based, online survey conducted on 1 st year medical students from all over India. Result: Students preferred the traditional (face to face) examinations over the OA in terms of usefulness, motivation, answering long answer questions, adequacy of allotted time, and ease of performance. However, they favored OA in terms of examination anxiety, examiner bias, and answering the objective type of questions. The lack of good Internet connectivity was considered a major hindrance. Conclusion: This information might be helpful for respective authorities to establish an effective online platform which could deliver an authentic and valid OA in future during any crisis. © 2022 Medknow. All rights reserved.

Post-COVID-19 HSV encephalitis: a review.

BACKGROUND: Herpes simplex virus encephalitis (HSVE) is one of the most common infectious causes of sporadic encephalitis. Coronavirus disease (COVID-19) has been associated with immune dysregulation of the host that might increase the risk of infections like HSVE following SARS-CoV-2 infection. There is paucity of literature on post COVID-19 HSVE. This study was conducted with the aim of analyzing the clinical presentation, brain imaging, and outcome of patients presenting with HSVE within 6 weeks of COVID-19 and providing a comprehensive review on the possible mechanisms of post-COVID-19 HSVE. METHODS: This observational study included patients who had laboratory-confirmed HSVE (type 1 or type 2) and a history of COVID-19 within the previous 6 weeks. Patients were followed up for 3 months. RESULTS: Eight patients were included and all of them had type 1 HSVE. The mean latency of onset of neurological symptoms from being diagnosed with COVID-19 is 23.87 days and a majority of the patients have received injectable steroids with a mean duration of 6.5 days. Behavioral abnormality was the commonest neurological presentation and typical brain imaging involved T2 FLAIR hyperintensities of the medial temporal lobes. All patients received intravenous acyclovir 10 mg/kg every eight hourly for atleast 14 days. One patient with concomitant rhinocerebral mucormycosis succumbed while the majority had a complete recovery. CONCLUSION: Possible immune dysregulation in COVID-19 may increase the susceptibility of HSVE in patients with a history of recent SARS-CoV-2 infection. The clinical manifestations and laboratory findings of HSVE in such patients are similar to typical HSVE.

Reversible cerebral vasoconstriction syndrome in a patient with COVID-19

COVID-19 infection is well-known to produce different neurological complications, including cerebrovascular diseases. Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by transient segmental vasoconstriction of the cerebral vasculature, has been rarely reported in association with COVID-19 infection. The causative agent, the novel coronavirus (SARS-CoV-2), binds to the angiotensin-converting enzyme 2 (ACE-2) receptors for its entry into the host cell. This leads to downregulation of the ACE-2 and increased activity of the renin-angiotensin-aldosterone (RAAS) axis resulting in sympathetic overactivity and vasoconstriction. This might be the possible mechanism of RCVS in COVID-19. We hereby report a case of RCVS occurring in a SARS-CoV-2infected patient. This was a 38-year-old male without any comorbidities or risk factors, who presented with headache and confusion. His SARS-CoV-2 RT-PCR was positive. MRI of the brain was normal but cerebral angiography revealed segmental vasoconstriction in bilateral middle cerebral arteries and the terminal part of the internal carotid arteries, which resolved almost completely after 2 weeks. He was treated with oral nimodipine 60 mg every 6 hourly. A database search revealed 2 previous cases of RCVS associated with COVID-19. In conclusion, RCVS is a rare complication of COVID-19. It is possibly under-recognized as only a few COVID-19 patients with headaches undergo cerebral angiography especially when parenchymal brain imaging is normal.

Inhibition of De Novo Pyrimidine Synthesis Depletes Acute Myleogenous Leukemia Stem Cells (LSCs) Burden and Triggers Apoptosis and Differentiation Associated with Oxidative Stress

Background: De novo nucleotide synthesis is necessary to meet the enormous demand for nucleotides, other macromolecules associated with acute myeloid leukemia (AML) progression 1, 2, 34. Hence, we hypothesized that targeting de novo nucleotide synthesis would lead to the depletion of the nucleotide pool, pyrimidine starvation and increase oxidative stress preferentially in leukemic cells compared to their non-malignant counterparts, impacting proliferative and differentiation pathways. Emvododstat (PTC299) is an inhibitor of dihydroorotate dehydrogenase (DHODH), a rate-limiting enzyme for de novo pyrimidine nucleotide synthesis that is currently in a clinical trial for the treatment of AML. Objectives: The goals of these studies were to understand the emvododstat-mediated effects on leukemia growth, differentiation and impact on Leukemia Stem Cells(LSCs). Comprehensive analyses of mitochondrial function, metabolic signaling in PI3K/AKT pathways, apoptotic signatures, and DNA damage responses were carried out. The rationale for clinical testing emvododstat was confirmed in an AML-PDX model. Results: Emvododstat treatment in cytarabine-resistant AML cells and primary AML blasts induced apoptosis, differentiation, and reduced proliferation, with corresponding decreased in cell number and increases in annexin V- and CD14-positive cells. Indeed, the inhibition of de novo nucleotide synthesis compromises the dynamic metabolic landscape and mitochondrial function, as indicated by alterations in the oxygen consumption rate (OCR) and mitochondrial ROS/membrane potential and corresponding differentiation, apoptosis, and/or inhibition of proliferation of LSCs. These effects can be reversed by the addition of exogenous uridine and orotate. Further immunoblotting and mass cytometry (CyTOF) analyses demonstrated changes in apoptotic and cell signaling proteins (cleaved PARP, cleaved caspase-3) and DNA damage responses (TP53, γH2AX) and PI3/AKT pathway downregulation in response to emvododstat. Importantly, emvododstat treatment reduced leukemic cell burden in a mouse model of AML PDX ( Complex karyotype, mutation in ASXL1, IDH2, NRAS), decreased levels of leukemia stem cells frequency (1 in 522,460 Vs 1 in 3,623,599 in vehicle vs emvododstat treated mice), and improved survival. The median survival 40 days vs. 30 days, P=0.0002 in primary transplantation and 36 days vs 53.5 days, P=0.005 in secondary transpantation in a PDX mouse model of human AML. This corresponded with a reduction in the bone marrow burden of leukemia and increased expression of differentiation markers in mice treated with emvododstat (Fig. 1). These data demonstrate effect of emvododstat on mitochondrial functions. Conclusion: Inhibition of de novo pyrimidine synthesis triggers differentiation, apoptosis, and depletes LSCs in AML models. Emvododstat is a novel dihydroorotate dehydrogenase inhibitor being tested in a clinical trial for the treatment of myeloid malignancies and COVID-19. Keywords: AML, emvododstat, DHODH, apoptosis, differentiation References: 1 Thomas, D. & Majeti, R. Biology and relevance of human acute myeloid leukemia stem cells. Blood 129, 1577-1585, doi:10.1182/blood-2016-10-696054 (2017). 2 Quek, L. et al. Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. The Journal of experimental medicine 213, 1513-1535, doi:10.1084/jem.20151775 (2016). 3 Villa, E., Ali, E. S., Sahu, U. & Ben-Sahra, I. Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides. Cancers (Basel) 11, doi:10.3390/cancers11050688 (2019). 4 DeBerardinis, R. J. & Chandel, N. S. Fundamentals of cancer metabolism. Sci Adv 2, e1600200, doi:10.1126/sciadv.1600200 (2016). [Formula presented] Disclosures: Weetall: PTC therapeutics: Current Employment. Sheedy: PTC therapeutics: Current Employment. Ray: PTC therapeutics: Current Employment. Andreeff: Karyopharm: Research Funding;AstraZeneca: Research Funding;Oxford Biomedica UK: Research Funding;Aptose: Consultancy;Daiich -Sankyo: Consultancy, Research Funding;Syndax: Consultancy;Breast Cancer Research Foundation: Research Funding;Reata, Aptose, Eutropics, SentiBio;Chimerix, Oncolyze: Current holder of individual stocks in a privately-held company;Novartis, Cancer UK;Leukemia & Lymphoma Society (LLS), German Research Council;NCI-RDCRN (Rare Disease Clin Network), CLL Foundation;Novartis: Membership on an entity's Board of Directors or advisory committees;Senti-Bio: Consultancy;Medicxi: Consultancy;ONO Pharmaceuticals: Research Funding;Amgen: Research Funding;Glycomimetics: Consultancy. Borthakur: ArgenX: Membership on an entity's Board of Directors or advisory committees;Protagonist: Consultancy;Astex: Research Funding;University of Texas MD Anderson Cancer Center: Current Employment;Ryvu: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy.

Parents' experiences with a sick or injured child during the COVID-19 lockdown: an online survey in the Netherlands.

OBJECTIVE: To assess the impact of the COVID-19 lockdown on parents' health-seeking behaviour and care for a sick or injured child in the Netherlands. DESIGN AND SETTING: An online survey on parents' experiences with a sick or injured child during the COVID-19 lockdown periods was disseminated through social media. PARTICIPANTS: Parents living in the Netherlands with a sick or injured child during the lockdown periods from March to June 2020 and from December 2020 to February 2021 were eligible to participate. OUTCOME MEASURES: Descriptive statistics and thematic analysis were used to analyse family and children's characteristics, parents' response to a sick or injured child, and the perceived impact of the lockdown on child's severity of illness and treatment reported by parents. Analyses were stratified for children with and without chronic conditions. RESULTS: Of the 105 parents who completed the survey, 83% reported they would have sought medical help before lockdown compared with 88% who did seek help during lockdown for the same specific medical problem. Parents reported that changes in health services affected their child's severity of illness (31%) and their treatment (39%), especially for children with chronic conditions. These changes included less availability of healthcare services and long waiting lists, which mostly led to worsening of the child's illness. During lockdown, there was no change in health-seeking behaviour by parents of children with a chronic condition (N=51) compared with parents of children without a chronic condition. CONCLUSION: Parents in the Netherlands who completed the survey were not deterred from seeking medical help for their sick or injured child during the COVID-19 lockdown periods. However, changes in health services affected child's severity of illness and treatment, especially for children with chronic conditions.