Physicians' mental health and coping during the COVID-19 pandemic: One year exploration.

Numerous cross-sectional studies have examined physicians' health and coping during the COVID-19 pandemic, while longitudinal studies are lacking. This study explores the progression over one year of physicians' physical and mental health symptoms, their strategies used to cope and discusses coping strategies in relation to physical and mental health symptoms. Two surveys, one year apart, exploring physicians' physical, mental health symptoms and employed coping strategies were sent to all physicians practicing in the province of Saskatchewan, Canada. A total of 117 physicians participated in Round I (RI) (November 2020-January 2021) and 158 participated in Round II (RII) (October 2021-February 2022). Physicians' physical and mental health symptoms remained high, irrespective of their specialty or COVID-19 exposure. COVID-related Post-Traumatic Stress Disorder increased by five times at RII (p = 0.02). In RI anxiety was most prevalent in middle-aged females. In RII depression was most prevalent in physicians with no children. Most coping was adaptive (90%) and included Behavioural, Relational, Cognitive, Spiritual, and Interventional strategies. After one-year, Spiritual coping decreased, while Interventional coping increased by eight times (p = 0.01). Despite efforts to employ adaptive coping, physicians' rates of psychological and physical health difficulties remained high or worsened over one year, offering insight into the protracted health care crisis, and the need for solutions. Our observation of physicians' needs for additional supports, camaraderie and appreciation as well as the shift in coping strategies as the pandemic progressed, offer targets for interventions meant to promote recovery.

Doctors' Professional and Personal Reflections: A Qualitative Exploration of Physicians' Views and Coping during the COVID-19 Pandemic.

Numerous studies have examined the risks for anxiety and depression experienced by physicians during the COVID-19 pandemic. Still, qualitative studies investigating physicians' views, and their discovered strengths, are lacking. Our research fills this gap by exploring professional and personal reflections developed by physicians from various specialties during the pandemic. Semi-structured interviews were conducted with physicians practicing in the province of Saskatchewan, Canada, during November 2020-July 2021. Thematic analysis identified core themes and subthemes. Seventeen physicians, including nine males and eight females, from eleven specialties completed the interviews. The pandemic brought to the forefront life's temporality and a new appreciation for life, work, and each other. Most physicians found strength in values, such as gratitude, solidarity, and faith in human potential, to anchor them professionally and personally. A new need for personal fulfilment and hybrid care emerged. Negative feelings of anger, fear, uncertainty, and frustration were due to overwhelming pressures, while feelings of injustice and betrayal were caused by human or system failures. The physicians' appreciation for life and family and their faith in humanity and science were the primary coping strategies used to build adaptation and overcome negative emotions. These reflections are summarized, and implications for prevention and resilience are discussed.

A beginner's guide to RT-PCR, qPCR and RT-qPCR

The development of the polymerase chain reaction (PCR), for which Kary Mullis received the 1992 Novel Prize in Chemistry, revolutionized molecular biology. At around the time that prize was awarded, research was being carried out by Russel Higuchi which led to the discovery that PCR can be monitored using fluorescent probes, facilitating quantitative real-time PCR (qPCR). In addition, the earlier discovery of reverse transcriptase (in 1970) laid the groundwork for the development of RT-PCR (used in molecular cloning). The latter can be coupled to qPCR, termed RT-qPCR, allowing analysis of gene expression through messenger RNA (mRNA) quantitation. These techniques and their applications have transformed life science research and clinical diagnosis.Copyright © The Authors.

ImageCLEF 2023 Highlight: Multimedia Retrieval in Medical, Social Media and Content Recommendation Applications

In this paper, we provide an overview of the upcoming ImageCLEF campaign. ImageCLEF is part of the CLEF Conference and Labs of the Evaluation Forum since 2003. ImageCLEF, the Multimedia Retrieval task in CLEF, is an ongoing evaluation initiative that promotes the evaluation of technologies for annotation, indexing, and retrieval of multimodal data with the aim of providing information access to large collections of data in various usage scenarios and domains. In its 21st edition, ImageCLEF 2023 will have four main tasks: (i) a Medical task addressing automatic image captioning, synthetic medical images created with GANs, Visual Question Answering for colonoscopy images, and medical dialogue summarization;(ii) an Aware task addressing the prediction of real-life consequences of online photo sharing;(iii) a Fusion task addressing late fusion techniques based on the expertise of a pool of classifiers;and (iv) a Recommending task addressing cultural heritage content-recommendation. In 2022, ImageCLEF received the participation of over 25 groups submitting more than 258 runs. These numbers show the impact of the campaign. With the COVID-19 pandemic now over, we expect that the interest in participating, especially at the physical CLEF sessions, will increase significantly in 2023. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

The African Union's Self-Financing-Mechanism: A Critical Analysis in terms of the World Trade Organisation's Rules and Regulations

The purpose of this paper is to critically analyse from a theoretical perspective the compatibility of the African Union's (AU's) self-financing mechanism (SFM) with the rules and regulations of the World Trade Organisation (WTO) Most-Favoured-Nation (MFN) principle, which forms an integral part of the anti-discrimination provisions. The AU consists of 55 African countries, most of them members of the WTO. The SFM agreed is in the form of a 0.2 per cent levy applied to all eligible goods imported from a non-AU member state into the territory of an AU member state. As most of the AU member states (AUMSs) are WTO members, they must adhere to all the rules and regulations of the WTO. It is against this backdrop that this paper analyses the AU SFM against the relevant WTO rules and regulations. Most importantly this paper will provide recommendations for the compatibility of the AUs SFM in terms of the existing WTO rules and principles, such as the operation of the Differential and More Favourable Treatment, Reciprocity and Fuller Participation of Developing Countries, more commonly referred to as the Enabling Clause, given the WTOs general classification of all African countries as developing or least developed countries. The need for the AU to be self-sustainable financially in order for it to achieve its goals and objectives has most recently been reinforced.by the economic repercussions of the COVID-19 pandemic both locally and internationally. © 2022, North-West Unversity. All rights reserved.

C-POST Protocol Update: A Phase 3, Randomized, Double-Blind Study of Adjuvant Cemiplimab vs. Placebo Post Surgery and Radiation Therapy in Patients with High-Risk Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with an incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is >95%, some patients have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Postoperative radiation therapy (RT) is recommended for these patients, but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for patients with high-risk CSCC. Here, we provide a summary of the most recent study protocol amendment. C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for patients with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50 Gy, within 10 weeks before randomization) (NCT03969004). Patients with at least one of the following high-risk features are eligible: (1) nodal disease with (a) extracapsular extension and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of extracapsular extension;(2) in-transit metastases;(3) T4 lesion;(4) perineural invasion;and (5) recurrent CSCC with at least one other risk factor. Patients with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), patients are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), patients in the placebo arm who experience disease recurrence and patients in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. The trial is expected to enroll 412 patients from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival;secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic. Not applicable (trial in progress) Not applicable (trial in progress) [ FROM AUTHOR] Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

C-POST protocol update: A phase 3, randomized, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation therapy (RT) in patients (pts) with high-risk cutaneous squamous cell carcinoma (CSCC)

Background: CSCC is the second most common skin cancer with an estimated incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is > 95%, some pts have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension (ECE), and prior treatment. Postoperative RT is recommended for these pts but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for pts with high-risk CSCC. Here, we provide summary of the most recent study protocol amendment. Methods: C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50Gy, within 10 weeks before randomization) (NCT03969004). Pts with at least one of the following high-risk features are eligible: (1) nodal disease with (a) ECE and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of ECE;(2) in-transit metastases;(3) T4 lesion;(4) perineural invasion;and (5) recurrent CSCC with at least one other risk factor. Pts with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), pts are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence and pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab for up to 96 weeks. The trial is expected to enrol 412 pts from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival;secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic.

Potential of the triad of fatty acids, polyphenols, and prebiotics from cucurbita against COVID-19 in diabetic patients: A review

Though the scientific community of the entire world has been struggling to create preventive and therapeutic drugs for coronavirus disease 2019 (COVID-19), the role of nutraceuticals has been hitherto neglected. Established role of fatty acids and polyphenols in combating lifestyle disease can be harnessed to play a significant role in the prevention of this disease. The synergistic effect of these phytonutrients and prebiotics is anticipated to prove beneficial for prevention as well as attenuation of COVID-19 infection. Presence of fatty acids, polyphenols and prebiotics in vegetables from the Cucurbitaceae family makes them an attractive choice for being used as a nutritional supplement during COVID-19. These are known to attenuate the excessive immune response which may prove to be beneficial in preventing and mitigating COVID-19. Use of prebiotics to promote the growth of probiotics has also been recommended for the prevention and cure of COVID-19. However, no such report exists in literature that throws light on such role of cucurbita plants. The present review focuses on the role of the triad of fatty acids, prebiotics and polyphenols present in cucurbita plants in controlling systemic inflammation and endothelial damage, the two main etiopathological factors involved in COVID-19. Cucurbita plants are rich in all these components and their inclusion in diet would be an effective strategy to combat COVID-19. The main focus of the review is to discuss the role of various components of the plants of Cucurbita family, taken as dietary component, in prevention and control of the ongoing pandemic COVID19.

Intrathecal inflammatory responses in the absence of SARS-CoV-2 nucleic acid in the CSF of COVID-19 hospitalized patients

Objective: Evaluate SARS-CoV-2 RNA and inflammatory cytokines and chemokines in the CSF of patients with acute COVID-19 and neurologic symptoms, and to compare these to controls and patients with known neurotropic pathogens. Background: Neurologic symptoms have been described in 30-60% of hospitalized patients with Coronavirus Disease 2019 (COVID-19). However, little is known about CSF profiles in these patients. Design/Methods: CSF from twenty-seven consecutive patients with COVID-19 and neurological symptoms was assayed for SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR) and unbiased metagenomic sequencing. Assays for blood brain barrier (BBB) breakdown (CSF:serum albumin ratio (Q-Alb)), and proinflammatory cytokines and chemokines (IL-6, IL-8, IL-15, IL-16, monocyte chemoattractant protein -1 (MCP-1) and monocyte inhibitory protein - 1β (MIP-1β)) were performed in 23 patients and compared to CSF from patients with HIV-1 (16 virally suppressed, 5 unsuppressed), West Nile virus (WNV) (n=4) and 16 healthy controls (HC). Results: Median CSF cell count for COVID-19 patients was 1 white blood cell/μL;two patients were infected with a second pathogen (Neisseria, Cryptococcus neoformans). No CSF samples had detectable SARS-CoV-2 RNA by either detection method. In patients with COVID-19 only, CSF IL-6, IL-8, IL-15, and MIP-1β levels were higher than HC and suppressed HIV (corrected-p < 0.05). MCP-1 and MIP-1β levels were higher, while IL-6, IL-8, IL-15 were similar in COVID-19 compared to WNV patients. Q-Alb correlated with all proinflammatory markers, with IL-6, IL-8, and MIP-1β (r≥0.6, p<0.01) demonstrating the strongest associations. Conclusions: Lack of SARS-CoV-2 RNA in CSF is consistent with pre-existing literature. Evidence of intrathecal proinflammatory markers in a subset of COVID-19 patients with BBB breakdown despite minimal CSF pleocytosis is atypical for neurotropic pathogens.

USE OF AN ADVANCE CARE PLAN CHECKLIST TO IMPROVE COMMUNICATION AND ASSESSMENT OF THE IMPACT ON HOSPITAL READMISSIONS

Introduction Advance care planning (ACP) is a vital part of holistic and person-centred care. It allows formalising of an individual’s wishes and best interests, and avoids unnecessary or unwanted interventions including, potentially, hospital admissions. It is crucial that any decisions or recommendations are communicated to all relevant healthcare professionals to ensure peoples’ wishes are upheld. We developed this project to review and improve documentation and communication on discharge when a decision had been made to limit care to the community and avoid admission. Method A checklist was developed comprising 11 criteria to be documented in the discharge letter and actions to disseminate information including;updating the ReSPECT form and alerting the hospital frailty and community out of hours teams. We carried out a closed loop audit of patients where admission should be avoided and reviewed discharge letters against the criteria. Where patients were readmitted we reviewed the notes to determine whether the admission was appropriate. Results We compared patients discharged between February 2020–February 2021 and then from March–September 2021. 161 and 27 patients were identified respectively. Average age was 84.6 and 87.3 years respectively. In cohort 2 48.1% of patients were readmitted, up from 8.7% during the previous cycle. 33% of admissions in cohort 2 and 38.9% of readmissions in cohort 1 were deemed appropriate. Documentation improved in 10 of the 11 criteria. Average length of stay for readmissions was reduced from 16.7 to 5.7 days. Conclusion As evidenced by our study utilising a checklist has improved documentation and dissemination of ACPs to the Community. This did not lead to a reduction in hospital admissions but this may have been skewed by factors relating to the Covid-19 pandemic. We did find a significant reduction in length of stay for those subsequently readmitted.

A fiber optic-nanophotonic approach to the detection of antibodies and viral particles of COVID-19

Dr. Deborah Birx, the White House Coronavirus Task Force coordinator, told NBC News on "Meet the Press" that "[T]he U.S. needs a 'breakthrough' in coronavirus testing to help screen Americans and get a more accurate picture of the virus' spread." We have been involved with biopathogen detection since the 2001 anthrax attacks and were the first to detect anthrax in real-time. A variation on the laser spectroscopic techniques we developed for the rapid detection of anthrax can be applied to detect the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2 virus). In addition to detecting a single virus, this technique allows us to read its surface protein structure. In particular, we have been conducting research based on a variety of quantum optical approaches aimed at improving our ability to detect Corona Virus Disease-2019 (COVID-19) viral infection. Indeed, the detection of a small concentration of antibodies, after an infection has passed, is a challenging problem. Likewise, the early detection of disease, even before a detectible antibody population has been established, is very important. Our team is researching both aspects of this problem. The paper is written to stimulate the interest ofboth physical and biological scientists in this important problem. It is thus written as a combination of tutorial (review) and future work (preview). We join Prof. Federico Capasso and Editor Dennis Couwenberg in expressing our appreciation to all those working so heroically on all aspects of the COVTD-19 problem. And we thank Drs. Capasso and Couwenberg for their invitation to write this paper. © 2021 Walter de Gruyter GmbH, Berlin/Boston. All rights reserved.

Demand for regional level III neonatal services is not reduced during national COVID lockdowns.

Following the first peak of the COVID-19 pandemic, reports from around the world suggested a reduction in preterm deliveries during lockdown periods. We reviewed preterm admissions to a large tertiary neonatal unit in inner North East London during two United Kingdom (UK) national lockdowns in 2020 and 2021. We found no evidence of difference in admissions during two national lockdowns compared to previous years. Based on these findings, we recommend that neonatal services remain as vigilant and prepared as ever for the unpredictable nature of preterm birth, and their staff protected to provide this highly specialist care.

Neuropathological Features of COVID-19

Objective: To report neuropathological findings and quantify SARS-CoV-2 viral burden for 18 consecutive coronavirus disease 2019 (COVID-19) autopsies. Background: COVID-19 is a respiratory disease caused by SARS-CoV-2, a virus known to infect lung epithelial cells, yet data about SARS-CoV-2 neuropathology in human brain autopsies is limited. Design/Methods: Brain tissue specimens were sampled from 18 subjects (10 standard areas), fixed in formalin, and stained with hematoxylin and eosin for histopathological analysis. SARSCoV-2 immunohistochemistry and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed on 10 brain sections from 2 subjects and 2 sections (medulla and frontal lobe with olfactory nerve) from the remaining 16 subjects. Results: Median age was 62 years (interquartile range, 53 to 75), and 14 patients (78%) were men. Presenting neurologic symptoms were myalgia (n=3), headache (n=2), and decreased taste (n=1);11 received mechanical ventilation. Acute hypoxic injury was detected in cerebrum, hippocampus, and cerebellum in all patients;rare foci of perivascular lymphocytes (n=2) or focal leptomeningeal inflammation (n=1) were also detected. RT-qPCR showed limited evidence of viral RNA. In 10 unique specimens from two subjects, results were equivocal (viral load <5.0 copies/mm3) in 4 and 5 sections, respectively. In the remaining 16 patients, 3 medulla sections and 3 frontal lobe and olfactory sections were positive (5.0 to 59.4 copies/mm3) while the rest were equivocal or negative. SARS-CoV-2 viral load did not correlate with the interval between the onset of symptoms and death or histopathological findings. Immunohistochemical staining for SARS-CoV-2 nucleocapsid protein was negative in neurons, glia, endothelium, and immune cells. Conclusions: Histopathology of brain specimens revealed hypoxia with limited evidence of direct viral damage, including no viral protein. Concordantly, although SARS-CoV-2 was detected by RT-qPCR in some sections, viral load was low and did not correlate with other pathological features.

A fiber optic-nanophotonic approach to the detection of antibodies and viral particles of COVID-19

Dr. Deborah Birx, the White House Coronavirus Task Force coordinator, told NBC News on "Meet the Press"that "[T]he U.S. needs a 'breakthrough' in coronavirus testing to help screen Americans and get a more accurate picture of the virus' spread."We have been involved with biopathogen detection since the 2001 anthrax attacks and were the first to detect anthrax in real-time. A variation on the laser spectroscopic techniques we developed for the rapid detection of anthrax can be applied to detect the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2 virus). In addition to detecting a single virus, this technique allows us to read its surface protein structure. In particular, we have been conducting research based on a variety of quantum optical approaches aimed at improving our ability to detect Corona Virus Disease-2019 (COVID-19) viral infection. Indeed, the detection of a small concentration of antibodies, after an infection has passed, is a challenging problem. Likewise, the early detection of disease, even before a detectible antibody population has been established, is very important. Our team is researching both aspects of this problem. The paper is written to stimulate the interest of both physical and biological scientists in this important problem. It is thus written as a combination of tutorial (review) and future work (preview). We join Prof. Federico Capasso and Editor Dennis Couwenberg in expressing our appreciation to all those working so heroically on all aspects of the COVID-19 problem. And we thank Drs. Capasso and Couwenberg for their invitation to write this paper. © 2020 Navid Rajil et al., published by De Gruyter, Berlin/Boston 2020.

A beginner's guide to RT-PCR, qPCR and RT-qPCR

The development of the polymerase chain reaction (PCR), for which Kary Mullis received the 1992 Novel Prize in Chemistry, revolutionized molecular biology. At around the time that prize was awarded, research was being carried out by Russel Higuchi which led to the discovery that PCR can be monitored using fluorescent probes, facilitating quantitative real-time PCR (qPCR). In addition, the earlier discovery of reverse transcriptase (in 1970) laid the groundwork for the development of RT-PCR (used in molecular cloning). The latter can be coupled to qPCR, termed RT-qPCR, allowing analysis of gene expression through messenger RNA (mRNA) quantitation. These techniques and their applications have transformed life science research and clinical diagnosis.