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Introduction/Aim: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is critical for COVID-19 outcomes. Our objective was to examine the prophylactic potential of IFN treatment to limit viral transmission Methods: A cluster-randomised clinical trial was undertaken to determine effects of IFNbeta-1a treatment on SARS-CoV-2 household transmission (clinicaltrials.gov: NCT04552379). Index cases were identified from confirmed SARS-CoV-2 cases in Santiago, Chile, with 341 index cases and 831 household contacts enrolled. Households received 125 mug subcutaneous pegylated-IFNbeta-1a on days 1, 6, & 11 (172 households, 607 participants), or standard care (169 households, 565 participants). Primary outcomes included: (1) duration of viral shedding in infected cases (IC-INF), (2) transmission to treatment-eligible household contacts (EHC-ITT) at day 11. Result(s): Of 1172 individuals randomised, 53 individuals withdrew from the study (IFNbeta-1a = 35, SOC = 18). Eighty-two households (IFNbeta-1a = 36, SOC = 46) where the index case was SARS-CoV-2 negative on days 1 & 6, or with no SARS-CoV-2 negative contacts at recruitment, were excluded from exploratory analyses. Treatment with IFNbeta-1a: had no effect on duration of viral shedding in the IC-INF population (primary outcome 1), had no effect on transmission of SARS-CoV-2 at day 11 in the EHC-ITT population (primary outcome 2) but an effect was observed in a sensitivity analysis at day 6 (EHC-ITT: OR = 0.493, 95% CI = 0.256-0.949), reduced duration of hospitalisation in the IC-INF population and incidence of hospitalisation in per-protocol index cases (secondary outcome 3). In exploratory frequentist analysis, a significant effect of IFNbeta-1a treatment on SARS-CoV-2 transmission by day 11 (OR = 0.55, 95% CI = 0.36-0.99), and a Bayesian analysis identified a significant reduction in the odds of transmission (OR = -0.85, 95% credible interval = -1.59--0.16). Conclusion(s): Ring prophylaxis with IFNbeta-1a had no effect on duration of viral shedding but reduces the probability of SARS-CoV-2 transmission to uninfected, post-exposure contacts within a household.
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Purpose: The coronavirus disease (COVID-19) has increased food delivery service demand, which generates massive amounts of solid waste, specifically plastic material. Therefore, this study aims to examine the determinants of consumers' intention to reuse food delivery containers (ITR) using the extended theory of planned behavior (TPB). Moral obligation was included as an antecedent, while behavioral expectation (BE) ahead of behavioral intention was an immediate predictor of consumers' pro-environmental behaviors. Design/methodology/approach: The hypotheses were tested on 348 food delivery service users in Malaysia and analyzed using the partial least squares structural equation modeling (PLS-SEM). Findings: The findings indicated that consumers' ITR is directly influenced by perceived behavioral control and attitude. Perceived behavioral control and attitude had a positive partial indirect effect on ITR through BE. Meanwhile, subjective norms and moral obligation had a positive full indirect effect on ITR through BE. Research limitations/implications: The findings can be directly applied to practical situations of food delivery companies and environmental protection organizations managing solid waste among food delivery services. Practical implications: Understanding consumers' ITR could promote practical environmental sustainability. Practically, the study provides insights to the food delivery service industry, policymakers and relevant stakeholders to encourage consumer behavior change by reusing food delivery containers in line with Sustainable Development Goal 12. Originality/value: The study enhances the existing literature by extending TPB with two psychological variables: moral obligation (independent variable) and BE (mediating variable). To the best of the authors' knowledge, this study is the first attempt to empirically investigate BE in consumers' pro-environmental behavioral intention in a high-context culture and developing economy. This study could benefit food and beverage merchants, food delivery companies, governments, non-governmental organizations and pro-environmental behavior researchers in this industry. © 2023, Emerald Publishing Limited.
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This paper attempts to identify the challenges faced by architecture students, learning in an online studio environment during the COVID-19 pandemic. In complying with COVID-19 Standards of Operations (SOPs), schools and universities in Sarawak, Malaysia, were closed and classes were forced to be conducted online. Despite prior integration of ICT-based learning into the architecture curriculum, the Architectural Design Studio subject still utilizes the conventional method for teaching and learning. Normally, Architectural Design Studio is conducted in a physical environment where lecturers would demonstrate critical hands-on skills such as drawing and model-making techniques, and conducting critique sessions and site analysis, all of which require students to participate in-person. Unfortunately, all of these activities were forced to be adapted to facilitate online-and-distanced learning due to the pandemic. As a result, students encountered several problems during the switch to the virtual design studio. The purpose of this study is to recognize the setbacks experienced by students in order to generate solutions that may improve the quality of online Architectural Design Studio. The research employs a quantitative descriptive study conducted using a survey method. The data was collected from undergraduate students from two architectural schools in Sarawak, namely the University of Malaysia, Sarawak (UNIMAS) and the University College of Technology Sarawak (UCTS) via a Google Forms questionnaire distributed to the students through WhatsApp groups. The analysis of students' responses confirms that Architectural Design Studio carried out in the conventional method is more effective than when conducted online. The results indicate that the major disadvantages of the online studio were the lack of infrastructure, poor Internet connection, limitations in project materials and data collection for site analysis, imbalance in levels of digital competency, and inefficacy of doing studio work at home. This paper will identify the current online teaching method's flaws that impede our progress toward a more resilient future in architecture. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
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Purpose: The Coronavirus disease 2019 (COVID-19) pandemic has increased the use of food delivery containers in the food and beverage industry. Based on the theory of planned behavior (TPB), the aim of this paper is twofold: Firstly, it examines the influence of three elements of TPB (attitude, perceived behavioral control and subjective norm) and time pressure on the intention to reuse reusable food delivery containers (ITR). Secondly, it examines ITR as an antecedent to the willingness to pay more for reusable food delivery containers (WTPM). Design/methodology/approach: Data were collected from 401 higher education institution (HEI) students and analyzed using partial least squares structural equation modelling (PLS-SEM). Findings: The study found that the three elements of TPB influenced ITR. Furthermore, the results revealed that ITR directly influenced WTPM. Surprisingly, time pressure did not influence ITR. Originality/value: The research is one of the earliest studies to investigate HEI students' intention to reuse food delivery containers during the COVID-19 pandemic. The study contributes to TPB by presenting a novel, integrated model to explain the independent roles of time pressure and ITR on ITR and WTPM, respectively. Finally, it contributes to the existing body of knowledge on pro-environmental behavior among HEI students and advances methodologically by establishing the PLS-SEM approach. © 2023, Emerald Publishing Limited.
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Background: The purpose of this paper is to describe the effects on preparation for sprinting performance in Hong Kong university-level athletes during the COVID-19 pandemic. Changes in training methods, and well-being of athletes due to COVID-19 pandemic were also investigated. Methods: Using Google Form, the study recall period was established during the closure of sports facilities in Hong Kong (2/2020-2/2021) during the COVID-19 pandemic. Physical state preparation (PSP), Mental state preparation (MSP), Nutritional preparation (NP), and Major changes in training methods (MTM) were analyzed. Results: The results demonstrated no significant mean difference between male and female athletes on the effects of COVID-19 regarding the PSP, MSP, NP, and MTM. However, both males and females were highly disrupted in relation to performance preparation. Conclusions: The pandemic affected physical performance, stress, and mental state, impacted on nutritional regimes, changed training locations and recovery strategies, and lowered training quantity and quality. In addition, athletes received less coaching, and had less accessibility to training equipment. Athletes and coaches should reflect on the effects of the COVID-19 pandemic to address personal training needs, while sports professionals need to carefully prepare themselves for sprinting performance, in relation to the current COVID-19 situation. © 2022 The Author(s).
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Wearing a cloth face mask has been shown to impair exercise performance; it is essential to understand the impact wearing a cloth face mask may have on cognitive performance. Participants completed two maximal cardiopulmonary exercise tests on a cycle ergometer (with and without a cloth face mask) with a concurrent cognitive task. Blood pressure, heart rate, oxygen saturation, perceived exertion, shortness of breath, accuracy, and reaction time were measured at rest, during each exercise stage, and following a 4-minute recovery period. The final sample included 35 adults (age = 26.1 ± 5.8 years; 12 female/23 male). Wearing a cloth face mask was associated with significant decreases in exercise duration (-2:00 ± 3:40 min, P = 0.003), peak measures of maximal oxygen uptake (-818.9 ± 473.3 mL/min, -19.0 ± 48 mL·min-1·kg-1, P < 0.001), respiratory exchange ratio (-0.04 ± 0.08, P = 0.005), minute ventilation (-36.9 ± 18 L/min), oxygen pulse (-3.9 ± 2.3, P < 0.001), heart rate (-7.9 ± 12.6 bpm, P < 0.001), oxygen saturation (-1.5 ± 2.8%, P = 0.004), and blood lactate (-1.7 ± 2.5 mmol/L, P < 0.001). While wearing a cloth face mask significantly impaired exercise performance during maximal exercise testing, cognitive performance was unaffected in this selected group of young, active adults.
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Background Real-world data is currently limited on the association between oral antiviral therapy and healthcare system burden in patients with mild-to-moderate COVID-19. This study aims to evaluate the clinical and cost effec-tiveness of Molnupiravir and Nirmatrelvir-ritonavir use in reducing mortality in this population. Methods This is a retrospective cohort study involving 54,355 COVID-19 patients during February 22-March 31,2022 in Hong Kong. Inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. Our exposure of interest was Molnupiravir/Nirmatrelvir-Ritonavir prescription, with all-cause mortality as the pri-mary outcome. IPTW-adjusted multivariate regressions were used to estimate treatment impact on clinic re -atten-dance and unplanned admissions. Finally, attributed cost and incremental cost-effectiveness ratios (ICER) were estimated. Findings In the outpatient cohort (N = 33,217, 61.1%), 16.1% used Molnupiravir and 13.4% used Nirmatrelvir-Ritona-vir, while in the inpatient cohort (N = 21,138, 38.9%), 3.8% used Molnupiravir and 1.3% used Nirmatrelvir-Ritonavir. IPTW-adjusted Cox model estimated that Molnupiravir (hazard ratio (HR)(95%CI)=0.31 (0.24-0.40), P< 0.0001) and Nirmatrelvir-Ritonavir (HR=0.10 (95%CI 0.05-0.21), P< 0.0001) were significantly associated with a reduced mortality hazard. In the outpatient cohort, both antiviral prescriptions were associated with reduced odds for unplanned hospital admissions (Molnupiravir: odds ratio (OR) =0.72 (0.52-0.98), P=0.039;Nirmatrelvir-Ritonavir: OR=0.37 (0.23-0.60), P<0.0001). Among hospitalised patients, both antiviral prescriptions were associated with sig-nificant reductions in the odds ratios for 28-days readmission (Molnupiravir: OR=0.71 (0.52-0.97), P=0.031;Nirma-trelvir-Ritonavir: OR=0.47 (0.24-0.93), P=0.030). ICERs for death averted for Molnupiravir stood at USD493,345.09 in outpatient settings and USD2,629.08 in inpatient settings. In outpatient settings, Nirmatrelvir-ritonavir cost USD331,105.27 to avert one death, but saved USD5,502.53 to avert one death in comparison with standard care. Interpretation In high-risk patients in Hong Kong with mild-to-moderate COVID-19, Molnupiravir and Nirmatrel-vir-Ritonavir prescriptions were associated with reduced all-cause mortality and significant cost savings.
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Introduction: Depression is a debilitating disorder affecting individuals' level of bio-psychosocial functioning across different age groups around the globe. The recent development of a new NIBS called Transcranial Pulse Stimulation (TPS), also known as low-intensity extracorporeal shock wave therapy (Li-ESWT), has been proven effective for only a 2-week treatment of 35 patients with Alzheimer's disease (AD). Patients' cognition and memory have shown significant improvement which lasted up to 3 months. However, there is a lack of scientific evidence on the efficacy of this TPS intervention on other psychiatric population such as Major Depressive Disorder (MDD), which is increasingly prevalent in Hong Kong and nationwide especially during the COVID-19 pandemic. Nonetheless, there is no trial evaluating the efficacy of TPS on other neuropsychiatric disorders. This gave us the impetus to evaluate the efficacy of TPS on young adults with Major Depressive Disorder (MDD) in Hong Kong. Method(s): In this single-blinded, randomized controlled trial, participants had a confirmed clinical diagnosis of MDD, recruited from the community, NGOs and private enterprise. The intervention was a 2-week TPS treatment comprised six 30-min TPS sessions, delivered by trained mental health professionals. A total of 30 participants were recruited and randomized into either the TPS group or the Waitlist Control (WC) group. Randomization was stratified by gender and age by an independent statistician on a 1:1 ratio. Our primary outcome was determined by whether participants' depressive symptom severity demonstrated significant reduction, compared with the WC group, using the Hamilton Depression Rating Scale-17 (HDRS17). This trial is registered with Clin.Trials.gov, number NCT05006365. Result(s): We recruited 30 participants from 1 August to 31 Oct 2021. They were between 18-54 years old and were predominantly female (73%), ethnically Chinese. There was a significant group x time interaction (F(1, 28) = 818.8, p <.001). Compared with the WC group, there was a significant reduction in the depressive symptom severity in the TPS group (mean difference = -6.60, p = 0.02, Cohen's d = -0.93). Results showed a significant intervention effect and the effect was large. Conclusion(s): TPS is safe and effective to reduce depressive symptoms among young individuals with MDD in this trial. Therefore, TPS may be considered as a top treatment option for neuropsychiatric disorders in clinical psychiatry. Funding(s): This trial is funded by the Departmental General Research Fund, the Hong Kong Polytechnic University, Hong Kong SAR, China. Copyright © 2022
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Introduction/Background: Whipps Cross University Hospital is a District General Hospital (DGH) in London. Children with musculoskeletal and rheumatic conditions are looked after by a paediatric multidisciplinary team (MDT). In approximately one third of cases (around 50 patients), care is shared with tertiary teams.It is widely cited in literature that patients with specialist conditions benefit from receiving specialist care. However, there are many positives of shared-care where patients also receive treatment in the local hospital. The provision of immunosuppressive treatment, regular blood monitoring, and appointments with MDT professionals (e.g. doctors/physiotherapists/ophthalmologists/community nurses) can add further complexities to shared-care. Description/Method: Our objective was to identify the strengths and weaknesses of the current Paediatric Rheumatology shared-care service at our DGH and to provide an action plan for improving the service.Children and young people looked after by our DGH for a rheumatological condition, on immunosuppressants, whose care was shared with the tertiary centre were selected. Data collection was done via one-to-one telephone interviews with families based on a semi-structured questionnaire including the following four themes:1. Views of shared care rheumatology.2. Blood tests and the blood monitoring experience.3. Medication related issues: obtaining, collecting and giving medication.4. Views on transition to adult care.The questionnaire was produced jointly by a paediatric doctor, the lead paediatric pharmacist and the lead nurse for the paediatric day unit, who is involved in blood tests, blood monitoring and delivering immunosuppressant medication. The questionnaire was piloted and modified. Interviews were conducted by a doctor not involved in the routine shared-care service to encourage honest answers, and to reduce observer and investigator bias. After data collection, quantitative and qualitative analysis (thematic analysis) were performed. Strengths and weaknesses of the service were identified. Discussion/Results: 20 patients met our selection criteria and all 20 responded. Questionnaires were completed between April and July 2020.On average, in the last year, patients visited their local DGH 2.5 times and their tertiary centre 2.9 times. 75% of these visits were outpatient appointments.Shared Care The following issues were identified by families through thematic analysis:1. Proximity to home for appointments was important. The local team is responsive to their care.2. Many appointments over both centres and missing school for appointments was a concern.3. Local and tertiary centres don’t always share information.4. Most families were happy to visit both hospitals.Blood Tests Blood testing was split between the GP, the local DGH, the tertiary hospital and community nurses. Blood tests were usually performed every 2-3 months. Families spoke positively about the blood testing experience. The suggested improvements were:1. Proximity to home for blood tests to avoid missing school.2. Better communication of results between hospitals.3. A record of blood test results to keep at home.Medication-Related Issues 70% of our cohort were taking methotrexate, and 20% were taking biologic medications. Prescriptions were provided by the GP, the local DGH and the tertiary centre.Issues identified by families were:1. Barriers to collecting medications (e.g. unhappy to leave the house due to COVID-19;unsure where to collect medication from;problems with obtaining prescriptions from the GP).2. Better communication needed between hospitals about when new medication will start.3. Patients would like to reduce the pain of the injection.4. Methotrexate has too many side effects.Transitioning to Adult Care Most young people (60%) preferred to stay local to home and move to adult services at their local DGH, if there were to be an adolescent service with overlap between paediatric and adult services. Key learning points/Conclusion: The strengths and weaknesses of shared-car rheumatology were identified by families at our DGH. Strengths were that families felt both the local and tertiary centres played a necessary role in care. Weaknesses were that families had many appointments over both centres and missing school was problematic. Some families reported communication between hospitals could be improved.The paediatric MDT proposed a list of quality improvement interventions:1. Set up a one-stop Paediatric Rheumatology Super MDT clinic, to see the physiotherapist, ophthalmologist, paediatrician and pharmacist, if required, all in one morning. 2 one-stop clinics ran in March and May 2022. It is estimated that this super MDT clinic will save 3 to 4 DGH visits per year.2. Obtain remote access to the tertiary hospital computer system for the local Paediatric Rheumatology team. This will improve communication between hospitals.3. Encourage patients to view letters and results from the tertiary centre through the tertiary hospital patient app MyGOSH. This will improve timely information sharing.4. Set up an MDT meeting with the day unit nurse and pharmacist every 2 months to discuss each patient requiring hospital prescribed medication.5. The clinician to liaise with families around improving injection technique, and to discuss measures to mitigate side effects of medications.6. Establish a system for posting medication to parents by pharmacy. This is in place as of August 2020 with an aim of reducing barriers to collecting medications.7. Explore transitioning to alternative adolescent care closer to home.Our next steps will involve re-assessing if the interventions above have helped improve communication with the tertiary hospital, whether they have reduced the number of appointments, and whether medication concerns were resolved. We believe that this innovative project has improved patient access to appointments, as well as their experience of the shared-care service.
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Background: Patients with hematologic malignancies have a lower vaccine response and higher rates for SARS CoV-2 morbidity and mortality. We present preliminary data focusing on humoral vaccine responses and correlates with disease subtype and treatment exposure. Methods: We analyzed data from 332 patients with a hematologic malignancy from May 1, 2021 - Jan 31, 2022 who received SARSCoV-2 vaccination and performed a prospective cohort serologic study with the Elecsys®Anti-SARSCoV-2-S test. Patients received homologous or heterologous vaccine combination of BNT162b2, mRNA1273, ChAdOx1 nCoV-19, and/or Ad26.COV2.S. Blood samples were obtained before any vaccination, 2-6 weeks after the second vaccine (2V), before third vaccine (3V), and 2-6 weeks after 3V. Results: The median age was 67 years (range 18-91years) with 41.9% female. At 2V, 11.5% and at 3V, 23.8% received heterologous vaccines. Treatment status at first vaccine dose significantly affected peak 2V antibody response (p < 0.05). Seropositive rate and median antibody titer after 2V for previously untreated patients were higher compared to patients on active therapy or had previously been treated. Treatment naïve (n = 60;seropositivity 85.1%;median titer 1306 U/mL;[Q1-Q3:11.4-> 2499]);first-line (1L) active therapy (n = 127;65.4%;41.25 U/mL;[ < 0.8-592.5]);second-line and beyond (2L+) active therapy (n = 56;60.7%;2.6U/mL;[ < 0.8-154]);previous treatment with 1L (n = 66;64.8%;118 U/mL;[ < 0.8-> 2499]);previous treatment with 2L+ (n = 23;59.1%;4U/mL;[ < 0.8-229.5]). Of 61 patients that were seronegative at 2V, 17 (27.9%) seroconverted after 3V. Anti-CD20 monoclonal antibody (mAb) containing therapy as the most recent treatment from 2V had the greatest impact on humoral response. Exposure to anti-CD20 mAb based regimens or as monotherapy revealed low antibody responses (n = 84;seropositivity 22.6%;median titer < 0.8 U/mL;Q1-Q3 [ < 0.8-< 0.8]). On analysis of indolent B-cell Non-Hodgkin Lymphomas whereby antiCD-20 mAb are often incorporated, treatment proximity to 2V impacted responses: < 3 months (n = 33;22%;< 0.8 U/ mL;[ < 0.8-< 0.8]) vs. 12-24 months (n = 4;60%;228 U/mL;[ < 0.8-232]). In contrast, tyrosine kinase inhibitor (n = 38;100%;858 U/mL;[221-> 2499]), proteosome inhibitor monotherapy (n = 4;100%;median titer 1520 U/mL;[462-> 2499]) were among the subgroups with the highest numerical responses, however, the addition of corticosteroids impacted vaccine response as seen in proteosome inhibitor with corticosteroids (n = 7;85.7%;6.6 U/mL;[1.8-115.2]). Conclusions: The humoral response from our single institution cohort identifies diminished responses depending on treatment status and the type of treatment including the proximity of treatment exposure to receipt of vaccination. Furthermore, vaccine boosters can induce antibody responses in patients who were previously seronegative.
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In this Work-In-Progress paper, we describe our vision for a remote/virtual robotics lab and our progress towards realizing it. Robotics has been taught at our institution for four years with enrollment growing each year. Our program is part of the undergraduate Bachelor of Science in Computer Science and has an equal focus on robotics theory and practice, with the "Robot Operating System" (ROS) running on students' own computers, and a small robotics learning lab with a variety of ROS based robots. Our pandemic experience during 2020 led us to invest in a cloud-based shared "cloud" environment running on a Kubernetes cluster. We learned that there are real advantages to this in terms of scale and geographical reach. The success of this with our students, our Covid experience, preparation for teaching in our lab, and planning towards return to campus led directly to this work-in-progress paper, where we define, in one ion, a remote/virtual robotics learning lab, unifying local and remote access to both simulated and real robots. This work aims to extend our existing shared virtual cloud-based robotics learning environment and combine it with a remote-controlled robotics lab.
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Background: Ontario Health (Cancer Care Ontario) oversees ColonCancerCheck (CCC), Ontario's population-based organized colorectal cancer (CRC) screening program. CCC recommends average risk screening with the fecal immunochemical test (FIT), but colonoscopy is available opportunistically. A central lab mails FIT kits directly to people upon request from care providers. CCC's recommendations are promoted centrally with Regional Cancer Programs and regional clinical leaders. At the start of the COVID-19 pandemic, FIT kit mailing and mailed letters to invite/remind people to screen were paused. Colonoscopy capacity varied with the waves of the pandemic depending on local factors. Subsequently, CCC gradually implemented recovery activities, such as resuming FIT kit and letter mailing, and provided guidance on screening prioritization, which included conversion of low yield colonoscopy to FIT. Aim: To understand the impact of COVID-19 on CRC screening in Ontario across four periods: pre-, early-, mid- and late-COVID-19. Methods: We compared key performance indicators over time: percent overdue for CRC screening, FIT requisition volumes, FIT requisition rejection rates, FIT kit return rates, colonoscopy volumes and colonoscopy wait times. Results: Comparing pre- to late-COVID-19 periods, the percent of people overdue for CRC screening increased (39.5% vs. 43.1%). An increase in FIT participation was observed, with greater volumes of FIT kits being requested (101,925 vs. 119,113 per month) and improved FIT kit return rates (54.7% vs. 60.8%). However, FIT requisition rejection rates also increased (5.7% vs. 15.0%). Overall colonoscopy volumes declined (24,432 vs. 21,317 per month), with decreases in average risk screening colonoscopy (15.5% vs. 9.9%). The proportion of people getting a colonoscopy within 8 weeks of an abnormal FIT result improved (81.2% vs. 83.5%). Interpretation: While screening performance declined at the start of the pandemic, as screening activities resumed, it has improved in key areas, even exceeding pre-COVID metrics: greater FIT participation, a reduction in average risk screening colonoscopies, and improved colonoscopy wait times for abnormal FIT. Fewer patient-provider interactions and participant reluctance to seek healthcare may have led to an increase in the number of people overdue for CRC screening. CCC's centralized approach to FIT distribution and its pandemic response, including consistent messaging and a regional infrastructure, facilitated the uptake of pandemic guidance and may have led to improved performance. Conclusions: These results suggest that there are opportunities for organized screening programs to improve performance during times of crisis. Sustaining these program performance improvements post-pandemic is essential if CRC screening participation is to return to pre-pandemic levels. (Table Presented)
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DDW 2022 Author Disclosures: Daniel Scanlon: NO financial relationship with a commercial interest ;Brianna Shinn: NO financial relationship with a commercial interest ;Zachary Lieb: NO financial relationship with a commercial interest ;Brian Jacobs: NO financial relationship with a commercial interest ;Divya Chalikonda: NO financial relationship with a commercial interest ;Jason Ho: NO financial relationship with a commercial interest ;Abhishek Agnihotri: NO financial relationship with a commercial interest ;Anand Kumar: YES financial relationship with a commercial interest;Olympus:Consulting ;Anthony Infantolino: NO financial relationship with a commercial interest ;Christina Tofani: NO financial relationship with a commercial interest ;Alexander Schlachterman: NO financial relationship with a commercial interest Introduction: Endoscopic submucosal dissection (ESD) is a minimally invasive technique used for removal of superficial dysplastic or early cancerous esophageal lesions. Many of these lesions arise in a background of Barrett’s esophagus (BE) which is a known precursor of dysplasia and adenocarcinoma. Large lesions not amenable to endoscopic mucosal resection often have superficial forceps biopsies taken prior to referral for ESD. This study aims to evaluate the accuracy of superficial forceps biopsies compared with pathology from ESD. Methods: A retrospective medical record review was performed that included consecutive patients who underwent ESD for esophageal lesions at a tertiary care center between 6/2018 and 9/2021. Pathology results from outside hospital and same institution superficial forceps biopsies as well as ESD pathology reports were reviewed. The primary outcome measured was the number of patients found to have higher disease severity on ESD pathology compared with pre-ESD superficial forceps biopsies. Results: The 28 patients included in the study received superficial forceps biopsies at outside hospitals (n=9), the same institution (n=14), or both (n=5). An average of 99 days occurred between outside hospital superficial forceps biopsies and ESD compared with an average of 30 days between superficial forceps biopsies and ESD performed at the same institution. Delays between superficial forceps biopsies and ESD may be related to the COVID-19 pandemic leading to prolonged time between procedures. In the entire cohort, ESD pathology differed from superficial forceps biopsies in 13/28 patients (46%). 10 patients (36%) had their disease severity upgraded and 3 were newly diagnosed with cancer on ESD pathology. Findings were similar for patients with lesions arising in a background of BE (21/28) (Table 1). Of those with BE, 9/21 (43%) patients had ESD pathology that differed from superficial forceps biopsies with 6 patients (29%) receiving increased disease severity and 2 patients receiving a new cancer diagnosis on ESD pathology. Conclusion: Superficial forceps biopsies taken prior to resection of esophageal lesions via ESD were concordant with ESD pathology in the majority of cases, however 36% of patients received upgraded disease severity on ESD pathology. Findings were similar for patients with or without a background of Barrett’s esophagus. These results highlight the importance of en bloc resection not only for therapeutic benefit (60% of patients in this cohort achieved R0 resection), but for accurate staging of esophageal lesions. [Formula presented]
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Intro: Deregulated protein synthesis is a common trait across solid and hematologic malignancies and an attractive target for cancer therapy. Rocaglates compounds that inhibit eukaryotic initiation factor 4A1 (eIF4A1), the essential DEAD-box RNA helicase that resolves mRNA 5'UTR secondary structures during cap-dependent translation initiation. Rocaglates' unique mechanism of action causes sequence-selective mRNA binding by eIF4A1, clamping the inactive helicase onto the transcript. This suppresses translation globally and affects many oncogenic and pro-survival transcripts in particular. Zotatifin, the first-in class synthetic rocaglate, is currently in Phase I clinical trials for the treatment of solid tumors and as an antiviral against SARS-CoV2. Currently, eIF4A1 and DDX3 are the only reported targets of rocaglate-mediated RNA clamping. Employing unbiased proteomic approaches, we have discovered that rocaglates, thought to act as pure eIF4A/translation inhibitors, extensively remodel the translation machinery and translatome. Additionally, mass-spec interrogation for proteins interacting with specific RNA sequences reveals novel targets of rocaglate-mediated, sequence-specific RNA clamping. Methods: We conducted original mass-spectrometry analyses of translational reprogramming by rocaglates. TMT-pSILAC assessed acute changes in protein production, while MATRIX, which captures high-resolution profiles of the translation machinery, revealed translation factors that drive reprogramming in response to rocaglate exposure. We validated results biochemically, in cellulo, and in vivo using patient-derived xenograft (PDX) mouse models. To probe existing and novel rocaglate RNA-clamping targets, we developed unbiased “clampome” assays - in cellulo protein-RNA-pull downs followed by mass-spec analysis of proteins with increased binding to RNA in the presence of rocaglates. Results: We find rocaglates, including zotatifin, have effects far more complex than simple “translational inhibition” as currently defined. Indeed, translatome analysis by TMT-pSILAC revealed myriad up-regulated proteins that drive hitherto unrecognized cytotoxic mechanisms. The GEF-H1 guanine exchange factor, for example, drives anti-survival RHOA/JNK activation, suggesting novel candidate biomarkers of rocaglate clinical outcomes. Translation-machinery analysis by MATRIX identifed rocaglate-induced dependence on specific translation factors including eEF1ϵ1 that drive remodeling. Novel rocaglate RNA-binding targets revealed by clampome studies remain under detailed evaluation as mediators of drug activities. Discussion: Our original proteome-level interrogation revealed that the complete cellular response to these historical “translation inhibitors” is mediated by comprehensive translational landscape remodeling. Effects on a broader suite of RNA binding proteins than eIF4A1 alone we suggest mediate the potent antitumor activities of these unique compounds, elucidation of which permits development of novel precision approaches to targeted translational deregulation in cancer.
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Aim: To assess the quality of neurosurgical electronic discharge documents (EDDs) as per the Scottish Intercollegiate Guidelines Network's (SIGN) discharge document guidelines, and to implement interventions to ensure patient safety and continuity of care. Method: We performed a closed loop audit on the quality of EDDs at the neurosurgical unit at Ninewells Hospital. We collected six sets of twoweeks' worth of EDDs from the Tayside EDD system coinciding with foundation trainee changeover times for a representative sample of pre- and intra-COVID-19 EDDs. We analysed our findings and developed interventions in collaboration with the MDT. These included a copypaste template, educational poster, and presentation, and more.Weimplemented the interventions and reassessed EDDs after three months. Results: A total of 207 EDDs were included. Pre-interventions, 88% of the EDDs were inadequate in quality when compared to SIGN's guidelines. This had 33% reduction post-interventions. The percentage of EDDs adequate in quality doubled post-interventions, from 22% to 43%. The most commonly mistaken or missed criterion pre- and postintervention was the neurological status on admission and discharge. Others were mistaking presenting complaint for diagnosis and vice versa, and not mentioning follow-up or new medications. Conclusions: Accurate records of care, including discharge documents, are central to the principles of good medical practice outlined by the GMC. This study showed that EDD quality is compromised due to time pressures, lack of information and constant changeover due to COVID-19. We alleviated this by creating accessible interventions that assure safe patient care despite the challenges of changeover and COVID-19.
ABSTRACT
A lockdown was imposed in Wuhan, China, the alleged epicentre of the COVID-19 outbreak, on 23 January 2020. Rattled by the short notice and severity of the restrictions, many grabbed the last opportunity to escape, an act widely criticised on Weibo, China's popular microblogging site. This study aims to examine the unsavoury discourse deployed by Weibo users to express impoliteness and discursively construct negative identities of the lockdown escapees. Posts on Weibo criticising, reporting and threatening the escapees were analysed, revealing that the escapees were dehumanised through vivid animal metaphors to highlight their irresponsibility and call for their punishment. Animal metaphors can co-occur with various impoliteness triggers to intensify offensiveness, heightening the hostility of interlocutors towards a target. This use of metaphors also showcases online users' anger, distrust, and hatred towards the escapees, their solidarity-seeking behaviour online and their irrationality.
ABSTRACT
Container ports operate in more challenging and volatile environments at present times. Events such as US-China trade tensions and the COVID-19 pandemic severely affect numerous container ports at various levels. Strategies pursued by container ports are key to port development and management amidst these challenges. Drawing on configuration theory, this research employs Fuzzy-set Qualitative Comparative Analysis to investigate the relation between port strategies and container throughput. The research contributes to the literature by proposing an approach to account for complexity of the port sector and offers insights into strategies adopted by major container ports. The research further identifies 10 port strategies and proposed indicators that can represent the essence of these strategies. Being able to represent strategies in a quantitative format is important for strategy analysis and performance evaluation. Results reveal that major container ports employ a combination of strategies which address both the supply and demand-side aspects of the port business. Growing digitalization and digitization coupled with advancements in information capture, diagnostics capabilities and predictive abilities means a greater role for data analytics to influence container port strategy and performance. Implications for port managers, policy makers and researchers from the perspective of port policy and management are proposed.
ABSTRACT
Introduction:The association between thrombosis (TE) and cancer has been well established. The risk for thrombosis in Multiple Myeloma (MM) is further compounded by therapy-related factors, which increase the risk for both arterial and venous TE. Lenalidomide + dexamethasone (Ld) is the most widely used backbone therapy for MM and may increase the risk of TE. The current standard TE prophylaxis for patients on Ld is low dose aspirin (ASA) for low risk patients or low molecular weight heparin for high risk patients. Direct oral anticoagulants have been used empirically and have been evaluated in small prospective cohort studies with promising results. Methods: RithMM is an ongoing open label Canadian multicenter pilot feasibility RCT to assess the efficacy and safety of daily oral rivaroxaban 10 mg (Riva) versus ASA 81 mg in patients with MM on Ld-based therapy. Our primary objective is to assess the feasibility of accrual of patients with MM starting on Ld-based therapy. Patients not on therapeutic anticoagulation or antiplatelet agents for another indication (e.g. atrial fibrillation) are eligible for RithMM. Primary clinical endpoints are major cardiovascular (CV) events or major bleeding as per the ISTH criteria. The study will be considered feasible if 86 patients in 4 Canadian sites (London, Ottawa, Halifax, Niagara) can be enrolled in 12 months after each site activation. Sites are expected to accrue an average of 1.8 patients per month. Patients are randomly assigned to receive ASA (control) or Riva (intervention) using a simple randomization sequence run by the Redcap system, utilizing an automated assignment procedure. Patients enter the study at the time of anticoagulant initiation and are followed for 6 months, or until they withdraw from the study;die or develop a primary clinical outcome;whichever comes first. Herein we present the interim analysis of RithMM after study completion in 2 of 4 sites. Feasibility assessment: 17 patients were randomized to ASA and 17 to Riva (1 patient did not take the study drug). Feasibility assessment was severely impacted by the temporary but prolonged research activity closures secondary to the COVID-19 pandemic that limited direct patient accrual and led to significant delays in REB approval of the participating sites. The first patient was enrolled in January 2019 in London. Ottawa opened in October 2019, Halifax in December 2020 and Niagara in May 2021. A total of 34 patients have been enrolled: 22 London, 11 Ottawa and 2 Halifax. London was the only site actively accruing for 12 consecutive months. Ottawa opened for 3 months, held accrual for 9 months, then reopened for 7 months. Halifax was open for only 1 month. Niagara opened in May 2021, the time of study data lock for this . In addition, 7 potentially eligible patients were not screened given that they were enrolled in a MM treatment trial that did not permit enrolment in another trial. The accrual rate was excellent for London (105%) and Ottawa (52% in 10 months). The drop-out rate was 6% (2 patients) and drug compliance 100%. Clinical Outcomes: Baseline characteristics are depicted in the table. One patient in the ASA arm developed a proximal deep vein thrombosis 2 months after starting treatment, and another developed a clinically relevant nonmajor bleeding 6 weeks after starting ASA. Discussion: This is the interim analysis of the RithMM pilot trial that aims to evaluate the feasibility of accrual of MM patients on Ld -base therapy to assess the efficacy and safety of Riva versus ASA in preventing TE complications. The study was initiated during the COVID-19 pandemic turmoil, which severely impacted in the proper activation of 3 of the 4 participating sites. Despite this significant limitation, 2 sites were able to maintain the accrual of patients. Only 1 site remained opened according to the pre-specified consecutive 12- month study period. Despite this barrier, we could still attain an excellent accrual rate of 39.5% in 2 sites (London and Ottawa). The incidence of TE or bleeding was low, with o difference between ASA and Riva. However, the study was not powered to assess these outcomes. Lastly, Ld is the most widely used backbone therapy in MM, both in upfront and relapsed settings. Our group does not anticipate any barriers to achieving successful completion of accrual provided the hospital's activities remain safe and research activities open. [Formula presented] Disclosures: Louzada: Celgene: Honoraria;Janssen: Honoraria;Pfizer: Honoraria;Amgen: Honoraria. McCurdy: Sanofi: Honoraria;GSK: Consultancy, Honoraria;Takeda: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Celgene: Consultancy, Honoraria. Phua: Pfizer: Honoraria;Amgen: Honoraria;AstraZeneca: Honoraria;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Le Gal: Aspen: Honoraria;Bayer: Honoraria;Pfizer: Honoraria;LEO Pharma: Honoraria;BMS: Honoraria;Sanofi: Honoraria. Lam: Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees;Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees;Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees;SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Rivaroxaban 10 mg oral daily for thrombosis prophylaxis in myeloma patients on lenalidomide-based therapy. Health Canada approved the off label use for study purposes
ABSTRACT
Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.