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The recent and recurrent spillover of three highly pathogenic coronaviruses, SARS-CoV-1, MERS-CoV and SARS-CoV-2, into human populations has stressed the importance of pandemic preparedness. Here, we describe how, in the absence of antiviral therapeutic options against coronaviruses, early clinical investigations have focused on the prompt repurposing of approved antiviral therapies. We discuss how, despite international collaborative efforts, their outcomes so far have been disappointing as none of the early drugs tested demonstrated effective clinical efficacy. We also outline innovative strategies and tools developed to fast-track development of novel classes of antivirals. These capitalise on a deeper understanding of viral molecular pathogenesis and how coronaviruses hijack the host cellular machinery to maximise their replication and counteract host defences. Collectively, these approaches are crucial to identify and validate novel targets for therapeutic interventions and expand the repertoire of broad-spectrum antiviral agents, so that these can be promptly deployed for current and future pandemics.Copyright © ERS 2021.
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Background: Adjuvant chemotherapy has been an integral component of breast cancer care for decades. Advances in supportive care have been made, but despite this, infective complications of therapy remain a significant toxicity concern. Case Presentation: A premenopausal patient presented to the emergency department during the third wave of the Covid-19 pandemic with sepsis after a second course of adjuvant docetaxel-cyclophosphamide chemotherapy. Overnight she developed tetraplegia. An urgent MRI cervical spine revealed a pre-vertebral, vertebral, and epidural abscess. This was treated with an emergency C4-C7 posterior cervical laminectomy and decompression. Her inpatient care involved a protracted ICU admission followed by rehabilitation. She remains tetraplegic and requires continued inpatient care over a year after presentation. Restricted pandemic-related hospital visiting has compounded the impact of her illness. Conclusion: Infective complications of adjuvant breast cancer chemotherapy remain an issue despite advances in supportive care. This case highlights the devastating, life-altering impact that these complications can have as emphasized by the inclusion of the patient's perspective. Copyright © 2022.
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Drone technology is widely available and is rapidly becoming a crucial instrument in the functions of businesses and government agencies worldwide. The demand for delivery services is accelerating particularly since the Covid-19 pandemic. Both companies and customers want these services to be efficient, timely, safe, and sustainable, but these are major challenges. Last-mile delivery by lightweight short-range drones has the potential to address these challenges. However, there is a lack of consistency and transparency in assessing and reporting the sustainability of last-mile delivery services and drones. This paper presents a critical review of published assessments (specifically lifecycle assessment and circularity). The study reveals a lack of comprehensive studies, and a need to examine composite and battery manufacturing developments and provides key considerations for future study development. © 2022 Mitchell et al.
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Introduction Post-diagnostic support is key to ensuring the well-being of people with dementia and unpaid carers. The COVID-19 pandemic has caused a shift from in-person to remote service delivery, often with the use of information communication technologies (ICT) formats. This systematic review examined how ICT has been used to access remote post-diagnostic support services that address the needs people with dementia, or those of dyad, and explored care recipients' views on accessing dementia-related support remotely. Method Concepts relating to dementia and ICT were searched across six databases (PsychInfo, PubMed, Cochrane Library, CINAHL, Social Care Online, and Web of Science) in March 2021 and updated in March 2022. Studies published from 1990 and written in English, German or French were considered for inclusion. Methodological quality was appraised using the Hawker quality assessment tool and reporting structured according to PRISMA guidelines. Results The search yielded 8,485 citations. Following the removal of duplicates and two screening processes, 18 papers were included. Papers described a range of post-diagnostic support, including exercise classes and therapeutic sessions, which were largely delivered remotely on a one-to-one basis. Videoconferencing software was the most employed ICT format, and people with dementia were directly engaging with ICT to access post-diagnostic support in 13 studies. Whilst studies demonstrated the feasibility of accessing post-diagnostic service remotely, overall, care recipients' views were mixed. Conclusions Following the increased reliance on ICT during the pandemic, it is likely that service delivery will continue with a hybrid approach. Accessing post-diagnostic support remotely is likely to benefit some care recipients. However, to prevent widening inequalities in access, service provision is required to accommodate to people with dementia and unpaid carers who are digitally excluded. Future research should capture the support provided by unpaid carers facilitating the engagement of the person with dementia when accessing remote post-diagnostic support.
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Background. Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated postinfection/post-vaccination. Here we describe a novel medium-throughput flow cytometry based micro-neutralisation assay to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-2 Wild Type (D641G) and Variants of Concern (VoC) in convalescent/vaccinated populations. Methods. Micro-Neutralisation assay (Micro-NT) was performed in 96-well plates using clinical isolate 2019-nCoV/Italy-INMI1, D641G (SARS-CoV-2/human/ IRL/AIIDV1446/2020) and/or VOCs Beta (SARS-CoV-2/human/IRL/AIIDV1752/ 2021) and Omicron (SARS-Cov-2/human/IRL/AIIDV2326/2021). Plasma samples (All Ireland Infectious Diseases (AIID) Cohort) were serially diluted (8 points, halflog) from 1/20 and pre-incubated with SARS-CoV-2 (1h, 37degreeC). Virus-plasma mixture were added onto VERO E6/VERO-E6 TMPRSS2 cells for 18h. Percentage infected cells was analysed by automated flow cytometry following trypsinisation,fixation and SARS-CoV-2 Nucleoprotein intracellular staining. Half-maximal Neutralisation Titres (NT50) was determined using four-parameter logistic regression. Our assay was compared to Plaque Reduction Neutralisation Test (PRNT) and validated against WHO anti-SARS-CoV-2 Immunoglobulin Standards. Results. Using WHO Standards with low, medium or high anti-SARS-CoV-2 IgG, both Micro-NT and PRNT achieved comparable NT50 values (Table 1). Micro-NT was found to be highly reproducible (inter-assay CV of 11.39%). Screening 190 convalescent samples and 11 COVID-19 naive controls (AIID cohort) we achieved an assay sensitivity of 90% and specificity of 81%. We demonstrated that Micro-NT has broad dynamic range differentiating NT50s < 1/20 to > 1/5000 (Figure 1). We could also characterise immune-escape VoC, observing up to 10-fold reduction in NT50 against Beta (Figure 2). Table 1: NT50s of Low, Medium and High Titre Anti-SARS-CoV-2 IgG Standards measured against Live SARS-CoV-2 using PRNT and Micro-NT Neutralising Capacity of low, medium and high-titre anti-SARS-CoV-2 IgG (WHO, International Standards) against live SARS-CoV-2 (2019-nCoV/Italy-INMI1) measured using PRNT and Micro-NT Assays on Vero E6 cells, as well as the potency of NAbs in each sample in International Units (IU/ml) as determined by the WHO. Figure 1: Dynamic Range of Micro-NT Micro-NT has a broad Dynamic Range, distinguishing low (A), medium (B) and high (C) neutralising plasma samples against live SARS-CoV-2 (2019-nCoV/Italy-INMI1) from a cohort of COVID-19 convalescent individuals (AIID cohort), as well as negative samples from COVID-19 naive samples (D). Graphs show 3 representative samples of each NT50 range. (E) shows the population distribution of 190 Convalescent plasma samples as measured by Micro-NT on Vero E6 cells. Figure 2: Reduced Neutralisation Capacities measured against SARS-CoV-2 VoC using Micro-NT Low (A), Medium (B) and High (C) anti-SARS-CoV-2 IgG (WHO Standards) show different neutralising capacities against WT (D614G) SARS-CoV-2 and variants Beta and Omicron, measured using Micro-NT on Vero-E6-TMPRSS2 cells. Conclusion. Our flow-cytometry-based Micro-NT is a robust and reliable assay to quantify NAb titres, an important evaluation endpoint in clinical trials. It has higher throughput (96 well format versus 12 well) and reduced infection time (18h vs 48-96h) compared to the gold standard PRNT.
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Background. A wide array of assays to detect the serologic response to SARS-CoV-2 have been developed since the emergence of the pandemic. The majority of these are either qualitative or semi-quantitative, detect antibodies against one antigenic target, and are not adaptable to new antigens. Methods. We developed a new, multiplex immunoassay to detect antibodies against the receptor binding domain, S1 and S2 spike subunits and nucleocapsid (N) antigens of SARS-CoV-2 (the CEPHR SARS-CoV-2 Serology Assay). This assay uses electrochemiluminescence technology which allows for a broad dynamic range, and a linker format which allows for the addition of new antigenic targets. We tested this assay on a series of biobanked samples and validated its performance against the Abbott SARS-CoV-2 IgG and Abbott SARS-CoV-2 IgG II assays, and the MesoScale Diagnostics V-PLEX SARS-CoV-2 Panel 2 Kit. Results. Participant demographics are shown in Table 1. The mean (standard deviation (SD)) intra-assay (within plate) coefficient of variation (CV) of 80 plasma samples run on the same plate was 3.9% (2.9) for N, 3.8% (6.2) for RBD, 3.8% (5.9) for S1 and 3.9% (5.3) for S2. The mean (SD) inter-assay CV derived from 5 samples run across 3 days by two different operators was 11% (6.5) for N, 13% (5.7) for RBD, 14% (8.9) for S1 and 13% (5.1) for S2. In the convalescent group (n=193), overall sensitivity for each assay was;RBD 82% (95% CI 76-87), S1 86% (81-91%), S2 88% (83 - 92%) and N 72% (64 - 78%). Sensitivity improved when analysis included only individuals who were sampled more than 14 days from onset of symptoms (n=166), RBD 87% (81 - 95%), S1 91% (85 - 95%), S2 91% (85 - 95%) but not for the N-target (73% (66-80%)). In vaccinated individuals (n = 58), 100% (94-100%) had both detectable RBD and S1 antibodies. Overall specificity was 96% (87-99%) for RBD, 90% (78-97%) for S1, 94% (84-99%) for S2 and 90% (78-97%) for N. There was excellent correlation between the Abbott IgG II and both CEPHR anti-RBD IgG (rho 0.91) and CEPHR anti-S1 IgG (rho 0.9, both p < 0.001, Figure 1.) and the V-PLEX full spike and both CEPHR RBD IgG (rho 0.83) and S1 IgG (rho 0.82, both p < 0.001, Figure 4). Conclusion. The CEPHR SARS-CoV-2 Serology Assay is a robust, customisable, multiplex serologic assay for the detection of several different IgG specific to SARS-CoV-2.
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SESSION TITLE: What Lessons Will We Take From the Pandemic? SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Ethnic and racial disparities have been found to be influential drivers for poor outcomes in COVID-19 patients. Hispanic ethnic group has been recognized to have disproportionately higher COVID-19 infections and associated hospitalizations and deaths, which have been attributed to differences in socioeconomic and health factors, including high burden of comorbidities. However, studies specifically addressing the risk of death related to ethnicity alone are lacking. Therefore, we evaluated the association between Hispanic ethnicity and 30-day mortality in patients without comorbidities hospitalized with a COVID-19 diagnosis. METHODS: We included hospitalized patients with a COVID-19 diagnosis (based on the ICD-10 code U07.1) in an observational cohort study at the South Texas Veterans Health Care System (STVHCS) from April 1st, 2020 until December 31st, 2021. Additionally, we selected patients with no comorbidity burden based on a Charlson Comorbidity Index (excluding age) equal to zero. The index date was considered at the first documentation of COVID-19 diagnosis. We compared two independent groups: Hispanic vs. non-Hispanics. Our outcome of interest was 30-day all-cause mortality. Continuous variables were expressed as medians with interquartile ranges (IQR) and categorical variables were reported as absolute frequencies and percentages. A priori multivariable analysis was set to adjust for age, gender, and the probability of death at 30-days according to the validated Veterans Health Administration COVID-19 Index (VACO score). RESULTS: We identified 219 hospitalized COVID-19 patients with no comorbidities, stratified into Hispanics (n=87 [39.7%]) and non-Hispanics (n=132 [60.3%]). Demographic characteristics for Hispanics and non-Hispanics were comparable for median (IQR) age (48 [39-58] years vs. 51 [40-61] years), while there was a greater proportion of male gender in the Hispanic group (n=80 [92.0%] vs. n=110 [83.3%]). Hispanics had a lower probability of death according to the VACO score compared to non-Hispanics (0.22% [0.22%-2.95%] vs. 1.97% (0.22%-4.96%). Both groups had similar 30-day all-cause mortality, n=4 (4.6%) for Hispanics and n=4 (3.0%) for non-Hispanics with p-value=0.72. Due to the low number of deaths between the two groups, we were unable to perform a multivariate analysis. CONCLUSIONS: In this cohort of hospitalized COVID-19 patients without comorbidities, Hispanic ethnicity was not associated with an increased 30-day all-cause mortality. CLINICAL IMPLICATIONS: Our study demonstrates Hispanic ethnicity alone does not account for differences in outcomes of COVID-19 patients. Other factors, such as social determinants of health and comorbidity burden, have been shown to play significant roles and should be the focus of efforts to mitigate morbidity and mortality in COVID-19. DISCLOSURES: No relevant relationships by Liwayway Andrade No relevant relationships by Nicholas Hodgeman No relevant relationships by Michael Mader No relevant relationships by Marcos Restrepo No relevant relationships by Sandra Sanchez-Reilly
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SESSION TITLE: COVID-19: Other Considerations in Management SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 02:45 pm - 03:45 pm PURPOSE: In the context of COVID-19, dementia is a well-established risk factor for COVID-19 mortality compared to patients without dementia. To the date, however, there is limited understanding on how a preexisting dementia diagnosis may impact time to death following COVID-19 infection. Of note, identification of risk factors for earlier versus later mortality has the potential to influence treatment and hospice care decisions. Therefore, our aim was to investigate if Veterans with preexisting dementia experienced a longer time from COVID-19 diagnosis to death (all-cause mortality) compared to those without dementia who died of COVID-19. METHODS: We conducted a retrospective, cross-sectional chart review study utilizing data collected at the South Texas Veteran Health Care System from April 2020 to December 2021. Participants comprised deceased Veterans from all-cause mortality following COVID-19 infection, both with and without a preexisting dementia diagnosis in the 5 years prior to COVID-19 diagnosis. We conducted a univariate analysis of covariance, controlling for patient age, to investigate if days from COVID-19 diagnosis to death differed between patients with and without a preexisting dementia diagnosis. RESULTS: A total of N= 382 deceased subjects from all-cause mortality infected with COVID-19 were found in our data base, with a mean age of 73.74 years (SD = 12.33). The majority (64.65%;n = 247) did not have dementia, while 35 % (n = 135) had a preexisting dementia diagnosis in their medical record. Results indicated that number of days from COVID-19 diagnosis to death did not differ (F(1, 379) = 0.02, p = ns) between deceased subjects with dementia (M = 74.6 days, SD = 81.0) and without dementia (M = 75.6, SD = 93.6), controlling for patient age. Patient age was nonsignificant in the model (F(1,379) = 0.44, p = ns). CONCLUSIONS: Among patients deceased for all-cause mortality with COVID-19 infection, results did not indicate a significant difference in time to death following COVID-19 diagnosis between patients with preexisting dementia or without, controlling for age. Although dementia is an established risk factor for COVID-19 related death, it is likely one piece of a complex puzzle in terms of predicting earlier versus later mortality. Future research is needed to identify potential moderators of illness trajectory prior to death among patients following a COVID-19 diagnosis. CLINICAL IMPLICATIONS: Further studies are needed on this field. Limitations of our study were abscense of subgroups for different severity dementia classification, the diagnosis of COVD-19 for our data base was made based on the day an ICD code was entered on the subject’s chart, rather than physician diagnosis, patient’s symptoms starting day, or previous outside COVID-19 tests. Moreover, we didn’t account for other comorbidities, and most patients were male. DISCLOSURES: No relevant relationships by Lisa Kilpela No relevant relationships by Michael Mader No relevant relationships by Onachi Ofoma No relevant relationships by Carlos Perez Ruiz No relevant relationships by Marcos Restrepo No relevant relationships by Sandra Sanchez-Reilly
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SESSION TITLE: Post-COVID-19 Outcomes SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Asthma can be exacerbated by various triggers, including infections. One of the most frequent causes of exacerbations is respiratory viral infections. Therefore, asthmatics were expected to have worse outcomes during the COVID-19 pandemic. While mortality has often been measured in the first 30 days of diagnosis, there is paucity of data regarding the impact of pre-existing asthma in the long-term mortality after a hospitalization for COVID19. We investigated the association between pre-existing asthma and long-term all-cause mortality rate among hospitalized COVID-19 patients. METHODS: This is a retrospective cohort study from the South Texas Veterans Health Care System between April 1, 2020 and December 31, 2020 that included adults hospitalized with COVID-19. The cohort was stratified into two groups: pre-existing asthma vs. non-asthmatics patients. The patients were followed up to 365 post-index date of the COVID-19 diagnosis. The primary outcome was all-cause mortality within 365 days. Continuous variables were expressed as medians with interquartile ranges (IR) and categorical variables were reported as absolute frequencies and percentages. Multivariable analysis, including the Charlson Comorbidity Index was used to adjust for the comorbidity burden excluding asthma. RESULTS: We included 604 patients that required admission with a diagnosis of COVID-19. Pre-existing asthma occurred in 11% (n=66) of hospitalized patients with COVID-19. Asthmatic patients were younger with a median age of 64 years old (IQR 52-71) and less likely to be men (79%) compared to non-asthmatics with a median age of 68 (IQR 54-74) and 94% men, respectively. The Charlson Comorbidity Index was similar between asthmatics (median score of 3 [IQR of 2-7]) and non-asthmatic (median score of 3 [IQR 1-6]) COVID-19 hospitalized patients. The mortality rate within 365 days was numerically lower among asthmatics was 13.6% (n=9/66) when compared to non-asthmatics 21.6% (n=116/538) (p=0.13). Five of the 9 asthmatic patients died within the first 30 days post-COVID-19 diagnosis. In the multivariate analysis adjusted by Charlson Comorbidity Index, asthmatics had no statistically significant difference in mortality when compared to non-asthmatics COVID-19 patients (aOR=1.80;95%IC 0.84-3.87;p=0.13). CONCLUSIONS: There was no association between pre-existing asthma and all-cause mortality rate measured within 365 days after diagnosis of COVID-19 in hospitalized patients. CLINICAL IMPLICATIONS: Further assessment of asthma disease severity and specific therapies may assist clinicians on the potential protective effect seen in COVID-19 patients. DISCLOSURES: No relevant relationships by FRANKLIN ARGUETA No relevant relationships by Michael Mader Consultant relationship with GSK Please note: $5001 - $20000 by Diego Maselli Caceres, value=Consulting fee Consultant relationship with AstraZeneca Please note: $5001 - $20000 by Diego Maselli Caceres, value=Consulting fee Consultant relationship with Sanofi/Regeneron Please note: $5001 - $20000 by Diego Maselli Caceres, value=Consulting fee Speaker/Speaker's Bureau relationship with GSK Please note: 1 year by Diego Maselli Caceres, value=Consulting fee Speaker/Speaker's Bureau relationship with AstraZeneca Please note: 1 year by Diego Maselli Caceres, value=Honoraria Speaker/Speaker's Bureau relationship with Sanofi/Regeneron Please note: 1 year by Diego Maselli Caceres, value=Honoraria Consultant relationship with Amgen Please note: 10/1/2021 Added 04/04/2022 by Diego Maselli Caceres, value=Consulting fee No relevant relationships by Marcos Restrepo No relevant relationships by Sandra Sanchez-Reilly No relevant relationships by Kara Zabelny
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SESSION TITLE: Medications and Pulmonary Rehabilitation in COVID-19 Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Millions of people have survived COVID 19 infection and are living with post-acute sequelae of COVID (PASC). Multi-disciplinary programs have been established to provide follow-up to these patients. Currently, there are limited data regarding the effectiveness of these programs and it is uncertain if there is a mortality benefit. Here, we explore if the enrollment of Veterans into a multi-disciplinary COVID-19 follow-up program influences long term all-cause mortality. METHODS: We designed a retrospective cohort study at the South Texas Veteran Health Care system (STVHCS) from April 1, 2020, to December 31, 2020. Participants in the study were Veterans who survived a COVID 19 infection after 30 days and were eligible for enrollment in the STVHCS Convalescence Program (“The Program”), which conducts multi-disciplinary follow up care. Patients who died <30 days after COVID 19 diagnosis were not eligible. The primary outcome of long term all-cause mortality was defined as mortality within 31-365 days after the diagnosis of a COVID 19 infection. Demographic differences and primary outcome between the two groups (enrolled versus non-enrolled in The Program) were analyzed using Chi square for categorical variables. Continuous variables were analyzed using Student’s t-test. RESULTS: In total 2253 patients were eligible for enrollment, of which 557 were enrolled and 1696 were not enrolled. Long term all-cause mortality between the groups was 6/557 (1.07%) in the enrolled group compared to 78/1696 (4.59%) in the non-enrolled group with a p value of <0.001. There was no statistical difference between the groups based on the average Charlson comorbidity index score, 2.12 vs 2.09 respectively, with a p value = 0.85. CONCLUSIONS: Enrollment of Veterans in a COVID 19 multidisciplinary follow-up program is associated with a significant decrease in long term all-cause mortality. These differences could not be explained by inherent differences between groups. CLINICAL IMPLICATIONS: Our study shows the potential effectiveness of COVID-19 multidisciplinary follow-up programs to reduce long term all cause mortality in survivors of COVID. In addition there may be other benefits not yet explored such as reduction in symptom burden from COVID and decreased psychosocial distress. The generalizability of this study is limited by its observational study design, the voluntary nature of enrollment in the program and lack of non veterans in the population. DISCLOSURES: No relevant relationships by Ye Aung No relevant relationships by Ryan Choudhury No relevant relationships by Michael Mader No relevant relationships by Marcos Restrepo No relevant relationships by Sandra Sanchez-Reilly No relevant relationships by Monica Serra No relevant relationships by Ana Lucia Siu Chang No relevant relationships by Hanh Trinh
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Background: Although presence of SARS-CoV-2 neutralising antibodies can provide protection against development of COVID-19, how reflective circulating anti-SARS-CoV-2 antibody levels are of underlying neutralising capacity, and whether a threshold exists to predict sufficient neutralising capacity remains unclear. Methods: In plasma from individuals with PCR-confirmed COVID-19 recruited to the All Ireland Infectious Diseases Cohort Study, we measured IgG concentrations against RBD, Spike protein sub-unit 1 and 2 (S1, S2) and Nucleocapsid (NC) using multiplex electrochemiluminescence (normalised to World Health Organisation reference serum as IU/mL). Neutralising capacity was measured against live SARS-CoV-2 virus (clinical isolate 2019-nCoV/Italy-INMI1) by determining the maximum plasma dilution required to maintain 50% inhibition of infection of Vero E6 cells (50% Neutralisation Titre (NT50)), by flow cytometry-based micro-neutralisation assay. Given that the Beta SARS-CoV-2 variant of concern (VOC) reduces neutralising activity up to six fold, we estimated a NT50 of 1:1000 against wild type SARS-CoV-2 would maintain neutralising activity against VOC. We used Spearman correlation and linear regression to model relationships between NT50 and IgG concentrations. Data are presented as median (IQR) unless specified. Results: In 190 individuals (age 50 (40-64) years, 55% female, time from symptom onset 98 (35-179) days), NT50 most highly correlated with anti-RBD IgG (Rho 0.81 p<0.001, Fig 1a) compared with other IgG classes (S1;Rho 0.8, S2;0.73, NC;0.72, all p<0.001). Median RBD titre was 246 (71-662) but trended lower over time, with a median of 319 (61-1012) IU/ml at 0-90 days, 244 (86-523) IU/ml at 90-180 days and 157 (80-364) IU/ml at >180 days post symptom onset respectively (p=0.08, Fig 1b). RBD IgG titres of 476 IU/ml corresponded to a NT50 of 1:1000. Overall, RBD ≥476 IU/ml predicted NT50 ≥1:1000 with a sensitivity of 77 (95% CI 65-87)% and specificity 89 (95% CI 82-93)%. This improved in an analysis restricted to convalescent samples (>30 days post symptom onset, n=148), with a sensitivity 88% (95% CI 74-96%) and specificity 90% (95%CI 82-95%) respectively. Conclusion: In convalescent plasma, RBD IgG titres ≥476IU/mL is sensitive and specific for predicting robust underlying neutralising capacity. Further research is required to validate these findings in other cohorts and confirm these thresholds in post-vaccinated individuals.
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Study Objectives: Loperamide (LOP) is a safe, effective antidiarrheal medication available over-the-counter (OTC) for over 30 years with a maximum dose of 8 mg/day for adults. Intentional LOP abuse/misuse (ingesting 70-200 mg/day to self-treat opioid withdrawal symptoms or achieve euphoria) was first reported in online forums in 2005. Following a 2016 US Food and Drug Administration (FDA) Drug Safety Communication on the potential risk of cardiovascular adverse events with high doses of LOP, the OTC industry initiated a communications campaign (www.LoperamideSafety.org) to educate health professionals, including emergency medicine specialists, about LOP abuse/misuse awareness and prevention. Retrospective surveillance (eg, FDA Adverse Event Reporting System database and National Poison Data System) has traditionally been employed to track reports of drug abuse/misuse. We utilized modern online social listening technology to observe and analyze comments/conversations (posts) about LOP abuse/misuse on various websites and online social media platforms to gain earlier insight into potential LOP abuse/misuse. Methods: Utilizing the software tools Crimson Hexagon and Synthesio, we scanned thousands of publicly accessible user posts in online blogs, forums, and social networks – including major platforms such as Twitter, Facebook, YouTube, Reddit, and Forums – from January 2015 to March 2021 to observe posts about LOP abuse/misuse. Listening consisted of keyword-based scrapes of user-generated content using search terms including loperamide, Imodium, overdose, OD, get high, getting high, withdrawal, and related terms/phrases. Findings were analyzed and reported quarterly. Results: From January 2015 to March 2021, there were 27,213 user posts regarding LOP abuse/misuse among all observed online platforms. Annual post volume peaked in 2016 before declining in 2019/2020, consistent with the pattern of annual intentional exposure cases reported by the American Association of Poison Control Centers. Over 2015-2021, there was an average of 390 posts per month. Since May 2018, Reddit contained the majority of posts (70%), followed by Twitter (18%), YouTube (6%), Forums (4%), Facebook (<1%), and other sites (<1%). Reddit and Forums accounted for an increasing percentage of posts over time with a decrease for all other platforms. Posts primarily addressed the use of high-dose LOP for easing withdrawal symptoms (73%) or seeking euphoria (17%). Posts about risks and dangers of misuse/abuse were 16% of Reddit posts from Q2 2020 to Q1 2021, with a peak of 22% in Q2 2020. Spikes in posts coincided with key events, including journal article publications regarding effects of high doses (2,499 posts in May 2016 and 830 posts in January 2017) and FDA Drug Safety Communications regarding abuse/misuse of LOP (650 posts in June 2016 and 1,400 posts in January 2018). Post volume also appeared to increase in relation to US COVID-19 infection rates in 2020/2021 slightly. Conclusion: Online chatter about LOP abuse/misuse rose from 2015 to a peak in 2016 before declining in 2019/2020, consistent with the pattern of reported annual intentional exposure cases. While not a substitute for epidemiological surveillance, online social media listening is a useful adjunct surveillance strategy for earlier insight into potential LOP abuse/misuse by observing and analyzing online comments/conversations, sentiments and contexts. [Formula presented]
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Background: The SARS-Cov-2 pandemic led to significant ongoing disruptive change in healthcare from 3/2020 to the present. The impact and legacy on a national clinical trials organisation was assessed. Methods: A review was conducted of prospectively acquired communications, team logs and time sheets, trial activation, closure, and accrual, for the period 2019-present. An online survey of the impact of the pandemic on clinical investigators was performed. During lock-down periods hospital sites closed to monitoring visits and remote visits were not always possible due to paper- based health information systems. Overall accrual to academic cancer clinical trials decreased by 49%. Results: In the 9 months after the pandemic was declared clinical trial accrual fell by 54%, radiotherapy trial accrual by 90% and translational studies by 36%. Staff reassignment occurred in 60% of units. Monitoring visits by Clinical Research Associates was reduced by 42% and remote monitoring rose from 5% to 20% of monitoring visits. The opening of new trials fell by 67%. 77% of investigators experienced burnout, 71% had less time for trials and 53% reported less support for trials. Conclusions: The pandemic has had a significant negative impact on cancer clinical trial activity in Ireland with a notable decline in academic-led trial activity compared to pharmaceutical-led trials. Protected staff assignments, electronic records to facilitate remote monitoring and enhanced support for clinical trials staff is needed to increase resilience in the system. Legal entity responsible for the study: Cancer Trials Ireland. Funding: Cancer Trials Ireland. Disclosure: The author has declared no conflicts of interest.