ABSTRACT
South Africa has experienced several waves of SARS-CoV-2 infection following a slow vaccine roll-out. This resulted in extremely high population infection, with >98% of South Africans seropositive, and multiple cases of reinfection with diverse variants, which has shaped the quality and titers of antibody responses. South Africa also bears the brunt of the HIV pandemic, with 7.5 million PLWH. Of these, 2 million people do not access antiretroviral therapy, with implications for their ability to mount effective humoral responses, and to clear SARS-CoV-2 infection. Here, Moore will describe population-level vaccine-induced and hybrid humoral immunity in PLWH and HIV-uninfected individuals.
ABSTRACT
Symposium title: Addressing chronic pain and the opioid epidemic using auricular neuromodulation Symposium description: Our proposed symposium integrates a diverse group of scientist and clinician experts (Drs. Cunningham, Wilkes, Khodaparast, Badran) who have committed to exploring the anti-nociceptive and opioid sparing effects of auricular neuromodulation to progress toward non-opioid interventions for chronic pain and opioid use disorders. The demand for chronic pain therapies has increased at an unprecedented rate over the last several decades, contributing in part to a surge in prescription and illicit opioid demand. Countless patients were escalated to prolonged, high-dose opioid regimens over years of treatment. By 2014, 5.4% of U.S. adults were estimated to use prescription opioids on a long-term basis. As the harms of opioid proliferation became increasingly clear, a dramatic paradigm shift occurred in which these drugs are now perceived as more dangerous than beneficial for chronic pain. New clinical guidelines highlight the risks of high-dose regimens as well as the limited benefits, particularly insufficient analgesia and hyperalgesia, associated with long-term use. According to this new perspective, the preferred therapeutic modality for many patients is to safely taper, or even completely stop, using opioids. Transcutaneous auricular neurostimulation (tAN) is a novel therapeutic paradigm that includes stimulation of both the auricular branch of the vagus nerve and auriculotemporal nerve (branch of trigeminal). tAN therapy results in clinically significant reductions in opioid withdrawal symptoms associated with opioid detoxification and tapering. Either adjunctive vagal or trigeminal stimulation modulates pain transmission suggesting overlapping common effector pathways, possibly targeting the endogenous opioid system, which could lead to a synergistic therapeutic benefit for pain. This symposium will explore the scientific basis for this hypothesis across targeted and interconnected topics, including fundamental neuropharmacological mechanisms underlying pain and opioids, clinical challenges of tapering opioids, managing opioid withdrawal symptoms with tAN, and the prospects for tAN to deliver a safe alternative treatment option for pain disorders. The United States is experiencing an epidemic for prescription and non-prescription opioids, which have continued to rise since the 1990s. During 2015, approximately 2.1 million people were severely dependent on prescription opioids, and 513,000 on heroin. In 2020, the Centers for Disease Control reported 93,331 substance use overdose deaths. The continuing increase in opioid-related deaths from 2015 (18%) to 2020 (60%) is partly attributed to the mental health crisis during the Covid-19 pandemic. Aside from pain mitigation, individuals with opioid use disorder (OUD) may be motivated to continue drug-seeking by both the positive reinforcement of the euphoric effects of opioids and the negative reinforcement of opioid withdrawal symptoms due to cessation. Alternative approaches for OUD are a major priority for government agencies given the substantial impact on health, social, and economic welfare. Transcutaneous auricular neurostimulation (tAN) is a non-invasive form of vagus and trigeminal neuromodulation that was recently proven to be an efficacious non-pharmacologic based treatment for reducing opioid withdrawal symptoms. In 2021, tAN therapy received FDA clearance as an adjunctive treatment for opioid withdrawal symptoms in adults. tAN therapy was also proven safe and effective in reducing symptoms of neonatal opioid withdrawal syndrome (NOWS) in neonates. tAN as an adjuvant was safe, well-tolerated, while facilitating the successful rapid weaning of oral morphine and decreasing length of stay in the neonatal ICU. Based on these preliminary findings, tAN therapy is currently in two NIH-funded pivotal clinical trials to: 1) evaluate the long-term effects of tAN on opioid use relapse prevention and cravings in adults with OUD, and 2) determine f tAN therapy can reduce withdrawal symptoms and reduce morphine length of treatment for neonates with NOWS. Lastly, we will explore how tAN could be utilized as neuromodulatory approach for opioid sparing, and ultimately pain mitigation. Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Vagus Nerve Stimulation, Opioid Use Disorder, Pain, NeurostimulationCopyright © 2023
ABSTRACT
Background: South Africa is one of the African countries most affected by the COVID-19 pandemic. SARS-CoV-2 seroprevalence surveys provide valuable epidemiological information given the existence of asymptomatic cases. We report the findings of the first nationwide household-based population estimates of SARS-CoV-2 seroprevalence among people aged 12 years and older in South Africa. Methods: The survey used a cross-sectional multi-stage stratified cluster design undertaken over two separate time periods (November 2020-February 2021 and April-June 2021) which coincided with the second and third waves of the pandemic in South Africa. The Abbott® and Euroimmun® ani-SARS CoV-2 antibody assays were used to test for SARS-CoV-2 antibodies, the latter being the final result. The survey data was weighted with final individual weights benchmarked against 2020 mid-year population estimates by age, race, sex, and province. Frequencies were used to describe characteristics of the study population and SARS-CoV-2 seroprevalence. Bivariate and multivariate logistics regression analysis were used to identify factors associated with SARS-CoV-2 seropositivity. Results: 13640 participants gave a blood sample. The SARS-CoV-2 seroprevalence using the Euroimmun assay was 19.6% (95% CI 17.9-21.3) over the study period, translating to an estimated 8 675 265 (95% CI 7 508 393-9 842 137) estimated infections among people aged 12 years and older across South Africa by June 2021. Seroprevalence was higher in the Free State (26.8%), and Eastern Cape (26.0%) provinces (Figure). Increased odds of seropositivity were associated with prior PCR testing [aOR=1.29 (95% CI: 0.99-1.66)], being female [aOR=1.28 (95% CI 1.00-1.64), p=0.048] and hypertension, [aOR=1.28 (95% CI 1.00-1.640, p=0.048]. Conclusion: These findings highlight the burden of infection in South Africa by June 2021, and support testing strategies that focus on individuals with known exposure or symptoms since universal testing is not feasible. Females and younger people were more likely to be infected suggesting need for additional strategies targeting these populations. The estimated number of infections was 6.5 times higher than the number of SARS-CoV-2 cases reported nationally, suggesting that the country's testing strategy and capacity partly explain the dynamics of the pandemic. It is therefore essential to bolster testing capacity and to rapidly scale up vaccinations in order to contain the spread of the virus in the country.
ABSTRACT
Background: Accurate and reliable serological assays are essential for epidemiological surveillance of SARS-CoV-2. Several commercial anti-SARS assays are available and use cases for serological testing includes surveillance. However, there is growing evidence of varying performance of SARS-CoV-2 assays dependent of their format. We compare the performance of 3 different assays used in a national serosurvey undertaken between April and June 2021, in South Africa before widescale vaccination roll out. Methods: Venous blood samples from participants ≥12 years were transported under cold chain to a central testing laboratory within 24 hours of collection. Samples were tested for SARS CoV-2 antibodies with the Abbott nucleocapsid (NC)-based Architect anti-SARS CoV-2 chemiluminescent microparticle immunoassay (CMIA), the EuroImmun Spike (S)-based assay and the Roche total IgG NC-based Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay (ECLIA) on the Cobas e411 platform. We compared antibody detection proportions. Results: 8146 participants (median age 40 years, IQR 26-55) 5.6% of whom reported ≥1 SARS-CoV-2 symptom in the preceding 3 months gave a blood sample. Samples were tested on the Abbott assay with different cut-offs:-15.5% tested positive at the 1.40 cut-off and 26.8% at the 0.49 lower cut-off. 21.6% of the samples tested positive on the Euroimmun and 39.0% tested positive on the Roche assay (Table). 286 samples were from respondents self-reporting a prior positive PCR test, and among them 149(52.1%), 156(54.6%), and 206(72.3%) were positive on the Abbott (1.40 cut-off), Euroimmun and Roche assays respectively. 116/286(40.6%) of these were positive on all three assays and with 21(7.3%) positive on Roche only. 224/286(78.3%) of those reporting prior PCR test positivity were positive at the lower Abbott cut-off, with 47(16.4%) positive on Abbott only. Conclusion: These samples collected before wide scale vaccination roll out in South Africa show variable performance of these assays with the Roche NC assay detecting more infections that both the Abbott NC assay(0.40 cut-off) and the Euroimmun S assay.This could be reflective of seroreversion previously reported with Abbott and Euroimmun, and the greater sensitivity of Roche assay targeting the more abundant NC as an epitope. Use of direct, double Antigen-sandwich-based assays that are stable and have increased sensitivity over time may be optimal to detect both natural and vaccine-induced immunity in serosurveys.
ABSTRACT
Evaluation of E-Learning resources plays a significant role in the context of pedagogic systems. Resource evaluation is important in both conventional ‘talk-and-chalk’ teaching and in blended learning. In on-line (e-learning) teaching [an enforced feature of pedagogic systems in tertiary education during the Covid-19 pandemic] the effective evaluation of teaching resources has obtained importance given the lack of ‘face-to-face’ student-teached interaction. Moreover, the enforced use of e-learning has demonstrated the effectiveness of on-line pedagogic systems, which has been argued in blended learning pedagogic systems. Additionally, in e-learning, the lack of ‘face-to-face’ meetings [between teaching staff and students and in staff meetings] makes feedback (positive and negative) important for all actors in the pedagogic system. In this paper we present a novel approach to enable effective evaluation of teaching resources, which provides effective group decision-support designed to evaluate e-learning resources, enhancing students’ satisfaction. The proposed approach employs Picture Fuzzy Sets to quantify survey responses from actors, including: agree, disagree, neutral, and refuse to answer. In our approach, the system can manage the evaluation of e-learning resources based on both explicit and tacit knowledge using a picture fuzzy rule-based approach in which linguistic semantic terms are used to express rules and preferences. The proposed system has been tested using e-learning case studies with the goal of enhancing the learning experience and increasing students' satisfaction. Experimental results demonstrate that our proposed approach achieves a significant improvement in performance in the evaluation of e-learning resources. Copyright © International Journal of Mathematical, Engineering and Management Sciences.
ABSTRACT
Evaluation of E-Learning resources plays a significant role in the context of pedagogic systems. Resource evaluation is important in both conventional 'talk-and-chalk' teaching and in blended learning. In on-line (e-learning) teaching [an enforced feature of pedagogic systems in tertiary education during the Covid-19 pandemic] the effective evaluation of teaching resources has obtained importance given the lack of 'face-to-face' student-teached interaction. Moreover, the enforced use of e-learning has demonstrated the effectiveness of on-line pedagogic systems, which has been argued in blended learning pedagogic systems. Additionally, in e-learning, the lack of 'face-to-face' meetings [between teaching staff and students and in staff meetings] makes feedback (positive and negative) important for all actors in the pedagogic system. In this paper we present a novel approach to enable effective evaluation of teaching resources, which provides effective group decision-support designed to evaluate e-learning resources, enhancing students' satisfaction. The proposed approach employs Picture Fuzzy Sets to quantify survey responses from actors, including: agree, disagree, neutral, and refuse to answer. In our approach, the system can manage the evaluation of e-learning resources based on both explicit and tacit knowledge using a picture fuzzy rule-based approach in which linguistic semantic terms are used to express rules and preferences. The proposed system has been tested using e-learning case studies with the goal of enhancing the learning experience and increasing students' satisfaction. Experimental results demonstrate that our proposed approach achieves a significant improvement in performance in the evaluation of e-learning resources.
ABSTRACT
[Figure: see text].
ABSTRACT
Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe disease that affects a small proportion of children exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Differences in SARS-CoV-2 antibody responses and immune gene expression between SARS-CoV-2-infected children who develop MIS-C and those who do not may provide insight into the mechanism of MIS-C. Objectives: To determine the difference in SARS-CoV2 antibody responses and immune gene expression in children with MIS-C and healthy children with evidence of previous SARS-CoV2 infection. Methods: Healthy children presenting for elective surgery and those with MIS-C were recruited between 22 June 2020 and 5 November 2020 from a single paediatric hospital during the first wave of SARSCoV- 2 in the region. Clinical data, whole blood RNA and serum were collected. Titres of SARS-CoV-2 spike-specific antibody (SAb) and their capacity to perform neutralization, antibody-dependent cellular phagocytosis (ADCP) and antibody dependant cellular cytotoxicity (ADCC) were measured. Whole blood RNA gene expression was measured using multiplex Fluidigm quantitative Polymerase Chain Reaction (qPCR) with a panel of 84 immune genes. Principal component analysis was performed to assess for differences in gene expression. A linear regression model was developed with a forward stepwise model selection method to assess which genes associated with Creactive protein (CRP) in MIS-C after controlling for the neutrophil to lymphocyte ratio (NLR). Results: Twenty-three children with MIS-C and 25 healthy children were recruited. Nine healthy children had detectable SARS-CoV-2 serum antibodies (healthy exposed). No children had preceding clinical disease related to SARS-CoV-2 infection. Comparing children with MIS-C and healthy exposed children showed no difference in SAb binding responses (p=0.372) or ADCC (p=0.992). Increased neutralisation titre (p=0.084) and ADCP (p=0.086) in children with MIS-C was observed although was non-significant. Antibody function or titre did not change over time or with treatment in MIS-C. There was a clear distinction in immune gene expression between healthy children and those with MIS-C. Immune gene expression in MIS-C resolved to become indistinct from healthy children with time. Whole blood immune gene expression associated with an abundance of neutrophils in MIS-C. In a model that accounted for 66% of the variance in CRP (adjusted R2 = 0.66) the expression of IL27 accounted for 64% of the model effect (B=35;p<0.001) followed by NLR (15%, B=6.6, p=0.002) and the expression of MCP2 (11%, B=-14.59, p=0.008). Conclusion: Comparing children infected with SARS-COV-2 from the same time period and region with or without MIS-C provides unique mechanistic insight into the disease. A trend towards higher SAb titres and ADCP implies a distinct humoral immune response to SARSCOV- 2 in children with MIS-C, although further studies are required to validate this observation. The resolution of the abnormal immune gene expression in MIS-C implies a monophasic immune perturbation. The association of IL27 and MCP2 with CRP suggests that these may be important targets in future studies for possible pathogenicity and as potential biomarkers in MIS-C.
ABSTRACT
The emergence of the COVID-19 viral pandemic has generated a renewed interest in pharmacologic agents that target the renin angiotensin system (RAS). Angiotensin-converting enzyme 1 (ACE1) inhibitors decrease the synthesis of angiotensin II (Ang II) from its precursor angiotensin I and inhibit the breakdown of bradykinin, while Ang II receptor blockers antagonize the action of Ang II at the receptor level downstream. The actions of both classes of drugs lead to vasodilation, a blunting of sympathetic drive and a reduction in aldosterone release, all beneficial effects in hypertension and congestive heart failure. ACE2 cleaves the vasoconstrictor Ang II to produce the anti-inflammatory cytoprotective angiotensin 1-7 (Ang 1-7) peptide, which functions through the G protein-coupled receptor MAS to counteract the pathophysiologic effects induced by Ang II via its receptors, including vasoconstriction, inflammation, hypercoagulation, and fibrosis. SARS-CoV-2 enters human cells by binding ACE2 on the cell surface, decreases ACE2 activity, competes for ACE2 receptor-binding sites, and shifts the RAS toward an overexpression of Ang II, accounting for many of the deleterious effects of the virus. Thus, there is great interest in developing recombinant ACE2 as a therapeutic for prevention or treatment of COVID-19. Notably, ACE2 is highly expressed in the oral cavity, and saliva and dorsum of the tongue are major reservoirs of SARS-CoV-2. Cost-effective methods to debulk the virus in the oral cavity may aid in the prevention of viral spread. Here we review the pharmacology of targeted small molecule inhibitors of the RAS and discuss novel approaches to employing ACE2 as a therapeutic for COVID-19.
Subject(s)
COVID-19 , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Humans , Renin-Angiotensin System , SARS-CoV-2ABSTRACT
Introduction: Device follow up was routinely performed in person pre-March 2020. When the COVID pandemic caused lockdown in the UK this led to new methods of performing the 4-6-week check: utilising remote monitoring and patients sending wound images. We wanted to investigate the patient’s perspective of this experience: comparing traditional follow up vs remote only follow up. We hypothesised that this would have no effect on satisfaction but would show limitations of remote only working in particular patient groups. Methods: Patients who had a device procedure in the months Jan-April 2020 would be asked to complete a telephone survey, excluding ILR devices. This survey consists in 25 questions, which were divided into 5 parts to define the stages of patient journey: pre implant, post implant on the ward, wound management, one-month post implant appointment and overall satisfaction. Each question is rated from 1 to 5 (negative to positive depending in the question). We will compare the results of in person follow up and remote only follow up. Results: A total of 222 patients completed the survey, 88 (40%) in the traditional face to face follow up and 134 (60%) in the remote only group. No difference was seen comparing the sections on pre implant, post implant, wound management and satisfaction of the two groups. For the 134 patients in the 1/12 virtual post implant check group, 92 patients found it very easy to set up their home monitor and 6 patients found it very difficult. Older patients found this slightly more difficult to set up the home monitor, however, patients up to the age of 91 did find this very easy. 60 patients found sending a wound image via email very easy and 60 patients found this very difficult. The age when patients started to struggle more was 71 years old (Fig 1). Of the 134 patients that received remote only follow up a total of £1317.50 was saved not having to pay for travel into clinic. Of these 134 patients 37 would have received free transport. For the 88 patients who visited clinic, £607.50 was spent to travel into clinic, of which 44 received free transport. For the future, 54% of patients would prefer remote only and 46% would prefer in clinic follow up. However, there was no difference in age for these patients. Discussion: Patients appear to be satisfied with both follow up plans. However, this survey highlighted key limitations for remote only 1/12 follow up. The ability to set up a remote monitor did slightly decrease with age. This will be helped by the majority of patients having remote monitoring set up prior to discharge. The difference between patients who were able to send an email with a photo of the wound site highlights a difference in patients’ technical ability at all ages, with older patients finding this more challenging. Centres wanting to adapt this model of care should be knowledgeable of this and consider other options, such as GP/practice nurse wound assessment, or in clinic follow up for these select patients. This difference would allow services to reduce their footfall into device clinics and financial savings to the patient. Unexpectedly patients were split in their option for future follow up which requires further investigation. Due to the COVID 19 pandemic services are socially distancing across the country. Remote only follow up has its limitations, most importantly being receiving the information from the patients. Services can develop pathways from this data to find out which patients would be best suited to this follow up schedule. [Image Omitted]
ABSTRACT
Background: On the 23rd March 2020 the UK went into lockdown due to COVID-19 with vulnerable patients advised to shield at home. Patients with implantable devices still required battery changes and other interventions during this period, both clinically urgent and routine. A new strategy for identifying those needing urgent procedures was introduced at a tertiary cardiac centre to balance the risks of delaying procedures vs coming out of shielding. Method: In normal circumstances, we perform 20-30 device re-intervention procedures per month including box changes, lead revisions, device upgrades and wound revisions. Patients are referred via device clinic or directly by a Consultant. Routinely we aim to box change patients at the time elective replacement indicator (ERI) is triggered. Most elective work was cancelled and patients requiring procedures were identified and booked in first. Working closely with Electrophysiology (EP) Consultants we developed new groups to sort patients (Table 1). An earlier referral threshold of 6 months till ERI was set to plan procedures in advance. Legacy device patients were sent remote monitors (RM) to maintain safety and delay procedures. Regular downloads for patients approaching ERI allowed them to isolate as long as possible. Results: During the months of March-May 2020 the number of requests increased from 25 to 56 requests (Figure 1). A peak in April 2020 of 50 device re-intervention procedures. Five patients hit ERI and had to be upgraded from Urgent to Very Urgent. Three of these had been delayed due to patient/family preference. One Fortify advisory had to be admitted due to prematurely triggering ERI. Three patients had their procedures done locally instead. Ten further patients have been referred for re-intervention locally. Three patients died on the waiting list, all sadly due to contracting COVID-19 in community. Two patients required input from the trust’s safeguarding team due to lack of contact with patient at predicted ERI and non-compliance with RM. From Jan-July 2020 the average referral to treatment time (RTTT) constantly averaged at 50 days. Discussion: Adaptations to this service involved multiple teams working together to maintain patient safety. This involved scheduling, pre admissions and Cardiac Scientists. We also transitioned to a Cardiac Scientist led service empowering the team to risk stratify patients. A further challenge presented itself: a subgroup of patients declined procedures. We compromised with some patients;three patients had procedures at a local centre to avoid travelling into London. Linked trusts referrals to our centre increased during this period, likely due similar measures of lowering thresholds. Linked trusts did not have access to RM, requiring them to directly refer for box changes rather than having the luxury of delaying procedures. Some legacy patients had devices that were incompatible with RM or declined a RM. Since lowering the referral threshold, a rise in referrals was expected, however, the results suggest that a back log of referrals, as the RTTT was indifferent. Collaborating with colleagues internally, local centres and enrolling on RM maintained shielding and device safety towards end of battery. This exemplifies solidarity across cardiac services during the COVID pandemic. [Image Omitted] [Image Omitted]