Evaluation of self-reported confidence amongst radiology staff in initiating basic life support across hospitals in the Cape Town Metropole West region

Introduction: The immediate response to a cardiac arrest is regarded as one of the most time-critical interventions in clinical medicine. First responders for cardiac arrest in imaging departments are often radiology staff. The study aim was to determine radiology staff-members' confidence in initiating basic life support. Methods: A multi-centre, cross-sectional survey was conducted using peer-validated, anonymous questionnaires. Confidences were recorded using a 10-point Likert scale for recognising cardiac arrest, securing an airway, providing rescue breaths and initiating cardiac compressions. Questionnaires were distributed to and completed by radiology staff working in public sector hospitals within the Cape Town Metropole West. Due to the limited subject pool a convenience sample was collected (with no power calculation). Data were therefore statistically analysed using only summary statistics (mean, standard deviation (SD), proportions, etc.). Detailed between group comparisons were not made, given the sample size and type. Results: We disseminated 200 questionnaires, of which 74 were completed (37%). There were no incomplete questionnaires or exclusions from the final sample. Using the Likert scale, the mean ability to recognise cardiac arrest was 6.45 (SD±2.7), securing an airway 4.86 (SD±2.9), and providing rescue breaths and initiating cardiac compressions 6.14 (SD±2.9). Only 2 (2.7%) of the participants had completed a basic life support course in the past year, while 11 (14.8%) had never completed any basic life support course and 28 (37.8%) had never completed any type of life support or critical care course. Radiologists, radiology trainees and nurses had the greatest confidence in providing rescue breaths and initiating cardiac compressions from all the groups. Conclusion: The study demonstrates substantial lack of confidence in providing basic life support in a large part of the staff in Cape Town’s public hospital imaging departments. The participants indicated that regular training and improved support systems would increase confidence levels and improve skills

Plant-based production of highly potent anti-HIV antibodies with engineered posttranslational modifications

Broadly neutralising antibodies (bNAbs) against human immunodeficiency virus type 1 (HIV-1), such as CAP256-VRC26 are being developed for HIV prevention and treatment. These Abs carry a unique but crucial post-translational modification (PTM), namely O-sulfated tyrosine in the heavy chain complementarity determining region (CDR) H3 loop. Several studies have demonstrated that plants are suitable hosts for the generation of highly active anti-HIV-1 antibodies with the potential to engineer PTMs. Here we report the expression and characterisation of CAP256-VRC26 bNAbs with posttranslational modifications (PTM). Two variants, CAP256-VRC26 (08 and 09) were expressed in glycoengineered Nicotiana benthamiana plants. By in planta co-expression of tyrosyl protein sulfotransferase 1, we installed O-sulfated tyrosine in CDR H3 of both bNAbs. These exhibited similar structural folding to the mammalian cell produced bNAbs, but non-sulfated versions showed loss of neutralisation breadth and potency. In contrast, tyrosine sulfated versions displayed equivalent neutralising activity to mammalian produced antibodies retaining exceptional potency against some subtype C viruses. Together, the data demonstrate the enormous potential of plant-based systems for multiple posttranslational engineering and production of fully active bNAbs for application in passive immunisation or as an alternative for current HIV/AIDS antiretroviral therapy regimens.The Department of Science and Technology (DST), South African Medical Research Council - Strategic Health Innovation Partnership (SAMRC SHIP) and Council for Scientific and Industrial Research (CSIR).http://www.nature.com/srepam2021Plant Production and Soil ScienceProduction Animal Studie

Study protocol for a phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis [LASER-TBM] [version 1; peer review: 2 approved]

Background: Tuberculous meningitis (TBM) is the most lethal form of tuberculosis with a mortality of ~50% in those co-infected with HIV-1. Current antibiotic regimens are based on those known to be effective in pulmonary TB and do not account for the differing ability of the drugs to penetrate the central nervous system (CNS). The host immune response drives pathology in TBM, yet effective host-directed therapies are scarce. There is sufficient data to suggest that higher doses of rifampicin (RIF), additional linezolid (LZD) and adjunctive aspirin (ASA) will be beneficial in TBM yet rigorous investigation of the safety of these interventions in the context of HIV associated TBM is required. We hypothesise that increased dose RIF, LZD and ASA used in combination and in addition to standard of care for the first 56 days of treatment with be safe and tolerated in HIV-1 infected people with TBM. Methods: In an open-label randomised parallel study, up to 100 participants will receive either; i) standard of care (n=40, control arm), ii) standard of care plus increased dose RIF (35mg/kg) and LZD (1200mg OD for 28 days, 600mg OD for 28 days) (n=30, experimental arm 1), or iii) as per experimental arm 1 plus additional ASA 1000mg OD (n=30, experimental arm 2). After 56 days participants will continue standard treatment as per national guidelines. The primary endpoint is death and the occurrence of solicited treatment-related adverse events at 56 days. In a planned pharmacokinetic (PK) sub-study we aim to assess PK/pharmacodynamic (PD) of oral vs IV rifampicin, describe LZD and RIF PK and cerebrospinal fluid concentrations, explore PK/PD relationships, and investigate drug-drug interactions between LZD and RIF. Safety and pharmacokinetic data from this study will inform a planned phase III study of intensified therapy in TBM. Clinicaltrials.gov registration: NCT03927313 (25/04/2019