The impact of the South African Covid-19 lockdown on incidence and severity of traumatic brain injury at Tshepong hospital: A multivariate retrospective cohort study.

Background: Globally traumatic brain injuries (TBIs) are the leading cause of death in people under the age of 45. 2020 saw a series of social lockdowns as a response to the COVID-19 pandemic. We aimed to unveil the impact of the different levels of lockdown on TBI incidence at Tshepong Hospital. Method: A retrospective review of patients with TBIs during the first 30 days of each of the 5 lockdown levels, between 1st of April -20th October 2020 was conducted. Each lockdown level was compared to a control of a similar period in 2019. Results: Level 5 lockdown resulted in a 66% reduction in total incidence of TBI, with a decrease in the daily incidence median value to 0 when compared to its control group median of 1 (P-value 0.004). However, Level 3 and 2 resulted in a significant 133% and 200% increase respectively in TBI incidence for similar period the year before.There was a 0,75% decrease in total trauma during the non-lockdown periods in relation to the lock down periods with a lockdown mean incidence of 53,4 (std Dev. 26.6) and non-lockdown mean of 53 (std Dev 20.8). Conclusion: The cumulative effect of the lockdowns made miniscule changes in the overall TBI incidence but led to significant variation in TBI incidence in the comparative months. A "rebound trauma" phenomena is observed in transitioning from severe social restrictions to milder ones with unemployment and unbanning of alcohol as possible contributary factors. Further studies are needed to investigate these complex interactions.

Improving mycobacterial sputum culture collection in adult patients during the highly effective modulator therapy era

Background: Taking annual mycobacterial sputum cultures (MSCx) is a best practice standard for surveillance of nontuberculous mycobacterium (NTM) infection. MSCx collection among sputum-producing people with CF (PwCF) is essential for early identification and management of NTM. Initiation of highly effective modulator therapy (HEMT), elexacaftor/ tezacaftor/ivacaftor in 2019, resulted in a reduction in sputum production in PwCF. The concurrent emergence of the COVID-19 pandemic led to a shift from in-person to virtual clinic visits. These two events led to a dramatic decline in the rate of MSCx collection at our center-from 52.7% (2019) to 26.5% (2020) based on our CF Patient Registry report. We used a multidisciplinary approach to evaluate and implement continuous quality improvement (CQI) measures with the aim of increasing MSCx collection from 52.7% to 65% in 12 months. Eligibility was defined as producing 1 mL or more of sputum and no MSCx within the past 12 months. Method(s): The Minnesota CF Center care team consists of multidisciplinary specialties and approximately 450 PwCF. The CQI team generated the aim and developed a process map highlighting key stakeholders and barriers to MSCx collection. The team used a plan-do-study-act (PDSA) model to optimize key steps involved in MSCx collection. The first PDSA model included microbiology lab leadership identifying optimal (5-10 mL) and acceptable (>=1 mL) sputum volumes to avoid rejected specimens. Next, providers approved a new protocol to prioritize first sputum collection for MSCx and subsequent collection for CF bacterial cultures in eligible PwCF. Development of a certified medical assistant flowchart guided determination of eligibility for MSCx collection (Figure 1). Certified medical assistant then used a paper tool to document eligibility, specimen type, and lab orders placed for PwCF in clinic during the 4-week PDSA cycle. The paper tool was adapted using electronic health record (EHR) capabilities to generate date of last MSCx and allow electronic documentation of specimen collection type and orders placed. Result(s):With the use of HEMT, the percentage of sputum-producing PwCF declined from 74% to 40%. Use of process mapping and paper tool identified barriers to collecting MSCx in our clinic. Workflows were established through recurrent PDSA cycles to identify actionable interventions (education of lab personnel, paper tool, EHR documentation), which has led to collection of 53% of eligible samples-up from 26.5% in 2020 and on Figure 1 : Certified medical assistant (CMA) flowchart for mycobacterial sputum culture (MSCx) collection to determine patient eligibility and order placement(Figure Presented) track for 65% MSCx collection for the year. The paper tool revealed that the greatest barrier to obtaining MSCx was lab cancellation. By November, the team will complete another PDSA cycle after further lab education with the aim of decreasing the number of MSCx that the lab erroneously rejects. Conclusion(s): Despite the reduction in sputum production after use of HEMT, approximately 40% of PwCF still produce sufficient sputum for MSCx monitoring. Applying effective CQI tools including process mapping, PDSA cycles, pareto charts, and run charts to implement an improved, standardized workflow can increase the rate of MSCx, which will aid in detection and management of NTM infections and inform the epidemiology of NTM in the era of HEMT Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

SARS-CoV-2 Epitopes following Infection and Vaccination Overlap Known Neutralizing Antibody Sites.

Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites, but can be laborious. Herein, we employed peptide microarrays to map linear peptide epitopes (LPEs) recognized following SARS-CoV-2 infection and vaccination. LPEs detected by nonhuman primate (NHP) and patient IgMs after SARS-CoV-2 infection extensively overlapped, localized to functionally important virus regions, and aligned with reported neutralizing antibody binding sites. Similar LPE overlap occurred after infection and vaccination, with LPE clusters specific to each stimulus, where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function. Vaccine-specific LPEs tended to map to sites known or likely to be affected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein. Mapping LPEs to regions of known functional importance in this manner may accelerate vaccine evaluation and discovery of targets for site-specific therapeutic interventions.

Rationale and design of the pragmatic randomized trial of icosapent ethyl for high cardiovascular risk adults (MITIGATE).

OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.