Validation of dried blood spot sampling for detecting SARS-CoV-2 antibodies and total immunoglobulins in a large cohort of asymptomatic young adults.

BACKGROUND: Detecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. METHODS: We compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. RESULTS: Baseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. CONCLUSIONS: This is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.

A telemedical interface for at-home cognitive testing

BACKGROUND: The COVID-19 pandemic has limited in-lab cognitive testing. While at-home alternatives exist (testing over the phone), differences in test design and delivery complicate direct comparison of most in-lab and at-home tests. Here we describe the design, infrastructure, and implementation of the California Cognitive Assessment Battery (CCAB), a cognitive test battery and administration system. Using automated remote administration over cellular networks, identical computerized cognitive tests can be administered at-home or in the lab.

Phenocomb, a Tool for Evaluating Complex Phenotypes in High-Dimension Cytometry Datasets

Background Modern cytometry can simultaneously measure dozens of markers, empowering investigation of complex phenotypes. However, manual gating relies on previous biological knowledge, and clustering/dimension-reduction tools fail to capture discrete phenotypes. Consequently, complex phenotypes with potential biological importance are often overlooked. To address this, we developed PhenoComb, an R package that allows agnostic exploration of complex phenotypes by assessing the frequencies of all marker combinations in cytometry datasets. Methods PhenoComb uses signal intensity thresholds to assign markers to discrete states (e.g. negative, low, high). As Pheno- Comb works in a memory-safe manner, time and disk space are the only constraints to the number of markers and discrete states that can be evaluated. Next, the number of cells per sample from all possible marker combinations are counted and frequencies assessed. PhenoComb provides several approaches to perform statistical comparisons, evaluate the relevance of phenotypes, and assess the independence of identified phenotypes. PhenoComb also allows users to guide analysis by adjusting several function arguments such as identifying parent populations of interest, filtering low-frequency populations, and defining a maximum marker complexity. PhenoComb is compatible with local computer or server-based use. Results In testing of PhenoComb's performance on synthetic datasets, computation on 16 markers was completed in the scale of minutes and up to 26 markers in hours. We applied PhenoComb to two publicly available datasets: an HIV flow cytometry dataset (12 markers and 421 samples) and the COVIDome CyTOF dataset (40 markers and 99 samples). In the HIV dataset, PhenoComb identified immune phenotypes associated with HIV seroconversion, including those highlighted in the original publication. In the COVID dataset, we identified several immune phenotypes with altered frequencies in infected individuals relative to healthy individuals. Conclusions PhenoComb is a unique and powerful tool for agnostically assessing phenotypes. By more fully utilizing the high-dimension data in single cell datasets, PhenoComb empowering exploratory data analysis and discovery of phenotypes for further characterization.

Healing Right Way RCT: Novel interventions to enhance the cultural security of rehabilitation services for Aboriginal Australians with brain injury

Background: Access to rehabilitation services for Aboriginal people following acquired brain injury (ABI) is frequently hindered by challenges navigating: i) complex medical systems, ii) geographical distances from services and iii) culturally insecure service delivery. Healing Right Way is the first randomised control trial (RCT) to address these issues in partnership with multiple health service providers across Western Australia (WA). Aims: To outline the multicomponent Healing Right Way intervention by providing case studies, and describing challenges, facilitators and implications for rehabilitation services. Method: This stepped-wedge cluster RCT involved four metropolitan and four regional sites across WA. Aboriginal adults hospitalised for ABI were recruited from 2018-2021. Intervention components comprised ABI-related cultural security training (CST) for hospital staff, and employment of Aboriginal Brain Injury Coordinators (ABICs) to support ABI survivors for six months post-injury. The primary outcome was quality of life (measured with Euro QOL-5D-3L VAS) at 26 weeks. Secondary outcomes included participants' overall function and disability, anxiety and depression, carer strain, and changes to service delivery across the 26-week follow-up period. Detailed process and cost evaluations were also undertaken. Results: 108 participants were recruited from the participating sites. The CST was delivered across all eight participating hospitals with 250 hospital staff trained. ABICs supported 61 participants, 70% residing in regional, rural or remote areas. Challenges to implementation of the intervention included impacts from COVID-19 responses, hospital staff turnover and availability, recruitment of people with traumatic brain injury and methods for maintaining contact with participants and next-of-kin across locations. Collaboration with Aboriginal health providers and community networks were invaluable to maintaining contact with participants during follow-up, as was telehealth and research partnerships. Discussion/Conclusions: This landmark trial provides a novel multicomponent intervention in an underserviced population to inform muchneeded service improvements for Aboriginal people with ABI across metropolitan and rural settings.

Online or onsite? Comparison of the relative merit of delivery format of Aboriginal cultural-awareness-training to undergraduate chiropractic students

Purpose: The purpose of this paper is to work with Aboriginal and Torres Strait Islander people (ATSI), it is expected that non-ATSI health-care professionals become culturally aware;however, participants’ perceptions of the relative merit of cultural awareness training (CAT) formats is uncertain. Design/methodology/approach: The authors compared undergraduate students’ perceptions of an asynchronous online format with onsite delivery formats of CAT using a mixed-method design. Students from five successive cohorts (n = 64) in an undergraduate programme were invited to complete a post-training survey which gathered quantitative and qualitative data. Findings: Whilst feedback was positive regarding both formats, the onsite format was preferred qualitatively with several valuable learning outcome themes emerging from the results. These themes included;“perceived benefits of self-evaluation of students’ own culture whilst learning about Aboriginal culture”;“encouraging to be provided with scenarios, examples and exercises to enhance cultural awareness” and “engagement with the interactive facilitator approach”. There were differing views about the benefits of learning the history of oppression which warrant further research. Research limitations/implications: Results may be applicable to undergraduate allied health students who participate in clinical immersion placements (CIPs) who participate in Aboriginal CAT. Practical implications: Given the changing dynamic in education forced by the COVID-19 pandemic, more resources may need to be directed to improving online training and possibly combining formats in course delivery. Social implications: The strength of the study is that the authors achieved a response rate of 100%, thus the results are highly significant for the sample. This sample represents 41.3% of chiropractic students who attended CAT and CIPs at this university over the course of 9 years, thus the results could be generalized to chiropractic students who participated in these types of placements. Originality/value: To the best of the authors’ knowledge, this is the first study to compare student perceptions of different formats of Aboriginal CAT for final year chiropractic undergraduate students in Australia. © 2021, Emerald Publishing Limited.

Manipulation under anaesthetic for frozen shoulder: Does post-operative supervised physiotherapy affect the outcome?

Introduction: This study compares two pathways for patients undergoing MUA for FS, one where physiotherapy advice is only given to the patient (Group 1), and the other where supervised hydrotherapy and physiotherapy occur post operatively (Group 2). Method: A descriptive analysis of pre-and post-operative Oxford Shoulder Scores and change scores were performed. Analysis of covariance (ANCOVA) was used to measure the effect of physiotherapy on post-operative OSS, with pre-operative OSS as the only covariate. Results: The results for post-operative OSS were significantly greater for Group 2 than for Group 1 (40.7 for NHS and 44.7 for private, improvement of 17.32 for NHS and 18.23 for Private). The estimated effect of physiotherapy on postoperative OSS was an increase of 3.2 (95% confidence interval 1.5-4.8). Conclusions: We detected a statistically significant increase in postoperative OSS in patients treated for frozen shoulder with MUA + physiotherapy compared with patients receiving MUA plus advice alone. These results suggest that physiotherapy does confer a real benefit, however the increased OSS is below the clinically significant level. Therefore, in a resource poor environment, such as may exist after COVID in many health care systems, MUA plus physio advice alone gives an excellent outcome for the treatment of FS.

The use of routine blood tests to assist the diagnosis of COVID-19 in symptomatic hospitalized patients.

INTRODUCTION: Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19. METHOD: A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient's clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation. RESULTS: Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of -0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR. DISCUSSION: Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.

Does vitamin D supplementation prevent SARS-CoV-2 infection in military personnel? Review of the evidence.

For most individuals residing in Northwestern Europe, maintaining replete vitamin D status throughout the year is unlikely without vitamin D supplementation and deficiency remains common. Military studies have investigated the association with vitamin D status, and subsequent supplementation, with the risk of stress fractures particularly during recruit training. The expression of nuclear vitamin D receptors and vitamin D metabolic enzymes in immune cells additionally provides a rationale for the potential role of vitamin D in maintaining immune homeostasis. One particular area of interest has been in the prevention of acute respiratory tract infections (ARTIs). The aims of this review were to consider the evidence of vitamin D supplementation in military populations in the prevention of ARTIs, including SARS-CoV-2 infection and consequent COVID-19 illness. The occupational/organisational importance of reducing transmission of SARS-CoV-2, especially where infected young adults may be asymptomatic, presymptomatic or paucisymptomatic, is also discussed.