COVID-19-Related Encephalitis in a Child with PIK3CD Defect

Introduction: COVID-19 related encephalitis has been reported in pediatric patients;however, there are no reports in patients with inborn errors of immunity (IEI). Activated PI3K Delta Syndrome (APDS) is a disease of immune dysregulation with immunodeficiency, autoimmunity, and abnormal lymphoproliferation resulting from autosomal dominant gain-offunction variants in PIK3CD or PIK3R1 genes. We investigate a family with APDS, one mother and three children, one of whom developed COVID-19 related encephalitis. Method(s): Patients were consented to an IRB-approved protocol at our institution. Medical records and detailed immunophenotyping were reviewed. Family members were sequenced for IEI with a targeted gene panel. Result(s): The index case is a 10-year-old female with a known pathogenic variant in PIK3CD (c.3061 G > A, p.Glu1021Lys), who contracted SARS-COV-2 despite one COVID-19 vaccination in the series. Her disease course included COVID-related encephalitis with cerebellitis and compression of the pons, resulting in lasting truncal ataxia and cerebellar mutism. At that time, the patient was not on immunoglobulin replacement therapy (IgRT), but was receiving Sirolimus. Besides the index case, 3 family members (2 brothers, 1 mother) also share the same PIK3CD variant with variable clinical and immunological phenotypes. All children exhibited high transitional B-cells, consistent with developmental block to follicular B cell stage. Increased non-class switched IgM+ memory B cells and skewing towards CD21lo B cell subset, which is considered autoreactive-like, was observed in all patients. Of note, the patient had low plasmablasts, but normal immunoglobulins. Of her family members, only one was receiving both sirolimus and IgRT. Conclusion(s): We describe a rare case of COVID-19-related encephalitis in a patient with inborn error of immunity while not on IgRT. This may indicate infection susceptibility because of a lack of sufficient immunity to SARS-CoV-2, unlike the rest of her family with the same PIK3CD variant.Copyright © 2023 Elsevier Inc.

Characteristics and Clinical Implications of Anti-IFN-alpha cytokine antibodies in partial Recombinase Activating Gene Deficiency patients before and during the COVID-19 Pandemic

Introduction: With the onset of the COVID-19 pandemic, there was increased attention on anti- IFN-alpha autoantibodies and its correlation with severe clinical outcomes in a large group of patients. However, this correlation has not been extensively investigated in patients with partial Recombinase Activating Gene Deficiency (pRD) who are known to have increased prevalence of anti- IFN-alpha autoantibodies. Therefore, there is a need to assess the presence of anti- IFN-alpha antibodies in pRD patients before and after the COVID-19 pandemic and explore the relationship between anti- IFN-alpha antibody presence and clinical outcomes. Method(s): Sera was collected from the whole blood after informed consent and Enzyme-Linked Immunosorbent Assay was conducted to confirm the presence of IgG-specific anti- IFN-alpha autoantibodies. Positive samples were determined as OD values above 3 standard deviations of the healthy donor OD mean. Result(s): Our cohort included both adult (n = 13) and pediatric (n = 9) patients with variants in RAG1 and RAG2. Eleven patients (50%) out of the 22 showed elevated anti- IFN-alpha autoantibodies levels. Five patients (23%) were defined as low positive for anti- IFN-alpha autoantibodies, and 6 patients had no autoantibody titers. Of the 22 patients, 16 were symptomatic with infectious and non-infectious complications including recurrent viral and/or bacterial infections, autoimmune cytopenias, and lymphoproliferation. Ten (63%) of the symptomatic patients demonstrated high anti-IFN-alpha autoantibodies titers. Of the 11 patients with no or low neutralizing anti- IFN-alpha autoantibodies levels, 5 were asymptomatic. In temporal comparison, 16 samples were collected pre-COVID-19 pandemic;8 samples were collected during the pandemic, 2 of which belonged to patients with samples collected before and during the pandemic. In the pre-pandemic cohort, 66% had anti- IFN-alpha autoantibodies. Conversely, during the COVID-19 pandemic, 89% had anti- IFN-alpha autoantibodies. Of note, one patient who had neutralizing anti- IFN-alpha autoantibodies remained positive both before and during the pandemic despite HSCT. Patient also had a SARS-CoV-2 infection in summer of 2022 with a mild clinical course. Conclusions & Next Steps: We observed persistence of anti-IFN-alpha autoantibodies in our cohort post-pandemic and even post-HSCT. It is unclear whether the presence of anti-cytokine antibodies are risk factor for severe COVID-19.Copyright © 2023 Elsevier Inc.

Anti-interferon-alpha autoantibodies in patients with inborn errors of Immunity and rheumatic diseases before and during the COVID-19 pandemic

Introduction: Type 1 interferon (IFN) autoantibodies, such as anti-IFNalpha, have pathogenic significance in life-threatening COVID-19 pneumonia. Ten to twenty percent of severe COVID cases are associated with type I IFN autoantibodies. These autoantibodies likely pre-exist while others arise de novo relative to SARS-CoV-2 infection. It is unclear to what extent type I anti-IFN autoantibodies are induced by SARS-CoV-2 infection and contribute to COVID-19 severity. We investigated these phenomena in those with inborn errors of immunity (IEI) and rheumatic disease (RHE). Aim(s): We aim to compare the prevalence and neutralization ability of anti-IFNalpha autoantibodies in IEI and RHE patients using archived blood samples before and after the COVID-19 pandemic began. Method(s): We determined the presence of autoantibodies against IFNalpha in plasma samples by enzyme linked immunosorbent assay in 453 patients with IEI or RHE who were testing either before or after the COVID-19 pandemic began in March 2020. Using flow cytometry, we determined the function of IFNalpha autoantibodies in plasma to block CD4T cell activation by inhibiting STAT-1 phosphorylation. Result(s): We found that 25 patients with IEI or RHE were positive for anti-IFNalpha autoantibodies. 10 out of 229 patient samples collected before the pandemic (4.2%) tested positive whereas 15 out of 224 patient samples collected after the pandemic began (7.0%) were positive. Seven of the 25 patients (28%) who tested positive had neutralizing antibodies in plasma, which prevented STAT-1 phosphorylation in CD4T cells;all of these patients had partial recombination activating gene deficiency (pRD) except for one patient with autoimmunity, leukemia and selective IgA deficiency. One pRD patient had anti-IFNalpha autoantibodies with neutralization capacity before the pandemic, which persisted after hematopoietic stem cell transplantation (HSCT) with full immune reconstitution. The patient was immunized for SARS-CoV-2 before and after HSCT and acquired COVID-19 infection a year after HSCT. The patient was symptomatic but never hospitalized and fully recovered despite having anti-IFNalpha autoantibodies. Conclusion(s): Anti-IFNalpha autoantibody levels were comparable before and after the start of the COVID-19 pandemic in IEI and RHE patients but only 28% of cases were neutralizing. The clinical implications of these autoantibodies are yet to be determined.Copyright © 2023 Elsevier Inc.

A tailored COVID-19 vaccination pathway for children 5 to 11 years in Victoria, Australia

Background Procedural anxiety was anticipated in children 5 to 11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway. Methods The Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child's support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5-11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message. Results Between 9 February and 31 May 2022 there were 9203 responses;865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%;8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%;23/88) or families with a first language other than English (23.5%;42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs. Conclusion A tailored COVID-19 vaccination program for children 5 to 11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.

A tailored COVID-19 vaccination pathway for children 5-11 years in Victoria, Australia.

BACKGROUND: Procedural anxiety was anticipated in children 5-11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway. METHODS: The Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child's support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5-11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message. RESULTS: Between 9 February and 31 May 2022 there were 9203 responses; 865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%; 8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%; 23/88) or families with a first language other than English (23.5%; 42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs. CONCLUSION: A tailored COVID-19 vaccination program for children 5-11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.

Can NeuroIS improve executive employee recruitment? Classifying levels of executive functions using resting state EEG and data science methods

Based on the assumption that the success of an organization is largely determined by the knowledge and skills of its employees, human resource (HR) departments invest considerable resources in the employee recruitment process with the aim of selecting the best, most suitable employees. Due to the high cost of the recruitment process along with its high rate of uncertainty, HR recruiters utilize a variety of methods and instruments to improve the efficiency and effectiveness of this process. Thus far, however, neurological methods, in which neurobiological signals from an examined person are analyzed, have not been utilized for this purpose. This study is the first to propose a neuro-based decision support system to classify cognitive functions into levels, whose target is to enrich the information and indications regarding the candidate along the employee recruitment processes. We first measured relevant functional and cognitive abilities of 142 adult participants using traditional computer-based assessment, which included a battery of four tests regarding executive functions and intelligence score, consistent with actual recruitment processes. Second, using electroencephalogram (EEG) technology, which is one of the dominant measurement tools in NeuroIS research, we collected the participants' brain signals by administering a resting state EEG (rsEEG) on each participant. Finally, using advanced machine and deep learning algorithms, we leveraged the collected rsEEG to classify participants' levels of executive functions and intelligence score. Our empirical analyses show encouraging results of up to 72.6% accuracy for the executive functions and up to 71.2% accuracy for the intelligence score. Therefore, this study lays the groundwork for a novel, generic (non-stimuli based) system that supports the current employee recruitment processes, that is based on psychological theories of assessing executive functions. The proposed decision support system could contribute to the development of additional medium of assessing employees remotely which is especially relevant in the current Covid-19 pandemic. While our method aims at classification rather than at explanation, our intriguing findings have the potential to push forward NeuroIS research and practice. © 2023 Elsevier B.V.

Patterns of multimorbidity show strong association between many chronic condition pairs

Background: Many people with chronic conditions do not have a single condition: 4.9 million (20%) Australians had multimorbidity (2 or more chronic conditions) in 2017-18. Understanding which conditions co-occur can inform treatment guidelines. Aim/Objectives: This study performed analysis on Australian Bureau of Statistics 2017-18 National Health Survey (NHS) data to identify conditions that commonly co-occur, and that co-occur at a higher than expected prevalence. Due to limitations of the 2020-21 NHS, the 2017-18 NHS remains the most recent, robust source of self-report chronic condition information for national reporting. This work provides baseline information on chronic condition multimorbidity in Australia, before the COVID-19 pandemic. Method(s): Analysis was restricted to people aged 45 and over (most people with multimorbidity). Using 10 selected chronic conditions, weighted age-adjusted estimates of observed and expected events for each combination of two conditions were calculated. To identify pairs of conditions that co-occurred at a higher than expected prevalence, the ratio of observed to expected prevalence was assessed using a 95% confidence interval. Finding(s): Over half of the condition pairs tested were significantly associated. The most strongly associated conditions were asthma with COPD (with co-occurrence 3.5 times as high as expected), diabetes with chronic kidney disease (2.5 times as high), and cardiovascular diseases with chronic kidney disease (2.3 times as high). Implications: Multimorbidity is common, with many conditions co-occurring more frequently than expected by chance. There were strong associations between asthma and COPD, diabetes and chronic kidney disease, and cardiovascular diseases and chronic kidney disease. Developing treatment guidelines that consider common multimorbidities would support holistic patient care.

Trends in Scope of Practice for Oral Health Care: Future Transformative Effects.

KNOWLEDGE TRANSFER STATEMENT: The results of this study can help key stakeholders, such as health care facilities, educational and research institutions, insurance companies, and governmental bodies, plan future activities and policies on dental practice and education.

If You Build It, Will They Come? Is Test Site Availability a Root Cause of Geographic Disparities in COVID-19 Testing?

Objectives The purpose of this study was to examine the relationship between test site availability and testing rate within the context of social determinants of health. Study Design A retrospective ecological investigation was conducted using statewide COVID-19 testing data between March 2020 and December 2021. Methods Ordinary least squares and geographically weighted regression were used to estimate state and zip code level associations between testing rate and testing sites per capita, adjusting for neighbourhood level confounders. Results Findings indicate that site availability is positively associated with the zip code level testing rate and that this association is amplified in communities of greater economic deprivation. Additionally, economic deprivation is a key factor for consideration when examining ethnic differences in testing in medically underserved states. Conclusion The study findings could be used to guide delivery of testing facilities in resource-constrained states.

Quality Improvement Project on Trauma and Orthopaedic Junior Doctor Knowledge and Assessment/Management of Common Peri/Post-Operative Complications

Introduction: Foundation doctors knowledge of common peri/post-operative complications can be hugely variable when commencing Trauma and Orthopaedic rotations. This can result in reduced awareness and confidence in the assessment and initial management of surgical complications. A quality improvement project was therefore designed with the following objectives: 1. To assess the confidence of foundation doctors on the assessment and management of common peri and post-operative complications on starting and finishing their T&O placement;2. To offer regular orthogeriatric teaching on assessment and management of common peri and post-operative complications;3. To review and produce a booklet on assessment and management of common peri and post-operative complications and deliver to all T&O foundation doctors and possibly expand to all surgical specialties;4. To review if the above methods were successful in improving doctors' knowledge of assessment and management of common peri and post-operative complications. Methods: PDSA cycle. Anonymous survey pre and post rotation sent out to all F1 and F2 doctors. This assessed their confidence before and after their rotation in seven different common complications. We also asked for feedback regarding how they felt their confidence would be improved (formal teaching, sim sessions, producing a guide, etc.). This was repeated over the course of the year covering three sets of four month rotations. Results: The QIP illustrated that foundation doctors improved confidence in managing complications with a combination of regular formal teaching, receiving a complications handbook/guide and through informal feedback on ward rounds. The audit illustrated areas where confidence was low and did not improve (wound healing) or the guide lacked information (diabetes management and COVID). Through improvements in teaching and the guide we were able to see increasing confidence levels throughout the subsequent cycles of the QIP. Conclusion: (1) F1 and F2 doctors often have low confidence when starting a T&O rotation in dealing with common peri/post-operative complications. (2) By offering formal teaching, producing a booklet and feedback and assessing F1s and F2s regularly during their rotation we were able to see an increase in confidence. (3) Further QIP cycles should be undertaken to further pursue ways of engaging and improving junior doctor confidence.

Measles, Mumps, and Rubella Booster Immunization Practices

Reported cases of mumps infection in the United States (U.S.) have dropped since the introduction of the single-component mumps vaccine in 1967. After introduction of the multi-component measles, mumps, rubella (MMR) vaccine, cases in the U.S. and worldwide fell to the point where the International Task Force for Disease Eradication identified mumps for eventual global eradication. By 1991, all military recruits received an MMR vaccine. By 2010, the Department of Defense (DoD) had adopted a policy of immunizing recruits with MMR vaccine only if their antibody titers to measles or rubella had dropped below threshold levels established by the commercial testing laboratories as indicative of immunity. As part of a 2010 Defense Health Board (DHB) review of MMR immunization practices by the Department of the Navy, the DHB recommended that the Navy continue the practice of MMR immunization based on serosurveillance, but that universal MMR vaccination be re-instituted in the event of an increased risk of a mumps outbreak.

Brief report: Cause of death among people discharged from infective endocarditis related hospitalization-West Virginia, 2016-2019.

BACKGROUND AND OBJECTIVES: Compare proportion of all-cause and cause-specific mortality among West Virginia Medicaid enrollees who were discharged from infective endocarditis (IE) hospitalization with and without opioid use disorder (OUD) diagnosis. METHODS: The proportions of cause-specific deaths among those who were discharged from IE-related hospitalizations were compared by OUD diagnosis. RESULTS: The top three underlying causes of death discharged from IE hospitalization were accidental drug poisoning, mental and behavioral disorders due to polysubstance use, and cardiovascular diseases. Of the total deaths occurring among patients discharged after IE-related hospitalization, the proportion has increased seven times from 2016 to 2019 among the OUD deaths while it doubled among the non-OUD deaths. DISCUSSION AND CONCLUSIONS: Of the total deaths occurring among patients discharged after IE-related hospitalization, the increase is higher in those with OUD diagnosis. OUD is becoming a significantly negative impactor on the survival outcome among IE patients. It is of growing importance to deliver medication for OUD treatment and harm reduction efforts to IE patients in a timely manner, especially as the COVID-19 pandemic persists.