SARS-CoV-2 Antibody Response Is Associated with Age and Body Mass Index in Convalescent Outpatients.

COVID-19 has had an unprecedented global impact on human health. Understanding the Ab memory responses to infection is one tool needed to effectively control the pandemic. Among 173 outpatients who had virologically confirmed SARS-CoV-2 infection, we evaluated serum Ab concentrations, microneutralization activity, and enumerated SARS-CoV-2-specific B cells in convalescent human blood specimens. Serum Ab concentrations were variable, allowing for stratification of the cohort into high and low responders. Neither participant sex, the timing of blood sampling following the onset of illness, nor the number of SARS-CoV-2 spike protein-specific B cells correlated with serum Ab concentration. Serum Ab concentration was positively associated with microneutralization activity and participant age, with participants under the age of 30 showing the lowest Ab level. These data suggest that young adult outpatients did not generate as robust Ab memory, compared with older adults. Body mass index was also positively correlated with serum Ab levels. Multivariate analyses showed that participant age and body mass index were independently associated with Ab levels. These findings have direct implications for public health policy and current vaccine efforts. Knowledge gained regarding Ab memory following infection will inform the need for vaccination in those previously infected and allow for a better approximation of population-wide protective immunity.

Choosing Wisely in Adult Hospital Medicine: Co-creation of New Recommendations for Improved Healthcare Value by Clinicians and Patient Advocates.

BACKGROUND: The American Board of Internal Medicine Foundation's Choosing Wisely campaign has resulted in a vast number of recommendations to reduce low-value care. Implementation of these recommendations, in conjunction with patient input, remains challenging. OBJECTIVE: To create updated Society of Hospital Medicine Adult Hospitalist Choosing Wisely recommendations that incorporate patient input from inception. DESIGN AND PARTICIPANTS: This was a multi-phase study conducted by the Society of Hospital Medicine's High Value Care Committee from July 2017 to January 2020 involving clinicians and patient advocates. APPROACH: Phase 1 involved gathering low-value care recommendations from patients and clinicians across the USA. Recommendations were reviewed by the committee in phase 2. Phase 3 involved a modified Delphi scoring in which 7 committee members and 7 patient advocates voted on recommendations based on strength of evidence, potential for patient harm, and relevance to either hospital medicine or patients. A patient-friendly script was developed to allow advocates to better understand the clinical recommendations. KEY RESULTS: A total of 1265 recommendations were submitted by clinicians and patients. After accounting for similar suggestions, 283 recommendations were categorized. Recommendations with more than 10 mentions were advanced to phase 3, leaving 22 recommendations for the committee and patient advocates to vote upon. Utilizing a 1-5 Likert scale, the top combined recommendations were reducing use of opioids (4.57), improving sleep (4.52), minimizing overuse of oxygen (4.52), reducing CK-MB use (4.50), appropriate venous thromboembolism prophylaxis (4.43), and decreasing daily chest x-rays (4.43). CONCLUSIONS: Specific voting categories, along with the use of patient-friendly language, allowed for the successful co-creation of recommendations.

Association of MHC class II haplotypes with reduced faecal nematode egg count and IgA activity in British Texel sheep.

Nematode infection is one of the principal diseases suffered by sheep and the class II region of the MHC has been repeatedly associated with differences in susceptibility and resistance to infection. The aim of this study was to examine the association of MHC class II haplotypes in a flock of Texel sheep with faecal egg counts and antibody responsiveness. Two haplotypes carried the DRB1*11:01 allele which has previously been associated with reduced egg counts in Scottish Blackface and Suffolk sheep. One of the two haplotypes was associated with reduced egg counts in the Texel breed, and both haplotypes were associated with reduced IgA activity against an extract from fourth-stage larvae. The reduced IgA activity is probably a consequence of reduced numbers of fourth-stage larvae in sheep carrying the resistance allele. The association of specific MHC alleles with reduced egg counts, reduced worm numbers and decreased IgA activity provides a mechanism for the density-dependent regulation of parasite growth and fecundity.

Failure of the Anti-Inflammatory Parasitic Worm Product ES-62 to Provide Protection in Mouse Models of Type I Diabetes, Multiple Sclerosis, and Inflammatory Bowel Disease.

Parasitic helminths and their isolated secreted products show promise as novel treatments for allergic and autoimmune conditions in humans. Foremost amongst the secreted products is ES-62, a glycoprotein derived from Acanthocheilonema viteae, a filarial nematode parasite of gerbils, which is anti-inflammatory by virtue of covalently-attached phosphorylcholine (PC) moieties. ES-62 has been found to protect against disease in mouse models of rheumatoid arthritis, systemic lupus erythematosus, and airway hyper-responsiveness. Furthermore, novel PC-based synthetic small molecule analogues (SMAs) of ES-62 have recently been demonstrated to show similar anti-inflammatory properties to the parent molecule. In spite of these successes, we now show that ES-62 and its SMAs are unable to provide protection in mouse models of certain autoimmune conditions where other helminth species or their secreted products can prevent disease development, namely type I diabetes, multiple sclerosis and inflammatory bowel disease. We speculate on the reasons underlying ES-62's failures in these conditions and how the negative data generated may help us to further understand ES-62's mechanism of action.

The genetic architecture of the MHC class II region in British Texel sheep.

Understanding the structure of the major histocompatibility complex, especially the number and frequency of alleles, loci and haplotypes, is crucial for efficient investigation of the way in which the MHC influences susceptibility to disease. Nematode infection is one of the most important diseases suffered by sheep, and the class II region has been repeatedly associated with differences in susceptibility and resistance to infection. Texel sheep are widely used in many different countries and are relatively resistant to infection. This study determined the number and frequency of MHC class II genes in a small flock of Texel sheep. There were 18 alleles at DRB1, 9 alleles at DQA1, 13 alleles at DQB1, 8 alleles at DQA2 and 16 alleles at DQB2. Several haplotypes had no detectable gene products at DQA1, DQB1 or DQB2, and these were defined as null alleles. Despite the large numbers of alleles, there were only 21 distinct haplotypes in the population. The relatively small number of observed haplotypes will simplify finding disease associations because common haplotypes provide more statistical power but complicate the discrimination of causative mutations from linked marker loci.

Effectiveness of the Koorliny Moort out-of-hospital health care program for Aboriginal and Torres Strait Islander children in Western Australia.

OBJECTIVES: To determine whether the Koorliny Moort program could reduce emergency department presentations, hospital admissions and length of stay, and improve attendance at out-of-hospital appointments for Aboriginal and Torres Strait Islander children in Western Australia. DESIGN: Children were enrolled in the program from 1 August 2012. Each child acted as their own control. Evaluation data were collected from 1 August 2010 to 31 July 2014. Occasions of service and person-time in days were compared for each child before and after referral to the program. SETTING AND PARTICIPANTS: Aboriginal children aged 0-16 years residing in three WA regions (Kimberley, Pilbara, Perth metropolitan) who were referred to the Koorliny Moort program. INTERVENTIONS: Partnerships with primary care providers; nurse-led care coordination; and outreach care by paediatricians, nurses and social workers closer to the home of the child. MAIN OUTCOME MEASURES: Emergency department presentations; hospital admissions; length of hospital stay; non-attended appointments. RESULTS: A total of 942 children were referred to the program. There were significant decreases after referral to the program in the incidence of emergency department presentations (incident rate ratio [IRR], 0.47; 95% CI, 0.43-0.53; P < 0.001), of hospitalisation (IRR, 0.70; 95% CI, 0.62-0.79; P < 0.001), and of non-attended appointments (IRR, 0.83; 95% CI, 0.74-0.94; P < 0.001), as well as in the mean length of hospital stay (IRR, 0.23; 95% CI, 0.21-0.25; P < 0.001). CONCLUSIONS: Health-seeking behaviour and health outcomes for Aboriginal children can be improved by engaging Aboriginal families in their health care, providing effective communication between health service providers, and delivering a coordinated program of Aboriginal service provider-led care.

Pathway of actin filament branch formation by Arp2/3 complex revealed by single-molecule imaging.

Actin filament nucleation by actin-related protein (Arp) 2/3 complex is a critical process in cell motility and endocytosis, yet key aspects of its mechanism are unknown due to a lack of real-time observations of Arp2/3 complex through the nucleation process. Triggered by the verprolin homology, central, and acidic (VCA) region of proteins in the Wiskott-Aldrich syndrome protein (WASp) family, Arp2/3 complex produces new (daughter) filaments as branches from the sides of preexisting (mother) filaments. We visualized individual fluorescently labeled Arp2/3 complexes dynamically interacting with and producing branches on growing actin filaments in vitro. Branch formation was strikingly inefficient, even in the presence of VCA: only ~1% of filament-bound Arp2/3 complexes yielded a daughter filament. VCA acted at multiple steps, increasing both the association rate of Arp2/3 complexes with mother filament and the fraction of filament-bound complexes that nucleated a daughter. The results lead to a quantitative kinetic mechanism for branched actin assembly, revealing the steps that can be stimulated by additional cellular factors.

Bottom-up regulation of malaria population dynamics in mice co-infected with lung-migratory nematodes.

When and how populations are regulated by bottom up vs. top down processes, and how those processes are affected by co-occurring species, are poorly characterised across much of ecology. We are especially interested in the community ecology of parasites that must share a host. Here, we quantify how resources and immunity affect parasite propagation in experiments in near-replicate 'mesocosms'' - i.e. mice infected with malaria (Plasmodium chabaudi) and nematodes (Nippostrongylus brasiliensis). Nematodes suppressed immune responses against malaria, and yet malaria populations were smaller in co-infected hosts. Further analyses of within-host epidemiology revealed that nematode co-infection altered malaria propagation by suppressing target cell availability. This is the first demonstration that bottom-up resource regulation may have earlier and stronger effects than top-down immune mechanisms on within-host community dynamics. Our findings demonstrate the potential power of experimental ecology to disentangle mechanisms of population regulation in complex communities.

Increased exposure to Plasmodium chabaudi antigens sustains cross-reactivity and avidity of antibodies binding Nippostrongylus brasiliensis: dissecting cross-phylum cross-reactivity in a rodent model.

Mounting an antibody response capable of discriminating amongst and appropriately targeting different parasites is crucial in host defence. However, cross-reactive antibodies that recognize (bind to) multiple parasite species are well documented. We aimed to determine if a higher inoculating dose of one species, and thus exposure to larger amounts of antigen over a longer period of time, would fine-tune responses to that species and reduce cross-reactivity. Using the Plasmodium chabaudi chabaudi (Pcc)-Nippostrongylus brasiliensis (Nb) co-infection model in BALB/c mice, in which we previously documented cross-reactive antibodies, we manipulated the inoculating dose of Pcc across 4 orders of magnitude. We investigated antigen-specific and cross-reactive antibody responses against crude and defined recombinant antigens by enzyme linked immunosorbent assay, Western blot and antibody depletion assays. Contrary to our hypothesis that increasing exposure to Pcc would reduce cross-reactivity to Nb, we found evidence for increased avidity of a subpopulation of antibodies that recognized shared antigens. Western blot indicated proteins of apparent monomer molecular mass 28 and 98 kDa in both Nb and Pcc antigen preparations and also an Nb protein of similar size to recombinant Pcc antigen, merozoite surface protein-1(19). The implications of antibodies binding antigen from such phylogenetically distinct parasites are discussed.

Emerging role of interleukin-33 in autoimmune diseases.

Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It predominantly induces type 2 immune responses and thus is protective against atherosclerosis and nematode infections but contributes to allergic airway inflammation. Interleukin-33 also plays a pivotal role in the development of many autoimmune diseases through mechanisms that are still not fully understood. In this review, we focus on the recent advances in understanding of the expression and function of IL-33 in some autoimmune disorders, aiming to provide insight into its potential role in disease development.

Navigating challenges and opportunities: Nursing student's views on generative AI in higher education.

AIM: This qualitative study aims to explore the perspectives of nursing students regarding the application and integration of generative Artificial Intelligence (AI) tools in their studies. BACKGROUND: With the increasing prevalence of generative AI tools in academic settings, there is a growing interest in their use among students for learning and assessments. DESIGN: Employing a qualitative descriptive design, this study used semi-structured interviews with nursing students to capture the nuanced insights of the participants. METHODS: Semi-structured interviews were digitally recorded and then transcribed verbatim. The research team reviewed all the data independently and then convened to discuss and reach a consensus on the identified themes. RESULTS: This study was conducted within the discipline of nursing at a regional Australian university. Thirteen nursing students, from both first and second year of the programme, were interviewed as part of this study. Six distinct themes emerged from the data analysis, including the educational impact of AI tools, equitable learning environment, ethical considerations of AI use, technology integration, safe and practical utility and generational differences. CONCLUSIONS: This initial exploration sheds light on the diverse perspectives of nursing students concerning the incorporation of generative AI tools in their education. It underscores the potential for both positive contributions and challenges associated with the integration of generative AI in nursing education and practice.

Reduction in catheter-associated urinary tract infections by bundling interventions.

OBJECTIVE: Urinary tract infections (UTIs) are the most common type of hospital-acquired infection, and most are associated with indwelling urinary catheters, that is, catheter-associated UTIs (CAUTIs). Our goal was to reduce the CAUTI rate. INTERVENTIONS: We retrospectively examined the feasibility and cost-effectiveness of a bundle of four evidence-based interventions upon the incidence rate (IR) of CAUTIs in a community hospital. The first intervention was the exclusive use of silver alloy catheters in the hospital's acute care areas. The second intervention was a securing device to limit the movement of the catheter after insertion. The third intervention was repositioning of the catheter tubing if it was found to be touching the floor. The fourth intervention was removal of the indwelling urinary catheter on postoperative Day 1 or 2, for most surgical patients. MAIN OUTCOME MEASURE: Rates of CAUTI per 1000 catheter days were estimated and compared using the generalized estimating equations Poisson regression analysis. RESULTS: During the study period, 33 of the 2228 patients were diagnosed with a CAUTI. The CAUTI IR for the pre-intervention period was 5.2/1000. For the 7 months following the implementation of the fourth intervention, the IR was 1.5/1000 catheter days, a significant reduction relative to the pre-intervention period (P = 0.03). The annualized projection for the cost of implementing this bundle of four interventions is $23 924. CONCLUSION: A bundle of four evidence-based interventions reduced the incidence of CAUTIs in a community hospital. It is relatively simple, appears to be cost-effective and might be sustainable and adaptable by other hospitals.

Presentations and outcomes among sickle cell disease patients with COVID-19 at a large southern healthcare system.

OBJECTIVES: Compared with the general population, patients with sickle cell disease (SCD) typically have substantially reduced life expectancies. It is unclear whether SCD patients who acquire COVID-19 have higher rates of complications and mortality than the general population. We sought to elucidate COVID-19 presentation and outcomes in patients with SCD. METHODS: Using retrospective chart review, we evaluated demographic characteristics, presenting symptoms, chest imaging findings, blood transfusion requirements, need for mechanical ventilation or pressor support, medication administration (including remdesivir and dexamethasone), and survival among individuals with SCD hospitalized with COVID-19 from March 2020 to December 2021. RESULTS: Among 72 SCD patients, increased pain was the most common presenting symptom followed by cough, fever, and dyspnea. Thirty-seven (44%) received simple transfusion and 14 (17%) underwent exchange transfusion. Lung imaging findings suggestive of COVID-19 were observed in 27 (37%) patients; 21 (29%) patients were treated with remdesivir and 26 (35%) received dexamethasone. Three patients (4%) required mechanical ventilation and pressor support; all three died from COVID complications. CONCLUSIONS: Pain is the most common presenting symptom in SCD patients with COVID-19. We observed a mortality rate higher than that among the general population among patients who required mechanical ventilation and pressor support.

Effect of mild COVID-19 on health-related quality of life.

Background: Little is known about the effects of a mild SARS-CoV-2 infection on health-related quality of life. Methods: This prospective observational study of symptomatic adults (18-87 years) who sought outpatient care for an acute respiratory illness, was conducted from 3/30/2020 to 4/30/2021. Participants completed the Short Form Health Survey (SF-12) at enrollment and 6-8 weeks later, to report their physical and mental health function levels as measured by the physical health and mental health composite scores (PHC and MHC, respectively). PHC and MHC scores for COVID-19 cases and non-COVID cases were compared using t-tests. Multivariable regression modeling was used to determine predictors of physical and mental health function at follow-up. Results: Of 2301 enrollees, 426 COVID-19 cases and 547 non-COVID cases completed both surveys. PHC improved significantly from enrollment to follow-up for both COVID-19 cases (5.4 ± 0.41; P < 0.001) and non-COVID cases (3.3 ± 0.32; P < 0.001); whereas MHC improved significantly for COVID-19 cases (1.4 ± 0.51; P < 0.001) and decreased significantly for non-COVID cases (-0.8 ± 0.37; P < 0.05). Adjusting for enrollment PHC, the most important predictors of PHC at follow-up included male sex (ß = 1.17; SE = 0.5; P = 0.021), having COVID-19 (ß = 1.99; SE = 0.54; P < 0.001); and non-white race (ß = -2.01; SE = 0.70; P = 0.004). Adjusting for enrollment MHC, the most important predictors of MHC at follow-up included male sex (ß = 1.92; SE = 0.63; P = 0.002) and having COVID-19 (ß = 2.42; SE = 0.67; P < 0.001). Conclusion: Both COVID-19 cases and non-COVID cases reported improved physical health function at 6-8 weeks' convalescence; whereas mental health function improved among COVID-19 cases but declined among non-COVID cases. Both physical and mental health functioning were significantly better among males with COVID-19 than females.

Blood Inflammatory Biomarkers Differentiate Inpatient and Outpatient Coronavirus Disease 2019 From Influenza.

Background: The ongoing circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a diagnostic challenge because symptoms of coronavirus disease 2019 (COVID-19) are difficult to distinguish from other respiratory diseases. Our goal was to use statistical analyses and machine learning to identify biomarkers that distinguish patients with COVID-19 from patients with influenza. Methods: Cytokine levels were analyzed in plasma and serum samples from patients with influenza and COVID-19, which were collected as part of the Centers for Disease Control and Prevention's Hospitalized Adult Influenza Vaccine Effectiveness Network (inpatient network) and the US Flu Vaccine Effectiveness (outpatient network). Results: We determined that interleukin (IL)-10 family cytokines are significantly different between COVID-19 and influenza patients. The results suggest that the IL-10 family cytokines are a potential diagnostic biomarker to distinguish COVID-19 and influenza infection, especially for inpatients. We also demonstrate that cytokine combinations, consisting of up to 3 cytokines, can distinguish SARS-CoV-2 and influenza infection with high accuracy in both inpatient (area under the receiver operating characteristics curve [AUC] = 0.84) and outpatient (AUC = 0.81) groups, revealing another potential screening tool for SARS-CoV-2 infection. Conclusions: This study not only reveals prospective screening tools for COVID-19 infections that are independent of polymerase chain reaction testing or clinical condition, but it also emphasizes potential pathways involved in disease pathogenesis that act as potential targets for future mechanistic studies.

A Randomized Controlled Trial to Compare Immunogenicity to Cell-Based Versus Live-Attenuated Influenza Vaccines in Children.

BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069.

Catastrophic Neurological Complications in 2 Patients With Sickle Cell Disease and COVID-19.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is commonly associated with neurological complications. Patients with sickle cell disease are at increased risk of developing neurologic complications throughout their lifetimes and often have underlying cardiopulmonary comorbidities that may predispose them to poor outcomes during serious infections. In this case series, we describe 2 patients with sickle cell disease who developed devastating neurologic complications following SARS-CoV-2 infection, which ultimately led to brain edema and death. We highlight the unusual manifestations of coronavirus disease 2019 in patients with sickle cell disease and address the risk of these patients to develop catastrophic neurologic injury due to COVID-19, if not recognized promptly.

Defining existing practices to support the sleep of hospitalized patients: A mixed-methods study of top-ranked hospitals.

The objective of this study was to understand the existing practices and attitudes regarding inpatient sleep at the 2020 US News and World Report (USNWR) Honor Roll pediatric (n = 10) and adult (n = 20) hospitals. Section chiefs of Hospital Medicine from these institutions were surveyed and interviewed between June and August 2021. Among 23 of 30 surveyed physician leaders (response rate = 77%), 96% (n = 22) rated patient sleep as important, but only 43% (n = 10) were satisfied with their institutions' efforts. A total of 96% (n = 22) of institutions lack sleep equity practices. Fewer than half (48%) of top hospitals have sleep-friendly practices, with the most common practices including reducing overnight vital sign monitoring (43%), decreasing ambient light in the wards (43%), adjusting lab and medication schedules (35%), and implementing quiet hours (30%). Major themes from qualitative interviews included: importance of universal sleep-friendly cultures, environmental changes, and external incentives to improve patient sleep.

Indications for the Use of Proton Pump Inhibitors for Stress Ulcer Prophylaxis and Peptic Ulcer Bleeding in Hospitalized Patients.

Proton pump inhibitors are widely used throughout the world for the treatment of gastrointestinal disorders that are related to acid secretion, such as peptic ulcer disease and dyspepsia. Another common indication for proton pump inhibitors is stress ulcer prophylaxis. Proton pump inhibitors have proven efficacy for the treatment of acid-related gastrointestinal disorders, but there is concern that their use may be associated with the development of significant complications, such as fractures, Clostridium difficile infection, acute kidney injury, chronic kidney disease, and hypomagnesemia. Proton pump inhibitors are overused in the hospital setting, both for stress ulcer prophylaxis and gastrointestinal bleeding, and then they are often inappropriately continued after discharge from the hospital. This narrative review article outlines the evidence surrounding appropriate proton pump inhibitor use for stress ulcer prophylaxis and peptic ulcer bleeding.