11 research outputs found

    Immunoglobulin Replacement Therapy During COVID-19 Pandemic: Practical and Psychological Impact in Patients with Antibody Deficiency

    Get PDF
    Purpose: The COVID-19 pandemic has impacted on how health services deliver care and the mental health of the population. Due to their clinical vulnerability, to reduce in-hospital attendances during the COVID-19 pandemic, modifications in immunoglobulin treatment regimens were made for patients with antibody deficiency. These patients were also likely to experience social isolation due to shielding measure that were advised. We aimed to investigate the impact of modifying immunoglobulin treatment regimen on infection and mental health burden during shielding restrictions.// Method: Patients on immunoglobulin replacement therapy (IGRT) responded to a standardised questionnaire examining self-reported infection frequency, anxiety (GAD-7), depression (PHQ-8), fatigue (FACIT), and quality of life during the pandemic. Infection frequency and immunoglobulin trough levels were compared to pre-pandemic levels.// Results: Patients who did not change treatment modality or those who received immunoglobulin replacement at home during the pandemic reported fewer infections. In patients who received less frequent hospital infusions, there was no significant increase in infections whilst immunoglobulin trough levels remained stable. There was no significant difference in anxiety, or depression scores between the treatment modality groups. Patients reported higher fatigue scores compared to the pre-COVID general population and in those discharged following hospitalisation for COVID.// Conclusion: Changing immunoglobulin treatment regimen did not negatively impact infection rates or psychological wellbeing. However, psychological welfare should be prioritised for this group particularly given uncertainties around COVID-19 vaccination responsiveness and continued social isolation for many

    Curation and expansion of Human Phenotype Ontology for defined groups of inborn errors of immunity.

    Get PDF
    BACKGROUND: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms. OBJECTIVES: We sought to systematically review available terms in HPO for the depiction of IEIs, to expand HPO, yielding more comprehensive sets of terms, and to reannotate IEIs with HPO terms to provide accurate, standardized phenotypic descriptions. METHODS: We initiated a collaboration involving expert clinicians, geneticists, researchers working on IEIs, and bioinformaticians. Multiple branches of the HPO tree were restructured and extended on the basis of expert review. Our ontology-guided machine learning coupled with a 2-tier expert review was applied to reannotate defined subgroups of IEIs. RESULTS: We revised and expanded 4 main branches of the HPO tree. Here, we reannotated 73 diseases from 4 International Union of Immunological Societies-defined IEI disease subgroups with HPO terms. We achieved a 4.7-fold increase in the number of phenotypic terms per disease. Given the new HPO annotations, we demonstrated improved ability to computationally match selected IEI cases to their known diagnosis, and improved phenotype-driven disease classification. CONCLUSIONS: Our targeted expansion and reannotation presents enhanced precision of disease annotation, will enable superior HPO-based IEI characterization, and hence benefit both IEI diagnostic and research activities

    Controlo químico de infestantes

    Get PDF
    Uma planta √© considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada. As infestantes competem com as culturas para o espa√ßo, a luz, √°gua e nutrientes, podendo atrasar e prejudicar as opera√ß√Ķes de colheita, depreciar o produto final e assegurarem a reinfesta√ß√£o nas culturas seguintes. Dado o modo de propaga√ß√£o diferenciado das diversas esp√©cies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propaga√ß√£o atrav√©s de √≥rg√£os vegetativos (rizomas, bolbos, tub√©rculos, etc.), assim, tamb√©m o seu controlo quer qu√≠mico, quer mec√Ęnico ter√° que ser diferenciado, ou seja, para controlar infestantes anuais ser√° suficiente destruir a sua parte a√©rea, enquanto para controlar infestantes perenes teremos que destruir os seus √≥rg√£os reprodutivos. O controlo de infestantes poder√° ser qu√≠mico, atrav√©s da utiliza√ß√£o de herbicidas, ou mec√Ęnico pela utiliza√ß√£o de alfaias agr√≠colas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a t√©cnica utilizada na instala√ß√£o das culturas √© a sementeira directa, o controlo das infestantes ter√° que ser obrigatoriamente qu√≠mico, enquanto se o recurso √† mobiliza√ß√£o do solo for a t√©cnica mais utilizada (sistema de mobiliza√ß√£o tradicional ou sistema de mobiliza√ß√£o reduzida), o controlo das infestantes tanto poder√° ser qu√≠mico como mec√Ęnico. Neste trabalho iremos abordar apenas, o controlo qu√≠mico de infestantes

    Donor T cells with inducible caspase safety switch following haploidentical transplants

    Get PDF
    Haplo-identical donors are alternative source of hematopoietic stem cells for patients without a more closely matched donor or who need an urgent allogeneic hematopoietic stem cell transplant (HSCT). Because the donor graft for such haploidentical transplants (haplo-HSCT) has a high frequency of alloreactive T cells recognizing the non-shared HLA haplotype, extensive T-cell depletion remains a fundamental prerequisite if the graft is not to cause fatal acute graft-versus-hostdisease (GvHD). While extensive T-cell removal of the graft effectively prevents GvHD, it increases the risk of graft rejection, relapse, viral and opportunistic infections. Consequently, efforts were made to retain the desired T cells while selectively depleting alloreactive T cells (Aversa et al, 2005 and Mielke et al, 2008). Engineered T cells with safety switches have been developed to increase the feasibility of higher numbers of donor-derived T cells whilst providing a tool to control the increased risk of aGvHD that maybe associated with incomplete abrogation of alloreactivity against the recipient [Amrolia et al, 2006]. This thesis presents data from a phase I/II first- in- man use of TCRőĪő≤/CD19 depleted transplant followed by adoptive transfer of genetically modified donor T cells. These donor T cells were modified through gamma-retroviral vector that carried inducible suicide gene (inducible caspase 9; icas9) which makes cells die on exposure to a drug called AP1903. This thesis also examines the development of an alternative lentiviral vector for icas9 gene transfer, investigates the effect of immune suppressive medications on genetically modified T cells and investigates mechanism of resistance to AP1903

    Curation and expansion of Human Phenotype Ontology for defined groups of inborn errors of immunity

    Get PDF
    Background: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms. Objectives: We sought to systematically review available terms in HPO for the depiction of IEIs, to expand HPO, yielding more comprehensive sets of terms, and to reannotate IEIs with HPO terms to provide accurate, standardized phenotypic descriptions. Methods: We initiated a collaboration involving expert clinicians, geneticists, researchers working on IEIs, and bioinformaticians. Multiple branches of the HPO tree were restructured and extended on the basis of expert review. Our ontology-guided machine learning coupled with a 2-tier expert review was applied to reannotate defined subgroups of IEIs. Results: We revised and expanded 4 main branches of the HPO tree. Here, we reannotated 73 diseases from 4 International Union of Immunological Societies‚Äďdefined IEI disease subgroups with HPO terms. We achieved a 4.7-fold increase in the number of phenotypic terms per disease. Given the new HPO annotations, we demonstrated improved ability to computationally match selected IEI cases to their known diagnosis, and improved phenotype-driven disease classification. Conclusions: Our targeted expansion and reannotation presents enhanced precision of disease annotation, will enable superior HPO-based IEI characterization, and hence benefit both IEI diagnostic and research activities
    corecore