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1.
medRxiv ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39040188

ABSTRACT

Infections are increasingly recognized as a common complication of chimeric antigen receptor (CAR) T-cell therapy. The incidence of clinically-defined infection after CD19.CAR T-cell therapy for relapsed/refractory lymphoma ranges from 60-90% in the first year after CAR T-cell therapy and is the most common cause for non-relapse mortality. However, infectious risk after CAR T-cell therapy targeting other malignancies is not well understood. Herein, we report for the first time, infectious complications after CD30.CAR T-cell treatment for patients with Hodgkin's lymphoma and peripheral T-cell lymphoma. Since CD30 is only expressed on a subset of activated T and B-cells, we hypothesized that CD30.CAR T-cell patients would have reduced incidence and severity of infections after infusion compared to CD19.CAR T-cell patients. We retrospectively evaluated all 64 patients who received CD30.CAR T-cells at a single institution between 2016-2021, and assessed infections within one year after cell infusion, comparing these data to a contemporary cohort of 50 patients who received CD19.CAR T-cells at the same institution between 2018-2021. 23 CD30.CAR T-cell patients (36%) and 18 CD19.CAR T-cell patients (36%) developed a microbiologically confirmed infection. Infection severity and bacterial infections were higher in the CD19.CAR T-cell group compared to CD30.CAR T-cell recipients who more commonly had grade 1 respiratory viral infections. Our data reflect expected outcomes for severity and infection type in CD19.CAR T-cell patients and provide a benchmark for comparison with the novel CD30.CAR T-cell product. Although our findings require replication in a larger cohort, they have implications for antimicrobial prophylaxis guidelines after CD30.CAR T-cell therapy. KEY POINTS: 1) The incidence of infections within the first year after CD30.CAR T-cell therapy was equivalent to that following CD19.CAR T-cell therapy2) Viral infections were more common after CD30.CAR T-cell therapy but bacterial infections predominated after CD19.CAR T-cell therapy.

2.
J Immunother Cancer ; 12(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955420

ABSTRACT

BACKGROUND: Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy. METHODS: 84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC. RESULTS: Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts. CONCLUSIONS: Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.


Subject(s)
Bendamustine Hydrochloride , Biological Products , Lymphoma, Large B-Cell, Diffuse , Humans , Bendamustine Hydrochloride/therapeutic use , Bendamustine Hydrochloride/administration & dosage , Male , Female , Middle Aged , Aged , Lymphoma, Large B-Cell, Diffuse/drug therapy , Biological Products/therapeutic use , Biological Products/adverse effects , Adult , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Antigens, CD19/immunology , Antigens, CD19/therapeutic use
3.
Blood ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968138

ABSTRACT

While chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed / refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, nine of whom successfully received CAR19-22 followed by NKTR-255. There were no dose limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with eight out of nine patients (89%) achieving measurable residual disease negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854).

4.
BMJ Open ; 14(7): e082275, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39053955

ABSTRACT

INTRODUCTION: Global surveillance of physical activity (PA) of children and adolescents with questionnaires is limited by the use of instruments developed in high-income countries (HICs) lacking sociocultural adaptation, especially in low- and middle-income countries (LMICs); under-representation of some PA domains; and omission of active play, an important source of PA. Addressing these limitations would help improve international comparisons, and facilitate the cross-fertilisation of ideas to promote PA. We aim to develop and assess the reliability and validity of the app-based Global Adolescent and Child Physical Activity Questionnaire (GAC-PAQ) among 8-17 years old in 14 LMICs and HICs representing all continents; and generate the 'first available data' on active play in most participating countries. METHODS AND ANALYSIS: Our study involves eight stages: (1) systematic review of psychometric properties of existing PA questionnaires for children and adolescents; (2) development of the GAC-PAQ (first version); (3) content validity assessment with global experts; (4) cognitive interviews with children/adolescents and parents in all 14 countries; (5) development of a revised GAC-PAQ; (6) development and adaptation of the questionnaire app (application); (7) pilot-test of the app-based GAC-PAQ; and, (8) main study with a stratified, sex-balanced and urban/rural-balanced sample of 500 children/adolescents and one of their parents/guardians per country. Participants will complete the GAC-PAQ twice to assess 1-week test-retest reliability and wear an ActiGraph wGT3X-BT accelerometer for 9 days to test concurrent validity. To assess convergent validity, subsamples (50 adolescents/country) will simultaneously complete the PA module from existing international surveys. ETHICS AND DISSEMINATION: Approvals from research ethics boards and relevant organisations will be obtained in all participating countries. We anticipate that the GAC-PAQ will facilitate global surveillance of PA in children/adolescents. Our project includes a robust knowledge translation strategy sensitive to social determinants of health to inform inclusive surveillance and PA interventions globally.


Subject(s)
Exercise , Psychometrics , Humans , Adolescent , Child , Surveys and Questionnaires/standards , Reproducibility of Results , Male , Female , Developing Countries , Research Design
5.
Blood Adv ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861351

ABSTRACT

Multiple chimeric antigen receptor (CAR) T cell therapies are FDA approved, and several are under development. While effective for some cancers, toxicities remain a limitation. The most common toxicities, i.e. cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), are well described. With increasing utilization, providers worldwide are reporting on other emergent, and often complicated toxicities. Given the evolving toxicity profiles and urgent need to catalogue these emerging and emergent CAR T toxicities and describe management approaches, the American Society of Hematology Subcommittee on Emerging Gene and Cell Therapies organized the first Scientific Workshop on CAR T cell toxicities during the annual society meeting. The workshop functioned to 1) aggregate reports of CAR T emergent toxicities, including movement disorders after BCMA CAR T, coagulation abnormalities, and prolonged cytopenias; 2) disseminate bedside to bench efforts elucidating pathophysiological mechanisms of CAR-T toxicities, including the intestinal microbiota and systemic immune dysregulation; and 3) highlight gaps in the availability of clinical tests such as cytokine measurements, which could be utilized to expand our knowledge around the monitoring of toxicities. Key themes emerged. First, while clinical manifestations may develop before the pathophysiologic mechanisms are understood, these must be studied to aid in the detection and prevention of such toxicities. Second, systemic immune dysregulation appears central to these emergent toxicities and research is needed to elucidate links between tumor, CAR T, and microbiota. Finally, there was consensus around an urgency to create a repository to capture emergent CAR-T toxicities and the real-world management.

6.
bioRxiv ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38895335

ABSTRACT

Hematopoietic stem cells (HSCs) with multilineage potential are critical for effective T cell reconstitution and restoration of the adaptive immune system after allogeneic Hematopoietic Cell Transplantation (allo-HCT). The Kit lo subset of HSCs is enriched for multipotential precursors, 1, 2 but their T-cell lineage potential has not been well-characterized. We therefore studied the thymic reconstituting and T-cell potential of Kit lo HSCs. Using a preclinical allo-HCT model, we demonstrate that Kit lo HSCs support better thymic recovery, and T-cell reconstitution resulting in improved T cell responses to infection post-HCT. Furthermore, Kit lo HSCs with augmented BM lymphopoiesis mitigate age-associated thymic alterations, thus enhancing T-cell recovery in middle-aged hosts. We find the frequency of the Kit lo subset declines with age, providing one explanation for the reduced frequency of T-competent HSCs and reduced T-lymphopoietic potential in BM precursors of aged mice. 3, 4, 5 Chromatin profiling revealed that Kit lo HSCs exhibit higher activity of lymphoid-specifying transcription factors (TFs), including Zbtb1 . Deletion of Zbtb1 in Kit lo HSCs diminished their T-cell potential, while reinstating Zbtb1 in megakaryocytic-biased Kit hi HSCs rescued T-cell potential, in vitro and in vivo . Finally, we discover an analogous Kit lo HSC subset with enhanced lymphoid potential in human bone marrow. Our results demonstrate that Kit lo HSCs with enhanced lymphoid potential have a distinct underlying epigenetic program.

8.
Health Place ; 87: 103253, 2024 May.
Article in English | MEDLINE | ID: mdl-38692226

ABSTRACT

Our study sought to understand adult decision-makers' views on what was important for actualising children's ideas using co-design, towards creating health-promoting local environments. Ten adult decision-makers, experienced in co-design with children aged 5-13 years in Aotearoa New Zealand, participated in individual interviews. We generated three themes (Empowering children within co-design; Being intentional about children's influence; Curating who is involved) using reflexive thematic analysis. Our themes informed a novel framework of 'impactful co-design' accompanied by a practical checklist for adult decision-makers (practitioners, policy-makers, and researchers). Study findings affirm co-designing local neighbourhoods as an inherently social and technical endeavour, advocate for greater consideration of inclusivity and cultural context, and highlight the need for co-design with children to include safety, empowerment, and evaluation. We position impactful co-design as one useful process to enact children's meaningful participation.


Subject(s)
Health Promotion , Residence Characteristics , Humans , New Zealand , Child , Female , Male , Adolescent , Health Promotion/methods , Adult , Child, Preschool , Decision Making , Interviews as Topic , Qualitative Research , Environment Design , Empowerment
9.
Transplant Cell Ther ; 30(6): 559-564, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608806

ABSTRACT

A shortage of transplant and cellular therapy (TCT) physicians is expected given the expansion of TCT indications and the scope of practice of TCT programs in recent years. American Society of Transplantation and Cellular Therapy (ASTCT) conducted a survey of early career transplant physicians and trainees to assess the factors that prompted them to pursue to career in TCT. This was a cross-sectional survey conducted via emails sent to the ASTCT membership. Fifty-nine respondents completed the survey. The vast majority of respondents decided to pursue a career in TCT during their hematology/oncology fellowship (41%), followed by during residency (25%) or medical school (18%), and a majority of them had some exposure to TCT in their clinical training already. The most common reason for choosing to specialize in TCT was interest in the clinical practice of TCT (81%) closely followed by the scientific allure of the field (75%). Most respondents were extremely committed to remaining in this field of practice. We found that those in the field report high levels of satisfaction despite factors that would otherwise predispose them to burnout. A systematic and sustained effort to promote trainee engagement that could result in improved recruitment and retention in the field of TCT is needed. Professional societies in partnership with educational institutions could conduct outreach and help attract trainees from diverse backgrounds.


Subject(s)
Hematopoietic Stem Cell Transplantation , Physicians , Humans , Cross-Sectional Studies , Physicians/psychology , Career Choice , Male , Female , Surveys and Questionnaires , Cell- and Tissue-Based Therapy , Adult , Advisory Committees , Societies, Medical , United States
10.
Nat Microbiol ; 9(3): 614-630, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38429422

ABSTRACT

Microbial transformation of bile acids affects intestinal immune homoeostasis but its impact on inflammatory pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that T cell-driven inflammation decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of unconjugated and microbe-derived bile acids. Several microbe-derived bile acids attenuated farnesoid X receptor (FXR) activation, suggesting that loss of these metabolites during inflammation may increase FXR activity and exacerbate the course of disease. Indeed, mortality increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells during mouse GVHD. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and microbe-derived bile acids. In addition, the FXR antagonist ursodeoxycholic acid reduced the proliferation of human T cells and was associated with a lower risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of microbe-derived bile acids during inflammation may be an important mechanism to amplify T cell-mediated diseases.


Subject(s)
Graft vs Host Disease , T-Lymphocytes , Humans , Intestines , Inflammation , Bile Acids and Salts
11.
Blood Adv ; 8(12): 3314-3326, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38498731

ABSTRACT

ABSTRACT: Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas (BCLs). CAR19 cell expansion is necessary for CAR19 function but is also associated with toxicity. To define the impact of CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene ciloleucel) for mantle cell lymphoma (MCL), follicular lymphoma, and large BCL (LBCL) over the course of 5 years and obtained CAR19 expansion data using peripheral blood immunophenotyping for 188 of these patients. CAR19 expansion was higher in patients with MCL than other lymphoma histologic subtypes. Notably, patients with MCL had increased toxicity and required fourfold higher cumulative steroid doses than patients with LBCL. CAR19 expansion was associated with the development of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and the requirement for granulocyte colony-stimulating factor 14 days after infusion. Younger patients and those with elevated lactate dehydrogenase (LDH) had significantly higher CAR19 expansion. In general, no association between CAR19 expansion and LBCL treatment response was observed. However, when controlling for tumor burden, we found that lower CAR19 expansion in conjunction with low LDH was associated with improved outcomes in LBCL. In sum, this study finds CAR19 expansion principally associates with CAR-related toxicity. Additionally, CAR19 expansion as measured by peripheral blood immunophenotyping may be dispensable to favorable outcomes in LBCL.


Subject(s)
Antigens, CD19 , Immunophenotyping , Immunotherapy, Adoptive , Humans , Male , Antigens, CD19/immunology , Middle Aged , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Female , Aged , Receptors, Chimeric Antigen/immunology , Adult , Lymphoma, Mantle-Cell/immunology , Lymphoma, Mantle-Cell/blood , Aged, 80 and over , Biological Products
12.
BMC Public Health ; 24(1): 188, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38229064

ABSTRACT

BACKGROUND: Insufficient physical activity, high screen time, and unhealthy dietary patterns among adolescents may have worsened during the pandemic, but data are lacking. This study compared physical activity, screen time and fruit and vegetable intake in adolescents from Dunedin, New Zealand, 5-6 years before (Study 1) and during (Study 2) the COVID-19 pandemic. METHODS: Adolescents completed an online survey as part of the Built Environment and Active Transport to School (BEATS) studies in 2014/2015 (Study 1; n = 1,266; age: 15.3 ± 1.4 years; 54.6% female) and 2021/2022 (Study 2; n = 819; age: 15.2 ± 1.4 years; 47.4% female). The proportion of adolescents meeting guidelines for physical activity (≥ 60 min/day of moderate-to-vigorous physical activity), outside school screen time (≤ 2 h/day) and fruit and vegetable intake (> 1 serving/day for both fruit and vegetables) was calculated. Data were analysed using multivariable linear and logistic regression modelling. RESULTS: Few adolescents met recommended health behaviour guidelines. Compared to Study 1, significantly greater proportions of adolescents at Study 2 met guidelines for physical activity (16.7% vs. 23.1%; p < 0.001) and outside school screen time (13.3% vs. 18.3%; p < 0.001) while fruit and vegetable intake was not different (29.6% vs. 27.0%; p = 0.322). Compared to Study 1, average outside school screen time at Study 2 was lower on both weekdays (5.0 ± 2.9 vs. 4.6 ± 2.9; p < 0.001) and weekend days (6.9 ± 3.5 vs. 6.1 ± 3.6 h/day; p < 0.001). Reported frequency of consuming sweets was higher and soft drinks lower at Study 2 versus Study 1. CONCLUSIONS: Despite observed higher levels of physical activity and lower levels of outside school screen time during the pandemic compared to the pre-pandemic levels, few adolescents met health behaviour guidelines at both time points. Therefore, comprehensive health promotion that aims to improve physical activity levels, screen time and dietary patterns for adolescents is still necessary to prevent chronic health conditions adulthood.


Subject(s)
COVID-19 , Pandemics , Humans , Female , Adolescent , Adult , Male , Screen Time , New Zealand/epidemiology , COVID-19/epidemiology , Diet , Exercise
13.
Blood Adv ; 8(6): 1474-1486, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38295285

ABSTRACT

ABSTRACT: CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development after CD19 CAR T-cell therapy in patients with MCL. All patients (N = 26) who received standard-of-care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (grade ≥3) ICANS. All patients with ICANS had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. Overall, 92% of EEGs revealed interictal changes; no patients experienced frank seizures because of ICANS. In total, 86% of patients with severe ICANS with postinfusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of postinfusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in patients with severe ICANS, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.


Subject(s)
Lymphoma, Mantle-Cell , Neurotoxicity Syndromes , Humans , Adult , Lymphoma, Mantle-Cell/therapy , Immunotherapy, Adoptive/adverse effects , Adaptor Proteins, Signal Transducing , Antigens, CD19 , Brain , Cytokine Release Syndrome
14.
SSM Popul Health ; 25: 101603, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38283547

ABSTRACT

This study explored the relationship between green space accessibility (GSA) in residential area and adolescents' mental well-being, and whether the relationship was moderated by sociodemographic factors (sex, ethnicity, neighbourhood deprivation), identities (gender and sexuality minority, disability) and perceived neighbourhood safety simultaneously. Data from 3813 adolescents who lived in Tamaki Makaurau Auckland, Aotearoa New Zealand were obtained from the Youth19 Rangatahi Smart Survey. A Gaussian-based two-step floating catchment area method was employed to measure the spatial accessibility to green space at the neighbourhood level. The World Health Organization-5 Well-being Index was used to assess emotional well-being (EW), and the Reynolds Adolescent Depression Scale-short form was employed to measure depressive symptoms (DS). Through moderation analyses, results showed that perceived neighbourhood safety plays a vital role in the GSA - mental well-being association, with a negative trend in adolescents who reported being less safe in neighbourhoods. Adverse associations of GSA were found in gender and sexuality minority, disabled, Asian and Pacific adolescents, under the condition of not feeling safe in neighbourhoods all the time. The results showed marginalised adolescents tended to feel less safe in neighbourhoods, have lower EW and a higher level of DS. Additionally, the results from bivariate correlations showed there were inequalities in GSA for adolescents who lived in most deprived neighbourhoods and adolescents of Maori ethnicity. This study provides novel evidence of the importance of safe and inclusive green space for effectively promoting mental health and mitigating health inequalities of adolescents in urban areas.

15.
Wellbeing Space Soc ; 5: 100174, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38074072

ABSTRACT

There has been a growing interest in policies that encourage local living by promoting accessible and walkable communities, such as the 20-minute neighbourhood concept. Despite the widespread adoption of this policy in cities worldwide, little research has been conducted on the characteristics of children's 20-minute neighbourhoods and their association with time spent locally. This study aimed to explore the features of Scottish children's 20-minute neighbourhoods by analysing an 800-meter road and path network buffer surrounding 687 children's homes. Based on existing literature, the study identified key features associated with children's time spent locally and the 20-minute neighbourhood policy. The study then examined variations in these features by socioeconomic status, urbanicity, and gender. The findings revealed significant inequalities in the presence of health-benefiting (e.g., green spaces, recreational facilities, healthy food outlets) and health-harming (e.g., major roads, unhealthy commodity retailers) environments within children's 20-minute neighbourhoods. Children from more deprived areas had access to more of both types of environments. The study also found that having a school within a 20-minute neighbourhood was associated with an increased amount of time spent locally (IRR 1.62, 95% CI 1.5 to 1.8, p<0.001). The study suggests that the 20-minute neighbourhood policy should extend beyond mere access to local amenities and prioritise creating healthy 20-minute neighbourhoods, particularly in socioeconomically deprived areas. The research highlights the importance of promoting equal access to quality local environments, which can contribute to improved health and well-being outcomes for children.

17.
N Z Med J ; 136(1577): 12-21, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37778316

ABSTRACT

AIMS: Disabled people, particularly children and adolescents, tend to participate in less physical activity than their non-disabled peers on average. However, disabled children and youth (i.e., young people [YP]) are typically underrepresented in physical activity (PA) research, with little data available in Aotearoa New Zealand to guide policy makers to alter societal factors that contribute to disability inequities. The purpose of this study was to conduct a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis of the PA sector in Aotearoa New Zealand with respect to PA participation and promotion among disabled YP. METHODS: Focus group discussions, underpinned by the SWOT framework, were facilitated with stakeholders (n=11) engaged in the Aotearoa New Zealand PA sector. Data were transcribed and analysed using content analysis. Desirable and accessible opportunities were essential enablers of PA in disabled YP. RESULTS: Communication, transport, equipment costs, awareness of activities, and social support were identified as factors that influence PA participation. Schools also have a considerable influence on PA participation among disabled YP, while greater funding for and cohesion/collaboration among PA providers is key to continued growth in PA participation. CONCLUSIONS: Communication, accessibility, funding, and collaborative/coordinated multi-level efforts were identified as areas in need of strengthening to provide equitable opportunities for disabled YP in Aotearoa New Zealand to participate in PA.


Subject(s)
Disabled Persons , Exercise , Child , Adolescent , Humans , New Zealand , Focus Groups , Schools
19.
Blood ; 141(20): 2430-2442, 2023 05 18.
Article in English | MEDLINE | ID: mdl-36989488

ABSTRACT

The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential in facilitating the widespread use. Preemptive interventions to prevent more severe toxicities have improved safety, facilitating CAR T-cell therapy in medically frail populations and in those at high risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic because it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities.


Subject(s)
Cytokine Release Syndrome , Immunotherapy, Adoptive , Humans , Immunotherapy, Adoptive/adverse effects , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/therapy , Consensus , Interleukin 1 Receptor Antagonist Protein , Receptors, Antigen, T-Cell
20.
BMC Public Health ; 23(1): 150, 2023 01 23.
Article in English | MEDLINE | ID: mdl-36690969

ABSTRACT

BACKGROUND: The purpose of this study was to examine socio-demographic differences in physical activity (aerobic and muscle-strengthening) among young adults (18-24 years). METHODS: Data collected between 2017-2019 as a part of Sport New Zealand's Active NZ survey were examined using logistic regression analyses to determine the odds of participants meeting aerobic, muscle-strengthening and combined physical activity recommendations. Gender, ethnicity, employment/student status, disability status, and socio-economic deprivation were included as explanatory variables in analyses. RESULTS: The proportion of young adults meeting recommendations varied according to physical activity type (aerobic:63.2%; strength:40.1%; combined:37.2%). Young adults not employed/studying had lower odds of meeting recommendations than those full-time employed (OR = 0.43 [0.34-0.54]). Physical activity levels differ according to gender and this intersects with ethnicity, employment/student status, and social deprivation. For example, the odds of Pasifika young adults meeting combined physical activity recommendations compared to Europeans were not different (OR = 0.95 [0.76-1.19]), but when stratified by gender the odds were significantly higher for men (OR = 1.55 [1.11-2.16]) and significantly lower for women (OR = 0.64 [0.47-0.89]. Similarly, young adults in high deprivation areas had lower odds of meeting combined physical activity recommendations than those in low deprivation areas (OR = 0.81 [0.68-0.95]), but this was mainly due to the difference among women (OR = 0.68 [0.54-0.85]) as there was no difference among men (OR = 0.97 [0.76-1.25]). CONCLUSIONS: Intersections between socio-demographic characteristics should be considered when promoting physical activity among young adults in Aotearoa New Zealand, particularly young adults not employed/studying, and young women who live in deprived areas or identify as Asian or Pasifika. Tailored approaches according to activity type for each of these groups are required.


Subject(s)
Exercise , Sports , Male , Humans , Female , Young Adult , New Zealand , Socioeconomic Factors , Poverty
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