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Background: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. Methods: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. Results: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. Conclusion: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow

Aim: To scope the international literature about registered nurses delegated models of care to unlicenced workers, identify gaps and reflect upon how the evidence relates to nursing in multiple contexts. Design: Scoping review of the peer reviewed literature from the year 2000 onwards, using the PRISMA-ScR checklist. Methods: The study searched the following databases in February 2022: CINAHL, Medline, ProQuest, and SCOPUS, and included keywords, Boolean operators and subject headings relevant to registered nurses delegating the provision of care to unlicenced workers. Results: A total of 49 articles met the eligibility criteria for this study, and relevant data were extractedThree models of delegation were highlighted within the literature: direct, indirect and a mixture of both. The data highlighted that direct delegation mainly occurred in acute contexts, with delegation decreasing with increasing patient acuity and/or complexity but the threshold of when this would occur was not clear. There was one intervention study that measured patient outcomes which could aid in the determination of what is effective delegation. For studies that did report on it (n = 6), there were few examples of better patient outcomes in cases where care was delegated from registered nurses to unlicenced workers. Conclusions: The scoping review highlighted heterogeneity in practice areas and methods of delegation practice. A key gap in literature is the absence of studies focusing on patient outcomes, with a clear baseline to measure and identify effective delegation practices. Additionally, the legal and logistical implications presented in both direct and indirect delegation practices is not evident in the literature. Implications for the Profession: Decisions related to delegation are often made at the service level and prescribed to those who work within the service, suggesting that models of indirect delegation are in fact not delegation at all, rather a re-distribution of nurses' w

People with intellectual disability and/or autism are likely to be in hospital more often, for longer, and have poorer health outcomes. Few audit tools exist to identify their barriers in mainstream healthcare environments. This study aimed to identify evidence of audit characteristics of healthcare contexts specifically for people with intellectual disability and/or autism, for conceptual development of an auditing framework. A scoping review of evaluations of healthcare environments was completed in January 2023. Findings were presented using the PAGER framework. Of the sixteen studies identified, most originated in the UK, nine focused on intellectual disability, four on autism, and three were concerned with mixed diagnosis. Six domains for auditing healthcare environments were identified: care imperatives, communication to individuals, understanding communication from individuals, providing supportive environments of care, supporting positive behaviour, and actions to make things go well. Further research is recommended to refine an audit framework.

Background: The Australian National Disability Insurance Scheme (NDIS) is conceptually grounded in the social model of disability, which focuses on removing disabling structures of society to allow people with disabilities full participation and improved quality of life. The social model rests on a dichotomous relationship against a medical model and its focus on treating impairments, and incorrectly places nursing within this paradigm. Aim: To undertake a discourse analysis of nursing as represented in the NDIS pricing guide and eligibility criteria, and to understand how the profession is conceptualised and valued within the scheme. Methods: Informed by Lauclau and Mouffe's poststructuralist theory, a discourse analysis of the floating signifier of nursing against the dominant nodal point of the social model of disability was undertaken through a close reading of the NDIS pricing guide and eligibility criteria. Findings: The nursing scope of practice is confined to physical/medicalised supports for people with disabilities. Nursing is excluded from offering therapeutic and behaviour supports and is structured and fiscally valued differently to other professions. Discussion: Despite its base in holistic and person-centred care, due to its conceptualisation within the medical model, the full scope of nursing practice is restrictive within the NDIS. This misarticulation of nursing excludes key aspects of adaptive, therapeutic, and holistic practice which can improve health outcomes for people with disabilities. Conclusion: The NDIS in its conceptual construction based on the social model of disability has upheld a vision of nursing inconsistent with practice relevant to caring for people with disabilities.

Female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy have a strongly increased risk of breast cancer (BC), but the treatment-specific BC risk in male survivors of HL has not been evaluated. We assessed BC risk in a cohort of 3077 male survivors of 5-year HL treated at age ≤51 years in 20 Dutch hospitals between 1965 and 2013. We estimated standardized incidence ratios (SIRs), absolute excess risks per 10 000 person-years, and cumulative BC incidences. After a 20-year median follow-up, we observed 8 cases of male with BC. Male survivors of HL experienced a 23-fold (95% confidence interval [CI], 10.1-46.0) increased BC risk compared with the general population, representing 1.6 (95% CI, 0.7-3.3) excess BC incidences per 10 000 person-years. The 20- and 40-year cumulative BC incidences after HL treatment were 0.1% (95% CI, 0.02-0.3) and 0.7% (95% CI, 0.3-1.4), respectively. Treatment with chest radiotherapy without alkylating chemotherapy yielded a strongly increased SIR (20.7; 95% CI, 2.5-74.8), which was not significantly different for chest radiotherapy and alkylating chemotherapy (41.1; 95% CI, 13.4-96.0). Males treated with chest radiotherapy and anthracyclines had an SIR of 48.1 (95% CI, 13.1-123.1). Two patients died from BC (median follow-up, 4.7 years). To ensure early diagnosis and treatment, clinicians should be alert to BC symptoms in male survivors of HL.

The MCPA herbicide mobilizes trace metals in soil by outcompeting adsorption by soil minerals[1]. Trace metal tracers are too immobile for the relatively short observation times available with positron emission tomography (PET). For the first time, however, timelapse movies of Cu migration in columns filled with artificial soil (68 % sand, 26 % silt, 5 % illite clay, 1 % goethite) were recorded. Soil solution was supplied from bottom up at a flow rate of 100 µL/min, low enough to allow for equilibration while maintaining a residence time in the order of tracer half-life (12.7 h). Up to 5 mL or 250 MBq of Cu-64 tracer was applied in one pulse run. The figure show volume renderings at different times (voxel size = 1 mm³, column high = 10 cm). The radiolabeled Cu-MCPA complex breakthrough occurred just about 10-fold slower than the inert solute tracer [F-18]KF used in control columns shown in the lower row of the figure. Imaging movies are accessible at [2]. 1. Kulenkampff J. et al. (2018). Sci. Rep., 8(7091). Open access CC BY 4.0. 2. URL https://zenodo.org/record/852968

Hematological toxicity is the most common adverse event after chimeric antigen receptor (CAR) T-cell therapy. Cytopenias can be profound and long-lasting and can predispose for severe infectious complications. In a recent worldwide survey, we demonstrated that there remains considerable heterogeneity in regard to current practice patterns. Here, we sought to build consensus on the grading and management of immune effector cell–associated hematotoxicity (ICAHT) after CAR T-cell therapy. For this purpose, a joint effort between the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) involved an international panel of 36 CAR T-cell experts who met in a series of virtual conferences, culminating in a 2-day meeting in Lille, France. On the basis of these deliberations, best practice recommendations were developed. For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia. Detailed recommendations on risk factors, available preinfusion scoring systems (eg, CAR-HEMATOTOX score), and diagnostic workup are provided. A further section focuses on identifying hemophagocytosis in the context of severe hematotoxicity. Finally, we review current evidence and provide consensus recommendations for the management of ICAHT, including growth factor support, anti-infectious prophylaxis, transfusions, autologous hematopoietic stem cell boost, and allogeneic hematopoietic cell transplantation. In conclusion, we propose ICAHT as a novel toxicity category after immune effector cell therapy, provide a framework for its grading, review literature on risk factors, and outline expert recommendations for the diagnostic workup and short- and long-term management.

Aim: To describe Australian registered nurses' awareness, and implementation of reasonable adjustments within their practice when caring for people with intellectual disability and/or autism. Additionally, the association between key demographic, workforce, and respondent variables and familiarity of the term and regularity of use was explored. Design: Cross-sectional survey. Methods: Survey data were collected between August and October 2020 using an online survey tool. Data were analysed using descriptive and inferential statistics. Results: Familiarity of the concept of reasonable adjustments was relatively low, compared to respondents who report applying adjustments when caring for people with intellectual disability and/or autism. Higher levels of confidence, comfort, and knowledge when caring for this cohort were associated with greater awareness and application of reasonable adjustments. Conclusion: A higher volume, and diversity in type of, nursing education related to care for people with intellectual disability and/or autism is indicated.

BACKGROUND Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines. METHODS We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy. Patients were randomly assigned to receive tisagenlecleucel with optional bridging therapy (tisagenlecleucel group) or salvage chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT) (standard-care group). The primary end point was event-free survival, defined as the time from randomization to stable or progressive disease at or after the week 12 assessment or death. Crossover to receive tisagenlecleucel was allowed if a defined event occurred at or after the week 12 assessment. Other end points included response and safety. RESULTS A total of 322 patients underwent randomization. At baseline, the percentage of patients with high-grade lymphomas was higher in the tisagenlecleucel group than in the standard-care group (24.1% vs. 16.9%), as was the percentage with an International Prognostic Index score (range, 0 to 5, with higher scores indicating a worse prognosis) of 2 or higher (65.4% vs. 57.5%). A total of 95.7% of the patients in the tisagenlecleucel group received tisagenlecleucel; 32.5% of the patients in the standard-care group received autologous HSCT. The median time from leukapheresis to tisagenlecleucel infusion was 52 days. A total of 25.9% of the patients in the tisagenlecleucel group had lymphoma progression at week 6, as compared with 13.8% of those in the standard-care group. The median event-free survival in both groups was 3.0 months (hazard ratio for event or death in the tisagenlecleucel group, 1.07; 95% confidence interval, 0.82 to 1.40; P=0.61).

Despite promising clinical results in a small subset of malignancies, therapies based on engineered chimeric antigen receptor and T-cell receptor T cells are associated with serious adverse events, including cytokine release syndrome and neurotoxicity. These toxicities are sometimes so severe that they significantly hinder the implementation of this therapeutic strategy. For a long time, existing preclinical models failed to predict severe toxicities seen in human clinical trials after engineered T-cell infusion. However, in recent years, there has been a concerted effort to develop models, including humanized mouse models, which can better recapitulate toxicities observed in patients. The Accelerating Development and Improving Access to CAR and TCR-engineered T cell therapy (T2EVOLVE) consortium is a public-private partnership directed at accelerating the preclinical development and increasing access to engineered T-cell therapy for patients with cancer. A key ambition in T2EVOLVE is to design new models and tools with higher predictive value for clinical safety and efficacy, in order to improve and accelerate the selection of lead T-cell products for clinical translation. Herein, we review existing preclinical models that are used to test the safety of engineered T cells. We will also highlight limitations of these models and propose potential measures to improve them.