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BACKGROUND: Most cardiac surgery clinical prediction models (CPMs) are developed using pre-operative variables to predict post-operative outcomes. Some CPMs are developed with intra-operative variables, but none are widely used. The objective of this systematic review was to identify CPMs with intra-operative variables that predict short-term outcomes following adult cardiac surgery. METHODS: Ovid MEDLINE and EMBASE databases were searched from inception to December 2022, for studies developing a CPM with at least one intra-operative variable. Data were extracted using a critical appraisal framework and bias assessment tool. Model performance was analysed using discrimination and calibration measures. RESULTS: A total of 24 models were identified. Frequent predicted outcomes were acute kidney injury (9/24 studies) and peri-operative mortality (6/24 studies). Frequent pre-operative variables were age (18/24 studies) and creatinine/eGFR (18/24 studies). Common intra-operative variables were cardiopulmonary bypass time (16/24 studies) and transfusion (13/24 studies). Model discrimination was acceptable for all internally validated models (AUC 0.69-0.91). Calibration was poor (15/24 studies) or unreported (8/24 studies). Most CPMs were at a high or indeterminate risk of bias (23/24 models). The added value of intra-operative variables was assessed in six studies with statistically significantly improved discrimination demonstrated in two. CONCLUSION: Weak reporting and methodological limitations may restrict wider applicability and adoption of existing CPMs that include intra-operative variables. There is some evidence that CPM discrimination is improved with the addition of intra-operative variables. Further work is required to understand the role of intra-operative CPMs in the management of cardiac surgery patients.
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Bleeding per rectum in children is an infrequent presentation associated with a wide range of differential diagnoses, from benign to life-threatening. Irrespective of the underlying aetiology, it is typically a worrisome symptom for caregivers. Published data are limited, particularly for the UK population, from which to provide clear evidence-based guidance for assessment and management of infants, children and young people presenting with bleeding per rectum. In this Fifteen-Minute Consultation, we therefore explore the common aetiologies and combine opinions from acute paediatrics, paediatric gastroenterology and paediatric surgery to offer a structure for a diagnostic approach and initial management of lower gastrointestinal bleeding in infants, children and young people.
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Hemorragia Gastrointestinal , Recto , Lactante , Humanos , Niño , Adolescente , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Derivación y Consulta , Diagnóstico DiferencialRESUMEN
CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.
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Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Antígenos CD19/uso terapéutico , Síndrome de Liberación de Citoquinas , Humanos , Inmunoterapia Adoptiva/métodos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Estudios Prospectivos , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: There is growing support within the therapy professions for using talking therapy in alternative environments, such as outdoor spaces. The aim of the present study was to further understand how the organizational culture in clinical psychology may prevent or enable practitioners to step outside the conventional indoor consulting room. DESIGN: Informed grounded theory methodology was used within a pragmatist philosophy. METHODS: Participants (N = 15; nine male, six female) were identified using theoretical sampling. The sample consisted of experts and leaders within the profession of clinical psychology (e.g., heads of services, training programme directors, chairs of professional bodies, and developers of therapy models; M years in the profession = 34.80, SD = 9.77). One-to-one interviews and analysis ran concurrently over 9 months (April-December 2020). Mason's model of safe uncertainty was drawn upon to illuminate and organize themes. RESULTS: The main themes comprised organizational factors that either support a practitioner in maintaining a position of curiosity and flexibility towards the environment where therapy is located ('environmental safe uncertainty'), or push them towards adopting a more fixed position ('environmental certainty'). Themes included influences from therapy traditions, accessibility of alternative environments, internalized risk, workplace subcultures, business models, biomedical approaches, and the COVID-19 pandemic. CONCLUSIONS: Whether therapy is located in a consulting room, outdoors, clients' homes, or digitally, practitioners, clients, and services are encouraged to maintain a position of environmental safe uncertainty. PRACTITIONER POINTS: The therapy process and outcomes are influenced by the physical environment in which talking therapy is situated. Practitioners have often remained fixed in their preferred therapy environment, such as the indoor consulting room, without exploring the potential benefits of alternative environments or involving the client in this decision-making (i.e., 'environmental certainty'). Outdoor environments, as well as other alternatives to the consulting room (e.g., digital, home visits, and public places), can support access to therapy, subsequent engagement, and therefore health care equity. Practitioners and clients are encouraged to adopt a position of 'environmental safe uncertainty', which is defined as having openness, critical curiosity, and collaboration regarding the therapy environment and the possibility of other environments being more conducive to therapy.
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COVID-19 , Pandemias , Femenino , Humanos , Masculino , SARS-CoV-2 , Incertidumbre , Lugar de TrabajoRESUMEN
BACKGROUND: Anastomotic stricture is a significant cause of morbidity after repair of esophageal atresia (EA). Exposure to gastric acid has been postulated to contribute to stricture development and severity leading to prophylactic antacid use by some surgeons. We investigated the association between administration of antacid medication and the development of anastomotic strictures. METHODS: Retrospective case-note review of consecutive infants undergoing repair of EA with distal tracheoesophageal fistula (type C) between January 1994 and December 2014. Only infants who underwent primary esophageal anastomosis at initial surgical procedure were included. Stricture-related outcomes were compared initially for infants who received prophylactic antacid medication (PAAM) versus no prophylaxis, and the role of PAAM in stricture prevention was explored in a multivariate model. Outcomes were also compared for infants grouped by antacid use at any stage. RESULTS: One hundred fourteen infants were included. Sixteen infants received PAAM at surgeon preference. Of the remaining 98 infants, 44 subsequently received antacid as treatment for gastroesophageal reflux (GER) and 54 never received antacid medication. There was no statistically significant association between incidence of stricture in the first year (10 of 16 versus 41 of 98; P = 0.18) nor time to first stricture (median, 57 d [41-268] versus 102 d [43-320]; P = 0.89) and administration of PAAM. Similarly, there were no statistically significant associations between incidence of stricture, age at first stricture and number of dilatations, and administration of antacid medication either as prophylaxis nor when given as treatment for symptoms or signs of GER. CONCLUSIONS: These data do not support the hypothesis that PAAM reduces the incidence or severity of anastomotic stricture after repair of EA. Treatment with antacids may be best reserved for those with symptoms or signs of GER. Further prospective investigation of the role of antacid prophylaxis on stricture formation after EA repair is warranted.
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Anastomosis Quirúrgica/efectos adversos , Antiácidos/uso terapéutico , Atresia Esofágica/cirugía , Estenosis Esofágica/prevención & control , Complicaciones Posoperatorias/prevención & control , Estenosis Esofágica/etiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosAsunto(s)
Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/inmunología , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Receptores Quiméricos de Antígenos/inmunología , Resultado del Tratamiento , Masculino , FemeninoRESUMEN
We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment. Lymph node responses were rapid and associated with a concurrent lymphocytosis. Eleven of 12 evaluable patients with mantle cell lymphoma (92%) responded (median treatment duration, 40 weeks). Eleven of 31 non-germinal center B-cell diffuse large B-cell lymphoma patients (35%) responded but median treatment duration was 12 weeks due to development of progressive disease. ONO/GS-4059 was very well tolerated with 75% of adverse events (AEs) being Common Toxicity Criteria for Adverse Events version 4.0 grade 1 or grade 2. Grade 3/4 AEs were mainly hematologic and recovered spontaneously during therapy. One CLL patient experienced a grade 3 treatment-related bleeding event (spontaneous muscle hematoma) but no clinically significant diarrhea, cardiac dysrhythmias, or arthralgia were observed. No maximal tolerated dose (MTD) was reached in the CLL cohort. In the non-Hodgkin lymphoma cohort, 4 patients developed a dose-limiting toxicity, yielding an MTD of 480 mg once daily. ONO/GS-4059 has significant activity in relapsed/refractory B-cell malignancies without major drug-related toxicity. The selectivity of ONO/GS-4059 should confer advantages in combination therapies. This trial was registered at www.clinicaltrials.gov as #NCT01659255.
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Linfocitos B/efectos de los fármacos , Imidazoles/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/uso terapéutico , Adulto , Agammaglobulinemia Tirosina Quinasa , Anciano , Anciano de 80 o más Años , Linfocitos B/patología , Estudios de Cohortes , Femenino , Humanos , Imidazoles/efectos adversos , Imidazoles/sangre , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/sangre , Pirimidinas/efectos adversos , Pirimidinas/sangreRESUMEN
There is growing evidence that lymphocyte trafficking contributes to the clinical course of chronic lymphocytic leukemia (CLL), but to date, only static in vitro cultures have been used to study these phenomena. To address this lack of data, we have developed a dynamic in vitro model in which CLL cells experience shear forces equivalent to those in capillary beds and are made to flow through capillary-like hollow fibers lined with endothelial cells. CLL cells treated in this way increased their expression of CD62L and CXCR4 (both P < .0001) and of CD49d and CD5 (both P = .003) directly as a result of the shear force. Furthermore, CLL cells migrated through the endothelium into the "extravascular" space (mean migration, 1.37% ± 2.14%; n = 21). Migrated CLL cells had significantly higher expression of CD49d (P = .02), matrix metallopeptidase-9 (P = .004), CD38 (P = .009), CD80 (P = .04), and CD69 (P = .04) compared with CLL cells that remained in the circulation. The degree of migration observed strongly correlated with CD49d expression (r(2), 0.47; P = .01), and treatment with the CD49d-blocking antibody natalizumab resulted in significantly decreased migration (P = .01). Taken together, our data provide evidence for a novel, dynamic, and tractable in vitro model of lymphocyte migration and confirm that CD49d is a critical regulator of this process in CLL.
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Técnicas de Cultivo de Célula , Quimiotaxis de Leucocito , Leucemia Linfocítica Crónica de Células B/patología , Linfocitos/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Técnicas de Cultivo de Célula/instrumentación , Células Cultivadas , Técnicas de Cocultivo/instrumentación , Técnicas de Cocultivo/métodos , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Linfocitos/patología , Microfluídica , Persona de Mediana Edad , Modelos Teóricos , Resistencia al CorteRESUMEN
BACKGROUND: The Behaviour Problems Inventory-Short Form (BPI-S) is a spin-off of the BPI-01 that was empirically developed from a large BPI-01 data set. In this study, the reliability and factorial validity of the BPI-S was investigated for the first time on newly collected data from adults with intellectual disabilities. METHODS: The sample consisted of 232 adults with intellectual disabilities who represented all levels of intellectual functioning. They were recruited at several day programs in the USA (n = 148) and the UK (n = 84). RESULTS: We found acceptable reliability in terms of internal consistency, inter-rater agreement and test-retest reliability. Confirmatory factor analysis validated the three BPI-S subscale structure. CONCLUSIONS: We corroborated the factor structure underly-ing the three subscales and found the BPI-S to have adequate to good psychometric properties in a newly collected sample of adults with intellectual disabilities.
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Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/psicología , Problema de Conducta/psicología , Encuestas y Cuestionarios/normas , Adolescente , Adulto , Anciano , Agresión/psicología , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Conducta Autodestructiva/diagnóstico , Conducta Autodestructiva/psicología , Índice de Severidad de la Enfermedad , Reino Unido , Estados Unidos , Adulto JovenAsunto(s)
Imidazoles/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/mortalidad , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/administración & dosificación , Agammaglobulinemia Tirosina Quinasa , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Imidazoles/efectos adversos , Leucemia Linfocítica Crónica de Células B/epidemiología , Masculino , Pirimidinas/efectos adversos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Coping with health problems requires some degree of self-management; however, an individual's ability to self-manage can be threatened during challenging times, such as the COVID-19 pandemic. Exploring differences and changes in psychological well-being and coping strategies between those with low and high patient activation may inform appropriate interventions to support psychological coping. METHODS: People with chronic kidney disease (CKD) (non-dialysis and transplant) were recruited from 11 hospital sites across England between August and December 2020. Participants responded to an online survey study, including the Brief Coping Orientation to Problem Experienced (COPE) Inventory, Depression, Anxiety and Stress Scale (DASS-21), Short Health Anxiety Index (SHAI), and Patient Activation Measure (PAM-13). A follow-up survey was conducted 6-9 months later. Paired t tests assessed within-group changes, and chi-squared tests compared coping strategies utilised by low- and high-activated participants. General linear modelling was performed to determine the relationship between patient activation and coping strategies, and covariates. RESULTS: Two hundred and fourteen participants were recruited (mean age: 60.7, 51% male, mean eGFR: 38.9 ml/min/1.73 m2). Low-activated participants were significantly more anxious than high-activated participants (P = 0.045). Health anxiety significantly decreased (i.e., got better) for high-activated participants (P = 0.016). Higher patient activation scores were associated with greater use of problem-focused strategies (ß = 0.288, P < 0.001). Age (ß = - 0.174, P = 0.012), sex (ß = 0.188, P = 0.004), and education level (ß = 0.159, P = 0.019) significantly predicted use of problem-focused strategies. DISCUSSION: Those with higher activation had lower levels of anxiety, and more frequently used adaptive coping strategies during the pandemic. Targeted support and interventions may be required for people with CKD to enhance patient activation, encourage more positive adaptive coping strategies, and mitigate maladaptive coping strategies.
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Adaptación Psicológica , COVID-19 , Insuficiencia Renal Crónica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ansiedad/psicología , Ansiedad/epidemiología , Habilidades de Afrontamiento , COVID-19/psicología , COVID-19/epidemiología , Inglaterra/epidemiología , Participación del Paciente/psicología , Insuficiencia Renal Crónica/psicología , Insuficiencia Renal Crónica/terapia , Automanejo/psicología , Encuestas y CuestionariosRESUMEN
PURPOSE: Recent series of newborn Oesophageal Atresia (OA) repair continue to report widespread use of chest drains, gastrostomy, routine contrast studies and parenteral nutrition (PN) despite evidence suggesting these are superfluous. We report outcomes using a minimally interventional approach to post-operative recovery. METHODS: Ethically approved (15/WA/0153), single-centre, retrospective case-note review of consecutive infants with OA 2000-2022. Infants with OA and distal trache-oesophageal fistula undergoing primary oesophageal anastomosis at initial surgery were included (including those with comorbidities such as duodenal atresia, anorectal malformation and cardiac lesions). Our practice includes routine use of a trans-anastomotic tube (TAT), no routine chest drain nor gastrostomy, early enteral and oral feeding, no routine PN and no routine contrast study. Data are median (IQR). RESULTS: Of total 186 cases of OA treated during the time period, 157 met the inclusion criteria of which 2 were excluded as casenotes unavailable. TAT was used in 150 infants. A chest drain was required in 13 (8%) and two infants had a neonatal gastrostomy. Enteral feeds were started on postoperative day 2 (2-3), full enteral feeds established by day 4 (4-6) and oral feeds started on day 5 (4-8). PN was required in 15%. Median postoperative length of stay was 10 days (8-17). Progress was quicker in term infants than preterm. One infant died of cardiac disease prior to neonatal discharge. Two planned post-operative contrast studies were performed (surgeon preference) and a further 7 due to clinical suspicion of anastomotic leak. Contrast study was therefore avoided in 94%. There were 2 anastomotic leaks; both presented clinically at day 4 and day 8 after oral feeds had been started. CONCLUSION: Our minimally interventional approach is safe. It facilitates prompt recovery with lower resource use, reduced demand on nursing staff, reduced radiation burden, and early discharge home compared to published series without adversely affecting outcomes. LEVEL OF EVIDENCE: Level 4.
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Atresia Esofágica , Recién Nacido , Lactante , Humanos , Atresia Esofágica/cirugía , Nutrición Enteral , Estudios Retrospectivos , Fuga Anastomótica , GastrostomíaRESUMEN
Over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients who receive chimeric antigen receptor (CAR) T cells will experience disease progression. There is no standard next line of therapy and information in this setting is scarce and heterogeneous. We analyzed 387 R/R LBCL patients who progressed after CAR T cells from July 2018 until March 2022 in Spain and the United Kingdom. Median overall survival (OS) was 5.3 months, with significant differences according to the interval between infusion and progression (<2 months [1.9 months], 2-6 months [5.2 months], and >6 months [not reached]). After progression, 237 (61%) patients received treatment. Focusing on the first subsequent therapy, overall (complete) response rates were 67% (38%) for polatuzumab-bendamustine-rituximab (POLA), 51% (36%) for bispecific antibodies (BsAb), 45% (35%) for radiotherapy (RT), 33% (26%) for immune checkpoint inhibitors (ICIs), 25% (0%) for lenalidomide (LENA), and 25% (14%) for chemotherapy (CT). In terms of survival, 12-month progression-free survival and OS was 36.2% and 51.0% for POLA, 32.0% and 50.1% for BsAb, 30.8% and 37.5% for RT, 29.9% and 27.8% for ICI, 7.3% and 20.8% for LENA, and 6.1% and 18.3% for CT. Thirty-two (14%) patients received an allogeneic hematopoietic cell transplant with median OS not reached after a median follow-up of 15.1 months. In conclusion, patients with R/R LBCL who progress within the first 2 months after CAR T-cell therapy have dismal outcomes. Novel targeted agents, such as polatuzumab and BsAbs, can achieve prolonged survival after CAR T-cell therapy failure.
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BACKGROUND: Allogeneic erythrocyte transfusion in cardiac surgical patients is associated with a fourfold increase in pulmonary complications. Our understanding of the processes underlying these observations is poor and there is no experimental model of transfusion-related acute lung injury that shows homology to cardiac surgical patients. Our objective was to develop a novel swine recovery model to determine how two clinical risk factors, allogenic erythrocyte transfusion and cardiopulmonary bypass, interact in the genesis of postcardiac surgery acute lung injury. METHODS: Thirty-six pigs were infused with allogeneic 14- or 42-day-old erythrocytes or they underwent cardiopulmonary bypass with or without transfusion of 42-day erythrocyte. Controls received saline. All pigs were recovered and assessed for pulmonary dysfunction, inflammation, and endothelial activation at 24 h. RESULTS: Transfusion of stored allogeneic erythrocytes in pigs compared with sham caused pulmonary dysfunction characterized by reduced lung compliance (mean difference -3.36 [95% CI, -5.31 to -1.42] ml/cm H2O), an increase in protein levels in bronchoalveolar lavage fluid, histological lung injury inflammation, and endothelial activation. Transfusion of blood stored for up to 42 days resulted in greater protein levels in bronchoalveolar lavage fluid, macrophage infiltration, platelet activation, and depletion of T-lymphocytes in recipient lungs versus 14-day-old blood. Transfusion interacted with cardiopulmonary bypass to increase lung injury in the absence of platelet activation. CONCLUSIONS: In this novel large animal model of allogeneic erythrocyte transfusion, pulmonary dysfunction occurs in the absence of any priming event, is increased when combined with other inflammatory stimuli, and is mediated by monocyte activation and T-lymphocyte depletion.
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Puente Cardiopulmonar/efectos adversos , Transfusión de Eritrocitos/efectos adversos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/fisiopatología , Animales , Modelos Animales de Enfermedad , Femenino , Inflamación/etiología , Inflamación/fisiopatología , Rendimiento Pulmonar , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Factores de Riesgo , PorcinosRESUMEN
Prevalence of conditions which raise cardiovascular risk, such as hypertension and type 2 diabetes are seeing a dramatic rise in Sub Saharan Africa. A large proportion of these cases remain undiagnosed and there is limited resource to provide patients with self-management support and education once diagnosed. This study aimed to identify and catalogue community-based assets for the purposes of developing and deploying a screening and education programme for cardiometabolic risk factors (diabetes and hypertension) within religious organisations in a local community in a rural Ghanaian context. We utilised a community-based form of participatory research made up of a number of different components including community-based asset mapping and stakeholder consultation, supplemented by 18 in-depth interviews and 10 focus groups with n = 115 service users, to map existing assets with relevance to cardiometabolic health in this setting and context. Thematic analysis of interview and focus group data was performed to identify themes related to successful implementation of health screening. Two stakeholder workshops with local healthcare professionals, faith leaders and health policy makers were delivered to co-produced a prioritised list of recommendations and 'asset map' to aid deployment of mass screening within faith organisations in this context. The findings of this research highlight a number of 'hidden' community assets and motivational mechanisms at an individual, community and institutional levels; these have informed a list of recommendations which have been co-developed with the stakeholder group and local community to support the development of effective screening strategies for cardiometabolic conditions within faith organisations in this context. We have identified key mechanisms and assets which would support a sustainable screening approach designed to engage an underserved community at high CVD risk to promote general community health and well-being.
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The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterized. Current practice is guided through physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve both CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult patients with LBCL in relation to outcomes after axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel) administration. The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity or mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death after CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of polatuzumab-containing chemotherapy regimens. Our data suggested that complete or partial response to BT may be more important for Tisa-cel than for Axi-cel, because all patients receiving Tisa-cel with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned toward optimal response and disease debulking, to improve patient outcomes associated with CD19CAR-T. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete or partial response to BT before Tisa-cel administration may prompt consideration of further lines of BT where possible.
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Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Adulto , Humanos , Recurrencia Local de Neoplasia , Terapia Puente , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD19/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológicoRESUMEN
Observations in human tumours, as well as mouse models, have indicated that telomere dysfunction may be a key event driving genomic instability and disease progression in many solid tumour types. In this scenario, telomere shortening ultimately results in telomere dysfunction, fusion and genomic instability, creating the large-scale rearrangements that are characteristic of these tumours. It is now becoming apparent that this paradigm may also apply to haematological malignancies; indeed these conditions have provided some of the most convincing evidence of telomere dysfunction in any malignancy. Telomere length has been shown in several malignancies to provide clinically useful prognostic information, implicating telomere dysfunction in disease progression. In these malignancies extreme telomere shortening, telomere dysfunction and fusion have all been documented and correlate with the emergence of increased genomic complexity. Telomeres may therefore represent both a clinically useful prognostic tool and a potential target for therapeutic intervention.
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Neoplasias Hematológicas/genética , Telómero/fisiología , Enfermedad Aguda , Enfermedades de la Médula Ósea/genética , Progresión de la Enfermedad , Inestabilidad Genómica , Humanos , Leucemia/genética , Linfoma de Células B/genética , Mieloma Múltiple/genética , Pronóstico , Acortamiento del Telómero/genéticaRESUMEN
OBJECTIVES: To identify the time required to achieve optimal palatability of a cup of tea without risk of harm (oral scalding) using the resources available in a standard hospital staff room, and to identify the best accompanying biscuit for nutritional content, crunchiness, and integrity when dunking. DESIGN: Prospective, non-masked, biscuit based, comparative study. SETTING: Staff room in the surgery department of a UK hospital. PARTICIPANTS: Four different varieties of round, non-chocolate biscuit: oat, digestive, rich tea, and shortie. A standardised cup of tea was determined on the basis of the investigators' preference for colour and palatability and pragmatic tea making methods. MAIN OUTCOME MEASURES: The main outcome was time to achieve a safe temperature for consumption of tea, and the best biscuit to pair with the tea on the basis of nutritional content, absorptive ability, crunchiness, and integrity after dunking. Biscuits were ranked first to last (according to scores 1-4), with penalty points given for adverse events such as scalds and breakability. RESULTS: Baseline data suggested that after adding 240 mL of freshly boiled water to an unwarmed mug containing a tea bag, the median temperature of a standard cup of tea was 82ºC (range 81-84ºC). Optimal palatability and agreed universal drinking temperature of 61ºC was achieved at 400 (range 360-420) seconds with 30 mL of cow's milk and 370 (330-450) seconds with 40 mL of milk. The investigators considered tea colour preferable with 40 mL of milk. CONCLUSION: Healthcare workers can safely consume a cup of tea after less than 10 minutes, especially if enjoyed with a biscuit. Making time for a cup of tea may help healthcare workers avoid their break point.
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Cafeína , Leche , Femenino , Animales , Bovinos , Estudios Prospectivos , Estado Nutricional , TéRESUMEN
Background: Social prescribing (SP) is a mechanism to link patients with community groups and third sector organizations. It offers a complimentary approach to the traditional medical models to address psychosocial needs of patients more effectively and in turn aims to reduce demand on the NHS. The aim of this study was to explore the economic benefits related to changes in the use of healthcare resources following a social prescribing intervention in four primary care practices in Wales. Methods: Quantitative data from routine healthcare usage was collected from the 78 participants pre and post-intervention. The participants were grouped into frequent attenders (FA) (n = 21) and frequent (n = 57) non-attenders (FNA), and a cost analysis was conducted to estimate cost variances based on healthcare unit usage over the length of the pilot intervention. These were then extrapolated forward to identify potential healthcare savings. Results: The SP as an intervention generated the largest cost saving for FAs. The cost variance when FAs participated in the intervention shows there is a direct cost saving of £6,113 or £78.37 per participant over the 5 months of the intervention. Conclusions: Results suggest there may be a cost saving associated with SP interventions, however caution should be exercised in interpreting the results due to the lack of control group in this study The cost saving were largest for FAs, where the intervention reduced healthcare unit usage as well as actual and inferred impact on associated healthcare costs. This suggests that in practice to generate the maximum cost benefit SP interventions could be targeted at FAs.
Asunto(s)
Atención Primaria de Salud , Humanos , Análisis Costo-Beneficio , GalesRESUMEN
BACKGROUND: Social prescribing (such as green social prescribing), aims to address health disparities cross-culturally to improve well-being. However, evidence highlights racial disparities in relation to access to quality green space (including local/national parks and recreational spaces). This review aimed to identify the psycho-socioeconomic barriers to green space access for racialised individuals/families and Black Indigenous People of Colour (BIPOC), to understand what cultural adaptations might be made to help support them to access green social prescribing within the UK. METHOD: A narrative systematic review was conducted to identify barriers to green space access for racialised individuals/families and BIPOC. Searches of publication databases (APA PsycInfo, Cochrane Database of Systematic Reviews [CDSR], Cochrane Central Register of Controlled Trials [CENTRAL], Cumulated Index to Nursing and Allied Health Literature [CINAHL], and SCOPUS Preview) were undertaken from January to February 2022, to identify quantitative peer reviewed studies. Of the 4493 abstracts identified, ten studies met the inclusion criteria and were included for final review. RESULTS: The results suggest that interpersonal, practical (such as transportation costs, entrance fees and lodging costs) and environmental factors can act as barriers to green space access for racialised individuals/families. Most frequently reported barriers were perceptions of safety and costs associated with travel and accessing green spaces, particularly for families. CONCLUSION: Factors such as diversity-friendly schemes (e.g., multiple languages on signs and additional prayer spaces in parks), funding and strategies to improve safety should be considered in the design and commissioning of green space and green social prescribing initiatives in primary care. By mitigating these barriers green space can become more accessible and improve inclusivity for racialised individuals/families. Future research could explore the inter-racial differences between racialised populations and which mechanisms reduce barriers to access and in what contexts.