Treatment outcomes in patients with large B-cell lymphoma after progression to chimeric antigen receptor T-cell therapy.

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.

A systematic review of cardiac surgery clinical prediction models that include intra-operative variables.

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.

Outcomes after chimeric antigen receptor T-cell therapy across large B-cell lymphoma subtypes.

Not available.

Patient activation and psychological coping strategies to manage challenging circumstances during the COVID-19 pandemic in people with kidney disease.

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.

A Minimally Interventional Approach to Oesophageal Atresia Repair With Early Enteral Feeding is Safe, Optimises Neonatal Outcomes, and Reduces Resource use.

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.

Cardiovascular disease prevention: Community Based Asset Mapping within religious networks in a rural Sub-Saharan African neighbourhood.

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.

Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma.

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.

Fifteen-minute consultation: Rectal bleeding in children.

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.

Direct Uptake of Nutrition and Caffeine Study (DUNCS): biscuit based comparative study.

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.

Induction of labour for predicted macrosomia: study protocol for the 'Big Baby' randomised controlled trial.

INTRODUCTION: Large-for-gestational age (LGA) fetuses have an increased risk of shoulder dystocia. This can lead to adverse neonatal outcomes and death. Early induction of labour in women with a fetus suspected to be macrosomic may mitigate the risk of shoulder dystocia. The Big Baby Trial aims to find if induction of labour at 38+0-38+4 weeks' gestation, in pregnancies with suspected LGA fetuses, reduces the incidence of shoulder dystocia. METHODS AND ANALYSIS: The Big Baby Trial is a multicentre, prospective, individually randomised controlled trial of induction of labour at 38+0 to 38+4 weeks' gestation vs standard care as per each hospital trust (median gestation of delivery 39+4) among women whose fetuses have an estimated fetal weight >90th customised centile according to ultrasound scan at 35+0 to 38+0 weeks' gestation. There is a parallel cohort study for women who decline randomisation because they opt for induction, expectant management or caesarean section. Up to 4000 women will be recruited and randomised to induction of labour or to standard care. The primary outcome is the incidence of shoulder dystocia; assessed by an independent expert group, blind to treatment allocation, from delivery records. Secondary outcomes include birth trauma, fractures, haemorrhage, caesarean section rate and length of inpatient stay. The main trial is ongoing, following an internal pilot study. A qualitative reporting, health economic evaluation and parallel process evaluation are included. ETHICS AND DISSEMINATION: The study received a favourable opinion from the South West-Cornwall and Plymouth Health Research Authority on 23/03/2018 (IRAS project ID 229163). Study results will be reported in the National Institute for Health Research journal library and published in an open access peer-reviewed journal. We will plan dissemination events for key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN18229892.

Social prescribing for frequent attenders in primary care: An economic analysis.

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.

Prevalence, Predictors, and Experience of Moral Suffering in Nursing and Care Home Staff during the COVID-19 Pandemic: A Mixed-Methods Systematic Review.

(1) Background: Nursing and care home staff experienced high death rates of older residents and increased occupational and psychosocial pressures during the COVID-19 pandemic. The literature has previously found this group to be at risk of developing mental health conditions, moral injury (MI), and moral distress (MD). The latter two terms refer to the perceived ethical wrongdoing which contravenes an individual's moral beliefs and elicits adverse emotional responses. (2) Method: A systematic review was conducted to explore the prevalence, predictors, and psychological experience of MI and MD in the aforementioned population during the COVID-19 pandemic. The databases CINAHL, APA PsychINFO, APA PsychArticles, Web of Science, Medline, and Scopus were systematically searched for original research studies of all designs, published in English, with no geographical restrictions, and dating from when COVID-19 was declared a public health emergency on the 30 January 2020 to the 3 January 2022. Out of 531 studies screened for eligibility, 8 studies were selected for review. A thematic analysis was undertaken to examine the major underpinning themes. (3) Results: MI, MD, and related constructs (notably secondary traumatic stress) were evidenced to be present in staff, although most studies did not explore the prevalence or predictors. The elicited major themes were resource deficits, role challenges, communication and leadership, and emotional and psychosocial consequences. (4) Conclusions: Our findings suggest that moral injury and moral distress were likely to be present prior to COVID-19 but have been exacerbated by the pandemic. Whilst studies were generally of high quality, the dearth of quantitative studies assessing prevalence and predictors suggests a research need, enabling the exploration of causal relationships between variables. However, the implied presence of MI and MD warrants intervention developments and workplace support for nursing and care home staff.

A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience.

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.

Nature-Based Interventions for Psychological Wellbeing in Long-Term Conditions: A Systematic Review.

BACKGROUND: With the global burden of disease increasing, particularly in relation to often preventable chronic diseases, researchers and clinicians are keen to identify interventions that can mitigate ill health and enhance the psychological wellbeing of people living with long-term conditions (LTCs). It is long established that engagement with nature can support human health and wellbeing, and in recent years, nature-based interventions (NBIs) have been advanced as of potential benefit. This review thus sought to systematically appraise published evidence of the application of NBIs to address psychological wellbeing for those living with LTCs. METHODS: A systematic search of three databases, PsycINFO, MEDLINE and SCOPUS, was undertaken, and the BestBETs quality assessment checklist was used to appraise methodological quality of elicited studies. RESULTS: Of 913 studies identified, 13 studies (12 using quantitative methods, one qualitative) were used. Included papers reported use of a variety of psychological outcomes alongside more circumscribed physiological outcomes. Quality appraisal showed modest robustness, some methodological weaknesses and a dominance of application in developed countries, yet synthesis of studies suggested that reported psychological and physiological outcomes present a strong argument for NBIs having a promising and positive impact on psychological wellbeing. CONCLUSIONS: NBIs have positive psychological and physiological impacts on people with LTCs, suggesting they may be a suitable addition to current maintenance treatment. Future research should focus on minimising study bias and increasing the potential for cross-cultural applications.

Examining Psychosocial and Economic Barriers to Green Space Access for Racialised Individuals and Families: A Narrative Literature Review of the Evidence to Date.

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.

Organizational perspectives on outdoor talking therapy: Towards a position of 'environmental safe uncertainty'.

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.

Kidney Care during COVID-19 in the UK: Perspectives of Healthcare Professionals on Impacts on Care Quality and Staff Well-Being.

In light of the rapid changes in healthcare delivery due to COVID-19, this study explored kidney healthcare professionals' (HCPs) perspectives on the impact of these changes on care quality and staff well-being. Fifty-nine HCPs from eight NHS Trusts across England completed an online survey and eight took part in complementary semi-structured interviews between August 2020 and January 2021. Free-text survey responses and interviews were analysed using inductive thematic analysis. Themes described the rapid adaptations, concerns about care quality, benefits from innovations, high work pressure, anxiety and mental exhaustion in staff and the team as a well-being resource. Long-term retention and integration of changes and innovations can improve healthcare access and efficiency, but specification of conditions for its use is warranted. The impact of prolonged stress on renal HCPs also needs to be accounted for in quality planning. Results are further interpreted into a theoretical socio-technical framework.

Neurological updates: neurological complications of CAR-T therapy.

Chimeric antigen receptor (CAR)-expressing T cells now offer an effective treatment option for people with previously refractory B cell malignancies and are under development for a wide range of other tumours. However, neurological toxicity is a common complication of CAR-T cell therapy, seen in over 50% of recipients in some cohorts. Since 2018, the term immune effector cell-associated neurotoxicity syndrome (ICANS) has been used to describe and grade neurotoxicity seen after CAR-T cells and other similar therapies. ICANS following CAR-T therapy is usually self-limiting but can necessitate admission to the intensive care unit and is rarely fatal. As CAR-T therapies enter routine clinical practice, it is important for neurologists to be aware of the nature of neurological complications. Here, we summarise the clinical manifestations, mechanisms, investigations and recommended treatment of CAR-T-related neurotoxicity, focusing on the licensed CD19 products.

Association Between Administration of Antacid Medication and Anastomotic Stricture Formation After Repair of Esophageal Atresia.

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.

'Into the Wild': A meta-synthesis of talking therapy in natural outdoor spaces.

Time spent in natural outdoor spaces has physiological and psychological benefits, such as reduced stress responses and improved mood. Mental health practitioners have begun to harness nature's restorative capacity by challenging convention and taking talking therapies outdoors. This review synthesises the experiences of these practitioners and their clients, with the aim of establishing a framework for best practice. A thematic synthesis was used to provide a systematic and integrative exploration of multiple therapy professions. Articles (N = 38, published from 1994 to 2019) comprised 322 practitioners and 163 clients. A mixed-method meta-synthesis resulted in a framework of higher and lower level themes. The outdoor context for therapy ranged in intensity from sitting or walking in urban parks and woodland to remote wilderness expeditions. The outdoors provided either a passive backdrop to therapy or was more actively incorporated through behavioural analysis, relationship building, metaphor, narrative therapy, role play, modelling, and stabilisation. Practical, therapeutic, and organisational issues were mitigated through assessment and formulation, informed consent, process contracting, enhancing predictability where possible, and awareness of professional competency. Therapy was subsequently enriched by added mutuality, freedom of expression, mind-body holism, interconnectedness with the natural world, and practitioner well-being. The question of whether therapy in natural spaces should become a more mainstream option for clients and practitioners is discussed.