The Potential of a Digital Weight Management Program to Support Specialist Weight Management Services in the UK National Health Service: Retrospective Analysis.

BACKGROUND: Digital weight management interventions (DWMIs) have the potential to support existing specialist weight management services (SWMS) in the National Health Service (NHS) to increase access to treatment for people living with obesity and type 2 diabetes. At present, there is limited real-world evidence and long-term outcomes on the potential effectiveness of DWMIs to support such services. OBJECTIVE: This study aimed to examine real-world data to evaluate the impact of Second Nature's 12-month DWMI for patients living with obesity with or without type 2 diabetes, referred from NHS primary care services, on sustained weight loss over a 2-year period. METHODS: Retrospective data were extracted in August 2023 for participants who participated in the program between January 1, 2017, and January 8, 2021. Eligible participants were adults with a BMI ≥35 kg/m2, with or without type 2 diabetes. The primary outcomes were weight change in kilograms and percentage weight change at 2 years. Secondary outcomes were weight loss at 1 year, program engagement, and the proportion of participants who achieved >5% and >10% weight loss. Differences in weight loss between baseline and the 1- and 2-year follow-up points were compared using paired 2-tailed t tests. Linear regression models were used to examine whether participants' ethnicity, indices of multiple deprivation, presence of type 2 diabetes, or program engagement were associated with weight loss at 1 year or 2 years. RESULTS: A total of 1130 participants with a mean baseline BMI of 46.3 (SD 31.6) kg/m2 were included in the analysis. Of these participants, 65% (740/1130) were female (mean age 49.9, SD 12.0 years), 18.1% (205/339) were from Black, Asian, mixed, or other ethnicities, and 78.2% (884/1130) had type 2 diabetes. A total of 281 (24.9%) participants recorded weight readings at 2 years from baseline, with a mean weight loss of 13.8 kg (SD 14.2 kg; P<.001) or 11.8% (SD 10.9%; P<.001). A total of 204 (18.1%) participants achieved ≥5% weight loss, and 130 (11.5%) participants reached ≥10% weight loss. Weight loss did not significantly differ by ethnicity, indices of multiple deprivation, presence of type 2 diabetes, or engagement in the program. CONCLUSIONS: The findings suggested that Second Nature's DWMI has the potential to support people living with obesity and type 2 diabetes remotely to achieve clinically significant and sustained weight loss at 2 years from baseline. Further research is needed to compare the intervention to standard care and assess integration with multidisciplinary clinical teams and pharmacotherapy in order to support this study's findings.

Dietary intervention in gestational diabetes: a qualitative study of the acceptability and feasibility of a novel whole-diet intervention in healthcare professionals.

Gestational diabetes is treated with medical nutrition therapy, delivered by healthcare professionals; however, the optimal diet for affected women is unknown. Randomised controlled trials, such as the DiGest (Dietary Intervention in Gestational Diabetes) trial, will address this knowledge gap, but the acceptability of whole-diet interventions in pregnancy is unclear. Whole-diet approaches reduce bias but require high levels of participant commitment and long intervention periods to generate meaningful clinical outcomes. We aimed to assess healthcare professionals' views on the acceptability of the DiGest dietbox intervention for women with gestational diabetes and to identify any barriers to adherence which could be addressed to support good recruitment and retention to the DiGest trial. Female healthcare professionals (n 16) were randomly allocated to receive a DiGest dietbox containing 1200 or 2000 kcal/d including at least one weeks' food. A semi-structured interview was conducted to explore participants' experience of the intervention. Interviews were audio-recorded, transcribed verbatim and analysed thematically using NVivo software. Based on the findings of qualitative interviews, modifications were made to the dietboxes. Participants found the dietboxes convenient and enjoyed the variety and taste of the meals. Factors which facilitated adherence included participants having a good understanding of study aims and sufficient organisational skills to facilitate weekly meal planning in advance. Barriers to adherence included peer pressure during social occasions and feelings of deprivation or hunger (affecting both standard and reduced calorie groups). Healthcare professionals considered random allocation to a whole-diet replacement intervention to be acceptable and feasible in a clinical environment and offered benefits to participants including convenience.

Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.

PURPOSE: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation. MATERIALS AND METHODS: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration. RESULTS: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics. CONCLUSION: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

Experiences of emotional eating in an Acceptance and Commitment Therapy based weight management intervention (SWiM): A qualitative study.

BACKGROUND: Emotional eating is a barrier to weight management. Interventions based on Acceptance and Commitment Therapy (ACT) promote the acceptance of uncomfortable feelings, which can reduce the urge to use food as a coping mechanism. We aimed to explore how participants of an ACT-based weight management intervention (WMI) experience emotional eating and relevant intervention content. METHODS: We conducted semi-structured telephone interviews with participants of a digital ACT-based guided self-help WMI. Fifteen participants were purposefully selected to represent a range of demographic characteristics and emotional eating scores. We used reflexive thematic analysis to explore experiences of emotional eating. RESULTS: We generated five themes. Participants improved emotional eating by disconnecting emotions from behaviours though increased self-awareness (theme 1) and by implementing alternative coping strategies, including preparation, substitution, and acceptance (theme 2). Most participants maintained improvements in emotional eating over time but wished for more opportunities to re-engage with intervention content, including more immediate support in triggering situations (theme 3). Participants who struggled to engage with emotional eating related intervention content often displayed an external locus of control over emotional eating triggers (theme 4). The perceived usefulness of the intervention depended on participants' prior experiences of emotional eating, and was thought insufficient for participants with complex emotional experiences (theme 5). DISCUSSION: This ACT-based WMI helped participants with emotional eating by improving self-awareness and teaching alternative coping strategies. Intervention developers may consider adding ongoing forms of intervention that provide both real-time and long-term support. Additionally, a better understanding of how to support people with an external locus of control and people with complex experiences of emotional eating is needed. Future research may explore ways of personalising WMIs based on participants' emotional needs.

A Remotely Delivered, Semaglutide-Supported Specialist Weight Management Program: Preliminary Findings From a Retrospective Service Evaluation.

BACKGROUND: Digital weight management interventions have the potential to increase access to novel pharmacotherapy for people living with obesity. At present, there is limited real-world evidence on the effectiveness, feasibility, and acceptability of this type of intervention. OBJECTIVE: This retrospective service evaluation examines real-world data to evaluate the preliminary impact of Second Nature's 24-month, remotely delivered, semaglutide-supported weight management intervention for adults living with obesity at 12 weeks. METHODS: Retrospective data were extracted in October 2023 for participants who started the intervention between June 8, 2023, and July 22, 2023. The primary outcomes were weight change (kg) and percentage of weight change at 12 weeks. The secondary outcomes were the proportion of participants who achieved ≥5% and ≥10% weight loss and the feasibility and acceptability of this type of intervention. Descriptive statistics were used to evaluate the baseline characteristics, retention, engagement, prevalence of side effects, and weight change. A paired 2-tailed t test was used to determine the significance of weight change. Content analysis was used to analyze the free-text questionnaire responses. RESULTS: A total of 113 participants with a mean baseline BMI of 38.4 kg/m2 (SD 7.3) were included in the analysis (n=102, 90.4% women, mean age 46.6, SD 11.1 years). Over 12 weeks, 23% (n=26) of participants withdrew from the intervention. A total of 70.8% (n=80) of participants provided weight data at 12 weeks. The average weight loss observed over this 12-week period was 6.5 (SD 4.4) kg (P<.001) or 6.4% (SD 4.2%) of their starting weight (P<.001). Of the 80 participants who recorded weight readings, 62.5% (n=50) achieved ≥5% weight loss, and 11.3% (n=9) achieved ≥10% weight loss. Engagement with the app-based program declined from a mean of 131 (SD 142.6) home screen views in week 0 to 35 (SD 57.1) in week 11. Common side effects reported over 12 weeks included feeling more tired than usual, constipation, and feeling sick. However, a significant proportion of participants reported no side effects. Most participants (n=106, 93.8%) did not experience any difficulties in medication administration. Qualitative data showed that most participants had a positive or neutral experience of the intervention, with some reporting perceived benefits as early as 4 weeks. Most participants did not feel that improvements in the intervention were needed; however, some participants faced issues with medication shipping or logistics. CONCLUSIONS: This retrospective preliminary service evaluation suggests that a remotely delivered semaglutide-supported weight management intervention has the potential to be effective, feasible, and acceptable for self-paying consumer adults with obesity in the United Kingdom. Areas for further improvement were highlighted, including user engagement in an app-based program. A full-service evaluation at the end of the 24-month intervention with a larger sample size is required to support these early findings.

Tumor inflammation-associated neurotoxicity.

Cancer immunotherapies have unique toxicities. Establishment of grading scales and standardized grade-based treatment algorithms for toxicity syndromes can improve the safety of these treatments, as observed for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) in patients with B cell malignancies treated with chimeric antigen receptor (CAR) T cell therapy. We have observed a toxicity syndrome, distinct from CRS and ICANS, in patients treated with cell therapies for tumors in the central nervous system (CNS), which we term tumor inflammation-associated neurotoxicity (TIAN). Encompassing the concept of 'pseudoprogression,' but broader than inflammation-induced edema alone, TIAN is relevant not only to cellular therapies, but also to other immunotherapies for CNS tumors. To facilitate the safe administration of cell therapies for patients with CNS tumors, we define TIAN, propose a toxicity grading scale for TIAN syndrome and discuss the potential management of this entity, with the goal of standardizing both reporting and management.

SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report.

BACKGROUND: Immunocompromised patients are at increased risk of SARS-CoV-2 infections. Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). While SARS-CoV-2 mortality rates of 33%-40% are reported in adult CAR T-cell recipients, outcomes in pediatric and young adult CAR T-cell recipients are limited. METHODS: We created an international retrospective registry of CAR T recipients aged 0-30 years infected with SARS-CoV-2 within 2 months prior to or any time after CAR T infusion. SARS-CoV-2-associated illness was graded as asymptomatic, mild, moderate, or severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C). To assess for risk factors associated with significant SARS-CoV-2 infections (infections requiring hospital admission for respiratory distress or supplemental oxygen), univariate and multivariable regression analyses were performed. RESULTS: Nine centers contributed 78 infections in 75 patients. Of 70 SARS-CoV-2 infections occurring after CAR T infusion, 13 (18.6%) were classified as asymptomatic, 37 (52.9%) mild, 11 (15.7%) moderate, and 6 (8.6%) severe COVID-19. Three (4.3%) were classified as MIS-C. BCA was not significantly associated with infection severity. Prior to the emergence of the Omicron variant, of 47 infections, 19 (40.4%) resulted in hospital admission and 7 (14.9%) required intensive care, while after the emergence of the Omicron variant, of 23 infections, only 1 (4.3%) required admission and the remaining 22 (95.7%) had asymptomatic or mild COVID-19. Death occurred in 3 of 70 (4.3%); each death involved coinfection or life-threatening condition. In a multivariable model, factors associated with significant SARS-CoV-2 infection included having two or more comorbidities (OR 7.73, CI 1.05 to 74.8, p=0.048) and age ≥18 years (OR 9.51, CI 1.90 to 82.2, p=0.014). In the eight patients infected with SARS-CoV-2 before CAR T, half of these patients had their CAR T infusion delayed by 15-30 days. CONCLUSIONS: In a large international cohort of pediatric and young adult CAR-T recipients, SARS-CoV-2 infections resulted in frequent hospital and intensive care unit admissions and were associated with mortality in 4.3%. Patients with two or more comorbidities or aged ≥18 years were more likely to experience significant illness. Suspected Omicron infections were associated with milder disease.

Supporting Weight Management during COVID-19 (SWiM-C): twelve-month follow-up of a randomised controlled trial of a web-based, ACT-based, guided self-help intervention.

OBJECTIVES: We developed a guided self-help intervention (Supporting Weight Management during COVID-19, "SWiM-C") to support adults with overweight or obesity in their weight management during the COVID-19 pandemic. This parallel, two-group trial (ISRCTN12107048) evaluated the effect of SWiM-C on weight and determinants of weight management over twelve months. METHODS: Participants (≥18 years, body-mass-index ≥25 kg/m2) were randomised to the SWiM-C intervention or to a standard advice group (unblinded). Participants completed online questionnaires at baseline, four months, and twelve months. The primary outcome was change in self-reported weight from baseline to twelve months; secondary outcomes were eating behaviour (uncontrolled eating, emotional eating, cognitive restraint of food intake), experiential avoidance, depression, anxiety, stress, wellbeing and physical activity. INTERVENTIONS: SWiM-C is based on acceptance and commitment therapy (ACT). Participants had access to an online web platform with 12 weekly modules and email and telephone contact with a trained, non-specialist coach. Standard advice was a leaflet on managing weight and mood during the COVID-19 pandemic. RESULTS: 388 participants were randomised (SWiM-C: n = 192, standard advice: n = 196). The baseline-adjusted difference in weight change between SWiM-C (n = 119) and standard advice (n = 147) was -0.81 kg (95% CI: -2.24 to 0.61 kg). SWiM-C participants reported a reduction in experiential avoidance (-2.45 [scale:10-70], 95% CI: -4.75 to -0.15), uncontrolled eating (-3.36 [scale: 0-100], 95% CI: -5.66 to -1.06), and emotional eating (-4.14 [scale:0-100], 95% CI: -7.25 to -1.02) and an increase in physical activity (8.96 [MET-min/week], 95% CI: 0.29 to 17.62) compared to standard advice participants. We found no evidence of an effect on remaining outcomes. No adverse events/side effects were reported. CONCLUSIONS: Whilst we were unable to conclude that the intervention had an effect on weight, SWiM-C improved eating behaviours, experiential avoidance and physical activity. Further refinement of the intervention is necessary to ensure meaningful effects on weight prior to implementation in practice. TRIAL REGISTRATION NUMBER: ISRCTN 12107048.

Development of clinical pathways to improve multidisciplinary care of high-risk pediatric oncology patients.

Clinical pathways are evidence-based tools that have been integrated into many aspects of pediatric hospital medicine and have proven effective at reducing in-hospital complications from a variety of diseases. Adaptation of similar tools for specific, high-risk patient populations in pediatric oncology has been slower, in part due to patient complexities and variations in management strategies. There are few published studies of clinical pathways for pediatric oncology patients. Pediatric patients with a new diagnosis of leukemia or lymphoma often present with one or more "oncologic emergencies" that require urgent intervention and deliberate multidisciplinary care to prevent significant consequences. Here, we present two clinical pathways that have recently been developed using a multidisciplinary approach at a single institution, intended for the care of patients who present with hyperleukocytosis or an anterior mediastinal mass. These clinical care pathways have provided a critical framework for the immediate care of these patients who are often admitted to the pediatric intensive care unit for initial management. The goal of the pathways is to facilitate multidisciplinary collaborations, expedite diagnosis, and streamline timely treatment initiation. Standardizing the care of high-risk pediatric oncology patients will ultimately decrease morbidity and mortality associated with these diseases to increase the potential for excellent outcomes.

Participants' experiences of mental health during a COVID-19 tailored ACT-based behavioural weight management intervention: a qualitative study.

PURPOSE: We aimed to explore participants' experiences of mental health during an acceptance and commitment therapy (ACT)-based guided self-help intervention to support weight management in adults with overweight or obesity during the COVID-19 pandemic (SWiM-C: Supporting Weight Management during COVID-19). METHODS: We conducted semi-structured telephone interviews with twenty participants and used reflexive thematic analysis to identify patterns of meaning across the dataset relevant to mental health. RESULTS: Four themes were conceptualized: i) Mental health changes associated with SWiM-C, ii) External factors negatively impacted mental health and intervention engagement, iii) Use and impact of coping responses, and iv) Intervention preferences based on psychological needs. CONCLUSIONS: Findings suggest that participants were exposed to multiple factors, both related to and external to the intervention, that negatively impact their mental health, yet ACT-based aspects of the SWiM-C intervention appeared to support participants to adaptively manage the decline in their mental health. The findings can be used to inform the development of future weight management interventions, such as through intervention personalization and the inclusion of more strategies that target emotional regulation.Trial registration: ISRCTN 12107048, https://www.isrctn.com/ISRCTN12107048.

Perceived weight-related stigma, loneliness, and mental wellbeing during COVID-19 in people with obesity: A cross-sectional study from ten European countries.

BACKGROUND: Increased weight-related stigma during the COVID-19 pandemic has amplified the need to minimise the impacts on mental wellbeing. We investigated the relationship between the perceived changes in the representation of obesity in the media and mental wellbeing during the pandemic in a sample of people with obesity across 10 European countries. We also investigated the potential moderating effect of loneliness. METHODS: Between September to December 2020 during the COVID-19 pandemic, participants reported data on demographics, mental wellbeing (measured by World Health Organisation Five Wellbeing Index and Patient Health Questionaire-4), loneliness (measured by De Jong Gierveld short scale), and perceived change in the representation of obesity in media (measured by a study-specific question) using the online, cross-sectional EURopean Obesity PatiEnt pANdemic Survey (EUROPEANS). Data were analysed using linear mixed-effects models, controlling for age, gender, body mass index, and shielding status, with random incept for country. RESULTS: The survey was completed by 2882 respondents. Most identified as female (56%) and reported their ethnicity as White or White-mix (92%). The total sample had a mean age of 41 years and a BMI of 35.4 kg/m2. During the peak of the pandemic, compared to pre-pandemic, perceiving more negative representation of people with obesity on social media was associated with worse psychological distress, depression, and wellbeing. Perceiving more positive representation, compared to no change in representation, of people with obesity on television was associated with greater wellbeing, yet also higher psychological distress and anxiety. Loneliness, as a moderator, explained ≤0.3% of the variance in outcomes in any of the models. CONCLUSIONS: Perceiving negative representation of obesity on social media was associated with poorer mental wellbeing outcomes during the pandemic; positive representation on television was associated with both positive and negative mental wellbeing outcomes. We encourage greater media accountability when representing people with obesity.

Acceptability and feasibility of an acceptance and commitment therapy-based guided self-help intervention for weight loss maintenance in adults who have previously completed a behavioural weight loss programme: the SWiM feasibility study protocol.

INTRODUCTION: The cost-effectiveness and long-term health impact of behavioural weight management programmes depends on post-treatment weight-loss maintenance. Growing evidence suggests that interventions using acceptance and commitment therapy (ACT) could improve long-term weight management. We developed an ACT-based, guided self-help intervention to support adults who have recently completed a behavioural weight loss programme. This study will assess the feasibility and acceptability of this type of intervention and findings will inform the development of a full-scale trial. METHODS AND ANALYSIS: This is a pragmatic, randomised, single-blind, parallel group, two-arm, feasibility study with an embedded process evaluation. We will recruit and randomise 60 adults who have recently completed a behavioural weight loss programme to the ACT-based intervention or standard care, using a computer-generated sequence with 2:1 allocation stratified by diabetes status and sex. Baseline and 6-month measurements will be completed using online questionnaires. Qualitative interviews will be conducted with a subsample of participants and coaches about their experiences at 3 (mid-intervention) and 6 (postintervention) months. Feasibility and acceptability of the intervention, and a full-scale trial will be assessed using a number of outcomes, including adherence to, and engagement with the intervention, recruitment and retention rates, proportion of missing data for each outcome measure, participants' experiences of the intervention and study, and coaches' experiences of delivering intervention support. Quantitative and qualitative findings will be integrated and summarised to contribute to the interpretation of the main feasibility evaluation findings. Value of information methods will be used to estimate the decision uncertainty associated with the intervention's cost-effectiveness and determine the value of a definitive trial. ETHICS AND DISSEMINATION: Ethical approval was received from Cambridge South Research Ethics Committee on 15/03/2021 (21/EE/0024). This protocol (V.2) was approved on 19 April 2021. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. TRIAL REGISTRATION NUMBER: ISRCTN12685964.

Supporting Weight Management during COVID-19: A Randomized Controlled Trial of a Web-Based, ACT-Based, Guided Self-Help Intervention.

INTRODUCTION: Adults with overweight and obesity are vulnerable to weight gain and mental health deterioration during the COVID-19 pandemic. We developed a web-based, guided self-help intervention based on Acceptance and Commitment Therapy (ACT) that aims to support adults with overweight and obesity to prevent weight gain by helping them to manage their eating behaviours, be more physically active, and protect their emotional wellbeing ("SWiM-C"). SWiM-C is a guided self-help programme using non-specialist guides to enhance scalability and population reach while minimizing cost. This study evaluated the effect of SWiM-C on bodyweight, eating behaviour, physical activity, and mental wellbeing in adults with overweight and obesity over 4 months during the COVID-19 pandemic in the UK. METHODS: We randomized adults (BMI ≥25 kg/m2) to SWiM-C or to a wait-list standard advice group. Participants completed outcome assessments online at baseline and 4 months. The primary outcome was self-measured weight; secondary outcomes were eating behaviour, physical activity, experiential avoidance/psychological flexibility, depression, anxiety, stress, and wellbeing. We estimated differences between study groups in change in outcomes from baseline to 4 months using linear regression, adjusted for outcome at baseline and the randomization stratifiers (BMI, sex). The trial was pre-registered (ISRCTN12107048). RESULTS: 486 participants were assessed for eligibility; 388 participants were randomized (196 standard advice, 192 SWiM-C), and 324 were analysed. The adjusted difference in weight between SWiM-C and standard advice was -0.60 kg (-1.67 to 0.47, p = 0.27). SWiM-C led to improvements in uncontrolled eating (-3.61 [-5.94 to -1.28]), cognitive restraint (5.28 [2.81-7.75]), experiential avoidance (-3.39 [-5.55 to -1.23]), and wellbeing (0.13 [0.07-0.18]). CONCLUSIONS: SWiM-C improved several psychological determinants of successful weight management and had a protective effect on wellbeing during the pandemic. However, differences in weight and some other outcomes were compatible with no effect of the intervention, suggesting further refinement of the intervention is needed.

A systematic review of inequalities in the uptake of, adherence to, and effectiveness of behavioral weight management interventions in adults.

The extent to which behavioral weight management interventions affect health inequalities is uncertain, as is whether trials of these interventions directly consider inequalities. We conducted a systematic review, synthesizing evidence on how different aspects of inequality impact uptake, adherence, and effectiveness in trials of behavioral weight management interventions. We included (cluster-) randomized controlled trials of primary care-applicable behavioral weight management interventions in adults with overweight or obesity published prior to March 2020. Data about trial uptake, intervention adherence, attrition, and weight change by PROGRESS-Plus criteria (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) were extracted. Data were synthesized narratively and summarized in harvest plots. We identified 91 behavioral weight loss interventions and 12 behavioral weight loss maintenance interventions. Fifty-six of the 103 trials considered inequalities in relation to at least one of intervention or trial uptake (n = 15), intervention adherence (n = 15), trial attrition (n = 32), or weight outcome (n = 34). Most trials found no inequalities gradient. If a gradient was observed for trial uptake, intervention adherence, and trial attrition, those considered "more advantaged" did best. Alternative methods of data synthesis that enable data to be pooled and increase statistical power may enhance understanding of inequalities in behavioral weight management interventions.

'Joining a group was inspiring': a qualitative study of service users' experiences of yoga on social prescription.

BACKGROUND: Yoga is becoming an increasingly popular holistic approach in the West to manage long-term health conditions. This study presents the evaluation of a pilot yoga intervention, Yoga4Health, that was developed for the NHS to be socially prescribed to patients at risk of developing specific health conditions (risk factors for cardiovascular disease, pre-diabetes, anxiety/depression or experiencing social isolation). The aim of this qualitative study was to explore service users' experiences of Yoga4Health and the acceptability of the programme. METHODS: Qualitative data were collected from three sources: 1. Open-ended questions on questionnaires completed by services users at three different time-points (baseline, post intervention and 3 months); 2. Interviews and focus groups with a subset of participants (n = 22); 3. interviews with yoga teachers delivering Yoga4Health (n = 7). Each data source was analysed thematically, then findings were combined. RESULTS: Of participants completing baseline questionnaires (n = 240), 82.5% were female, 50% White, with a mean age of 53 (range 23-82) years. Baseline questionnaires revealed key motivations to attend Yoga4Health were to improve psychological and physical health, and believing Yoga4Health would be accessible for people with their health condition. Post-intervention, participants reported a range of benefits across psychological, physical and social domains from Yoga4Health. Increased confidence in self-management of health was also reported, and a number of participants described making positive lifestyle changes after attending the programme. Unanticipated benefits of yoga emerged for participants, such as enjoyment and social connectedness, which facilitated ongoing attendance and practice. Also key to facilitating practice (during and after the intervention) were suitability of the classes for those with health conditions, practising with a group and qualities of the yoga teacher. Home practice was supported by course materials (manual, videos), as well as the teaching of techniques for everyday application that offered immediate benefits, such as breathing practices. Follow-up questionnaires revealed a key challenge was continuation of practice once the intervention had finished, with the structure of a class important in supporting practice. CONCLUSIONS: Yoga4Health was a highly acceptable intervention to services users, which brought a range of biopsychosocial improvements, suggesting yoga is an appropriate intervention to offer on social prescription.

GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas.

Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system1. We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells2, providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 106 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly3. Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG.

Association between patient activation, self-management behaviours and clinical outcomes in adults with diabetes or related metabolic disorders: a systematic review and meta-analysis protocol.

INTRODUCTION: Diabetes and related metabolic disorders such as obesity and cardiovascular diseases (CVD) are a growing global issue. Equipping individuals with the necessary 'knowledge, skills and confidence to self-manage their health' (ie, patient activation (PAct)) may lead to improvements in health outcomes. It is unclear whether existing evidence allows us to assume a causal relationship. We aim to synthesise and critically appraise evidence on the relationship between PAct and self-management behaviours and clinical outcomes of people living with diabetes and related metabolic disorders. METHODS AND ANALYSIS: The protocol is based on guidance on Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. We will search Medline, Embase, CENTRAL, PsycInfo, Web of Science and CINAHL using search terms related to PAct, diabetes, pre-diabetes, obesity and CVD. Any quantitative study design is eligible provided studies assess the association between PAct and clinical outcomes and/or self-management behaviours of diabetes and related metabolic disorders. Outcomes include behavioural (eg, diet) and clinical (eg, blood pressure) outcomes. Two reviewers will independently screen titles/abstracts and full texts and assess risk of bias using the revised Cochrane risk-of-bias tool for randomised trials or the Risk of Bias Assessment Tool for Nonrandomised Studies (RoBANS).One reviewer will extract data, with independent checking by a second reviewer. We will critically assess the level of evidence available for assuming a causal association between PAct and outcomes. Data permitting, we will use the Hunter-Schmidt random-effects method to meta-analyse correlations across studies. ETHICS AND DISSEMINATION: Ethical approval is not required. The review will be disseminated in the form of a peer-reviewed journal article, at conferences and other presentations. The findings of the review will be of interest to clinical commissioning groups, policymakers and intervention deliverers/developers. PROSPERO REGISTRATION NUMBER: CRD42021230727.

Development of a Web-Based, Guided Self-help, Acceptance and Commitment Therapy-Based Intervention for Weight Loss Maintenance: Evidence-, Theory-, and Person-Based Approach.

BACKGROUND: The long-term impact and cost-effectiveness of weight management programs depend on posttreatment weight maintenance. There is growing evidence that interventions based on third-wave cognitive behavioral therapy, particularly acceptance and commitment therapy (ACT), could improve long-term weight management; however, these interventions are typically delivered face-to-face by psychologists, which limits the scalability of these types of intervention. OBJECTIVE: The aim of this study is to use an evidence-, theory-, and person-based approach to develop an ACT-based intervention for weight loss maintenance that uses digital technology and nonspecialist guidance to minimize the resources needed for delivery at scale. METHODS: Intervention development was guided by the Medical Research Council framework for the development of complex interventions in health care, Intervention Mapping Protocol, and a person-based approach for enhancing the acceptability and feasibility of interventions. Work was conducted in two phases: phase 1 consisted of collating and analyzing existing and new primary evidence and phase 2 consisted of theoretical modeling and intervention development. Phase 1 included a synthesis of existing evidence on weight loss maintenance from previous research, a systematic review and network meta-analysis of third-wave cognitive behavioral therapy interventions for weight management, a qualitative interview study of experiences of weight loss maintenance, and the modeling of a justifiable cost for a weight loss maintenance program. Phase 2 included the iterative development of guiding principles, a logic model, and the intervention design and content. Target user and stakeholder panels were established to inform each phase of development, and user testing of successive iterations of the prototype intervention was conducted. RESULTS: This process resulted in a guided self-help ACT-based intervention called SWiM (Supporting Weight Management). SWiM is a 4-month program consisting of weekly web-based sessions for 13 consecutive weeks followed by a 4-week break for participants to reflect and practice their new skills and a final session at week 18. Each session consists of psychoeducational content, reflective exercises, and behavioral experiments. SWiM includes specific sessions on key determinants of weight loss maintenance, including developing skills to manage high-risk situations for lapses, creating new helpful habits, breaking old unhelpful habits, and learning to manage interpersonal relationships and their impact on weight management. A trained, nonspecialist coach provides guidance for the participants through the program with 4 scheduled 30-minute telephone calls and 3 further optional calls. CONCLUSIONS: This comprehensive approach facilitated the development of an intervention that is based on scientific theory and evidence for supporting people with weight loss maintenance and is grounded in the experiences of the target users and the context in which it is intended to be delivered. The intervention will be refined based on the findings of a planned pilot randomized controlled trial.

Patients' views and experiences of live supervised tele-exercise classes following bariatric surgery during the COVID-19 pandemic: The BARI-LIFESTYLE qualitative study.

The BARI-LIFESTYLE trial is a randomized controlled trial evaluating the efficacy of a post-surgery nutritional and behavioural tele-counselling, and supervised exercise programme to maximize the health benefits of bariatric surgery. Due to the coronavirus disease 2019 (COVID-19) pandemic, the in-person supervised exercise component had to be converted to remote tele-exercise. However, patients' acceptability of this method of exercise provision is unknown. Between 3 and 6 months following bariatric surgery, 13 adults participated in weekly, structured, 60-min supervised exercise classes delivered via Zoom by a trained exercise therapist. A total of 12 participants (n = 8 female), with a mean age of 46.3 (range 33-63) years, who had undergone either sleeve gastrectomy (n = 8) or Roux-en-Y gastric bypass (n = 4) surgery, participated in one-to-one semi-structured interviews following the tele-exercise classes. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Participants described how the tele-exercise classes helped them to cope with the changes to their lives brought about by the COVID-19 pandemic. Participants found the tele-exercise schedule, content and intensity to be acceptable, and were satisfied with the privacy, security and safety of the technology and classes. Professional supervision and guidance from an exercise therapist were described as central to the tele-exercise provision. Importantly, participation in the tele-exercise provided physical, emotional and social benefits. Few participants reported barriers to participation. Overall, the tele-exercise classes were deemed acceptable and compared favourably to in-person exercise classes.