Commissioning and co-production in health and care services in the United Kingdom and Ireland: An exploratory literature review.

INTRODUCTION: This exploratory literature review seeks to examine the literature around commissioning processes in the co-production of health and care services, focusing on two questions: How do health and care commissioning processes facilitate and/or pose barriers to co-production in service design and delivery? What are the contextual factors that influence these processes? METHOD: A systematic search of three databases (Medline, Public Health and Social Policy and Practice) and a search platform (Web of Science) was conducted for the period 2008-2023. A total of 2675 records were retrieved. After deduplication, 1925 were screened at title and abstract level. Forty-seven reports from 42 United Kingdom and Ireland studies were included in the review. A thematic synthesis of included studies was conducted in relation to the research questions. RESULTS: The review identified one overarching theme across the synthesised literature: the complexity of the commissioning landscape. Three interconnected subthemes illuminate the contextual factors that influence this landscape: commissioners as leaders of co-production; navigating relationships and the collective voice. CONCLUSION: Commissioning processes were commonly a barrier to the co-production of health and care services. Though co-production was an aspiration for many commissioners, the political and economic environment and service pressures meant that it was often not fully realised. More flexible funding models, longer-term pilot projects, an increased emphasis in social value across the health and care system and building capacity for strong leadership in commissioning is needed. PATIENT AND PUBLIC CONTRIBUTION: Patients and the public did not contribute to this review as it was a small piece of work following on from a completed project, with no budget for public involvement.

Practitioner Review: Effectiveness and mechanisms of change in participatory arts-based programmes for promoting youth mental health and well-being - a systematic review.

BACKGROUND: Participatory arts-based (PAB) programmes refer to a diverse range of community programmes involving active engagement in the creation process that appear helpful to several aspects of children's and young people's (CYP) mental health and well-being. This mixed-methods systematic review synthesises evidence relating to the effectiveness and mechanisms of change in PAB programmes for youth. METHOD: Studies were identified following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach. Eleven electronic databases were searched for studies of PAB programmes conducted with CYP (aged 4-25 years), which reported mental health and well-being effectiveness outcomes and/or mechanisms of change. A mixed-methods appraisal tool assessed study quality. A narrative synthesis was conducted of effectiveness and challenges in capturing this. Findings relating to reported mechanisms of change were integrated via a metasummary. RESULTS: Twenty-two studies were included. Evidence of effectiveness from quantitative studies was limited by methodological issues. The metasummary identified mechanisms of change resonant with those proposed in talking therapies. Additionally, PAB programmes appear beneficial to CYP by fostering a therapeutic space characterised by subverting restrictive social rules, communitas that is not perceived as coercive, and inviting play and embodied understanding. CONCLUSIONS: There is good evidence that there are therapeutic processes in PAB programmes. There is a need for more transdisciplinary work to increase understanding of context-mechanism-outcome pathways, including the role played by different art stimuli and practices. Going forward, transdisciplinary teams are needed to quantify short- and long-term mental health and well-being outcomes and to investigate optimal programme durations in relation to population and need. Such teams would also be best placed to work on resolving inter-disciplinary methodological tensions.

Impact of select PPE design elements and repeated laundering in firefighter protection from smoke exposure.

As the Fire Service becomes more aware of the potential health effects from occupational exposure to hazardous contaminants, personal protective equipment (PPE) manufacturers, and fire departments have responded by developing and implementing improved means of firefighter protection, including more frequent laundering of PPE after exposures. While laboratory testing of new PPE designs and the effect of laundering on PPE fabric provides a useful way to evaluate these approaches, laboratory scale testing does not necessarily translate to full garment protection. Utilizing a fireground smoke exposure simulator, along with air and/or filter-substrate sampling for polycyclic aromatic hydrocarbons (PAHs) and benzene, this pilot study tested the chemical-protective capabilities of firefighting PPE of different designs (knit hood vs. particulate-blocking hood, turnout jacket with zipper closure vs. hook & dee closure), including the impact of repeatedly exposing and cleaning (through laundering or decontamination on-scene) PPE 40 times. Overall, PAH contamination on filters under hoods in the neck region were higher (median PAHs = 14.7 µg) than samples taken under jackets in the chest region (median PAHs = 7.05 µg). PAH levels measured under particulate-blocking hoods were lower than levels found under knit hoods. Similarly, zippered closures were found to provide a greater reduction in PAHs compared to hook & dee closures. However, neither design element completely eliminated contaminant ingress. Measurements for benzene under turnout jackets were similar to ambient chamber air concentrations, indicating little to no attenuation from the PPE. The effect of laundering or on-scene decontamination on contaminant breakthrough appeared to depend on the type of contaminant. Benzene breakthrough was negatively associated with laundering, while PAH breakthrough was positively associated. More research is needed to identify PPE features that reduce breakthrough, how targeted changes impact exposures, and how fireground exposures relate to biological absorption of contaminants.

Playing with data differently: engaging with autism and gender through participatory arts/music and a performative framework for analysis.

There are increasing demands for Participatory Arts-Based (PAB) programs involved in health research to better evidence outcomes using robust quantitative evaluation methodologies taken from science, such as standardized questionnaires, to inform commissioning and scale-up decisions. However, for PAB researchers trying to do this, barriers arise from fundamental interdisciplinary differences in values and contexts. Researchers are required to navigate the tensions between the practice-based evidence produced by the arts and the evidence-based practice sought by psychologists. Consequently, there is a need for interdisciplinary arts-science collaborations to produce alternative methods of evaluation that are better aligned to PAB approaches, and which combine systematic rigor with a sensitivity to the values, contexts and strengths of this approach. The current article centers on the development of an alternative transdisciplinary analytic tool, the Participatory arts Play Framework (PP-Framework), undertaken as part of an arts-psychology collaboration for a UK AHRC-funded PAB research project: Playing A/Part: Investigating the identities and experiences of autistic girls. We present details of three stages in the development of the PP-Framework: 1. preliminary emergence of the framework from initial video analysis of observational data from participatory music and sound workshops run for 6 adolescent autistic girls (aged 11-16); 2. identification and application of modes of engagement; and 3. further testing of the framework as an evaluation tool for use in a real-world setting, involving professional musicians engaged in delivery of a creative music project at a center for homeless people. The PP-Framework maps types of participation in terms of performative behaviors and qualities of experience, understood as modes of play. It functions as a vehicle for analyzing participant engagement, providing a tool predicated on the processes of working in creative participatory contexts while also being sensitive to the esthetic qualities of what is produced and capable of capturing beneficial changes in engagement. It offers a conceptual approach for researchers to undertake observation of participatory arts practices, taking account of embodied engagement and interaction processes. It is informed by understandings of autistic performativity and masking in conjunction with an ecological understanding of sense making as being shaped by environments, social relations and sensing subjectivity. The framework has the potential to be a bi-directional tool, with application for both practitioners and participants.

RNA shielding of P65 is required to potentiate oncogenic inflammation in TET2 mutated clonal hematopoiesis.

TET2 mutations (mTET2) are common genetic events in myeloid malignancies and clonal hematopoiesis (CH). These mutations arise in the founding clone and are implicated in many clinical sequelae associated with oncogenic feedforward inflammatory circuits. However, the direct downstream effector of mTET2 responsible for the potentiation of this inflammatory circuit is unknown. To address this, we performed scRNA and scATAC-seq in COVID-19 patients with and without TET2-mutated CH reasoning that the inflammation from COVID-19 may highlight critical downstream transcriptional targets of mTET2. Using this approach, we identified MALAT1, a therapeutically tractable lncRNA, as a central downstream effector of mTET2 that is both necessary and sufficient to induce the oncogenic pro-inflammatory features of mTET2 in vivo. We also elucidate the mechanism by which mTET2 upregulate MALAT1 and describe an interaction between MALAT1 and P65 which leads to RNA "shielding" from PP2A dephosphorylation thus preventing resolution of inflammatory signaling.

Who cares? A scoping review on intellectual disability, epilepsy and social care.

PURPOSE: Nearly a quarter of people with Intellectual disability (PwID) have epilepsy. Many have seizures across their lifetime. In the UK supporting their epilepsy linked risks and needs, particularly in professional care settings and in the community, requires significant social care input. Therefore, the interface between social and health care services is important. This study aim is to identify key intersectional areas of social provision for PWID and epilepsy. METHODS: A scoping review of the literature was performed in accordance with PRISMA guidance with suitable search terms. The search was completed in CINAHL, Embase, Psych INFO, SCIE, and Cochrane electronic databases by an information specialist. A quality assessment was completed for the included studies where appropriate. The included studies were analysed qualitatively to identify key themes and provide a narrative description of the evidence by two reviewers. RESULTS: Of 748 papers screened, 94 were retrieved. Thirteen articles met the inclusion criteria with a range of methodologies. A thematic analysis generated four key categories for significant social care involvement i.e., staff training and education; emergency seizure management; holistic approach to care; and nocturnal monitoring and supervision. CONCLUSIONS: PwID with epilepsy have support needs that require fulfilling by various aspects of special care provision, many within the social ambit. Inspite of evidence of these needs and recurrent calls to work jointly with social care providers this has not happened. There is limited research into social care role in epilepsy management in PwID which needs addressing.

Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML.

PURPOSE: Preclinical studies in myeloid neoplasms have demonstrated efficacy of bromodomain and extra-terminal protein inhibitors (BETi). However, BETi demonstrates poor single-agent activity in clinical trials. Several studies suggest that combination with other anticancer inhibitors may enhance the efficacy of BETi. EXPERIMENTAL DESIGN: To nominate BETi combination therapies for myeloid neoplasms, we used a chemical screen with therapies currently in clinical cancer development and validated this screen using a panel of myeloid cell line, heterotopic cell line models, and patient-derived xenograft models of disease. We used standard protein and RNA assays to determine the mechanism responsible for synergy in our disease models. RESULTS: We identified PIM inhibitors (PIMi) as therapeutically synergistic with BETi in myeloid leukemia models. Mechanistically, we show that PIM kinase is increased after BETi treatment, and that PIM kinase upregulation is sufficient to induce persistence to BETi and sensitize cells to PIMi. Furthermore, we demonstrate that miR-33a downregulation is the underlying mechanism driving PIM1 upregulation. We also show that GM-CSF hypersensitivity, a hallmark of chronic myelomonocytic leukemia (CMML), represents a molecular signature for sensitivity to combination therapy. CONCLUSIONS: Inhibition of PIM kinases is a potential novel strategy for overcoming BETi persistence in myeloid neoplasms. Our data support further clinical investigation of this combination.

Food cravings and food cue responding across the menstrual cycle in a non-eating disordered sample.

The study aim was to examine changes in food cue-elicited cravings and the macronutrient content of craved foods across menstrual cycle phases in a non-eating disordered sample. Thirty-five college females attended laboratory sessions in the late follicular and late luteal phases. In each session they completed a measure of state food craving before and after exposure to preferred, high fat/high sugar chocolate candy. Candy consumption following cue exposure was measured during an ad libitum "taste test." Additionally, participants rated their desire to eat foods differing systematically and significantly in macronutrient content. Ovulation was confirmed with luteinizing hormone detection kits. Results show that whereas the food cue increased cravings, this effect did not differ between cycle phases examined. The macronutrient content of foods desired also did not differ significantly between cycle phases, however, a non-significant trend suggested that high fat/high complex carbohydrate and low fat/high protein foods were more strongly desired in the late luteal phase. Amount of chocolate candy eaten did not differ between cycle phases. These results suggest that cravings for high fat/high sugar foods do not differ between menstrual cycle phases examined, whereas cravings for other foods may fluctuate across cycle phases in non-eating disordered women.

Progenitor Hierarchy of Chronic Myelomonocytic Leukemia Identifies Inflammatory Monocytic-Biased Trajectory Linked to Worse Outcomes.

Myeloblast expansion is a hallmark of disease progression and comprises CD34+ hematopoietic stem and progenitor cells (HSPC). How this compartment evolves during disease progression in chronic myeloid neoplasms is unknown. Using single-cell RNA sequencing and high-parameter flow cytometry, we show that chronic myelomonocytic leukemia (CMML) CD34+ HSPC can be classified into three differentiation trajectories: monocytic, megakaryocyte-erythroid progenitor (MEP), and normal-like. Hallmarks of monocytic-biased trajectory were enrichment of CD120b+ inflammatory granulocyte-macrophage progenitor (GMP)-like cells, activated cytokine receptor signaling, phenotypic hematopoietic stem cell (HSC) depletion, and adverse outcomes. Cytokine receptor diversity was generally an adverse feature and elevated in CD120b+ GMPs. Hypomethylating agents decreased monocytic-biased cells in CMML patients. Given the enrichment of RAS pathway mutations in monocytic-biased cells, NRAS-competitive transplants and LPS-treated xenograft models recapitulated monocytic-biased CMML, suggesting that hematopoietic stress precipitates the monocytic-biased state. Deconvolution of HSPC compartments in other myeloid neoplasms and identifying therapeutic strategies to mitigate the monocytic-biased differentiation trajectory should be explored. SIGNIFICANCE: Our findings establish that multiple differentiation states underlie CMML disease progression. These states are negatively augmented by inflammation and positively affected by hypomethylating agents. Furthermore, we identify HSC depletion and expansion of GMP-like cells with increased cytokine receptor diversity as a feature of myeloblast expansion in inflammatory chronic myeloid neoplasms. This article is highlighted in the In This Issue feature, p. 476.

Impact of Repeated Exposure and Cleaning on Protective Properties of Structural Firefighting Turnout Gear.

The US fire service has become acutely aware of the need to clean PPE after fires. However, there is concern that damage from repeated cleaning may impact critical protection from fireground risk. Using a protocol that included repeated simulated fireground exposures (between 0 and 40 cycles) and/or repeated cleaning with techniques common in the fire service, we found that several important protective properties of NFPA 1971 compliant turnout gear are significantly changed. Outer shell and thermal liner tear strength showed a statistically significant reduction when laundered as compared to wet or dry decontamination. Larger changes in outer shell tear strength resulted when the coat closure incorporated hook & dee clasps as compared with garments using zippered closures. Total Heat Loss (THL) was reduced for all samples that underwent any form of cleaning while Thermal Protective Performance (TPP) was only increased in the gear that was laundered. These results suggest that some important protective properties of bunker gear can be decreased after repeated exposure/cleaning cycles relative to their levels when tested in a new condition. For the specific materials tested, outer shell trap tear strength in the fill direction and seam strength dropped below NFPA 1971 requirements after 40 laundering cycles. The findings for this study may have utility for setting preconditions for the measurement of certain performance properties in future editions of NFPA 1971.

Integrated Human and Murine Clinical Study Establishes Clinical Efficacy of Ruxolitinib in Chronic Myelomonocytic Leukemia.

PURPOSE: Chronic myelomonocytic leukemia (CMML) is a rare leukemia characterized by peripheral monocytosis with no disease-modifying therapies. CMML cells are uniquely hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) and robustly engraft in immunocompromised mice that secrete human cytokines. To leverage these unique biological features, we conducted an integrated human and murine study evaluating ruxolitinib, a JAK1/2 inhibitor that potently downregulates intracellular GM-CSF signaling. PATIENTS AND METHODS: A total of 50 patients with WHO-defined CMML were enrolled in this open-label, multi-institution phase I/II clinical study, with a ruxolitinib dose of 20 mg twice daily studied in phase II. In parallel, 49 patient-derived xenografts (PDX) derived from 13 study participants were generated and randomized to receive ruxolitinib or vehicle control. RESULTS: The most common grade 3/4 treatment-related toxicities observed were anemia (10%) and thrombocytopenia (6%). The clinical overall response rate was 38% by Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN) International Working Group (IWG) criteria and 43% of patients with baseline splenomegaly achieved a spleen response. Profiling of cytokine levels and somatic mutations at baseline failed to identify predictive biomarkers. PDX models derived from screening samples of study participants recapitulated responses seen in humans, particularly spleen responses, and corroborated ruxolitinib's clinical efficacy in a randomized murine study not feasible in human trials. CONCLUSIONS: Ruxolitinib demonstrated clinical efficacy and an acceptable adverse event profile in patients with CMML, identifying a potential novel therapeutic in this rare malignancy. Furthermore, this study demonstrates proof of concept that PDX modeling can recapitulate responses of patients treated on clinical trial and represents a novel correlative study that corroborates clinical efficacy seen in humans.See related commentary by Shastri and Adrianzen-Herrera, p. 6069.

Clinical implementation of a knowledge based planning tool for prostate VMAT.

BACKGROUND: A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. METHODS: A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. RESULTS: Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. CONCLUSIONS: The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.

The Dark Side of Top Level Sport: An Autobiographic Study of Depressive Experiences in Elite Sport Performers.

The general and sport psychology research converge to point to a complex relationship between depressive experiences and human performance. The purpose of this study was to explore the depressive experiences of top level athletes and the relationship of such experiences with sport performance. Twelve autobiographies of elite athletes representing eight sports were analyzed. The autobiographical analysis was informed by narrative tradition, using three types of narrative analysis: categorical content, categorical form, and holistic content. The analysis revealed a temporal aspect to the depressive experiences that the athletes reported. Initially, sport represented a form of escape from the depressive symptoms which had been exacerbated by both external stressors (e.g., experiencing bereavement) and internal stressors (e.g., low self-esteem). However, in time, the athletes typically reached a stage when the demands of their sport shifted from being facilitative to being debilitative in nature with an intensification of their depressive symptoms. This was accompanied by deliberations about continuing their engagement in sport and an acceptance that they could no longer escape from their symptoms, with or without sport. The findings extend the extant literature by suggesting a reciprocal relationship between depressive experiences and sport performance, and they support the general psychology literature relating to the negative impact of depression on performance. The applied implications of these findings are discussed emphasizing the importance of early identification of depressive symptoms and the adoption of a proactive approach in the prevention and management of symptoms.