Explaining differential socioeconomic effects in population health interventions: development and application of a new tool to classify intervention agentic demand.

BACKGROUND: The agentic demand of population health interventions (PHIs) might influence how interventions work. Highly agentic interventions (eg, information campaigns) rely on recipients noticing and responding to the intervention. Resources required for individuals to benefit from highly agentic interventions have a socioeconomical pattern, thus agentic demand might affect intervention effectiveness and equity. Systematic evidence exploring these associations is missing due to the absence of adequate tools to classify agentic demands. We aimed to develop such a tool and test its application. METHODS: Our iterative development process involved: (1) systematic identification of diet and physical activity PHIs; (2) coding of intervention actors and actions; (3) data synthesis; (4) expert qualitative feedback; and (5) reliability assessment. We searched nine databases for articles published between Jan 1, 2010, and Aug 17, 2020. For all included articles, we coded the actors (people required to act within an intervention) and their actions (what they were required to do for the intervention to have its intended effects). We combined these codes for similar intervention types to develop overarching schematic flow chart diagrams used to identify concepts, and we organised these into a draft tool. After expert feedback, and we assessed inter-rater reliability of the final version. We applied the final tool in a proof-of-concept review, extracting studies from three existing equity-focused systematic reviews on tool category, overall intervention effect, and differential socioeconomic effects and visualised findings. FINDINGS: We identified three concepts affecting agentic demands of intervention components: exposure, two levels (how recipients encounter the intervention); mechanism of action, five levels; and engagement, two levels (how recipients respond to the intervention). We then combined these concepts to form 20 categories that grouped together interventions with similar agentic demands. In the review, we applied the tool to 26 PHIs that included 163 components. Intervention components were concentrated in a small number of categories, and their categorisation was related to intervention equity but not to effectiveness. INTERPRETATION: We present a novel tool to classify the agentic demand of PHIs and demonstrate its feasibility within a systematic review. Linking intervention types to their effect on inequalities enables these factors to be considered when designing or selecting interventions. Users of the tool can avoid implementing intervention types that are likely to widen inequalities or implement them alongside counter-strategies to minimise any adverse equity effects. Applying this tool within future research, policy, and practice to design, select, evaluate, and synthesise evidence from PHIs has the potential to advance our understanding of how interventions work and their effect on socioeconomic inequalities. FUNDING: Public Health Policy Research Unit (PH-PRU), National Institute for Health and Care Research (NIHR) Policy Research Programme.

Adolescents' perspectives on soft drinks after the introduction of the UK Soft Drinks Industry Levy: A focus group study using reflexive thematic analysis.

BACKGROUND: The UK Soft Drinks Industry Levy (SDIL), announced in March 2016 and implemented in April 2018, is a fiscal policy to incentivise reformulation of eligible soft drinks. We aimed to explore perceptions of sugar, sugary drinks and the SDIL among adolescents in the UK post-implementation. METHODS: 23 adolescents aged 11-14 years participated in four focus groups in 2018-2019. A semi-structured topic guide elicited relevant perspectives and included a group task to rank a selection of UK soft drinks based on their sugar content. Braun and Clarke's reflexive thematic analysis was used to undertake inductive analysis. RESULTS: Four main themes were present: 1) Sweetened drinks are bad for you, but some are worse than others; 2) Awareness of the SDIL and ambivalence towards it 3) The influence of drinks marketing: value, pricing, and branding; 4) Openness to population-level interventions. Young people had knowledge of the health implications of excess sugar consumption, which did not always translate to their own consumption. Ambivalence and a mixed awareness surrounding the SDIL was also present. Marketing and parental and school restriction influenced their consumption patterns, as did taste, enjoyment and consuming drinks for functional purposes (e.g., to give them energy). Openness to future population-level interventions to limit consumption was also present. CONCLUSIONS: Our findings suggest that adolescents are accepting of interventions that require little effort from young people in order to reduce their sugar consumption. Further education-based interventions are likely to be unhelpful, in contexts where adolescents understand the negative consequences of excess sugar and SSB consumption.

A Phase 1/2 Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma.

PURPOSE: Leiomyosarcoma and liposarcoma frequently express PD-L1 but are generally resistant to PD-1/PD-L1 inhibition (immune checkpoint inhibitor). Trabectedin is FDA approved for leiomyosarcoma and liposarcoma. This study aimed to evaluate the safety and efficacy of trabectedin with anti-PD-L1 antibody avelumab in patients with advanced leiomyosarcoma and liposarcoma. PATIENTS AND METHODS: A single-arm, open-label, Phase 1/2 study tested avelumab with trabectedin for advanced leiomyosarcoma and liposarcoma. The phase I portion evaluated safety and feasibility of trabectedin (1, 1.2, and 1.5 mg/m2) with avelumab at standard dosing. Primary endpoint of the phase II portion was objective response rate (ORR) by RECIST 1.1. Correlative studies included T-cell receptor sequencing (TCRseq), multiplex IHC, and tumor gene expression. RESULTS: 33 patients were evaluable: 24 with leiomyosarcoma (6 uterine and 18 non-uterine) and 11 with liposarcoma. In Phase 1, dose-limiting toxicities (DLT) were observed in 2 of 6 patients at both trabectedin 1.2 and 1.5 mg/m2. The recommended Phase 2 dose (RP2D) was 1.0 mg/m2 trabectedin and 800-mg avelumab. Of 23 patients evaluable at RP2D, 3 (13%) had partial response (PR) and 10 (43%) had stable disease (SD) as best response. Six-month PFS was 52%; median PFS was 8.3 months. Patients with PR had higher Simpson Clonality score on TCRseq from peripheral blood mononuclear cells versus those with SD (0.182 vs. 0.067, P = 0.02) or progressive disease (0.182 vs. 0.064, P = 0.01). CONCLUSIONS: Although the trial did not meet the primary objective response rate endpoint, PFS compared favorably with prior studies of trabectedin warranting further investigation.

Stakeholder experiences of using online spatial data visualisation tools for local public health decision support: A qualitative study.

The distribution of food outlets within towns and cities and the provision of active travel infrastructure have been associated with health behaviours that can contribute to obesity risk. Decision-makers describe a lack of local data and research evidence as a barrier to policy adoption to improve the public's health. Online spatial data visualisation tools created by researchers can help to bridge this gap. We explored stakeholder experiences of using such tools for decision-support, with a focus on facilitators and barriers to use. We conducted 16 qualitative interviews with Public Health, Planning and Transport Planning professionals, who had used two recently-developed tools. Participants described the importance of tools being open access; their use in "story-telling", particularly to non-experts; and more broadly their use even when imperfect. They expressed that 'robustness' of underpinning data was important, however this was not easily defined. Participants employed personal heuristics, principally based on endorsement and developer credibility, to determine suitability for use. We present key learning points for future developers to maximise engagement and impact.

Assessment of Doxorubicin and Pembrolizumab in Patients With Advanced Anthracycline-Naive Sarcoma: A Phase 1/2 Nonrandomized Clinical Trial.

IMPORTANCE: Anthracycline-based therapy is standard first-line treatment for most patients with advanced and metastatic sarcomas. Although multiple trials have attempted to show improved outcomes in patients with soft-tissue sarcoma over doxorubicin monotherapy, each has fallen short of demonstrating improved outcomes. OBJECTIVE: To evaluate the safety and efficacy of doxorubicin in combination with pembrolizumab in patients with advanced, anthracycline-naive sarcomas. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized clinical trial used a 2-stage phase 2 design and was performed at a single, academic sarcoma specialty center. Patients were adults with good performance status and end-organ function. Patients with all sarcoma subtypes were allowed to enroll with the exception of osteosarcoma, Ewing sarcoma, and alveolar and embryonal rhabdomyosarcoma. INTERVENTIONS: Two dose levels of doxorubicin (45 and 75 mg/m2) were tested for safety in combination with pembrolizumab. MAIN OUTCOMES AND MEASURES: Objective response rate (ORR) was the primary end point. Overall survival (OS) and progression-free survival (PFS) were secondary end points. Correlative studies included immunohistochemistry, gene expression, and serum cytokines. RESULTS: A total of 37 patients (22 men; 15 women) were treated in the combined phase 1/2 trial. The median (range) patient age was 58.4 (25-80) years. The most common histologic subtype was leiomyosarcoma (11 patients). Doxorubicin plus pembrolizumab was well tolerated without significant unexpected toxic effects. The ORR was 13% for phase 2 patients and 19% overall. Median PFS was 8.1 (95% CI, 7.6-10.8) months. Median OS was 27.6 (95% CI, 18.7-not reached) months at the time of this analysis. Two of 3 patients with undifferentiated pleomorphic sarcoma and 2 of 4 patients with dedifferentiated liposarcoma had durable partial responses. Tumor-infiltrating lymphocytes were present in 21% of evaluable tumors and associated with inferior PFS (log-rank P = .03). No dose-limiting toxic effects were observed. CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, doxorubicin plus pembrolizumab was well tolerated. Although the primary end point for ORR was not reached, the PFS and OS observed compared favorably with prior published studies. Further studies are warranted, especially those focusing on undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02888665.

Interventions to reduce the negative effects of alcohol consumption in older adults: a systematic review.

BACKGROUND: Older individuals are consuming alcohol more frequently yet there is limited evidence on the effectiveness of current interventions. This systematic review aims to investigate interventions that target alcohol use in individuals aged 55 + . METHODS: CINAHL, ERIC, MEDLINE, Science Direct, PsychInfo, SCOPUS, Web of Science and socINDEX were searched using terms devised from the PICO (Population, Intervention, Comparison and Outcome) tool. Studies using pharmaceutical interventions, or those that investigated comorbidities or the use of other substances were excluded. Peer reviewed empirical studies written in the English language that compared the outcomes of alcohol related interventions to standard care were included in this review. Studies were appraised and assessed for quality using the relevant Critical Appraisal Skills Programme checklist. RESULTS: Seven papers were included in this review. Six were conducted in the United States of America and one in Denmark. The interventions were carried out in primary care centres and in community based groups. The studies included in this review showed varying levels of success. Participants showed improvements in at least one area of alcohol consumption or frequency of consumption however, these did not always reach significance. CONCLUSION: Individuals in this age group appear to respond well to interventions aimed at reducing alcohol consumption. However, included studies had limitations, in particular many did not include a clear intervention description; leaving us unable to fully investigate the components required for success. Further research is needed on the effective components of alcohol interventions targeting older people.

Developing an Engineering Design Process Assessment using Mixed Methods.

Recent reforms in science education worldwide include an emphasis on engineering design as a key component of student proficiency in the Science, Technology, Engineering, and Mathematics disciplines. However, relatively little attention has been directed to the development of psychometrically sound assessments for engineering. This study demonstrates the use of mixed methods to guide the development and revision of K-12 Engineering Design Process (EDP) assessment items. Using results from a middle-school EDP assessment, this study illustrates the combination of quantitative and qualitative techniques to inform item development and revisions. Overall conclusions suggest that the combination of quantitative and qualitative evidence provides an in-depth picture of item quality that can be used to inform the revision and development of EDP assessment items. Researchers and practitioners can use the methods illustrated here to gather validity evidence to support the interpretation and use of new and existing assessments.