Using Routine Data to Improve Lesbian, Gay, Bisexual, and Transgender Health.

The collection of sexual orientation in routine data, generated either from contacts with health services or in infrastructure data resources designed and collected for policy and research, has improved substantially in the United Kingdom in the last decade. Inclusive measures of gender and transgender status are now also beginning to be collected. This viewpoint considers current data collections, and their strengths and limitations, including accessing data, sample size, measures of sexual orientation and gender, measures of health outcomes, and longitudinal follow-up. The available data are considered within both sociopolitical and biomedical models of health for individuals who are lesbian, gay, bisexual, transgender, queer, or of other identities including nonbinary (LGBTQ+). Although most individual data sets have some methodological limitations, when put together, there is now a real depth of routine data for LGBTQ+ health research. This paper aims to provide a framework for how these data can be used to improve health and health care outcomes. Four practical analysis approaches are introduced-descriptive epidemiology, risk prediction, intervention development, and impact evaluation-and are discussed as frameworks for translating data into research with the potential to improve health.

Engaging Long-Term Care Workers in Research: Recruitment Approaches and Participant Characteristics From a Randomized Controlled Trial to Improve COVID-19 Vaccine Confidence.

OBJECTIVE: To describe and compare the recruitment methods employed in a randomized controlled trial targeting long-term care workers, and resulting participant baseline characteristics. DESIGN: We used a multifaceted recruitment process to enroll long-term care workers in our 3-arm randomized controlled trial comparing 2 interventions to enhanced usual practice, for improving COVID-19 vaccine confidence and other outcomes. SETTING AND PARTICIPANTS: Adult long-term care workers living in the United States employed within the last 2 years were invited to join the study. Participants also had to meet specific screening criteria related to their degree of worry about the vaccine and/or their vaccination status. METHODS: We used a participatory approach to engage our long-term care stakeholders in codesigning and executing a combination of recruitment methods, including targeted e-recruitment, paid e-recruitment, and in-person recruitment. Participants were screened, consented, and enrolled online. We implemented a participant verification process to ensure the integrity of our study data, and used a tailored participant management platform to manage enrollment. RESULTS: We enrolled 1930 long-term care workers between May 2022 and January 2023. We met our enrollment target, despite each recruitment method having limitations. Total variable costs of approximately $102,700 were incurred and differed on a per-enrolled participant basis across methods: $25.73 for targeted e-recruitment, $57.12 for paid e-recruitment, and $64.92 for in-person methods. Our sample differed from the national population in age, gender, race/ethnicity, education, and role in long-term care. Differences were also observed between online and in-person recruitment methods. CONCLUSIONS AND IMPLICATIONS: Our results support the feasibility of enrolling a large number of long-term care workers in a randomized controlled trial to increase COVID-19 vaccine confidence. Findings build upon the evidence base for engaging this important population in research, a critical step to improving long-term care resident health and well-being. Results from our trial are anticipated in 2024.

Wellbeing Impact Study of High-Speed 2 (WISH2): Protocol for a mixed-methods examination of the impact of major transport infrastructure development on mental health and wellbeing.

Although research has demonstrated that transport infrastructure development can have positive and negative health-related impacts, most of this research has not considered mental health and wellbeing separately from physical health. There is also limited understanding of whether and how any effects might be experienced differently across population groups, whether this differs according to the stage of development (e.g. planning, construction), and how changes to planned infrastructure may affect mental health and wellbeing. This paper presents a protocol for the Wellbeing Impact Study of HS2 (WISH2), which seeks to address these questions using a high-speed rail development in the UK as an applied example. WISH2 is a 10-year, integrated, longitudinal, mixed-methods project using general practices (primary medical care providers in the UK) as an avenue for participant recruitment and for providing a geographically defined population for which aggregated data on mental health indicators are available. The research comprises: (i) a combined longitudinal and repeated cross-sectional cohort study involving multiple waves of survey data collection and data from medical records; (ii) longitudinal, semi-structured interviews and focus groups with residents and community stakeholders from exposed areas; (iii) analysis of administrative data aggregated at the general practice population level; and (iv) health economic analysis of mental health and wellbeing impacts. The study findings will support the development of strategies to reduce negative impacts and/or enhance positive mental health and wellbeing impacts of high-speed rail developments and other large-scale infrastructure projects.

Clinician-Spoken Plain Language in Health Care Encounters: A Qualitative Analysis to Assess Measurable Elements.

PURPOSE: Good communication and use of plain language in health care encounters improve outcomes, including emotional health, symptom resolution, and functional status. Yet there is limited research on how to measure and report spoken plain language, which is the use of familiar, clear language. The authors aimed to describe key, measurable elements of spoken plain language that can be assessed and reported back to clinicians for self-reflection. METHOD: The authors conducted secondary analysis of transcripts from recorded encounters between breast cancer surgeons and patients with early-stage breast cancer. Two coders used a hybrid qualitative analysis with a framework based on U.S. Federal Plain Language Guidelines. To develop major themes, they examined (1) alignment with the Guidelines and (2) code frequencies within and across transcripts. They also noted minor themes. RESULTS: From 74 transcripts featuring 13 surgeons, the authors identified 2 major themes representing measurable elements of spoken plain language: (1) clinicians had a propensity to use both explained and unexplained medical terms, and (2) clinicians delivered information using either short turns (one unit of someone speaking) with 1 topic or long turns with multiple topics. There were 3 minor themes that were not indicative of whether or not clinicians used spoken plain language. First, clinicians regularly used absolute risk communication techniques. Second, question-asking techniques varied and included open-ended, close-ended, and comprehension checks. Third, some clinicians used imagery to describe complex topics. CONCLUSIONS: Clinicians' propensity to use medical terms with and without explanation and parse encounters into shorter or longer turns are measurable elements of spoken plain language. These findings will support further research on the development of a tool that can be used in medical education and other settings. This tool could provide direct and specific feedback to improve the plain language practices of clinicians in training and beyond.

Impact of vertical integration on patients' use of hospital services in England: an analysis of activity data.

BACKGROUND: Debate surrounding the organisation and sustainability of primary care in England highlights the desirability of a more integrated approach to patient care across all settings. One such approach is 'vertical integration', where a provider of specialist care, such as a hospital, also runs general practices. AIM: To quantify the impact of vertical integration on hospital use in England. DESIGN & SETTING: Analysis of activity data for NHS hospitals in England between April 2013 and February 2020. METHOD: Analysis of NHS England data on hospital activity, which looked at the following seven outcome measures: accident and emergency (A&E) department attendances; outpatient attendances; total inpatient admissions; inpatient admissions for ambulatory care sensitive conditions; emergency admissions; emergency readmissions; and length of stay. Rates of hospital use by patients of vertically integrated practices and controls were compared, before and after the former were vertically integrated. RESULTS: In the 2 years after a GP practice changes, for the population registered at that practice, compared with controls, vertical integration is associated with modest reductions in rates of A&E attendances (2% reduction [incidence rate ratio {IRR} 0.98, 95% confidence interval {CI} = 0.96 to 0.99, P<0.0001]), outpatient attendances (1% reduction [IRR 0.99, 95% CI = 0.99 to 1.00, P = 0.0061]), emergency inpatient admissions (3% reduction [IRR 0.97, 95% CI = 0.95 to 0.99, P = 0.0062]), and emergency readmissions within 30 days (5% reduction [IRR 0.95, 95% CI = 0.91 to 1.00, P = 0.039]), with no impact on length of stay, overall inpatient admissions, or inpatient admissions for ambulatory care sensitive conditions. CONCLUSION: Vertical integration is associated with modest reductions in use of some hospital services and no change in others.

Enhanced Antimalarial and Antisequestration Activity of Methoxybenzenesulfonate-Modified Biopolymers and Nanoparticles for Tackling Severe Malaria.

Severe malaria is a life-threatening condition that is associated with a high mortality. Severe Plasmodium falciparum infections are mediated primarily by high parasitemia and binding of infected red blood cells (iRBCs) to the blood vessel endothelial layer, a process known as sequestration. Here, we show that including the 5-amino-2-methoxybenzenesulfonate (AMBS) chemical modification in soluble biopolymers (polyglutamic acid and heparin) and poly(acrylic acid)-exposing nanoparticles serves as a universal tool to introduce a potent parasite invasion inhibitory function in these materials. Importantly, the modification did not add or eliminated (for heparin) undesired anticoagulation activity. The materials protected RBCs from invasion by various parasite strains, employing both major entry pathways. Two further P. falciparum strains, which either expose ligands for chondroitin sulfate A (CSA) or intercellular adhesion molecule 1 (ICAM-1) on iRBCs, were tested in antisequestration assays due to their relevance in placental and cerebral malaria, respectively. Antisequestration activity was found to be more efficacious with nanoparticles vs gold-standard soluble biopolymers (CSA and heparin) against both strains, when tested on receptor-coated dishes. The nanoparticles also efficiently inhibited and reversed the sequestration of iRBCs on endothelial cells. First, the materials described herein have the potential to reduce the parasite burden by acting at the key multiplication stage of reinvasion. Second, the antisequestration ability could help remove iRBCs from the blood vessel endothelium, which could otherwise cause vessel obstruction, which in turn can lead to multiple organ failure in severe malaria infections. This approach represents a further step toward creation of adjunctive therapies for this devastating condition to reduce morbidity and mortality.

Identifying where hospital and community trusts are managing general practices in England: a service mapping study.

BACKGROUND: Organisations providing secondary care in the NHS in England have historically not also provided primary health care, but this is changing. Data on where this kind of 'vertical integration' is happening is lacking, making it difficult to evaluate its impact. AIM: To compile a comprehensive list of instances of secondary care trusts running general practices in England, to enable evaluation of the impact of such arrangements. DESIGN AND SETTING: Review, collation, synthesis and analysis of published information describing secondary and primary care provision in the NHS in England in March 2021. METHOD: Desk-based collection, including hand-searching, of secondary care organisations' statutory annual reports. Triangulation via comparison with national data on general practices, the general practice workforce and practice contracts. RESULTS: It was possible to construct a database of all instances of trusts running general practices in England as at end-March 2021. We have identified 26 trusts running a total of 85 general practices, operating across a total of 116 practice sites. These practices have on average fewer patients and fewer GP full-time equivalents than other general practices, and before becoming vertically integrated were performing less well in the Quality and Outcomes Framework. CONCLUSION: We recommend that national statistics recording the details of general practices contracting with the NHS should include whether each practice is owned by another organisation and, whether that is an NHS trust, another public body or a private organisation. Such data are required to enable evaluation of the impacts of this kind of vertical integration.

Implementing mental health support teams in schools and colleges: the perspectives of programme implementers and service providers.

Background: Between 2018 and 2025, a national implementation programme is funding more than 500 new mental health support teams (MHSTs) in England, to work in education settings to deliver evidence-based interventions to children with mild to moderate mental health problems and support emotional wellbeing for all pupils. A new role, education mental health practitioner (EMHP), has been created for the programme.Aims: A national evaluation explored the development, implementation and early progress of 58 MHSTs in the programme's first 25 'Trailblazer' sites. This paper reports the views and experiences of people involved in MHST design, implementation and service delivery at a local, regional and national level.Methods: Data are reported from in-depth interviews with staff in five Trailblazer sites (n = 71), and the programme's regional (n = 52) and national leads (n = 21).Results: Interviewees universally welcomed the creation of MHSTs, but there was a lack of clarity about their purpose, concerns that the standardised CBT interventions being offered were not working well for some children, and challenges retaining EMHPs.Conclusions: This study raises questions about MHSTs' service scope, what role they should play in addressing remaining gaps in mental health provision, and how EMHPs can develop the skills to work effectively with diverse groups.

Sociodemographic characteristics and longitudinal progression of multimorbidity: A multistate modelling analysis of a large primary care records dataset in England.

BACKGROUND: Multimorbidity, characterised by the coexistence of multiple chronic conditions in an individual, is a rising public health concern. While much of the existing research has focused on cross-sectional patterns of multimorbidity, there remains a need to better understand the longitudinal accumulation of diseases. This includes examining the associations between important sociodemographic characteristics and the rate of progression of chronic conditions. METHODS AND FINDINGS: We utilised electronic primary care records from 13.48 million participants in England, drawn from the Clinical Practice Research Datalink (CPRD Aurum), spanning from 2005 to 2020 with a median follow-up of 4.71 years (IQR: 1.78, 11.28). The study focused on 5 important chronic conditions: cardiovascular disease (CVD), type 2 diabetes (T2D), chronic kidney disease (CKD), heart failure (HF), and mental health (MH) conditions. Key sociodemographic characteristics considered include ethnicity, social and material deprivation, gender, and age. We employed a flexible spline-based parametric multistate model to investigate the associations between these sociodemographic characteristics and the rate of different disease transitions throughout multimorbidity development. Our findings reveal distinct association patterns across different disease transition types. Deprivation, gender, and age generally demonstrated stronger associations with disease diagnosis compared to ethnic group differences. Notably, the impact of these factors tended to attenuate with an increase in the number of preexisting conditions, especially for deprivation, gender, and age. For example, the hazard ratio (HR) (95% CI; p-value) for the association of deprivation with T2D diagnosis (comparing the most deprived quintile to the least deprived) is 1.76 ([1.74, 1.78]; p < 0.001) for those with no preexisting conditions and decreases to 0.95 ([0.75, 1.21]; p = 0.69) with 4 preexisting conditions. Furthermore, the impact of deprivation, gender, and age was typically more pronounced when transitioning from an MH condition. For instance, the HR (95% CI; p-value) for the association of deprivation with T2D diagnosis when transitioning from MH is 2.03 ([1.95, 2.12], p < 0.001), compared to transitions from CVD 1.50 ([1.43, 1.58], p < 0.001), CKD 1.37 ([1.30, 1.44], p < 0.001), and HF 1.55 ([1.34, 1.79], p < 0.001). A primary limitation of our study is that potential diagnostic inaccuracies in primary care records, such as underdiagnosis, overdiagnosis, or ascertainment bias of chronic conditions, could influence our results. CONCLUSIONS: Our results indicate that early phases of multimorbidity development could warrant increased attention. The potential importance of earlier detection and intervention of chronic conditions is underscored, particularly for MH conditions and higher-risk populations. These insights may have important implications for the management of multimorbidity.

Single Particle Chemical Characterisation of Nanoformulations for Cargo Delivery.

Nanoparticles can encapsulate a range of therapeutics, from small molecule drugs to sensitive biologics, to significantly improve their biodistribution and biostability. Whilst the regulatory approval of several of these nanoformulations has proven their translatability, there remain several hurdles to the translation of future nanoformulations, leading to a high rate of candidate nanoformulations failing during the drug development process. One barrier is that the difficulty in tightly controlling nanoscale particle synthesis leads to particle-to-particle heterogeneity, which hinders manufacturing and quality control, and regulatory quality checks. To understand and mitigate this heterogeneity requires advancements in nanoformulation characterisation beyond traditional bulk methods to more precise, single particle techniques. In this review, we compare commercially available single particle techniques, with a particular focus on single particle Raman spectroscopy, to provide a guide to adoption of these methods into development workflows, to ultimately reduce barriers to the translation of future nanoformulations.

Vertical integration of general practices with acute hospitals in England: rapid impact evaluation.

Background: Vertical integration means merging organisations that operate at different stages along the patient pathway. We focus on acute hospitals running primary care medical practices. Evidence is scarce concerning the impact on use of health-care services and patient experience. Objectives: To assess the impact of vertical integration on use of hospital services, service delivery and patient experience and whether patients with multiple long-term conditions are affected differently from others. Design: Rapid, mixed methods evaluation with four work packages: (1) review of NHS trust annual reports and other sources to understand the scale of vertical integration across England; (2) development of the statistical analysis; (3) analysis of national survey data on patient experience, and national data on use of hospital services over the 2 years preceding and following vertical integration, comparing vertically integrated practices with a variety of control practices; and (4) focus groups and interviews with staff and patients across three case study sites to explore the impact of vertical integration on patient experience of care. Results: At 31 March 2021, 26 NHS trusts were in vertically integrated organisations, running 85 general practices across 116 practice sites. The earliest vertical integration between trusts and general practices was in 2015; a mean of 3.3 practices run by each trust (range 1-12). On average, integrated practices have fewer patients, are slightly more likely to be in the most deprived decile of areas, are more likely to hold an alternative provider medical services contract and have worse Quality and Outcomes Framework scores compared with non-integrated practices. Vertical integration is associated with statistically significant, modest reductions in rates of accident and emergency department attendances: 2% reduction (incidence rate ratio 0.98, 95% confidence interval 0.96 to 0.99; p < 0.0001); outpatient attendances: 1% reduction (incidence rate ratio 0.99, 95% confidence interval 0.99 to 1.00; p = 0.0061), emergency inpatient admissions: 3% reduction (incidence rate ratio 0.97, 95% confidence interval 0.95 to 0.99; p = 0.0062) and emergency readmissions: 5% reduction (incidence rate ratio 0.95, 95% confidence interval 0.91 to 1.00; p = 0.039), with no impact on length of stay, overall inpatient admissions or inpatient admissions for ambulatory care sensitive conditions. The falls in accident and emergency department and outpatient attendance rates are temporary. Focus groups and interviews with staff (N = 22) and interviews with patients (N = 14) showed that with vertical integration, health service improvements are introduced following a period of cultural interchange. Patients with multiple long-term conditions continue to encounter 'navigation work' choosing and accessing health-care provision, with diminishing continuity of care. Limitations: In the quantitative analysis, we could not replicate the counterfactual of what would have happened in those specific locations had practices not merged with trusts. There was imbalance across three case study sites with regard to staff and patients recruited for interview, and the latter were drawn from patient participation groups who may not be representative of local populations. Conclusions: Vertical integration can lead to modest reductions in use of hospital services and has minor or no impact on patient experience of care. Our analysis does not reveal a case for widespread roll-out of the approach. Future research: Further quantitative follow-up of the longer-term impact of vertical integration on hospital usage and more extensive interviewing of patients and their carers about patient experiences of navigating care. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (BRACE Project no. 16/138/31) and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 17. See the NIHR Journals Library website for further project information.

Evaluating the effectiveness of mindfulness alone compared to exercise and mindfulness on fatigue in women with gynaecology cancer (GEMS): Protocol for a randomised feasibility trial.

BACKGROUND: In 2020 Globocan reported nearly 1.4 million new cases of gynaecology cancer worldwide. Cancer related fatigue has been identified as a symptom that can be present for gynaecology cancer patients many years after treatment. The current evidence around the management of this symptom suggests that exercise has the most positive outcome. However, some ambiguity remains around the evidence and whether it can address all areas of fatigue effectively. More recently, other interventions such as mindfulness have begun to show a favourable response to the management of symptoms for cancer patients. To date there has been little research that explores the feasibility of using both these interventions together in a gynaecology cancer population. This study aims to explore the feasibility of delivering an intervention that involves mindfulness and mindfulness and exercise and will explore the effect of this on fatigue, sleep, mood and quality of life. METHODS/DESIGN: This randomised control trial will assess the interventions outcomes using a pre and post design and will also include a qualitative process evaluation. Participants will be randomised into one of 2 groups. One group will undertake mindfulness only and the other group will complete exercise and mindfulness. Both groups will use a mobile application to complete these interventions over 8 weeks. The mobile app will be tailored to reflect the group the participants have drawn during randomisation. Self-reported questionnaire data will be assessed at baseline prior to commencing intervention and at post intervention. Feasibility will be assessed through recruitment, adherence, retention and attrition. Acceptability and participant perspective of participation (process evaluation), will be explored using focus groups. DISCUSSION: This trial will hope to evidence and demonstrate that combination of two interventions such as mindfulness and exercise will further improve outcomes of fatigue and wellbeing in gynaecology cancer. The results of this study will be used to assess (i) the feasibility to deliver this type of intervention to this population of cancer patients using a digital platform; (ii) assist this group of women diagnosed with cancer to manage fatigue and other symptoms of sleep, mood and impact their quality of life. TRIAL REGISTRATION: NCT05561413.

Ethnic inequalities in age-related patterns of multiple long-term conditions in England: Analysis of primary care and nationally representative survey data.

Little is known about the patterning of multiple long-term conditions (MLTCs) by age, ethnicity and across conceptualisations of MLTCs (e.g. MLTCs with/without mental health conditions [MHCs]). We examined ethnic inequalities in age-related patterns of MLTCs, and combinations of physical and MHCs using the English GP Patient Survey and Clinical Practice Research Datalink. We described the association between MLTCs and age using multilevel regression models adjusting for sex and area-level deprivation with patients nested within GP practices. Similar analyses were repeated for MLTCs that include MHCs. We observed ethnic inequalities from middle-age onwards such as older Pakistani, Indian, Black Caribbean and Other ethnic people had increased risk of MLTCs compared to white British people, even after adjusting for area-level deprivation. Compared to white British people, Gypsy and Irish Travellers had higher levels of MLTCs across the age groups, and Chinese people had lower levels. Pakistani and Bangladeshi people aged 50-74 years were more likely than white people to report MLTCs that included MHCs. We find clear evidence of ethnic inequalities in MLTCs. The lower prevalence of MLTCs that include MHCs among some minoritised ethnic groups may be an underestimation due to underdiagnosis and/or inadequate primary care and requires further scrutiny.

Progression of stroke risk in patients aged <65 years diagnosed with atrial fibrillation: a cohort study in general practice.

BACKGROUND: As a result of new technologies, atrial fibrillation (AF) is more likely to be diagnosed in people aged <65 years. AIM: To investigate the risk of someone diagnosed with AF aged <65 years developing an indication for anticoagulation before they reach 65 years. DESIGN AND SETTING: Population-based cohort study of patients from English practices using the Clinical Practice Research Datalink, a primary care database of electronic medical records. METHOD: The study included patients aged <65 years newly diagnosed with AF. The CHA2DS2-VASc score was derived at time of diagnosis based on patients' medical records. Patients not eligible for anticoagulation were followed up until they became eligible or turned 65 years old. The primary outcome of interest was development of a risk factor for stroke in AF. RESULTS: Among 18 178 patients aged <65 years diagnosed with AF, 9188 (50.5%) were eligible for anticoagulation at the time of diagnosis. Among the 8990 patients not eligible for anticoagulation, 1688 (18.8%) developed a risk factor during follow-up before reaching 65 years of age or leaving the cohort for other reasons, at a rate of 6.1 per 100 patient-years. Hypertension and heart failure were the most common risk factors to occur, with rates of 2.65 (95% CI = 2.47 to 2.84) and 1.58 (95% CI = 1.45 to 1.72) per 100 patient-years, respectively. The rate of new diabetes was 0.95 (95% CI = 0.85 to 1.06) per 100 patient-years. CONCLUSION: People aged <65 years with AF are at higher risk of developing hypertension, heart failure, and diabetes than the general population, so may warrant regular review to identify new occurrence of such risk factors.

Revealing Population Heterogeneity in Vesicle-Based Nanomedicines Using Automated, Single Particle Raman Analysis.

The intrinsic heterogeneity of many nanoformulations is currently challenging to characterize on both the single particle and population level. Therefore, there is great opportunity to develop advanced techniques to describe and understand nanomedicine heterogeneity, which will aid translation to the clinic by informing manufacturing quality control, characterization for regulatory bodies, and connecting nanoformulation properties to clinical outcomes to enable rational design. Here, we present an analytical technique to provide such information, while measuring the nanocarrier and cargo simultaneously with label-free, nondestructive single particle automated Raman trapping analysis (SPARTA). We first synthesized a library of model compounds covering a range of hydrophilicities and providing distinct Raman signals. These compounds were then loaded into model nanovesicles (polymersomes) that can load both hydrophobic and hydrophilic cargo into the membrane or core regions, respectively. Using our analytical framework, we characterized the heterogeneity of the population by correlating the signal per particle from the membrane and cargo. We found that core and membrane loading can be distinguished, and we detected subpopulations of highly loaded particles in certain cases. We then confirmed the suitability of our technique in liposomes, another nanovesicle class, including the commercial formulation Doxil. Our label-free analytical technique precisely determines cargo location alongside loading and release heterogeneity in nanomedicines, which could be instrumental for future quality control, regulatory body protocols, and development of structure-function relationships to bring more nanomedicines to the clinic.

Role of Curvature-Sensing Proteins in the Uptake of Nanoparticles with Different Mechanical Properties.

Nanoparticles of different properties, such as size, charge, and rigidity, are used for drug delivery. Upon interaction with the cell membrane, because of their curvature, nanoparticles can bend the lipid bilayer. Recent results show that cellular proteins capable of sensing membrane curvature are involved in nanoparticle uptake; however, no information is yet available on whether nanoparticle mechanical properties also affect their activity. Here liposomes and liposome-coated silica are used as a model system to compare uptake and cell behavior of two nanoparticles of similar size and charge, but different mechanical properties. High-sensitivity flow cytometry, cryo-TEM, and fluorescence correlation spectroscopy confirm lipid deposition on the silica. Atomic force microscopy is used to quantify the deformation of individual nanoparticles at increasing imaging forces, confirming that the two nanoparticles display distinct mechanical properties. Uptake studies in HeLa and A549 cells indicate that liposome uptake is higher than for the liposome-coated silica. RNA interference studies to silence their expression show that different curvature-sensing proteins are involved in the uptake of both nanoparticles in both cell types. These results confirm that curvature-sensing proteins have a role in nanoparticle uptake, which is not restricted to harder nanoparticles, but includes softer nanomaterials commonly used for nanomedicine applications.

"It helps us say what's important..." Developing Serious Illness Topics: A clinical visit agenda-setting tool.

BACKGROUND: Skillful communication with attention to patient and care partner priorities can help people with serious illnesses. Few patient-facing agenda-setting tools exist to facilitate such communication. OBJECTIVE: To develop a tool to facilitate prioritization of patient and care partner concerns during serious illness visits. PATIENT OR FAMILY INVOLVEMENT: Two family members of seriously ill individuals advised. METHODS: We performed a literature review and developed a prototype agenda-setting tool. We modified the tool based on cognitive interviews with patients, families and clinicians. We piloted the tool with patients, care partners and clinicians to gain an initial impression of its perceived value. RESULTS: Interviews with eight patients, eight care partners and seven clinicians, resulted in refinements to the initial tool, including supplementation with visual cues. In the pilot test, seven clinicians used the tool with 11 patients and 12 family members. Qualitatively, patients and care partners reported the guide helped them consider and assert their priorities. Clinicians reported the tool complemented usual practice. Most participants reported no distress, disruption or confusion. DISCUSSION: Patients, care partners and clinicians appreciated centering patient priorities in serious illness visits using the agenda-setting tool. More thorough evaluation is required. PRACTICAL VALUE: The agenda-setting tool may operationalize elements of good serious illness care.

Breast, Prostate, Colorectal, and Lung Cancer Incidence and Risk Factors in Women Who Have Sex with Women and Men Who Have Sex with Men: A Cross-Sectional and Longitudinal Analysis Using UK Biobank.

BACKGROUND: There is limited evidence about cancer incidence for lesbian, gay and bisexual women and men, although the prevalence of cancer risk factors may be higher. AIM: To describe cancer incidence for four common cancers (breast, lung, colorectal and prostate). METHODS: This project used UK Biobank participant data. We explored risk factor prevalence (age, deprivation, ethnicity, smoking, alcohol intake, obesity, parity, and sexual history), and calculated cancer risk, for six groups defined based on sexual history; women who have sex exclusively with men (WSEM), or women (WSEW), women who have sex with men and women (WSWM); men who have sex exclusively with women (MSEW), or men (MSEM), and men who have sex with women and men (MSWM). RESULTS: WSEW, WSWM, MSEM, and MSMW were younger, more likely to smoke, and to live in more deprived neighbourhoods. We found no evidence of an association between sexual history and breast, colorectal, or prostate cancer in age-adjusted models. Lung cancer incidence was higher for WSWM compared with WSEM, HR (95%CI) 1.78 (1.28-2.48), p = 0.0005, and MSWM compared with MSEW, 1.43 (1.03-1.99), p = 0.031; after adjustment for smoking, this difference was no longer significant. CONCLUSIONS: Sexual minority groups have a higher risk for lung cancer, due to greater exposure to smoking.

The CONFIDENT study protocol: a randomized controlled trial comparing two methods to increase long-term care worker confidence in the COVID-19 vaccines.

BACKGROUND: Clinical and real-world effectiveness data for the COVID-19 vaccines have shown that they are the best defense in preventing severe illness and death throughout the pandemic. However, in the US, some groups remain more hesitant than others about receiving COVID-19 vaccines. One important group is long-term care workers (LTCWs), especially because they risk infecting the vulnerable and clinically complex populations they serve. There is a lack of research about how best to increase vaccine confidence, especially in frontline LTCWs and healthcare staff. Our aims are to: (1) compare the impact of two interventions delivered online to enhanced usual practice on LTCW COVID-19 vaccine confidence and other pre-specified secondary outcomes, (2) determine if LTCWs' characteristics and other factors mediate and moderate the interventions' effect on study outcomes, and (3) explore the implementation characteristics, contexts, and processes needed to sustain a wider use of the interventions. METHODS: We will conduct a three-arm randomized controlled effectiveness-implementation hybrid (type 2) trial, with randomization at the participant level. Arm 1 is a dialogue-based webinar intervention facilitated by a LTCW and a medical expert and guided by an evidence-based COVID-19 vaccine decision tool. Arm 2 is a curated social media web application intervention featuring interactive, dynamic content about COVID-19 and relevant vaccines. Arm 3 is enhanced usual practice, which directs participants to online public health information about COVID-19 vaccines. Participants will be recruited via online posts and advertisements, email invitations, and in-person visits to care settings. Trial data will be collected at four time points using online surveys. The primary outcome is COVID-19 vaccine confidence. Secondary outcomes include vaccine uptake, vaccine and booster intent for those unvaccinated, likelihood of recommending vaccination (both initial series and booster), feeling informed about the vaccines, identification of vaccine information and misinformation, and trust in COVID-19 vaccine information provided by different people and organizations. Exploration of intervention implementation will involve interviews with study participants and other stakeholders, an in-depth process evaluation, and testing during a subsequent sustainability phase. DISCUSSION: Study findings will contribute new knowledge about how to increase COVID-19 vaccine confidence and effective informational modalities for LTCWs. TRIAL REGISTRATION: NCT05168800 at ClinicalTrials.gov, registered December 23, 2021.