Estimating the risk of mortality attributable to recent late HIV diagnosis following admission to the intensive care unit: A single-centre observational cohort study

OBJECTIVES: Despite improvements in survival of people with HIV admitted to the intensive care unit (ICU), late diagnosis continues to contribute to in-ICU mortality. We quantify the population attributable fraction (PAF) of in-ICU mortality for recent late diagnosis among people with HIV admitted to a London ICU. METHODS: Index ICU admissions among people with HIV were considered from 2000 to 2019. Recent late diagnosis was a CD4 T-cell count < 350 cells/μL and/or AIDS-defining illness at/within 6 months prior to ICU admission. Univariate comparisons were conducted using Wilcoxon rank-sum/Cochran-Armitage/χ2 /Fisher's exact tests. We used Poisson regression (robust standard errors) to estimate unadjusted/adjusted (age, sex, calendar year of ICU admission) risk ratios (RRs) and regression standardization to estimate the PAF. RESULTS: In all, 207 index admissions were included [median (interquartile range) age: 46 (38-53) years; 72% male]; 58 (28%) had a recent late diagnosis, all of whom had a CD4 count < 350 cells/μL, and 95% had advanced HIV (CD4 count < 200 cells/μL and/or AIDS at admission) as compared with 57% of those who did not have a recent late diagnosis (p < 0.001). In-ICU mortality was 27% (55/207); 38% versus 22% in those who did and did not have a recent late diagnosis, respectively (p = 0.02). Recent late diagnosis was independently associated with increased in-ICU mortality risk (adjusted RR = 1.75) (95% confidence interval: 1.05-2.91), with 17.08% (16.04-18.12%) of deaths being attributable to this. CONCLUSIONS: There is a need for improved public health efforts focused on HIV testing and reporting of late diagnosis to better understand potentially missed opportunities for earlier HIV diagnosis in healthcare services

Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV-negative controls: A cross-sectional study nested within the POPPY cohort

BACKGROUND: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. METHODS: Older (>50 years) and younger (50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi-squared/Fisher's exact/Kruskal–Wallis tests. RESULTS: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV-negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14–0.52) than controls, but male sex (OR 2.45; 95% CI 1.20–4.50) and high waist-to-hip ratio (OR 3.04; 95% CI 1.74–5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV-related variables. CONCLUSIONS: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV-related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care

Exploring rationales for branding a university: Should we be seeking to measure branding in UK universities?

Although branding is now widespread among UK universities, the application of branding principles in the higher education sector is comparatively recent and may be controversial for internal audiences who question its suitability and efficiency. This paper seeks to investigate how and whether the effectiveness of branding activity in the higher education sector should be evaluated and measured, through exploratory interviews with those who often drive it; UK University marketing professionals. Conclusions suggest that university branding is inherently complex and therefore application of commercial approaches may be over simplistic. Whilst marketing professionals discuss challenges they do not necessarily have a consistent view of the objectives of branding activity although all were able to clearly articulate branding objectives for their university, including both qualitative and, to some extent, quantitative metrics. Some measures of the real value of branding activity are therefore suggested but a key debate is perhaps whether the objectives and role of branding in higher education needs to be clarified, and a more consistent view of appropriate metrics reached? Various challenges in implementing branding approaches are also highlighted

Using evidence-informed logic models to bridge methods in educational evaluation

Designs combining different types of data are increasingly used in educational evaluation, to provide both evidence of impact and an explanation of the processes by which impacts are created. Logic models are visual representations of how an intervention leads via a set of steps from resources and inputs to outputs and then sets of outcomes. Their use has become widespread to underpin evaluations; and they have become of more interest in education as they have been promoted by policy makers and funders including the Education Endowment Foundation (EEF) in England. This paper addresses the question: how can logic models be used to frame and implement educational evaluations using combinations of methods? To do so, the paper draws on theory-based evaluation literature to identify a set of issues to be considered: the role of implementation logic; causal mechanisms; the context of interventions; and the importance of considering and addressing issues around complexity. Using detailed examples from two study designs for EEF evaluations, the paper presents an evidence-informed logic model approach to deal with these issues. The paper concludes by reflecting on the practical and theoretical implications of this approach, laying out a set of key issues to address in future evaluations for which a design framed by an evidence-informed logic model may be appropriate

Emergency management in health: key issues and challenges in the UK

Background Emergency planning in the UK has grown considerably in recent years, galvanised by the threat of terrorism. However, deficiencies in NHS emergency planning were identified and the evidence-base that underpins it is questionable. Inconsistencies in terminologies and concepts also exist. Different models of emergency management exist internationally but the optimal system is unknown. This study examines the evidence-base and evidence requirements for emergency planning in the UK health context. Methods The study involved semi-structured interviews with key stakeholders and opinion leaders. Purposive sampling was used to obtain a breadth of views from various agencies involved in emergency planning and response. Interviews were then analysed using a grounded approach using standard framework analysis techniques. Results We conducted 17 key informant interviews. Interviewees identified greater gaps in operational than technical aspects of emergency planning. Social and behavioural knowledge gaps were highlighted with regards to how individuals and organisations deal with risk and behave in emergencies. Evidence-based approaches to public engagement and for developing community resilience to disasters are lacking. Other gaps included how knowledge was developed and used. Conflicting views with regards to the optimal configuration and operation of the emergency management system were voiced. Conclusions Four thematic categories for future research emerged: (i) Knowledge-base for emergency management: Further exploration is needed of how knowledge is acquired, valued, disseminated, adopted and retained. (ii) Social and behavioural issues: Greater understanding of how individuals approach risk and behave in emergencies is required. (iii) Organisational issues in emergencies: Several conflicting organisational issues were identified; value of planning versus plans, flexible versus standardized procedures, top-down versus bottom-up engagement, generic versus specific planning, and reactive versus proactive approaches to emergencies. (iv) Emergency management system: More study is required of system-wide issues relating to system configuration and operation, public engagement, and how emergency planning is assessed

Breast cancer derived GM-CSF regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment

Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (Arg-1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular L-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor derived GM-CSF as the primary regulator of myeloid cell Arg-1 expression and local immune suppression through a gene knockout screen of breast tumor cell-produced factors. The induction of myeloid cell Arg-1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3, p38 MAPK, and acid signaling through cAMP were required to activate myeloid cell Arg-1 expression in a STAT6 independent manner. Importantly, breast tumor cell-derived GM-CSF promoted tumor progression by inhibiting host anti-tumor immunity, driving a significant accumulation of Arg-1 expressing myeloid cells compared to lung and melanoma tumors with minimal GM-CSF expression. Blockade of tumoral GM-CSF enhanced the efficacy of tumor-specific adoptive T-cell therapy and immune checkpoint blockade. Taken together, breast tumor cell-derived GM-CSF contributes to the development of the immunosuppressive breast cancer microenvironment by regulating myeloid cell Arg-1 expression and can be targeted to enhance breast cancer immunotherapy

Therapeutic targets for bone metastases in breast cancer

Breast cancer is prone to metastasize to bone. Once metastatic cells are in the bone marrow, they do not, on their own, destroy bone. Instead, they alter the functions of bone-resorbing (osteoclasts) and bone-forming cells (osteoblasts), resulting in skeletal complications that cause pathological fractures and pain. In this review, we describe promising molecular bone-targeted therapies that have arisen from recent advances in our understanding of the pathogenesis of breast cancer bone metastases. These therapies target osteoclasts (receptor activator of nuclear factor kB ligand, integrin αvβ3, c-Src, cathepsin K), osteoblasts (dickkopf-1, activin A, endothelin A) and the bone marrow microenvironment (transforming growth factor β, bone morphogenetic proteins, chemokine CXCL-12 and its receptor CXCR4). The clinical exploitation of these bone-targeted agents will provide oncologists with novel therapeutic strategies for the treatment of skeletal lesions in breast cancer

The joint influence of marital status, interpregnancy interval, and neighborhood on small for gestational age birth: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Interpregnancy interval (IPI), marital status, and neighborhood are independently associated with birth outcomes. The joint contribution of these exposures has not been evaluated. We tested for effect modification between IPI and marriage, controlling for neighborhood.</p> <p>Methods</p> <p>We analyzed a cohort of 98,330 live births in Montréal, Canada from 1997–2001 to assess IPI and marital status in relation to small for gestational age (SGA) birth. Births were categorized as subsequent-born with <it>short </it>(<12 months), <it>intermediate </it>(12–35 months), or <it>long </it>(36+ months) IPI, or as firstborn. The data had a 2-level hierarchical structure, with births nested in 49 neighborhoods. We used multilevel logistic regression to obtain adjusted effect estimates.</p> <p>Results</p> <p>Marital status modified the association between IPI and SGA birth. Being unmarried relative to married was associated with SGA birth for all IPI categories, particularly for subsequent births with <it>short </it>(odds ratio [OR] 1.60, 95% confidence interval [CI] 1.31–1.95) and <it>intermediate </it>(OR 1.48, 95% CI 1.26–1.74) IPIs. Subsequent births had a lower likelihood of SGA birth than firstborns. <it>Intermediate </it>IPIs were more protective for married (OR 0.50, 95% CI 0.47–0.54) than unmarried mothers (OR 0.65, 95% CI 0.56–0.76).</p> <p>Conclusion</p> <p>Being unmarried increases the likelihood of SGA birth as the IPI shortens, and the protective effect of <it>intermediate </it>IPIs is reduced in unmarried mothers. Marital status should be considered in recommending particular IPIs as an intervention to improve birth outcomes.</p