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BACKGROUND: Palliative care for people experiencing homelessness is a complex field. Due to the intricate nuances and heterogeneity in the experience of palliative care for people without secure housing, it is essential that research is informed by people with lived experience of homelessness. However, as homelessness is often associated with loss, trauma and high levels of exposure to death, any co-production of research, particularly in the field of palliative and end-of-life-care, must be trauma-informed. AIM: To produce recommendations for co-producing palliative and end-of-life-care research with people with lived experience of homelessness. DESIGN: A qualitative study comprising semi-structured interviews and focus groups. Data were analysed using iterative, reflexive thematic analysis. SETTING/PARTICIPANTS: Twenty-seven participants were recruited. Sixteen professionals with experience of co-producing research with people with lived experience of homelessness; eleven people with lived experience of homelessness. RESULTS: Six key themes were developed: transparency, importance of engagement and rapport, facilitating equitable involvement via person centred approach, financial recognition of involvement, involvement and growth through a trauma-informed approach and navigating institutional resistance and attitudes. Recommendations corresponding to the core themes were developed (TIFFIN recommendations). CONCLUSIONS: Co-production of palliative care research with people with lived experience of homelessness is essential, but must be done carefully and sensitively. As a population with high levels of premature morbidity and mortality yet low access to palliative care, the TIFFIN recommendations could help to support the involvement of people with lived experience of homelessness in palliative and end-of-life-care care research.
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Grupos Focales , Personas con Mala Vivienda , Cuidados Paliativos , Investigación Cualitativa , Cuidado Terminal , Humanos , Personas con Mala Vivienda/psicología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Entrevistas como AsuntoRESUMEN
Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
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Metilación de ADN , Edad Materna , Metilación de ADN/genética , Humanos , Femenino , Recién Nacido , Niño , Adulto , Masculino , Preescolar , Islas de CpG/genética , EmbarazoRESUMEN
BACKGROUND: Epidemiological evidence suggests air pollution adversely affects cognition and increases the risk of Alzheimer's disease (AD), but little is known about the biological effects of fine particulate matter (PM2.5, particulate matter with aerodynamic diameter ≤2.5µm) on early predictors of future disease risk. OBJECTIVES: We investigated the association between 1-, 3-, and 5-y exposure to ambient and traffic-related PM2.5 and cerebrospinal fluid (CSF) biomarkers of AD. METHODS: We conducted a cross-sectional analysis using data from 1,113 cognitively healthy adults (45-75 y of age) from the Emory Healthy Brain Study in Georgia in the United States. CSF biomarker concentrations of Aß42, tTau, and pTau, were collected at enrollment (2016-2020) and analyzed with the Roche Elecsys system. Annual ambient and traffic-related residential PM2.5 concentrations were estimated at a 1-km and 250-m resolution, respectively, and computed for each participant's geocoded address, using three exposure time periods based on specimen collection date. Associations between PM2.5 and CSF biomarker concentrations, considering continuous and dichotomous (dichotomized at clinical cutoffs) outcomes, were estimated with multiple linear/logistic regression, respectively, controlling for potential confounders (age, gender, race, ethnicity, body mass index, and neighborhood socioeconomic status). RESULTS: Interquartile range (IQR; IQR=0.845) increases in 1-y [ß:-0.101; 95% confidence interval (CI): -0.18, -0.02] and 3-y (ß:-0.078; 95% CI: -0.15, -0.00) ambient PM2.5 exposures were negatively associated with Aß42 CSF concentrations. Associations between ambient PM2.5 and Aß42 were similar for 5-y estimates (ß:-0.076; 95% CI: -0.160, 0.005). Dichotomized CSF variables revealed similar associations between ambient PM2.5 and Aß42. Associations with traffic-related PM2.5 were similar but not significant. Associations between PM2.5 exposures and tTau, pTau tTau/Aß42, or pTau/Aß42 levels were mainly null. CONCLUSION: In our study, consistent trends were found between 1-y PM2.5 exposure and decreased CSF Aß42, which suggests an accumulation of amyloid plaques in the brain and an increased risk of developing AD. https://doi.org/10.1289/EHP13503.
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Contaminantes Atmosféricos , Contaminación del Aire , Enfermedad de Alzheimer , Adulto , Humanos , Estados Unidos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Enfermedad de Alzheimer/epidemiología , Estudios Transversales , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/análisis , Biomarcadores/análisisRESUMEN
BACKGROUND: Co-production of research aims to include people with lived experience of a phenomena throughout the research process. People experiencing homelessness often experience advance ill-health at a young age, yet access palliative care services at a disparately low rate to the level of palliative care need. The voices of people experiencing homelessness are infrequently heard throughout palliative care research, despite the complexities and intricacies of the area. AIM: To explore the experiences of experts in the field to identify key context considerations for involving people with lived experience of homelessness in palliative and end of life care research. METHODS: Qualitative study comprising two data collection streams: interviews with professionals with experience of involving people experiencing homelessness in their work, and focus groups with people with lived experience (PWLE) of homelessness. Data were analysed using iterative, reflexive thematic analysis. Patient and Public Involvement contributors gave feedback on themes. RESULTS: A total of 27 participants took part in semi-structured interviews (N = 16; professionals) or focus groups (N = 11; PWLE homelessness). Key considerations of involving people experiencing homelessness in palliative and end of life care research were developed into four key themes: complexity of lived experience of homelessness; representation of homelessness within experts by experience; professionalising lived experience; and methods for involvement. CONCLUSIONS: Involvement of people with lived experience of homelessness is important in developing palliative care research. This paper begins to outline some contextual considerations for promoting involvement in a complex and intricate field of research.
People experiencing homelessness often become unwell at a young age. They often experience several illnesses at the same time, and many people experiencing homelessness may also experience substance misuse disorders and/or mental illness.Despite this, they often are not identified as needing palliative care support, therefore rarely access services. Research into palliative care and homelessness may benefit from including people with lived experience of homelessness, yet this is rarely done, and is a sensitive and challenging area. The current study carried out interviews with professionals who have previously involved those with lived experience of homelessness in their work, and focus groups with people with lived experience of homelessness. Twenty seven participants took part: 16 professionals with extensive experience of supporting PEH and 11 people with lived experience. Key considerations of involving people experiencing homelessness in palliative care research were developed into four key themes: complexity of lived experience of homelessness; representation of homelessness within experts by experience; professionalising lived experience; and methods for involvement. Involvement of people with lived experience of homelessness is important in developing palliative care research. This paper begins to outline some contextual considerations for promoting involvement in a complex and intricate field of research.
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Epilepsy affects approximately 25 % of people with intellectual disability (ID). Despite this high prevalence, evidence of health disparity exists in healthcare access and health outcomes for this population. Patients with ID experience additional challenges in accessing appropriate epilepsy care, and are at greater risk of experiencing inappropriate prescribing, polypharmacy and misdiagnosis compared with the general population. The expectations, attitudes and actions of physicians are key in addressing health inequalities, particularly those which disproportionately impact a specific group of patients, such as patients with ID and epilepsy. This qualitative study aimed to explore the views of specialist physicians as to why they believe this patient group are at a disadvantage when it comes to accessing appropriate epilepsy care, and how physicians can intervene to ensure that patients with ID are given equal access to suitable epilepsy care, and equal opportunity to achieve the best possible treatment outcomes. Semi-structured interviews were carried out with six physicians, located in six countries, who specialise in the care of persons with ID who have epilepsy. Interviews sought views on prognostic expectations, experiences of disparities in epilepsy care, and suggestions for advocacy interventions. Interviews were analysed using reflexive thematic analysis. Three core themes and nine subthemes were identified. Core themes included (1) 'Nervousness in care and treatment,' which reflected participants' descriptions of a nervousness by colleagues when treating epilepsy in patients with ID. (2) 'Taking a deeper dive' captured the harmful effects of accepting "common dogma," as well as the issue of a lack of clarity around treatment pathways for patients with epilepsy and ID. (3) 'Teach me' illustrated the importance of shared expertise, reflective practice and continued research and advocacy. Findings reflected participants' recommendations to address disparities in epilepsy care for patients with ID. These recommendations highlighted education and training, taking time to learn how to communicate in different ways, and regular reflection on personal assumptions and biases as important contributors to addressing inequalities in epilepsy care for patients with ID. It is hoped that findings will prompt those providing epilepsy care to reflect on their own practice and identify ways in which they might intervene to minimise inadvertent harm and reduce health disparities in epilepsy care for patients with ID.
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Epilepsia , Discapacidad Intelectual , Humanos , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/terapia , Rol del Médico , Epilepsia/diagnóstico , Epilepsia/epidemiología , Epilepsia/terapia , Atención a la Salud , Encuestas y CuestionariosRESUMEN
This study explored how frequent gamblers perceive gambling marketing and the role they feel it has in their gambling behaviour. Ten frequent gamblers participated in semi-structured interviews oriented around their experiences of gambling marketing. An interpretative phenomenological analysis of the data led to three overarching themes: exploiting gambling marketing for personal gain; gambling marketing as a test of self-control; and safer gambling messages marketing perceived as ineffective. These themes encapsulated participants' views of gambling marketing as something they could take advantage of to increase their own gambling success. Marketing was also perceived as a test of self-control among self-identified experienced gamblers, although identified as a risk to those who are considered more vulnerable. Finally, safer gambling messages included within marketing was considered ineffective due to perceived insincerity and being seen as an 'afterthought' by marketers. In support of previous research, the current investigation highlights concerning narratives around self-control and perceived risk, as encapsulated within gambling marketing, and these are evident in the perceptions of frequent gamblers. Given gamblers' perceived lack of effectiveness of current safer gambling messages within marketing, future research should explore new avenues for safer gambling promotion.
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Juego de Azar , Humanos , Mercadotecnía , EmocionesRESUMEN
Regulators of G-protein signaling (RGS) proteins are potent negative modulators of signal transduction through G-protein-coupled receptors. They function by binding to activated (GTP-bound) Gα subunits and accelerating the rate of GTP hydrolysis. Modulation of RGS activity by small molecules is an attractive mechanism for fine-tuning GPCR signaling for therapeutic and research purposes. Here we describe the pharmacologic properties and mechanism of action of CCG-50014, the most potent small molecule RGS inhibitor to date. It has an IC(50) for RGS4 of 30 nM and is >20-fold selective for RGS4 over other RGS proteins. CCG-50014 binds covalently to the RGS, forming an adduct on two cysteine residues located in an allosteric regulatory site. It is not a general cysteine alkylator as it does not inhibit activity of the cysteine protease papain at concentrations >3000-fold higher than those required to inhibit RGS4 function. It is also >1000-fold more potent as an RGS4 inhibitor than are the cysteine alkylators N-ethylmaleimide and iodoacetamide. Analysis of the cysteine reactivity of the compound shows that compound binding to Cys(107) in RGS8 inhibits Gα binding in a manner that can be reversed by cleavage of the compound-RGS disulfide bond. If the compound reacts with Cys(160) in RGS8, the adduct induces RGS denaturation, and activity cannot be restored by removal of the compound. The high potency and good selectivity of CCG-50014 make it a useful tool for studying the functional roles of RGS4.