RESUMO
BACKGROUND: The retinal and cerebral microvasculature share similar embryological origins and physiological characteristics. Improved imaging technologies provide opportunistic non-invasive assessment of retinal microvascular parameters (RMPs) against cognitive outcomes. We evaluated baseline measures for associations between RMPs and mild cognitive impairment (MCI) from participants of the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA). METHODS: RMPs (central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension and tortuosity) were measured from optic disc centred fundus images and analysed using semi-automated software. Associations between RMPs and MCI were assessed by multivariable logistic regression with adjustment for potential confounders including age, sex, alcohol consumption, smoking status, educational attainment, physical activity, cardiovascular disease (CVD), hypertension, mean arterial blood pressure, triglycerides, diabetes, body mass index, and high density lipoprotein levels. P < 0.05 was considered statistically significant. RESULTS: Data were available for 1431 participants, of which 156 (10.9%) were classified with MCI defined by a Montreal Cognitive Assessment (MoCA) score ≤ 26, with subjective cognitive decline, in the absence of depression or problems with activities of daily living. Participants had a mean age of 62.4 ± 8.5 yrs. and 52% were female. As expected, individuals with MCI had a lower MoCA score than those without (23.5 ± 2.6 versus 26.3 ± 2.7, respectively), were more likely to be female, have a lower level of educational attainment, be less physically active, more likely to have CVD, have higher levels of triglycerides and lower levels of high density lipoprotein. No significant associations between RMPs and MCI were detected in unadjusted, minimally adjusted or fully adjusted regression models or subsequent sensitivity analyses. CONCLUSION: Previous studies have reported both increased retinal venular calibre and reduced fractal dimension in association with mild cognitive impairment. Our study failed to detect any associations between RMPs and those individuals at an early stage of cognitive loss in an older community-based cohort.
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Disfunção Cognitiva/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Idoso , Envelhecimento/patologia , Disfunção Cognitiva/complicações , Estudos de Coortes , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Estudos Longitudinais , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Irlanda do Norte , Retina/diagnóstico por imagem , Retina/patologiaRESUMO
INTRODUCTION: The retina shares similar anatomical and physiological features with the brain and subtle variations in retinal microvascular parameters (RMPs) may reflect similar vascular variation in the brain. The aim of this study was to assess associations between RMPs and measures of depression in the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: RMPs (arteriolar and venular caliber, fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Depression was characterised by the Centre for Epidemiologic Studies Depression Scale (CES-D) in the absence of mild cognitive impairment or use of anti-depressive medications. Associations between depression and RMPs were assessed by regression analyses with adjustment for potential confounders. RESULTS: Data were available for 1376 participants of which 113 (8.2%) and 1263 (91.8%) were classified with and without depression. Participants had a mean age of 62.0 ± 8.4 yrs., 52% were female, and 8% were smokers. Individuals with depression had a higher CES-D score than those without (22.0 ± 6.2 versus 4.4 ± 3.9). Lower values of arteriolar tortuosity were significantly associated with depression, before and after adjustment for potential confounders (odds ratio = 0.79; 95% confidence intervals: 0.65, 0.96; P = 0.02). CONCLUSION: Decreased retinal arteriolar tortuosity, a measure of the complexity of the retinal microvasculature was associated with depression in older adults independent of potential confounding factors. Retinal measures may offer opportunistic assessment of microvascular health associated with outcomes of depression.
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Depressão , Vasos Retinianos , Idoso , Envelhecimento , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Irlanda do Norte/epidemiologia , Retina , Vasos Retinianos/diagnóstico por imagem , Fatores de RiscoRESUMO
BACKGROUND: Previous studies have identified retinal microvascular features associated with renal dysfunction. Biopsies are necessary to confirm kidney microvascular damage and retinal imaging may enable evaluation of microangiopathic characteristics reflecting renal changes associated with chronic kidney disease (CKD). We evaluated retinal microvascular parameters (RMPs) for associations with renal function in a cross-sectional analysis of the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: RMPs (central retinal arteriolar/ venular equivalents [CRAE/CRVE], arteriolar to venular ratio [AVR], fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Associations were assessed with multivariable regression analyses between RMPs and estimated glomerular filtration rate (eGFR) defined by serum creatinine (eGFRscr) and cystatin C (eGFRcys) and also CKD status characterised by eGFR < 60 mL/min/1.73m2. Regression models were adjusted for potential confounders including age, sex, diabetes, smoking status, educational attainment, cardiovascular disease, body mass index, antihypertensive medication, systolic blood pressure, triglycerides, high- and low-density lipoprotein levels. RESULTS: Data were included for 1860 participants that had measures of renal function and retinal fundus images of sufficient quality for analysis. Participants had a mean age of 62.0 ± 8.5 yrs. and 53% were female. The mean eGFR for scr and cys were 82.2 ± 14.9 mL/min/1.73m2 and 70.7 ± 18.6 mL/min/1.73m2 respectively. eGFRcys provided lower estimates than eGFRscr resulting in a greater proportion of participants categorised as having CKD stages 3-5 (eGFRcys 26.8%; eGFRscr 7.9%). Multivariable regression analyses showed that increased venular tortuosity (OR = 1.30; 95%CI: 1.10, 1.54; P < 0.01) was associated with CKD stages 3-5 characterised by eGFRscr < 60 mL/min/1.73 m2. No additional associations between CKD status characterised by eGFRscr or with eGFRcys, were detected (P > 0.05). Multivariable regression failed to detect associations between CRAE, CRVE, AVR, fractal dimension or tortuosity and eGFRscr or eGFRcys (P > 0.05). CONCLUSION: Increased retinal venular tortuosity was associated with CKD stages 3-5 defined by eGFRscr < 60 mL/min/1.73 m2, in an older population independent of potential confounding factors. These retinal measures may provide non-invasive microvascular assessment of associations with CKD.
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Arteríolas/patologia , Insuficiência Renal Crônica/epidemiologia , Veia Retiniana/patologia , Vênulas/patologia , Idoso , Estudos de Coortes , Creatinina/sangue , Cistatina C/sangue , Feminino , Fundo de Olho , Taxa de Filtração Glomerular , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Irlanda do Norte/epidemiologia , Fotografação , Análise de Regressão , Insuficiência Renal Crônica/metabolismo , Índice de Gravidade de DoençaRESUMO
Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited. Patients and methods: For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology. Results: A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR) = 1.12; 95 % confidence interval (CI) = 1.04-1.20] and current smoking (HR = 1.29; 95% CI = 1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10 years = 0.78; 95% CI = 0.69-0.88; HR≥10 years = 0.78; 95% CI = 0.63-0.97) and CRC-specific survival (HR≥10 years = 0.76; 95% CI = 0.67-0.85). Conclusion: In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.
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Neoplasias Colorretais/mortalidade , Fumar/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Abandono do Hábito de FumarRESUMO
BACKGROUND: Strong evidence links the consumption of a Mediterranean diet (MD) with a reduced cardiovascular disease (CVD) risk; however, there is uncertainty as to whether non-Mediterranean regions will adopt this diet. The present qualitative research aimed to investigate attitudes towards a MD in individuals at high CVD risk in a Northern European population. This information is needed to inform development of MD interventions in non-Mediterranean high-risk populations. METHODS: Focus groups (n = 12) were held with individuals at high CVD risk from Northern Europe (≥2 CVD risk factors, aged ≥50 years, no established CVD/type 2 diabetes). Attitudes to dietary change towards a MD were explored. Data were analysed using inductive thematic analysis. RESULTS: Sixty-seven adults participated (60% female, mean age 64 years). There was some awareness of the term MD but limited knowledge of its composition. Barriers to general dietary change were evident, including perception of expense, concern over availability, expectation of time commitment, limited knowledge, lack of cooking skills, amount and conflicting nature of media information on diets, changing established eating habits and resistance to dietary change. Barriers specific to MD adoption were also identified, including perceived difficulty living in a colder climate, perceived impact on body weight, acceptability of a MD and cultural differences. CONCLUSIONS: Knowledge of a MD was limited in this Northern European sample at high CVD risk. In addition to general barriers to dietary change, barriers specific to a MD were identified. These findings have implications for the development of interventions aiming to promote MD adoption in non-Mediterranean populations.
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Terapia Comportamental/métodos , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea/psicologia , Comportamento Alimentar/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Idoso , Custos e Análise de Custo , Dieta Mediterrânea/economia , Europa (Continente) , Feminino , Grupos Focais , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Percepção , Fatores de RiscoRESUMO
OBJECTIVE: Scant evidence is available on the discordance between loneliness and social isolation among older adults. We aimed to investigate this discordance and any health implications that it may have. METHOD: Using nationally representative datasets from ageing cohorts in Ireland (TILDA) and England (ELSA), we created a metric of discordance between loneliness and social isolation, to which we refer as Social Asymmetry. This metric was the categorised difference between standardised scores on a scale of loneliness and a scale of social isolation, giving categories of: Concordantly Lonely and Isolated, Discordant: Robust to Loneliness, or Discordant: Susceptible to Loneliness. We used regression and multilevel modelling to identify potential relationships between Social Asymmetry and cognitive outcomes. RESULTS: Social Asymmetry predicted cognitive outcomes cross-sectionally and at a two-year follow-up, such that Discordant: Robust to Loneliness individuals were superior performers, but we failed to find evidence for Social Asymmetry as a predictor of cognitive trajectory over time. CONCLUSIONS: We present a new metric and preliminary evidence of a relationship with clinical outcomes. Further research validating this metric in different populations, and evaluating its relationship with other outcomes, is warranted. Copyright © 2016 John Wiley & Sons, Ltd.
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Envelhecimento/psicologia , Solidão/psicologia , Isolamento Social/psicologia , Idoso , Idoso de 80 Anos ou mais , Cognição/fisiologia , Estudos Transversais , Inglaterra , Feminino , Humanos , Irlanda , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
OBJECTIVES: We supplement existing findings on a link between social support and cognitive function in later life by considering the role of personality as an antecedent to both, and of social support as a mediator of the link between personality and cognitive function. STUDY DESIGN: An observational cohort study. METHODS: We evaluated social support using the Lubben Social Network Scale, across 624 adults aged over 60 years, and investigated this measure as a mediator of the relationships between extraversion and neuroticism at baseline 2007-2009, and cognitive function at follow-up, 2 years later. A half-longitudinal mediation design, within a structural equation modelling framework, was used. RESULTS: There was a direct effect of extraversion, such that lower levels were related to higher scores of cognitive function. There was no significant direct effect of neuroticism on cognitive function at follow-up. Social support partially mediated the paths between both extraversion and neuroticism and cognitive function at follow-up. Decomposing the mediation effects by using social support subscales (measuring support from friends, relatives and neighbours) showed meaningful indirect effects for both predictors. CONCLUSION: Results suggest that social support may offer a target for interventions for cognitively at-risk older adults and add to the existing empirical evidence describing the link between personality and cognitive function.
Assuntos
Transtornos de Ansiedade/psicologia , Cognição , Extroversão Psicológica , Personalidade , Apoio Social , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NeuroticismoRESUMO
BACKGROUND: To determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations. METHODS: The associations of HbA1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects ≥50 years from six population-based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA1c were defined as <5.0, 5.0 to <5.5, 5.5 to <6.0 and 6.0 to <6.5% (equals <31, 31 to <37, 37 to <42 and 42 to <48 mmol/mol), respectively, and low HbA1c was used as reference in Cox proportional hazards models. RESULTS: Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50% of the excess risk and attenuated hazard ratios (95 confidence interval) for increased HbA1c to 1.14 (1.03-1.27), 1.17 (1.00-1.37) and 1.19 (1.04-1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA1c levels lost statistical significance in this cohort after adjusting for these confounders. CONCLUSIONS: A linear association of HbA1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results.
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Envelhecimento/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Hemoglobinas Glicadas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Causas de Morte , Estudos de Coortes , Fatores de Confusão Epidemiológicos , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Behavioral factors are important in disease incidence and mortality and may explain associations between mortality and various psychological traits. PURPOSE: These analyses investigated the impact of behavioral factors on the associations between depression, hostility and cardiovascular disease(CVD) incidence, CVD mortality, and all-cause mortality. METHODS: Data from the PRIME Study (N = 6953 men) were analyzed using Cox proportional hazards models, following adjustment for demographic and biological CVD risk factors, and other psychological traits, including social support. RESULTS: Following initial adjustment, both depression and hostility were significantly associated with both mortality outcomes (smallest SHR = 1.24, p < 0.001). Following adjustment for behavioral factors, all relationships were attenuated both when accounting for and not accounting for other psychological variables. Associations with all-cause mortality remained significant (smallest SHR = 1.14, p = 0.04). Of the behaviors included, the most significant contribution to outcomes was found for smoking, but a role was also found for fruit and vegetable intakes and high alcohol consumption. CONCLUSIONS: These findings demonstrate well-known associations between depression, hostility, and mortality and suggest the potential importance of behaviors in explaining these relationships.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/psicologia , Depressão/psicologia , Hostilidade , Mortalidade , Doenças Cardiovasculares/complicações , Depressão/complicações , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Irlanda do Norte/epidemiologia , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
Using rewards may be an effective method to positively influence adolescent eating behaviour, but evidence regarding this approach is limited. The aim of this study was to explore young adolescent views about a proposed reward intervention associated with food choice in school canteens. Focus groups were held in 10 schools located in lower socioeconomic areas within Northern Ireland and involved 90 pupils aged 11-12 years (54 girls, 36 boys). Our findings indicated a high degree of acceptability for a reward scheme but there was major diversity in the type of rewards valued by pupils, largely defined by geographical area and socio-cultural differences. Pupils from rural areas tended to emphasize group-based and longer-term rewards, whereas pupils from urban-city schools tended to suggest individualistic and immediate rewards. The major factors influencing food choice were food price, value for money, taste and visual appearance. Pupils felt that factors outside of their control, such as being assigned to the second lunch sitting placed considerable constraints on their food choice. This research not only indicated a high degree of acceptability for a rewards-based intervention but also highlighted a number of socio-cultural and environmental factors that should be considered by researchers when developing such an intervention.
Assuntos
Comportamento do Adolescente/psicologia , Comportamento Alimentar/psicologia , Preferências Alimentares/psicologia , Promoção da Saúde , Recompensa , Adolescente , Criança , Feminino , Grupos Focais , Serviços de Alimentação , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Irlanda do Norte , Instituições AcadêmicasRESUMO
BACKGROUND: Incidence of central venous catheter (CVC)-related thrombosis in critically ill patients remains ambiguous and its association with potential hazardous sequelae unknown. The primary aim of the study was to evaluate the epidemiology of CVC-related thrombosis; secondary aims were to assess the association of catheter-related thrombosis with catheter-related infection, pulmonary embolism and mortality. METHODS: This was a single-center, prospective observational study conducted at a tertiary intensive care unit (ICU) in the Netherlands. The study population consisted of CVC placements in adult ICU patients with a minimal indwelling time of 48 h. CVC-related thrombosis was diagnosed with ultrasonography. Primary outcomes were prevalence and incidence, incidence was reported as the number of cases per 1000 indwelling days. RESULTS: 173 CVCs in 147 patients were included. Median age of patients was 64.0 [IQR: 52.0, 72.0] and 71.1 % were male. Prevalence of thrombosis was 0.56 (95 % CI: 0.49, 0.63) and incidence per 1000 indwelling days was 65.7 (95 % CI: 59.0, 72.3). No association with catheter-related infection was found (p = 0.566). There was a significant association with pulmonary embolism (p = 0.022). All 173 CVCs were included in the survival analysis. Catheter-related thrombosis was associated with a lower 28-day mortality risk (hazard ratio: 0.39, 95 % CI: 0.17, 0.87). CONCLUSION: In critically ill patients, prevalence and incidence of catheter-related thrombosis were high. Catheter-related thrombosis was not associated with catheter-related infections, but was associated with pulmonary embolism and a decreased mortality risk.
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Estado Terminal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Incidência , Idoso , Trombose/etiologia , Trombose/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Unidades de Terapia Intensiva , Países Baixos/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/mortalidade , Fatores de Risco , PrevalênciaRESUMO
OBJECTIVE: To examine the contribution of lifestyle behaviours to the socioeconomic gradient in all-cause mortality, and fatal and non-fatal cardiovascular events. METHOD: 10,600 men aged 50-59 years examined in 1991-1994 in Northern Ireland (NI) and France and followed annually for deaths and cardiovascular events for 10 years. Baseline smoking habit, physical activity, and fruit, vegetable, and alcohol consumption were assessed. RESULTS: All lifestyle behaviours showed marked socioeconomic gradients for most indicators in NI and France, with the exception of percentage of alcohol consumers in NI and frequency of alcohol consumption in NI and France. At 10 years, there were 544 deaths from any cause and 440 fatal and non-fatal cardiovascular events. After adjustment for country and age, socioeconomic gradients were further adjusted for lifestyle behaviours. For total mortality, the median residual contribution of lifestyle behaviours was 28% and for cardiovascular incidence, 41%. When cardiovascular risk factors were considered in conjunction with lifestyle behaviours these percentages increased to 38% and 67% respectively. CONCLUSION: Lifestyle behaviours contribute to the gradient in mortality and cardiovascular incidence between socioeconomic groups, particularly for cardiovascular incidence, but a substantial proportion of these differentials was not explained by lifestyle behaviours and cardiovascular risk factors.
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Doenças Cardiovasculares/epidemiologia , Estilo de Vida , Mortalidade , Consumo de Bebidas Alcoólicas/epidemiologia , Análise de Variância , Doenças Cardiovasculares/mortalidade , Distribuição de Qui-Quadrado , Dieta/estatística & dados numéricos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Irlanda do Norte/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fumar/epidemiologia , Estatísticas não ParamétricasRESUMO
BACKGROUND: Making trials more patient-centred improves recruitment and retention, patient satisfaction and makes research accessible to a more representative population. We aimed to understand the factors that influence participation and engagement in clinical trials in cystic fibrosis (CF) trials to guide the rational design and delivery of patient-centred trials. METHODS: We used a Delphi process, supported by extensive literature review and 3 workshops, to determine which factors stakeholders think exert significant influence in participation and engagement in CF trials. Panellists were recruited from across the UK and the study was administered online. RESULTS: We had representation from 19 CF centres; 28 people with CF (pwCF), 26 parents and 30 healthcare professionals (HCPs). Panels were presented with a shortlist of 104 factors and asked which they thought influence participation and engagement in CF trials. After 3 iterations, 43 statements met consensus for pwCF, 48 for the parents and 69 for the HCPs. CONCLUSIONS: We identified many targets to make trials more patient-centred. Whilst some require an overhaul of trial delivery, many are relatively easy to implement. We outline a list of 'dos and don'ts' for sponsors and research teams including: focus on good communication; recognise that lack of time is the greatest barrier to trial participation so minimise the frequency and length of visits; help participants fit trials around busy lives; remember trial participation can be a major life-event and support participants accordingly; and don't underestimate the impact of simple strategies e.g. on-site access to Wifi and cups of tea.
Assuntos
Ensaios Clínicos como Assunto , Fibrose Cística/tratamento farmacológico , Técnica Delphi , Projetos de Pesquisa , HumanosRESUMO
BACKGROUND: A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10-8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. RESULTS: Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-ß signalling and Th17 cell differentiation. CONCLUSIONS: Epigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.
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Metilação de DNA/genética , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/complicações , Epigênese Genética/genética , Falência Renal Crônica/genética , Adulto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/genética , Epigenômica/métodos , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/etiologia , MasculinoRESUMO
BACKGROUND: Adipokines play an important role in glucose, lipid and lipoprotein metabolisms, as well as in coagulation and inflammatory processes. So far, studies have evaluated the association of individual adipokines with future coronary heart disease (CHD) event and provided mixed results. OBJECTIVES: We sought to investigate the association of a set of adipocytokines, including total adiponectin, adipsin, resistin, leptin and plasminogen activator inihibitor-1 (PAI-1), with future CHD events in apparently healthy men. METHODS: We built a nested case-control study within the PRIME Study, a multicenter prospective cohort of 9779 healthy European middle-aged men. Total adiponectin, adipsin, resistin, leptin and PAI-1 were measured in the baseline plasma sample of 617 men who developed a first CHD event (coronary death, myocardial infarction, stable or unstable angina) during 10 years of follow-up and in 1215 study-matched controls, by multiplex assays using commercial kits. HRs for CHD were estimated by conditional logistic regression analysis. RESULTS: Median concentrations of total adiponectin, adipsin and resistin were similar in cases and in controls, whereas those of leptin and PAI-1 were higher in cases than in controls, 6.30 vs 5.40 ng ml(-1), and 10.09 vs 8.48 IU ml(-1), respectively. The risk of future CHD event increased with increasing quintiles of baseline leptin and PAI-1 concentrations only in unadjusted analysis (P-value for trend <0.003 and <0.0001, respectively). However, these associations were no longer significant after adjustment for usual CHD risk factors including hypertension, diabetes, smoking, total cholesterol, triglycerides and HDL cholesterol. Conversely, baseline CRP and IL-6 levels remained associated with CHD risk in multivariate analysis. CONCLUSIONS: In apparently healthy men, circulating total adiponectin, adipsin, resistin, leptin and PAI-1 were not independent predictors of future CHD event.
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Adipocinas/sangue , Doença das Coronárias/etiologia , Obesidade/sangue , Adiponectina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Doença das Coronárias/sangue , Humanos , Interleucina-6/sangue , Leptina/sangue , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Inibidor 1 de Ativador de Plasminogênio/sangue , Estudos Prospectivos , Resistina/sangue , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
AIMS: The aim of this study was to use general practice data to estimate the prevalence of diabetic nephropathy within the registered diabetes patients and examine variation in practice prevalence and management performance since introduction of this initiative. METHODS: Reported quality indicators from the Northern Ireland General Practice Quality and Outcomes Framework were analysed for diabetes and diabetic nephropathy prevalence and management in the period 2004-2008. Variation in prevalence at practice level was assessed using multiple linear regression adjusting for age, practice size, deprivation and glycaemic control. RESULTS: In 2006-2007, 57,454 (4.1%) adult diabetic patients were registered in the denominator population of 1.4 million compared with 51,923 (3.8%) in 2004-2005 (mean practice range 0.5-7.7%). Diabetic nephropathy prevalence was 15.1 and 11.5%, respectively (8688 and 5955 patients). Documented diabetic nephropathy prevalence showed marked variation across practices (range 0-100%) and was significantly negatively correlated with diabetes list size, albumin creatinine ratio testing rates and renin-angiotensin-aldosterone system blockade use and positively correlated with exception reporting rates. Specifically, for every increase in 100 diabetic patients to a register, documented diabetic nephropathy prevalence reduced by 40% (P=0.003). On the positive side, median albumin-creatinine ratio testing rates doubled to 82% compared with figures in the pre-Framework era. CONCLUSIONS: Implementation of the Northern Ireland General Practice Quality and Outcomes Framework has positively benefitted testing for diabetic nephropathy and increased numbers of detected patients in a short space of time. Large variation in diabetic nephropathy prevalence remains and is associated with diabetes registry size, screening and treatment practices, suggesting that understanding this variation may help detect and better manage diabetic nephropathy.
Assuntos
Creatina/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Falência Renal Crônica/epidemiologia , Atenção Primária à Saúde/estatística & dados numéricos , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/sangue , Masculino , Irlanda do Norte , Prevalência , Medição de RiscoRESUMO
OBJECTIVES: This study investigated whether oral health status, defined as number of natural teeth and subsequent prosthodontic rehabilitation, was associated with future dietary intake and diet quality in older adults in The Prospective Epidemiological Study of Myocardial Infarction (PRIME). METHODS: PRIME was originally established to explore cardiovascular risk factors in 50-59â¯year old men in Northern Ireland (1991-1994). A rescreening phase assessed oral health (2001-2004), while diet was assessed in 2015. Diet quality was characterised by the Dietary Diversity Score and Mediterranean Diet Score. In the current analysis, associations between oral health status, dietary intake and quality were assessed using regression models in 1096 participants. RESULTS: Amongst study participants, the overall mean number of teeth was 18.5, 51.5 % had ≥21 natural teeth and 49.6 % wore dentures. Oral health status was categorised into five groups: 21-28 teeth with (nâ¯=â¯111) and without (nâ¯=â¯453) dentures, 1-20 teeth with (nâ¯=â¯354) and without (nâ¯=â¯99) dentures and edentate with dentures (nâ¯=â¯79). After full adjustment, men with ≥21 teeth and dentures had a higher future intake of fruit, vegetables, and nuts, and diet quality scores, compared to those with <21 teeth with dentures. Edentate men with dentures were less likely to achieve the future fruit dietary recommendation. CONCLUSIONS: Having ≥21 natural remaining teeth positively affected the future intake of fruit, vegetables, and nuts, as well as diet quality. Dentures may be beneficial in men with ≥21 natural remaining teeth, as they were associated with an increased future intake of fruit, vegetables, and nuts and better diet quality. CLINICAL SIGNIFICANCE: Oral health status is associated with dietary intake, after an average time period of 13 years, with those with a larger number of natural teeth having a better diet quality. Further research is required to investigate this relationship in larger, diverse populations with more detailed dietary assessment.
Assuntos
Dieta/estatística & dados numéricos , Saúde Bucal , Idoso , Estudos Epidemiológicos , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Estudos Prospectivos , VerdurasRESUMO
AIMS/HYPOTHESIS: Glomerular hyperfiltration is a well-established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR. METHODS: A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement of GFR and presence or absence of hyperfiltration. RESULTS: We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20-6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p = 0.05, measure of degree of inconsistency = 48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min(-1) 1.73 m(-2) (95% CI 5.0-22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p < 0.01). CONCLUSIONS/INTERPRETATION: In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/epidemiologia , Taxa de Filtração Glomerular , Glomérulos Renais/fisiopatologia , Adolescente , Adulto , Idade de Início , Albuminúria/epidemiologia , Albuminúria/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Seguimentos , Hemodinâmica , Humanos , Seleção de Pacientes , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND AND METHODS: We conducted an all-Ireland population-based prospective epidemiological survey of motor neurone disease (MND) using the Northern Ireland and Republic of Ireland MND registers to examine the incidence and prevalence of the disease over the period 2004-2005. RESULTS AND CONCLUSIONS: Incidence of MND was 1.9 per 100 000 person-years and rates were comparable in both the north and south of Ireland. Prevalence of MND was 5.0 per 100 000 population. When compared with previous published surveys of MND performed in the Republic of Ireland over the last 10 years, rates of disease have remained relatively constant. When standardized to the 1990 US population, the incidence of MND in Ireland was found to be consistent with other European prospective surveys of MND.