RESUMO
BACKGROUND: The association between low levels of vitamin D and the occurrence of chronic widespread pain (CWP) remains unclear. The aim of our analysis was to determine the relationship between low vitamin D levels and the risk of developing CWP in a population sample of middle age and elderly men. METHODS: Three thousand three hundred sixty nine men aged 40-79 were recruited from 8 European centres for a longitudinal study of male ageing, the European Male Ageing Study. At baseline participants underwent assessment of lifestyle, health factors, physical characteristics and gave a fasting blood sample. The occurrence of pain was assessed at baseline and follow up (a mean of 4.3 years later) by shading painful sites on a body manikin. The presence of CWP was determined using the ACR criteria for fibromyalgia. Serum 25-hydroxyvitamin D (25-(OH) D) was assessed by radioimmunoassay. Logistic regression was used to determine the relationship between baseline vitamin D levels and the new occurrence of CWP. RESULTS: Two thousand three hundred thirteen men, mean age 58.8 years (SD = 10.6), had complete pain and vitamin data available and contributed to this analysis. 151 (6.5%) developed new CWP at follow up and 577 (24.9%) were pain free at both time points, the comparator group. After adjustment for age and centre, physical performance and number of comorbidities, compared to those in upper quintile of 25-(OH) D ( ≥36.3 ng/mL), those in the lowest quintile (<15.6 ng/mL) were more likely to develop CWP (Odds Ratio [OR] = 1.93; 95% CI = 1.0-3.6). Further adjustment for BMI (OR = 1.67; 95% CI = 0.93-3.02) or depression (OR = 1.77; 95% CI = 0.98-3.21), however rendered the association non-significant. CONCLUSIONS: Low vitamin D is linked with the new occurrence of CWP, although this may be explained by underlying adverse health factors, particularly obesity and depression.
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Envelhecimento/sangue , Dor Crônica/sangue , Dor Crônica/epidemiologia , Medição da Dor/tendências , Vitamina D/sangue , Adulto , Idoso , Envelhecimento/patologia , Biomarcadores/sangue , Dor Crônica/diagnóstico , Europa (Continente)/epidemiologia , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Fatores de RiscoRESUMO
Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8(+) or CD4(+) T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4(+) T cell and antibody response, which was maintained by both regiments at similar levels. However, CD8(+) T cell responses were significantly boosted in 3 out of 18 patients in Arm A after the first rF-NY-ESO-1 injection and such responses were maintained until the end of the trial, while no patients in Arm B showed similar CD8(+) T cell responses. In addition, our results clearly identified immunodominant regions in the NY-ESO-1 protein: NY-ESO-179-102 and NY-ESO-1115-138 for CD4+ T cells and NY-ESO-185-108 for CD8+ T cells in a large proportion of vaccinated patients. These regions of NY-ESO-1 protein should be considered in future clinical trials as immunodominant epitopes.
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Adjuvantes Imunológicos/farmacologia , Antígenos de Neoplasias/imunologia , Colesterol/farmacologia , Melanoma/terapia , Proteínas de Membrana/imunologia , Fosfolipídeos/farmacologia , Saponinas/farmacologia , Formação de Anticorpos , Antígenos de Neoplasias/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Combinação de Medicamentos , Vírus da Varíola das Aves Domésticas/genética , Humanos , Melanoma/imunologia , Proteínas de Membrana/genética , Vacinação , Vacinas Sintéticas/imunologiaRESUMO
BACKGROUND: HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased cardiac morbidity and mortality. The purpose of this study was to characterize myocardial abnormalities in a contemporary group of HIV-infected individuals undergoing combination antiretroviral therapy. METHODS AND RESULTS: Volunteers with HIV who were undergoing combination antiretroviral therapy and age-matched control subjects without a history of cardiovascular disease underwent cardiac magnetic resonance imaging and spectroscopy for the determination of cardiac function, myocardial fibrosis, and myocardial lipid content. A total of 129 participants were included in this analysis. Compared with age-matched control subjects (n=39; 30.23%), HIV-infected subjects undergoing combination antiretroviral therapy (n=90; 69.77%) had 47% higher median myocardial lipid levels (P <0.003) and 74% higher median plasma triglyceride levels (both P<0.001). Myocardial fibrosis, predominantly in the basal inferolateral wall of the left ventricle, was observed in 76% of HIV-infected subjects compared with 13% of control subjects (P<0.001). Peak myocardial systolic and diastolic longitudinal strain were also lower in HIV-infected individuals than in control subjects and remained statistically significant after adjustment for available confounders. CONCLUSIONS: Comprehensive cardiac imaging revealed cardiac steatosis, alterations in cardiac function, and a high prevalence of myocardial fibrosis in a contemporary group of asymptomatic HIV-infected subjects undergoing combination antiretroviral therapy. Cardiac steatosis and fibrosis may underlie cardiac dysfunction and increased cardiovascular morbidity and mortality in subjects with HIV.
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Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Infecções por HIV/complicações , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Adulto , Antirretrovirais/uso terapêutico , Cardiomiopatias/patologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fibrose , Infecções por HIV/tratamento farmacológico , Coração/fisiopatologia , Humanos , Metabolismo dos Lipídeos/fisiologia , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , PrevalênciaRESUMO
BACKGROUND: Before considering whether to use a multivariable (diagnostic or prognostic) prediction model, it is essential that its performance be evaluated in data that were not used to develop the model (referred to as external validation). We critically appraised the methodological conduct and reporting of external validation studies of multivariable prediction models. METHODS: We conducted a systematic review of articles describing some form of external validation of one or more multivariable prediction models indexed in PubMed core clinical journals published in 2010. Study data were extracted in duplicate on design, sample size, handling of missing data, reference to the original study developing the prediction models and predictive performance measures. RESULTS: 11,826 articles were identified and 78 were included for full review, which described the evaluation of 120 prediction models. in participant data that were not used to develop the model. Thirty-three articles described both the development of a prediction model and an evaluation of its performance on a separate dataset, and 45 articles described only the evaluation of an existing published prediction model on another dataset. Fifty-seven percent of the prediction models were presented and evaluated as simplified scoring systems. Sixteen percent of articles failed to report the number of outcome events in the validation datasets. Fifty-four percent of studies made no explicit mention of missing data. Sixty-seven percent did not report evaluating model calibration whilst most studies evaluated model discrimination. It was often unclear whether the reported performance measures were for the full regression model or for the simplified models. CONCLUSIONS: The vast majority of studies describing some form of external validation of a multivariable prediction model were poorly reported with key details frequently not presented. The validation studies were characterised by poor design, inappropriate handling and acknowledgement of missing data and one of the most key performance measures of prediction models i.e. calibration often omitted from the publication. It may therefore not be surprising that an overwhelming majority of developed prediction models are not used in practice, when there is a dearth of well-conducted and clearly reported (external validation) studies describing their performance on independent participant data.
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Avaliação de Resultados em Cuidados de Saúde , Estudos de Validação como Assunto , Interpretação Estatística de Dados , Humanos , Prognóstico , Reprodutibilidade dos TestesRESUMO
Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (nâ=â871) and two de novo replication cohorts (nâ=â4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, pâ=â1.2×10(-41) and rs6258, pâ=â2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (pâ=â5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
Assuntos
Proteínas Nucleares/genética , Globulina de Ligação a Hormônio Sexual/genética , Testosterona/sangue , Adulto , Idoso de 80 Anos ou mais , Alelos , Índice de Massa Corporal , Cromossomos Humanos X/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level. METHODS: We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses. RESULTS: In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism. CONCLUSIONS: Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).
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Depressão/etiologia , Disfunção Erétil/etiologia , Fadiga/etiologia , Hipogonadismo/diagnóstico , Testosterona/deficiência , Atividades Cotidianas , Adulto , Idade de Início , Idoso , Europa (Continente)/epidemiologia , Inquéritos Epidemiológicos , Humanos , Hipogonadismo/sangue , Hipogonadismo/complicações , Hipogonadismo/epidemiologia , Libido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Testosterona/sangueRESUMO
BACKGROUND: the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH. SETTING: cross-sectional analysis within the European Male Ageing Study (EMAS). PARTICIPANTS: a total of 1,504 community-dwelling men aged 60-79 years. METHODS: frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models. RESULTS: using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26-1.67) and frail (ROR = 1.89; 95% CI: 1.30-2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01-1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH. CONCLUSION: lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further.
Assuntos
Envelhecimento/sangue , Idoso Fragilizado , Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Fatores Etários , Idoso , Biomarcadores/sangue , Estudos Transversais , Europa (Continente)/epidemiologia , Humanos , Vida Independente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologiaRESUMO
Our population is ageing, and obesity is increasing in the elderly bringing massive and rapidly changing burdens of ill health related to increased body weights and fat as well as the main drivers of poor diet and inactivity. Overweight and obesity, and a static body mass index (BMI) commonly conceal sarcopenia (gain in body fat but loss of muscle mass and functional capacity) in older people, aggravated by inactivity. A systematic computerized literature search using an iterative manipulation process of the keywords: obesity, elderly, weight loss. The following databases were accessed on 20 October 2010: Medline, Cochrane Collaboration, Ovid and Scholar Google. A large number of clinical consequences of overweight and obesity are particularly problematic for elderly individuals, including type 2 diabetes mellitus, arthritis, urinary incontinence and depression. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults has often been misinterpreted that obesity is not as harmful in the elderly. BMI may be a less appropriate index in the elderly. All the medical consequences of obesity are multi-factorial but all are alleviated by modest, achievable weight loss (5-10 kg) with an evidence-based maintenance strategy. Since sarcopenic obesity is common in the elderly, a combination of exercise and modest calorie restriction appears to be the optimal method of reducing fat mass and preserving muscle mass. Reduction in polypharmacy is a valuable target for weight management. Age is not an obstacle to weight management interventions using moderate calorie restriction and exercise, and the currently licensed drug orlistat appears to have no age-related hazards. Overall balance of clinical outcomes has not been evaluated. In older people the risks from bariatric surgery outweigh benefits. Obesity, and specifically sarcopenic obesity, should also be prevented not only from younger age, but also during major life transitions including retirement, to improve better health outcomes and quality of life in later years, with a focus on those in 'obese families', where the main increases in obesity are located. Randomized controlled trials to determine health benefits and risks from long-term weight management in obese elderly are necessary.
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Obesidade/complicações , Obesidade/terapia , Redução de Peso , Adulto , Idoso , Envelhecimento/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Qualidade de Vida , Adulto JovemRESUMO
INTRODUCTION: A study was undertaken to test the hypothesis that musculoskeletal pain is associated with low vitamin D levels but the relationship is explained by physical inactivity and/or other putative confounding factors. METHODS: Men aged 40-79 years completed a postal questionnaire including a pain assessment and attended a clinical assessment (lifestyle questionnaire, physical performance tests, 25-hydroxyvitamin D3 (25-(OH)D) levels from fasting blood sample). Subjects were classified according to 25-(OH)D levels as 'normal' (> or = 15 ng/ml) or 'low' (< 15 ng/ml). The relationship between pain status and 25-(OH)D levels was assessed using logistic regression. Results are expressed as ORs and 95% CIs. RESULTS: 3075 men of mean (SD) age 60 (11) years were included in the analysis. 1262 (41.0%) subjects were pain-free, 1550 (50.4%) reported 'other pain' that did not satisfy criteria for chronic widespread pain (CWP) and 263 (8.6%) reported CWP. Compared with patients who were pain-free, those with 'other pain' and CWP had lower 25-(OH)D levels (n=239 (18.9%), n=361 (23.3) and n=67 (24.1%), respectively, p<0.05). After adjusting for age, having 'other pain' was associated with a 30% increase in the odds of having low 25-(OH)D while CWP was associated with a 50% increase. These relationships persisted after adjusting for physical activity levels. Adjusting for additional lifestyle factors (body mass index, smoking and alcohol use) and depression attenuated these relationships, although pain remained moderately associated with increased odds of 20% of having low vitamin D levels. CONCLUSIONS: These findings have implications at a population level for the long-term health of individuals with musculoskeletal pain.
Assuntos
Doenças Musculoesqueléticas/etiologia , Dor/etiologia , Deficiência de Vitamina D/complicações , Adulto , Idoso , Envelhecimento/sangue , Calcifediol/sangue , Fatores de Confusão Epidemiológicos , Europa (Continente)/epidemiologia , Fibromialgia/sangue , Fibromialgia/epidemiologia , Fibromialgia/etiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Atividade Motora , Doenças Musculoesqueléticas/sangue , Doenças Musculoesqueléticas/epidemiologia , Dor/sangue , Dor/epidemiologia , Medição da Dor/métodos , Prevalência , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologiaRESUMO
BACKGROUND: Although there is evidence that vitamin D inadequacy may be linked to adverse cognitive outcomes, results from studies on this topic have been inconsistent. The aim of this trial was to examine the association between 25-hydroxyvitamin D (25(OH)D) levels and cognitive performance in middle-aged and older European men. METHODS: This population-based cross-sectional study included 3,369 men aged 40-79 years from eight centres enrolled in the European Male Ageing Study. Cognitive function was assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Camden Topographical Recognition Memory (CTRM) test and the Digit Symbol Substitution Test (DSST). Serum 25(OH)D levels were measured by radioimmunoassay. Additional assessments included measurement of physical activity, functional performance and mood/depression. Associations between cognitive function and 25(OH)D levels were explored using locally weighted and linear regression models. RESULTS: In total, 3,133 men (mean (+/-SD) age 60+/-11 years) were included in the analysis. The mean (+/-SD) 25(OH)D concentration was 63+/-31 nmol/l. In age-adjusted linear regressions, high levels of 25(OH)D were associated with high scores on the copy component of the ROCF test (beta per 10 nmol/l = 0.096; 95% CI 0.049 to 0.144), the CTRM test (beta per 10 nmol/l = 0.075; 95% CI 0.026 to 0.124) and the DSST (beta per 10 nmol/l = 0.318; 95% CI 0.235 to 0.401). After adjusting for additional confounders, 25(OH)D levels were associated with only score on the DSST (beta per 10 nmol/l = 0.152; 95% CI 0.051 to 0.253). Locally weighted and spline regressions suggested the relationship between 25(OH)D concentration and cognitive function was most pronounced at 25(OH)D concentrations below 35 nmol/l. CONCLUSION: In this study, lower 25(OH)D levels were associated with poorer performance on the DSST. Further research is warranted to determine whether vitamin D sufficiency might have a role in preserving cognitive function in older adults.
Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Memória/fisiologia , Desempenho Psicomotor/fisiologia , Vitamina D/análogos & derivados , Adulto , Afeto/fisiologia , Idoso , Envelhecimento/sangue , Estudos Transversais , Europa (Continente) , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Testes Neuropsicológicos , Radioimunoensaio , Fatores de Risco , Vitamina D/sangueRESUMO
Life expectancy is increasing in most developed countries, in part due to improved socioeconomic conditions and in part to advances in healthcare. It is widely acknowledged that the promotion of healthy ageing by delaying, minimizing or preventing disabilities or diseases is one of the most important public health objectives in this century. In contrast to the menopausal transition in females, we know relatively little about the contribution of androgens and anabolic hormones to the quality of ageing in men. The European Male Ageing Study (EMAS) is a multicentre prospective cohort designed to examine the prevalence, incidence and geographical distribution of gender-specific and general symptoms of ageing in men, including their endocrine, genetic and psychosocial predictors. Men aged 40-79 years were recruited from eight European centres: Florence (Italy), Leuven (Belgium), Lodz (Poland), Malmö (Sweden), Manchester (UK), Santiago de Compostela (Spain), Szeged (Hungary) and Tartu (Estonia). Subjects were recruited from population registers and those who agreed to take part completed a detailed questionnaire including aspects of personal and medical history, lifestyle factors and sexual function. Objective measures of body size, cognition, vision, skeletal health and neuromuscular function were obtained. Blood and DNA specimens were collected for a range of biochemical and genetic analyses. After an average of 4 years, it is planned to resurvey the participants with similar assessments. A total of 3369 men with a mean age of 60 +/- 11 years were recruited. The mean centre response rate was 43%, and highest in those aged 50-59 years. Those who participated were marginally younger than those who were invited but declined to participate (60.0 vs. 61.1 years). Participants left education slightly later than a sample of non-participants, though there were no consistent differences in levels of general health, physical activity, or smoking. EMAS will provide new population-based data concerning the main features that characterize ageing in men and its critical determinants, particularly with reference to age-related changes in hormone levels. Such information is an important prerequisite to develop effective strategies to reduce age-related disabilities and optimise health and well-being into old-age.
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Envelhecimento/fisiologia , Adulto , Idoso , Antropometria , Densidade Óssea , Estudos de Coortes , Registros de Dieta , Europa (Continente) , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , Estudos de Amostragem , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: We determined levels of cognitive functioning in community dwelling men aged 40-79 (n = 3265) from eight European centres and investigated to what extent cognitive performance varied between centres, the association between different cognitive domains and age, educational level, co-morbidity and lifestyle factors and the respective contributions of centre and individual factors to cognitive performance. METHODS: Cognitive domains assessed were visuo-constructional ability and visual memory (Rey-Osterrieth Complex Figure test, ROCF), topographical memory (Camden Topographical Recognition Memory test, CTRM) and processing speed (Digit-Symbol Substitution test, DSST). RESULTS: There were significant between-centre differences in all four cognitive test scores. Using multilevel linear regression analysis (MLRA), age, education, depression, physical performance and smoking were independent predictors of cognitive function and these variables explained 10-13% of the variation in cognitive scores between centres and 17-36% of the variation in scores between individuals within centres. CONCLUSION: Our data suggest that although a proportion of the variance in cognitive function among European men is explained by individual level differences, a significant proportion is due to contextual phenomenon. Such contextual factors need to be considered when analysing multi-centre data and European men should not be treated as homogeneous when assessing cognitive performance using existing instruments.
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Transtornos Cognitivos/epidemiologia , Adulto , Fatores Etários , Idoso , Escolaridade , Europa (Continente)/epidemiologia , Nível de Saúde , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Inquéritos e QuestionáriosRESUMO
CONTEXT: The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. OBJECTIVE: The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men. DESIGN: This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40-79 yr from a prospective cohort study in eight European countries. RESULTS: Four predictors were associated with distinct modes of altered function: 1) age: lower free T (FT; -3.12 pmol/liter.yr, P < 0.001) with raised LH, suggesting impaired testicular function; 2) obesity: lower total T (TT; -2.32 nmol/liter) and FT (-17.60 pmol/liter) for body mass index (BMI; > or = 25 to < 30 kg/m(2)) and lower TT (-5.09 nmol/liter) and FT (-53.72 pmol/liter) for BMI 30 kg/m(2) or greater (P < 0.001-0.01, referent: BMI < 25 kg/m(2)) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction; 3) comorbidity: lower TT (-0.80 nmol/liter, P < 0.01) with unchanged LH in younger men but higher LH in older men; and 4) smoking: higher SHBG (5.96 nmol/liter, P < 0.001) and LH (0.77 U/liter, P < 0.01) with increased TT (1.31 nmol/liter, P < 0.001) but not FT, compatible with a resetting of T-LH-negative feedback due to elevated SHBG. CONCLUSIONS: Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men.
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Envelhecimento/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Testículo/fisiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Comorbidade , Estudos Transversais , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Relação Cintura-QuadrilRESUMO
INTRODUCTION: Assessment of male sexual dysfunction has been the focus of substantial scientific effort. Less research has focused on the development of instruments for the measurement of sexual functioning in aging men. AIMS: The aims of this study were: (i) to characterize the psychometric properties of a new brief, reliable, and valid measure of male sexual functioning for use in a large population survey of middle-aged and elderly European men; and (ii) specifically, to determine whether the new instrument, the European Male Ageing Study-sexual function questionnaire (EMAS-SFQ), discriminates between men with high and low levels of circulating testosterone (T) (total T, free T, and bioavailable T). METHOD: One thousand six hundred men aged 40-79 years completed the self-administered EMAS-SFQ, the Beck depression inventory, and provided a blood sample for assessment of sex hormones. Eighty-five men aged 35-74 years completed the EMAS-SFQ twice, 2 weeks apart to examine the test-retest reliability of the instrument. MAIN OUTCOME MEASURES: Scores on the EMAS-SFQ in relation to age and T levels. RESULTS: Principal component analysis showed that the EMAS-SFQ had four distinct domains (overall sexual functioning [OSF], masturbation, sexual functioning-related distress, and change in sexual functioning). The instrument demonstrated excellent internal and test-retest reliability, as well as convergent, divergent, and discriminant validity. Men with the lowest levels of total, free, and bioavailable T reported lower OSF scores compared to men with the highest T levels. CONCLUSIONS: The EMAS-SFQ is a valid and reproducible instrument, sensitive to age and T levels. It should be suitable for the assessment of sexual health in population samples of men in epidemiological studies of aging.
Assuntos
Envelhecimento , Saúde do Homem , Comportamento Sexual , Inquéritos e Questionários , Adulto , Idoso , Ansiedade/epidemiologia , Europa (Continente) , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Estudos Prospectivos , Psicometria , Testosterona/sangueRESUMO
OBJECTIVE: Chronic musculoskeletal pain is common in older adults but the nature of its relationship with ageing is unclear. The objective for this study was to test the hypothesis that the onset of widespread pain would be associated with a decrease in healthy ageing. METHODS: Population-based prospective cohort study. A "healthy ageing" index was constructed across biomedical, physical, psychosocial and lay components. Analysis was performed with 2949 adults aged 50 years and over who had complete index scores at baseline, 3 and 6-year follow-ups. RESULTS: At three and six year follow-up, 365 (16.8%) and 259 (14.3%) experienced the onset of widespread pain. The onset of widespread pain during the six-year period was associated with a 25% and a 46% decrease in healthy ageing index scores; this decrease was independent of age, sex, education, social networks, smoking status, alcohol consumption and physical inactivity. The decrease in healthy ageing attenuated to 20% and 39% following adjustment for diagnosed musculoskeletal conditions and analgesic and non-steroidal use. CONCLUSIONS: The onset of widespread pain was associated with a decrease in healthy ageing throughout the six-year period. When pain increased over time, the markers of unhealthy ageing increased also. Strong analgesia was associated with unhealthy ageing. Research could now usefully test whether early identification, improved treatment and prevention of pain prior to old age may facilitate healthy ageing.
Assuntos
Envelhecimento , Dor Musculoesquelética/diagnóstico , Idoso , Feminino , Seguimentos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Qualidade de Vida , Projetos de Pesquisa , Inquéritos e QuestionáriosRESUMO
BACKGROUND: For a randomized trial, the primary publication is usually the one which reports the results of the primary outcome and provides consolidated data from all study centers. Other aspects of a randomized trial's findings (that is, non-primary results) are often reported in subsequent publications. METHODS: We carried out a cross-sectional review of the characteristics and type of information reported in non-primary reports (n = 69) of randomized trials (indexed in PubMed core clinical journals in 2009) and whether they report pre-specified or exploratory analyses. We also compared consistency of information in non-primary publications with that reported in the primary publication. RESULTS: The majority (n = 56; 81%) of non-primary publications were large, multicenter trials, published in specialty journals. Most reported subgroup analyses (n = 27; 39%), analyzing a specific subgroup of patients from the randomized trial, or reported on secondary outcomes (n = 29; 42%); 19% (n = 13) reported extended follow-up. Less than half reported details of trial registration (n = 30; 43%) or the trial protocol (n = 27; 39%) and in 41% (n = 28) it was unclear from reading the abstract that the report was not the primary publication for the trial. Non-primary publications often analyzed and reported multiple different outcomes (16% reported >20 outcomes) and in 10% (n = 7) it was unclear how many outcomes had actually been assessed; in 42% (n = 29) it was unclear whether the analyses reported were pre-specified or exploratory. Only 39% (n = 27) of non-primary publications described the primary outcome of the randomized trial, 6% (n = 4) reported its numerical results and 9% (n = 6) details of how participants were randomized. CONCLUSION: Non-primary publications often lack important information about the randomized trial and the type of analyses conducted and whether these were pre-specified or exploratory to enable readers to accurately identify and assess the validity and reliably of the study findings. We provide recommendations for what information authors should include in non-primary reports of randomized trials.
Assuntos
Publicações Periódicas como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Acesso à Informação , Bibliometria , Estudos Transversais , Humanos , Disseminação de Informação , Estudos Multicêntricos como Assunto/métodos , Reprodutibilidade dos TestesRESUMO
The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance.
Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Sexualidade/fisiologia , Testosterona/fisiologia , Adulto , Idoso , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , População BrancaRESUMO
Few studies have directly compared the ability of the most commonly used models of frailty to predict mortality among community-dwelling individuals. Here, we used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to predict mortality in the EMAS. Participants were aged 40-79 years (n=2929) at baseline and 6.6% (n=193) died over a median 4.3 years of follow-up. The FI was generated from 39 deficits, including self-reported health, morbidities, functional performance and psychological assessments. The FP and FS consisted of five phenotypic criteria and both categorized individuals as robust when they had 0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI increased linearly with age (r(2)=0.21) and in Cox regression models adjusted for age, center, smoking and partner status the hazard ratio (HR) for death for each unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP or FS definitions, had a significantly increased risk of death compared to their robust counterparts. Compared to robust men, those who were FP frail at baseline had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All three frailty models significantly predicted future mortality among community-dwelling, middle-aged and older European men after adjusting for potential confounders. Our data suggest that the choice of frailty model may not be of paramount importance when predicting future risk of death, enabling flexibility in the approach used.
Assuntos
Idoso Fragilizado/estatística & dados numéricos , Mortalidade , Atividades Cotidianas , Adulto , Fatores Etários , Idoso , Europa (Continente)/epidemiologia , Nível de Saúde , Humanos , Estimativa de Kaplan-Meier , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Modelos Estatísticos , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar/mortalidade , Inquéritos e Questionários , Análise de SobrevidaRESUMO
BACKGROUND: There has been little research on how late-life frailty interrelates with sexual health. Our objective was to examine the association of frailty with sexual functioning and satisfaction among older men. METHODS: The study population consisted of 1,504 men aged 60 to 79 years, participating in the European Male Aging Study. Self-report questionnaires measured overall sexual functioning, sexual function-related distress, and erectile dysfunction. Frailty status was defined using a phenotype (FP) or index (FI). Associations between frailty and sexual function were explored using regression models. RESULTS: Based on the frailty phenotype, 5% of men were classified as frail, and the mean frailty index was 0.18 (SD = 0.12). Frailty was associated with decreasing overall sexual functioning and increasing sexual function-related distress in multiple linear regressions adjusted for age, smoking, alcohol consumption, living arrangements, comorbidities, and depression. Frailty was also associated with an increased odds of erectile dysfunction after adjustment for the same confounders: odds ratio = 1.99 (95% confidence interval = 1.14, 3.48) and 4.08 (95% confidence interval = 2.63, 6.36) for frailty phenotype and frailty index, respectively. CONCLUSIONS: Frailty was associated with impaired overall sexual functioning, sexual function-related distress, and erectile dysfunction. Individuals assessed for frailty-related deficits may also benefit from an appraisal of sexual health as an important aspect of well-being and quality of life.
Assuntos
Disfunção Erétil/epidemiologia , Idoso Fragilizado , Qualidade de Vida , Saúde Reprodutiva , Idoso , Avaliação Geriátrica/métodos , Humanos , Masculino , Satisfação Pessoal , Fatores de Risco , Autorrelato , Inquéritos e Questionários , Reino Unido/epidemiologia , População Branca/estatística & dados numéricosRESUMO
OBJECTIVE: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. DESIGN AND METHODS: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E(2)) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. RESULTS: In univariate analyses, free T levels were lower (P=0.02) and E(2) and LH levels were higher (P<0.05) in men with vitamin D deficiency (25(OH)D <50ânmol/l). 25(OH)D was positively associated with total and free T and negatively with E(2) and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001). CONCLUSIONS: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.