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    Subclinical Hypothyroidism

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    IMPORTANCE Subclinical hypothyroidism, defined as an elevated serum thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine (FT4) affects up to 10% of the adult population. OBSERVATIONS Subclinical hypothyroidism is most often caused by autoimmune (Hashimoto) thyroiditis.However, serum thyrotropin levels rise as people without thyroid disease age; serum thyrotropin concentrations may surpass the upper limit of the traditional reference range of 4 to 5mU/L among elderly patients. This phenomenon has likely led to an overestimation of the true prevalence of subclinical hypothyroidism in persons older than 70 years. In patients who have circulating thyroid peroxidase antibodies, there is a greater risk of progression from subclinical to overt hypothyroidism. Subclinical hypothyroidism may be associated with an increased risk of heart failure, coronary artery disease events, and mortality from coronary heart disease. In addition, middle-aged patients with subclinical hypothyroidism may have cognitive impairment, nonspecific symptoms such as fatigue, and altered mood. In the absence of large randomized trials showing benefit from levothyroxine therapy, the rationale for treatment is based on the potential for decreasing the risk of adverse cardiovascular events and the possibility of preventing progression to overt hypothyroidism.However, levothyroxine therapymay be associated with iatrogenic thyrotoxicosis, especially in elderly patients, and there is no evidence that it is beneficial in persons aged 65 years or older. CONCLUSIONS AND RELEVANCE Subclinical hypothyroidism iscommonand most individuals can be observed without treatment. Treatment might be indicated for patients with subclinical hypothyroidism and serum thyrotropin levels of 10mU/L or higher or for young and middle-aged individuals with subclinical hypothyroidism and symptoms consistent with mild hypothyroidis

    Subclinical hypothyroidism in older individuals

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    Subclinical hypothyroidism, which is defined as a thyroid-stimulating hormone concentration higher than the reference range (generally 4·5 mIU/L or higher) with normal free thyroxine concentrations, is frequently found in older individuals. International guidelines differ in recommendations for management of subclinical hypothyroidism in older individuals. We assessed published data during the past decade on the clinical significance and treatment of subclinical hypothyroidism in individuals aged 65 years and older. Meta-analyses, randomised clinical trials, and cohort studies are discussed in this narrative Review. Studies showed no significantly increased incidence in adverse cardiovascular, musculoskeletal, or cognitive outcomes in individuals aged 65 years or older when serum thyroid-stimulating hormone concentration was 4·5–7·0 mIU/L versus a euthyroid group. Moreover, in older individuals with subclinical hypothyroidism, symptoms of hypothyroidism and cardiac and bone parameters did not improve after levothyroxine treatment. These data suggest that treatment with levothyroxine should be considered for individuals aged 65 years or older with subclinical hypothyroidism when thyroid-stimulating hormone concentration is persistently 7 mIU/L or higher and to not initiate treatment with thyroid-stimulating hormone concentrations of less than 7 mIU/L. Levothyroxine doses should be personalised according to age, comorbidities, and life expectancy

    Association of IGF-I levels with muscle strength and mobility in older women

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    The functional consequences of the age-associated decline in IGF-I are unknown. We hypothesized that low IGF-I levels in older women would be associated with poor muscle strength and mobility. We assessed this question in a population representative of the full spectrum of health in the community, obtaining serum IGF-I levels from women aged 70-79 yr, enrolled in the Women's Health and Aging Study I or II. Cross-sectional analyses were performed using 617 women with IGF-I levels drawn within 90 d of measurement of outcomes. After adjustment for age, there was an association between IGF-I and knee extensor strength (P = 0.004), but not anthropometry or other strength measures. We found a positive relationship between IGF-I levels and walking speed for IGF-I levels below 50 microg/liter (P < 0.001), but no relationship above this threshold. A decline in IGF-I level was associated with self-reported difficulty in mobility tasks. All findings were attenuated after multivariate adjustment. In summary, in a study population including frail and healthy older women, low IGF-I levels were associated with poor knee extensor muscle strength, slow walking speed, and self-reported difficulty with mobility tasks. These findings suggest a role for IGF-I in disability as well as a potential target population for interventions to raise IGF-I levels

    Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women

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    The physiology of age-related functional decline is poorly understood, but may involve hormones and inflammation. We hypothesized that older women with both low IGF-I and high IL-6 levels are at high risk for disability and death. We assessed walking speed and disability in 718 women enrolled in the Women's Health and Aging Study I, a 3-yr cohort study with 5-yr mortality follow-up. Women with IGF-I levels in the lowest quartile and IL-6 levels in the highest quartile had significantly greater limitation in walking and disability in mobility tasks and instrumental activities of daily living than those with neither risk factor (adjusted odds ratios, 10.77, 5.14, and 3.66). Women with both risk factors were at greater risk for death (adjusted relative risk, 2.10) as well as incident walking limitation, mobility disability, and disability in activities of daily living compared with those with high IGF-I and low IL-6 levels. The combination of low IGF-I and high IL-6 levels confers a high risk for progressive disability and death in older women, suggesting an aggregate effect of dysregulation in endocrine and immune systems. The joint effects of IGF-I and IL-6 may be important targets for treatments to prevent or minimize disability associated with aging

    Diabetes, hyperglycaemia and mortality in disabled older women: The Women's Health and Ageing Study I

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    AIMS: Diabetes is associated with increased mortality in older adults, but the specific contributions of diabetes-associated clinical conditions and of increasing hyperglycaemia to mortality risk are unknown. We evaluated whether cardiovascular disease, comorbidities, or degree of hyperglycaemia, particularly severe hyperglycaemia, affected diabetes-related mortality risk in older, disabled women. METHODS: Six-year mortality follow-up of a random sample of 576 disabled women (aged 65-101 years), recruited from the Medicare eligibility list in Baltimore (MD, USA). All-cause and cardiovascular mortality were evaluated by diabetes status: no diabetes; diabetes with mild, moderate, and severe hyperglycaemia [defined by tertiles of glycosylated haemoglobin (GHB) among women with diabetes]. RESULTS: Diabetes with mild, moderate, and severe hyperglycaemia was associated with an increased hazard rate (HR) for all-cause mortality, even after adjustment for demographics, risks for cardiovascular disease, cardiovascular and non-cardiovascular conditions, and other known mortality risks. A dose-response effect was suggested [mild hyperglycaemia, HR 1.81, 95% confidence interval (CI) 1.03, 3.17; moderate hyperglycaemia, HR 2.02, 95% CI 1.34, 3.57; severe hyperglycaemia, HR 2.22, 95% CI 1.17, 4.25]. Women with diabetes had a significantly increased HR for non-cardiovascular death, but not for cardiovascular death, compared with those without diabetes. CONCLUSIONS: Diabetes, whether characterized by mild, moderate or severe hyperglycaemia, appears to be an independent risk factor for excess mortality in older disabled women and this risk may increase with increasing hyperglycaemia. This mortality risk is not completely explained by vascular complications, and involves non-cardiovascular deaths. Risks and benefits of diabetes management, including glycaemic control and management of vascular and other comorbidities, should be studied in older people with complications and comorbidities

    Serum Thyroxine Level and Cognitive Decline in Euthyroid Older Women

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    BACKGROUND: Clinical and subclinical hypothyroidism is associated with cognitive impairment. OBJECTIVE: This study investigated the association between thyroxine (T(4)) and thyroid-stimulating hormone (TSH) level and change over time in cognitive performance in a sample of older women with normal thyroid gland function. METHODS: T(4) and TSH were measured at baseline in 628 women (> or = 65 years) enrolled in the Women's Health and Aging Study, a community-based study of physically impaired women. Cognitive function was assessed at baseline and after 1, 2, and 3 years, using the Mini-Mental State Examination (MMSE). Incident cognitive decline was defined as a decrease of more than one point/year in MMSE score between baseline and the end of the follow-up. The analysis included 464 subjects with normal thyroid gland function with a baseline and at least one follow-up MMSE. RESULTS: At baseline there was no association between T(4) and TSH level and cognitive function. In longitudinal analysis, adjusting for age, race, level of education, and other covariates, compared with women in the highest T(4) tertile (8.1 to 12.5 microg/dL), those in the lowest tertile (4.5 to 6.5 microg/dL) had a greater decline in MMSE score (-0.25 point/year vs -0.12 point/year; p = 0.04). A total of 95 women (20.5%) had cognitive decline during the study period (mean MMSE decline, 5.5 points). Compared with women in the highest T(4) tertile, those in the lowest tertile had a twofold risk of cognitive decline (adjusted relative risk, 1.97; 95% CI, 1.10 to 3.50). The results were not modified by baseline cognitive and physical function. There was no association between baseline TSH level and change in cognitive function. CONCLUSIONS: In older women, low T(4) levels, within the normal range, were associated with a greater risk of cognitive decline over a 3-year period. Thyroid hormone levels may contribute to cognitive impairment in physically impaired women

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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