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1.
Diagn Microbiol Infect Dis ; : 115004, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32156450

RESUMO

We report a case of pulmonary mucormycosis in a patient with T-cell acute lymphoblastic leukemia. The diagnosis of mucormycosis was initially based on mycological examination of a pulmonary specimen. However, we describe how it could have been made 2 months earlier using polymerase chain reaction assays targeting Mucorales species on serum specimens.

2.
Brain Imaging Behav ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32141032

RESUMO

Brain-predicted age difference scores are calculated by subtracting chronological age from 'brain' age, which is estimated using neuroimaging data. Positive scores reflect accelerated ageing and are associated with increased mortality risk and poorer physical function. To date, however, the relationship between brain-predicted age difference scores and specific cognitive functions has not been systematically examined using appropriate statistical methods. First, applying machine learning to 1359 T1-weighted MRI scans, we predicted the relationship between chronological age and voxel-wise grey matter data. This model was then applied to MRI data from three independent datasets, significantly predicting chronological age in each dataset: Dokuz Eylül University (n = 175), the Cognitive Reserve/Reference Ability Neural Network study (n = 380), and The Irish Longitudinal Study on Ageing (n = 487). Each independent dataset had rich neuropsychological data. Brain-predicted age difference scores were significantly negatively correlated with performance on measures of general cognitive status (two datasets); processing speed, visual attention, and cognitive flexibility (three datasets); visual attention and cognitive flexibility (two datasets); and semantic verbal fluency (two datasets). As such, there is firm evidence of correlations between increased brain-predicted age differences and reduced cognitive function in some domains that are implicated in cognitive ageing.

3.
J Am Geriatr Soc ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170869

RESUMO

BACKGROUND/OBJECTIVES: Little work to date has examined the relationship between gait performance and blood pressure (BP) recovery after standing in later life. The aim of this study is to clarify the association of orthostatic BP with spatiotemporal gait parameters in a large cohort of older people. DESIGN: Cross-sectional study using multilevel linear regression to ascertain the difference in orthostatic BP patterns across tertiles of gait speed, and linear regression to analyze the association of orthostatic hypotension 30 seconds after standing (OH-30) with specific gait characteristics. SETTING: The Irish Longitudinal Study on Ageing. PARTICIPANTS: A total of 4311 community-dwelling adults, aged 50 years or older (mean age = 62.2 years; 54% female), one fifth (n = 791) of whom had OH-30. MEASUREMENTS: Continuous orthostatic BP was measured during active stand. OH-30 was defined as a drop in systolic BP of 20 mm Hg or more or drop in diastolic BP of 10 mm Hg or more at 30 seconds. Spatiotemporal gait was assessed using the GAITRite system, reporting gait speed, step length, step width, and double support time in both single and dual (cognitive task) conditions. RESULTS: OH-30 was associated with slower gait speed (ß = -3.01; 95% confidence interval [CI] = -4.46 to -1.56) and shorter step length (ß = -.73; 95% CI = -1.29 to -.16) in fully adjusted models during single task walking. Similar findings were observed in dual task conditions, in addition to increased double support phase (ß = .45; 95% CI = .02-.88). Multilevel models demonstrated that participants in the slowest tertile for gait speed had a significantly larger drop in systolic BP poststanding compared to those with faster gait speeds in single and dual task conditions. CONCLUSIONS: This study demonstrates that slower recovery of BP after standing is independently associated with poorer gait performance in community-dwelling older adults. Given the adverse outcomes independently associated with OH and gait problems in later life, increasing awareness that they commonly coexist is important, particularly as both are potentially modifiable.

4.
Parasite ; 27: 7, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32031519

RESUMO

BACKGROUND: Primary infection by Toxoplasma gondii in pregnant women can result in serious outcomes for the foetus. A false-positive IgG result during pregnancy can lead to a misdiagnosis of past infection and to stopping preventive measures. We collected 189 sera with positive Architect® Toxo IgG assay (Abbott Laboratories) and negative IgG results with at least two other serological tests, in order to find an explanation for the suspected false-positive IgG results. We used the recomLine Toxoplasma IgG® immunoblot (Mikrogen Diagnostik) to search for specific antigenic reactivities of the sera, and the LDBio Toxo II IgG® immunoblot (LDBio Diagnostics) as a confirmatory test. RESULTS: The bands GRA8 and/or GRA7 were positive for 148 samples (78.3%). GRA8 was the most frequent band, appearing in 133 patterns (70.4%), whereas GRA7 was present for 49 samples (25.9%). Of the 81 samples tested with LDBio®, 23 (28.4%) turned out to be positive. Of the 58 negative LDBio® tests (71.6%) (real false-positive Architect® IgG), 23 samples (39.6%) did not show either a GRA8 or p30 band by recomLine®. Their false positivity with Architect® remains unexplained since Abbott uses these two recombinant antigens for their assay. CONCLUSIONS: The Architect® IgG false positivity for T. gondii seems to be due to reactivity against GRA8 for the majority of the sera and GRA7 to a lesser extent. The hypothesis of past contact with parasites genetically close to T. gondii such as Hammondia hammondi or Neospora caninum seems promising and should be assessed further.

5.
Bioorg Med Chem Lett ; 30(7): 126955, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32035698

RESUMO

This article describes the discovery of aryl hydroxy pyrimidinones and the medicinal chemistry efforts to optimize this chemotype for potent APJ agonism. APJ is a G-protein coupled receptor whose natural agonist peptide, apelin, displays hemodynamic improvement in the cardiac function of heart failure patients. A high throughput screen was undertaken to identify small molecule hits that could be optimized to mimic the apelin in vitro response. A potent and low molecular weight aryl hydroxy pyrimidinone analog 30 was identified through optimization of an HTS hit and medicinal chemistry efforts to improve its properties.

6.
BMC Health Serv Res ; 20(1): 118, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059722

RESUMO

BACKGROUND: End-of-life experience is a subject of significant policy interest. National longitudinal studies offer valuable opportunities to examine individual-level experiences. Ireland is an international leader in palliative and end-of-life care rankings. We aimed to describe the prevalence of modifiable problems (pain, falls, depression) in Ireland, and to evaluate associations with place of death, healthcare utilisation, and formal and informal costs in the last year of life. METHODS: The Irish Longitudinal Study on Ageing (TILDA) is a nationally representative sample of over-50-year-olds, recruited in Wave 1 (2009-2010) and participating in biannual assessment. In the event of a participant's death, TILDA approaches a close relative or friend to complete a voluntary interview on end-of-life experience. We evaluated associations using multinomial logistic regression for place of death, ordinary least squares for utilisation, and generalised linear models for costs. We identified 14 independent variables for regressions from a rich set of potential predictors. Of 516 confirmed deaths between Waves 1 and 3, the analytic sample contained 375 (73%) decedents for whom proxies completed an interview. RESULTS: There was high prevalence of modifiable problems pain (50%), depression (45%) and falls (41%). Those with a cancer diagnosis were more likely to die at home (relative risk ratio: 2.5; 95% CI: 1.3-4.8) or in an inpatient hospice (10.2; 2.7-39.2) than those without. Place of death and patterns of health care use were determined not only by clinical need, but other factors including age and household structure. Unpaid care accounted for 37% of all care received but access to this care, as well as place of death, may be adversely affected by living alone or in a rural area. Deficits in unpaid care are not balanced by higher formal care use. CONCLUSIONS: Despite Ireland's well-established palliative care services, clinical need is not the sole determinant of end-of-life experience. Cancer diagnosis and access to family supports were additional key determinants. Future policy reforms should revisit persistent inequities by diagnosis, which may be mitigated through comprehensive geriatric assessment in hospitals. Further consideration of policies to support unpaid carers is also warranted.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32043687

RESUMO

OBJECTIVE: The potential role of education attained after the age of 50, for example, vocational training or recreational courses, in cognitive reserve has been unexplored. We examined the cross-sectional and prospective associations between late life education (LLE) and global cognitive function in older adults. METHODS: A total of 5306 participants (50+ years) in The Irish Longitudinal Study of Ageing answered questions about highest level of education completed and LLE (2010). Cognitive function was defined as the number of errors on the Montreal cognitive assessment (MoCA) assessed in 2010 and 2014. The association between LLE and MoCA-errors was examined using Poisson regression stratified by level of education. Sensitivity analyses were done to examine reverse causation and selection bias. RESULTS: In those with primary/no (n = 1312, incidence rate ratio [IRR] = 0.83, 95%CI = 0.70-0.99) and secondary education (n = 2208, IRR = 0.88, 95%CI = 0.80-0.97), but not tertiary education (n = 1786, IRR = 0.93, CI = 0.86-1.00), participating in LLE was associated with lower rate of MoCA errors. The prospective association between LLE and 4-year change in MoCA-errors was (borderline) statistically significant in those with primary/no education only (IRR = 0.86, CI = 0.74-1.00). Sensitivity analyses supported robustness of the findings. CONCLUSIONS: LLE may contribute to cognitive reserve and be a useful intervention to mitigate the increased risk of cognitive decline associated with low levels of education.

8.
Eur J Intern Med ; 72: 73-78, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31706708

RESUMO

BACKGROUND: Older people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to cognitive and psychomotor effects. BDZs may also have hypotensive effects. We investigated the association between BDZs and orthostatic blood pressure behaviour in older people. METHODS: We retrospectively analysed data from an outpatient clinic where people aged 60 or older underwent a geriatric assessment. Non-invasive beat-to-beat orthostatic systolic blood pressure (SBP) was assessed at regular time intervals before and after an active stand test. We compared clinical characteristics between BDZs users and non-users and also investigated if BDZs use was an independent predictor of baseline SBP. Factors associated with SBP change were investigated using a repeated measures general linear model. RESULTS: Of 538 participants (67.7% female, mean age 72.7), 33 (6.1%) reported regular BDZs use. BDZ users had lower baseline SBP (149 versus 161 mmHg, P < 0.05). Multiple linear regression confirmed BDZs use as independent predictor of baseline SBP in N = =538. At 10 s post-stand, the SBP difference between BDZs use groups became maximum (21 mmHg); at this point, SBP still seemed to be decreasing in BDZ-users, whereas in controls it seemed to be recovering. After adjustment (age, sex, hypertension, frailty, comorbidity, antihypertensives), BDZs were associated with greater SBP reduction between baseline and 10 s post-stand (P < 0.05). CONCLUSION: Older people taking BDZs may have a higher risk of orthostatic hypotension, perhaps due to an exaggerated immediate BP drop. This adds to other BDZ-related falls risks. BDZs should be avoided in older people at risk of falling.

9.
Qual Life Res ; 29(3): 733-743, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31676970

RESUMO

PURPOSE: Quality-adjusted life years (QALYs) represent a critical metric in economic evaluations impacting key healthcare decisions in many countries. However, there is widespread disagreement as to which is the best of the health state utility (HSU) instruments that are designed to measure the Q in the QALY. Instruments differ in their descriptive systems as well as their valuation methodologies; that is, they simply measure different things. We propose a visual framework that can be utilized to make meaningful comparisons across HSU instruments. METHODS: The framework expands on existing HRQoL models, by incorporating four distinctive continua, and by putting HRQoL within the broader notion of subjective well-being (SWB). Using this conceptual map, we locate the five most widely used HSU-instruments (EQ-5D, SF-6D, HUI, 15D, AQoL). RESULTS: By individually mapping dimensions onto this visual framework, we provide a clear picture of the significant conceptual and operational differences between instruments. Moreover, the conceptual map demonstrates the varying extent to which each instrument moves outside the traditional biomedical focus of physical health, to also incorporate indicators of mental health and social well-being. CONCLUSION: Our visual comparison provides useful insights to assess the suitability of different instruments for particular purposes. Following on from this comparative analyses, we extract some important lessons for a new instrument that cover the domains of physical, mental and social aspects of health, i.e. it is in alignment with the seminal 1948 WHO definition of health.

10.
J Gerontol A Biol Sci Med Sci ; 75(3): 495-503, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-31603985

RESUMO

Allostatic load (AL) and epigenetic clocks both attempt to characterize the accelerated aging of biological systems, but at present it is unclear whether these measures are complementary or distinct. This study examines the cross-sectional association of AL with epigenetic age acceleration (EAA) in a subsample of 490 community-dwelling older adults participating in The Irish Longitudinal study on Aging (TILDA). A battery of 14 biomarkers representing the activity of four different physiological systems: immunological, cardiovascular, metabolic, renal, was used to construct the AL score. DNA methylation age was computed according to the algorithms described by Horvath, Hannum, and Levine allowing for estimation of whether an individual is experiencing accelerated or decelerated aging. Horvath, Hannum, and Levine EAA correlated 0.05, 0.03, and 0.21 with AL, respectively. Disaggregation by sex revealed that AL was more strongly associated with EAA in men compared with women as assessed using Horvath's clock. Metabolic dysregulation was a strong driver of EAA in men as assessed using Horvath and Levine's clock, while metabolic and cardiovascular dysregulation were associated with EAA in women using Levine's clock. Results indicate that AL and the epigenetic clocks are measuring different age-related variance and implicate sex-specific drivers of biological aging.

11.
J Am Med Dir Assoc ; 21(2): 240-247.e5, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31401047

RESUMO

OBJECTIVES: To examine the associations between 3 frailty instruments and circulating micronutrients in a large representative sample of older adults. DESIGN: Cross-sectional data from a nationally representative cohort study conducted between October 2009 and July 2011. PARTICIPANTS AND SETTING: Adults age ≥50 years (n = 4068) living in the community in Ireland. MEASUREMENTS: Circulating micronutrients (lutein, zeaxanthin, folate, vitamin B-12, and vitamin D) were measured, transformed, and standardized. Frailty was assessed using the Frailty Phenotype, the Frailty Index, and the FRAIL Scale (fatigue, resistance, ambulation, illnesses, and loss of weight), instruments. Multinomial logistic regression determined associations between micronutrients and prefrailty or frailty. Models were adjusted for sociodemographic, lifestyle, health, and seasonal factors. RESULTS: Adjusting for age, sex, and educational attainment, all 3 measures of frailty were associated with lower levels of lutein [relative risk ratios (RRRs): 0.43‒0.63], zeaxanthin (RRRs: 0.49‒0.63), and vitamin D (RRRs: 0.51‒0.75), and with the accumulation of micronutrient insufficiencies (RRRs: 1.42‒1.90). Attenuated but significant associations were also observed with all measures of prefrailty for lutein, vitamin D, and number of micronutrient insufficiencies. The associations with frailty persisted following additional adjustment for social, lifestyle, and health and seasonal factors, and following multiple test correction. CONCLUSIONS AND IMPLICATIONS: We have presented the most consistent evidence in the largest study to date that micronutrient concentrations are associated with prefrailty and frailty in older adults. Our data suggest that low micronutrient status has potential as an easily modifiable marker and intervention target for frailty and supports further investigation into micronutrient supplementation and fortification to prevent frailty and disability among older adults.

12.
J Am Geriatr Soc ; 68(1): 120-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31579942

RESUMO

OBJECTIVE: This study assessed the distribution and correlates of objective sleep duration in the older population in Ireland. DESIGN: Cross-sectional study using population-derived data from wave 3 of The Irish Longitudinal Study on Ageing. SETTING: Community-dwelling adults. PARTICIPANTS: Adults, aged 50 years and older, who wore an accelerometer for at least 4 days (N = 1533). MEASUREMENTS: Sleep was measured for at least 4 days in 1533 participants using a GENEActiv wrist-worn accelerometer device. Sleep parameters included total sleep time (TST) and self-reported sleep problems. TST was categorized as short and long sleep duration using US National Sleep Foundation guidelines. Linear and multinomial logistic regression models assessed sociodemographic, health, and behavioral correlates of sleep duration. RESULTS: Mean TST for the sample was 463 minutes (SD = 72.6 minutes). Of participants, 13.9% and 16.5% measured short and long sleep duration, respectively. TST decreased as sleep problems increased, as did durations recorded in summer compared to winter recordings. Advancing age was associated with longer sleep, as was antidepressant use. Retired/unemployed participants recorded longer TST and were more likely to record long sleep compared to employed participants. Fair/poor self-rated health and separated/divorced participants were more likely to record short sleep. Those reporting moderate or high physical activity were less likely to record short or long sleep, respectively, compared to those reporting low physical activity. Participants reporting a limiting disability were less likely to record long sleep. CONCLUSION: Average TST was within recommended guidelines; however, a significant subset of older adults recorded sleep duration outside of the guidelines. Independent demographic and health correlates of suboptimal sleep were identified, many of which are modifiable. Patients and clinicians should be aware of factors potentially influencing sleep patterns. Longitudinal analyses to confirm directionality of relationships with potential risk factors are warranted. J Am Geriatr Soc 68:120-128, 2019.

13.
Hypertension ; 75(2): 524-531, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838912

RESUMO

Assessment of the cerebrovascular and cardiovascular response to standing has prognostic value for a range of outcomes in the older adult population. Studies generally attempt to control for standing speed differences by asking participants to stand in a specified time but little is known about the range of transition times observed. This study aimed to characterize how standing speed associates with cardiovascular and cerebrovascular measures following transition from supine to standing. Continuous cerebral oxygenation, heart rate, systolic and diastolic blood pressure were monitored for 3 minutes after transitioning from supine to standing. An algorithm was used to calculate the time taken to transition from existing Finometer data (from the height correction unit). Linear mixed-effects models were used to assess the influence of transition time on each of the signals while adjusting for covariates. Transition time ranged from 2 to 27 s with 17% of participants taking >10 s to stand. Faster transition was associated with a more extreme decrease 10 s after standing but improved recovery at 20 s for cerebral oxygenation and blood pressure. Standing faster was associated with an elevated heart rate on initiation of stand and a quicker recovery 10 to 20 s after standing. The speed of transitioning from supine to standing position is associated with cardiovascular and cerebrovascular response in the early period after standing (<40 s). Care should be taken in the interpretation of findings which may be confounded by standing speed and statistical adjustment for standing time should be applied where appropriate.

14.
Am J Geriatr Psychiatry ; 28(3): 274-284, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31727515

RESUMO

OBJECTIVE: To examine if antidepressants at baseline are associated with falls and syncope over 4 years follow-up and if any observed associations are explained by baseline gait speed. DESIGN: Longitudinal study (three waves). SETTING: The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort study. PARTICIPANTS: Two thousand ninety-three community-dwelling adults aged ≥60 years. MEASUREMENTS: Antidepressants (ATC code "N06A") were identified. Recurrent falls (≥2 falls), injurious falls (requiring medical attention), unexplained falls, and syncope were reported at either Wave 2 or 3. Usual gait speed was the mean of two walks on a 4.88 m GAITRite walkway. Poisson regression analysis was used to examine associations between baseline antidepressant use and future falls adjusting for sociodemographics, physical, cognitive and mental health, and finally, gait speed. RESULTS: Compared to non-antidepressant users, those on antidepressants at baseline were more likely to report all types of falls (24.8-40.7% versus 9.8-18%) at follow-up. Antidepressants at baseline were independently associated with injurious falls (incidence risk ratio: 1.58, 95% confidence interval: 1.21, 2.06, z = 3.38, p = 0.001, df = 32) and unexplained falls (incidence risk ratio: 1.49, 95% confidence interval: 1.04, 2.15, z = 2.17, p = 0.030, df = 32) independent of all covariates including gait speed. CONCLUSION: There was little evidence to support the hypothesis that gait would (partly) explain any observed associations between baseline use of antidepressants and future falls. The underlying mechanisms of the observed relationships may be related to depression, vascular pathology, or direct effects of antidepressants. Clinicians should identify the best treatment option for an individual based on existing risk factors for outcomes such as falls.

15.
J Gerontol A Biol Sci Med Sci ; 75(2): 257-265, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30412218

RESUMO

Experimental evidence to date largely supports an association between the stress hormone cortisol and cognitive performance. Older adults, in particular, may be vulnerable to the neurotoxic effects of prolonged increases in cortisol; however, the assessment of chronic hormone levels has previously been challenging. Hair cortisol analysis has advantages over other cortisol metrics for this purpose as it facilitates the assessment of total hormone secretion over several months. Cortisol and cortisone were measured in the scalp hair of 1,876 older adults from The Irish Longitudinal Study on Ageing. Participants underwent a battery of cognitive tests assessing global function, memory, executive function, and processing speed. After adjustment for hair characteristics, demographics, metabolic risk factors, cardiovascular conditions, and depression, regression analysis revealed an inverse relationship of hair glucocorticoids to immediate (cortisol: ß = -.12, p = .032; cortisone: ß = -.021, p = .036) and delayed (cortisol: ß = -.13, p = .003; cortisone: ß = -.23, p = .006) word recall performance. They were also associated with more errors on the Mini-Mental State Examination (cortisol: incidence rate ratio (IRR) = 1.06, p = .008; cortisone: IRR = 1.14, p = .002) and Montreal Cognitive Assessment (cortisone: IRR = 1.06, p = .015). Higher hair glucocorticoids are inversely associated with memory and global cognition in a population-based sample of older adults. Future work should explore the prognostic significance of these findings.

16.
J Gerontol A Biol Sci Med Sci ; 75(2): 249-256, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30256900

RESUMO

Older adults are at increased risk of malnutrition, which is associated with poorer health, quality of life, and worse disease outcomes. This study identifies predictors of incident malnutrition using data from a subsample (n = 1,841) of The Irish Longitudinal Study on Ageing. Participants were excluded if they were less than 65 years, missing body mass index data at baseline or follow-up, missing baseline weight loss data or malnourished at baseline (body mass index <20 kg/m2 or unplanned weight loss ≥4.5 kg in the previous year). Logistic regression analysis was performed with incident malnutrition (body mass index <20 kg/m2 and/or calculated weight loss >10% over follow-up) as the dependent variable. Factors showing significant (p < .05) univariate associations with incident malnutrition were entered into a multivariate model. The analysis was then repeated, stratified by sex. The 2-year incidence of malnutrition was 10.7%. Unmarried/separated/divorced status (vs married but not widowed), hospitalization in the previous year, difficulties walking 100 m, or climbing stairs independently predicted incident malnutrition at follow-up. When examined by sex, hospitalization in the previous year, falls during follow-up, and self-reported difficulties climbing stairs predicted malnutrition in males. Receiving social support and cognitive impairment predicted malnutrition in females. The development of malnutrition has a range of predictors. These can be assessed using simple questions to identify vulnerable persons.

17.
Brain Pathol ; 30(1): 191-202, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357238

RESUMO

We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD-DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α-synuclein pathology. We found moderate-severe vascular changes and high-vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub-set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α-synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging-related neurodegenerative disorders and characterize their end-stage clinical syndromes.

18.
Exp Gerontol ; 129: 110781, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31740390

RESUMO

Collagens and elastin are 'building blocks' of tissues and extracellular matrix. Mutations in these proteins cause severe congenital syndromes. Adverse genetic variations may accelerate the aging process in adults contributing to premature morbidity, disability and/or mortality. Favorable variants may contribute to longevity and/or healthy aging, but this is much less studied. We reviewed the association between variation in the genes of collagens and elastin and premature aging, accelerated aging, age-related diseases and/or frailty; and the association between genetic variation in those and longevity and/or healthy aging in humans. A systematic search was conducted in MEDLINE and other online databases (OMIM, Genetics Home Reference, Orphanet, ClinVar). Results suggest that genetic variants lead to aging phenotypes of known congenital disease, but also to association with common age-related diseases in adults without known congenital disease. This may be due to the variable penetrance and expressivity of many variants. Some collagen variants have been associated with longevity or healthy aging. A limitation is that most studies had <1000 participants and their criterion for statistical significance was p < 0.05. Results highlight the importance of adopting a lifecourse approach to the study of the genomics of aging. Gerontology can help with new methodologies that operationalize biological aging.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31802415

RESUMO

Heparin-induced thrombocytopenia (HIT) is a rare adverse drug reaction. The anti-PF4 antibody assay (ELISA) is utilized to assist in the clinical evaluation of HIT due to its high negative predictability and wide-spread availability. However, it also associated with false positive results. The 4T score can assist in predicting an individual's risk for HIT and the need for further laboratory testing. This was a single-center prospective observational cohort study. Orders for HIT testing were sent via page to a clinical pharmacist to calculate a 4T score. If low risk, the pharmacist contacted the ordering prescriber to recommend discontinuation of laboratory testing. During the study, a clinical support tool was implemented to assist prescribers with ordering HIT tests. The study was divided into a pharmacist intervention group and a control group. A total of 303 pages were received. One hundred nine were missed due to unavailability of the pharmacist at time of page. A pharmacist reviewed 194 pages and intervened on 132. One hundred seven were scored as low risk, 70 as intermediate risk and 9 as high risk. Pharmacist intervention resulted in discontinuing 64 ELISA and 11 serotonin release assay tests. The clinical support tool resulted in a yearly decrease of HIT testing by 27%. Laboratory cost savings totaled $11,000 but did not include avoidance of laboratory technician or drug cost. Pharmacist involvement in the clinical assessment of HIT and the use of a support tool resulted in the reduction of HIT tests in low risk patients.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31821404

RESUMO

Orthostatic hypotension (OH) is associated with increased risk of trauma and cardiovascular events. Recent studies have identified new genetic variants that influence orthostatic blood pressure (BP). The aim of this study was to investigate the associations of candidate gene loci with orthostatic BP responses in older adults. A total of 3,430 participants aged ≥50 years from The Irish Longitudinal Study on Ageing (TILDA) with BP measures and genetic data from twelve single-nucleotide polymorphism (SNP) linked to BP responses were analysed. Orthostatic BP responses were recorded at each 10 second interval and were defined as OH (SBP drop ≥20mmHg or DBP drop ≥10mmHg) at the time-points 40, 90 and 110 seconds. We defined sustained OH (SOH) as a drop that exceeded consensus BP thresholds for OH at 40, 90 and 110 seconds after standing. Logistic regression analyses modelled associations between the candidate SNP alleles and OH. We report no significant associations between OH and measured SNPs after correction for multiple comparisons apart from the SNP rs5068 where proportions of the minor allele was significantly different between cases and controls for SOH 40 (p=0.002). After adjustment for covariates in a logistic regression, those with the minor G allele (compared to the A allele) had a decreased incidence rate ratio (IRR) for SOH 40 (IRR 0.45, p=0.001, 95% CI 0.29-0.72). Only one SNP linked with increased natriuretic peptide concentrations was associated with OH. These results suggest that genetic variants may have a weak impact on OH but needs verification in other population studies.

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