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ABSTRACT: BACKGROUND: Acute myeloid leukemia (AML) is the common form of acute leukemia in adults, accounting for over 80% of all acute leukemias in individuals aged >18 years. Overall 5-year survival remains poor in older AML patients; it is <5% in patients aged >65 years. In this study, the authors examined whether survival has improved for subsets of geriatric AML patients over 3 successive decades. METHODS: Surveillance, Epidemiology and End Results (SEER) data were used to determine trends in relative survival by age among 19,000 patients with AML over 3 successive decades (1977-1986, 1987-1996, and 1997-2006). Relative survival rates (RRs) with 95% confidence intervals (CIs) were calculated as measures of survival. RESULTS: Overall, the RRs increased for each successive decade (1977-1986, 1987-1996, and 1997-2006) in patients ages 65 to 74 years, with improvements in 12-month survival from 20%, to 25%, to 30%, respectively. Findings were similar for 24-month, 36-month, 48-month, and 60-month survival. However, survival rates did not improve in patients aged ≥75 years. The oldest old patients (aged ≥85 years) had the lowest survival rates, with no apparent improvement. CONCLUSIONS: This analysis of a large data set demonstrated that, although overall survival remained unsatisfactory among older patients, it improved in the younger old (ages 65-74 years). Survival of older old AML patients has not been favorably impacted by available AML therapies or supportive care, and intervention in this age group is best undertaken on a clinical trial. Cancer 2013;. © 2013 American Cancer Society.
Cancer 04/2013; · 4.77 Impact Factor
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ABSTRACT: The red cell distribution width (RDW) is a component of the automated complete blood count (CBC) that quantifies heterogeneity in the size of circulating erythrocytes. Higher RDW values reflect greater variation in red blood cell (RBC) volumes and are associated with increased risk for cardiovascular disease (CVD) events. The mechanisms underlying this association are unclear, but RBC deformability might play a role. CBCs were assessed in 293 adults who were clinically examined. RBC deformability (expressed as the elongation index) was measured using a microfluidic slit-flow ektacytometer. Multivariate regression analysis identified a clear threshold effect whereby RDW values above 14.0% were significantly associated with decreased RBC deformability (β = -0.24; p = 0.003). This association was stronger after excluding anemic participants (β = -0.40; p = 0.008). Greater variation in RBC volumes (increased RDW) is associated with decreased RBC deformability, which can impair blood flow through the microcirculation. The resultant hypoxia may help to explain the previously reported increased risk for CVD events associated with elevated RDW.
Advances in experimental medicine and biology 01/2013; 765:211-6. · 1.09 Impact Factor
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ABSTRACT: Significant progress has been made in the treatment of breast cancer. However, treatment effect on survival in older patients, particularly the "oldest old" (85+ years), with breast cancer is not clear. Data from the Surveillance, Epidemiology, and End Results databases were used to determine relative survival of older patients with breast cancer for up to 9 years following diagnosis. We compared trends in survival and stage distribution in the years 1977-1986, 1987-1996, and 1997-2006 in patients from 65 to 74, 75 to 84, and 85+ years of age. Between 1977-1986 and 1997-2006, 1 year survival increased from 94.9 to 97.9 %, 93.6 to 96.7 %, and 88.5 to 93.5 % in the 65-74, 75-84, and 85+ age groups, respectively. Survival gains increased with each year in all three age groups with the largest improvement seen at 9 years of follow-up. Although the "oldest old" had the lowest survival rates, improvement in survival was greatest in this age group with greater than 20 % increase in survival at 9 years. There was an increased diagnosis of localized breast cancer and decrease in regional disease in all age groups over the three decades. In conclusion, relative survival for older patients has increased considerably in the interval between 1977 and 2006, with the largest improvement seen in those 85 years and older. These results likely indicate that the benefit from advances in therapy and supportive care also extends to older patients with breast cancer, including the 'oldest old', but the impact of early diagnosis on survival requires further clarification.
Breast Cancer Research and Treatment 06/2012; 134(2):853-7. · 4.43 Impact Factor
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Archives of gerontology and geriatrics 03/2012; 54(2):273-7. · 1.36 Impact Factor
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Nicola A Hanania,
Monroe J King,
Sidney S Braman,
Carol Saltoun,
Robert A Wise,
Paul Enright,
Ann R Falsey,
Sameer K Mathur,
Joe W Ramsdell,
Linda Rogers, [......],
Sandra R Wilson,
Cynthia Boyd,
Kushang V Patel,
Charles G Irvin,
Barbara P Yawn,
Ethan A Halm,
Stephen I Wasserman,
Mark F Sands, William B Ershler,
Dennis K Ledford
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ABSTRACT: Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.
The Journal of allergy and clinical immunology 09/2011; 128(3 Suppl):S4-24. · 9.17 Impact Factor
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ABSTRACT: Lenalidomide, an analog of thalidomide, modified responses of stimulated T cells from healthy young (ages 21-40 years) and old (≥ age 65 years) subjects. At 0.03 μM to 1 μM, lenalidomide enhanced generation of IL-2 and IFN-γ by T cell receptor-stimulated T cells of young subjects up to respective maximum increases of 17-fold and three-fold, but at 0.3 μM and 1 μM suppressed IL-17 generation. The same concentrations of lenalidomide enhanced IL-2 and IFN-γ generation by stimulated T cells of old subjects more, with greater respective maximal increases of up to 120-fold and six-fold, without suppressing IL-17 generation. Lenalidomide enhanced proliferation and suppressed apoptosis of stimulated T cells from old subjects, by IL-2-dependent mechanisms, and restored diminished T cell chemotactic responses to CCL21 and sphingosine 1-phosphate. The reversal of T cell abnormalities of immunosenescence by low concentrations of lenalidomide suggest a potential for improvement of immunity in the elderly.
Clinical Immunology 02/2011; 138(2):201-11. · 4.05 Impact Factor
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Luigi Ferrucci,
Richard D Semba,
Jack M Guralnik, William B Ershler,
Stefania Bandinelli,
Kushang V Patel,
Kai Sun,
Richard C Woodman,
Nancy C Andrews,
Robert J Cotter,
Tomas Ganz,
Elizabeta Nemeth,
Dan L Longo
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ABSTRACT: In patients with overt inflammatory diseases, up-regulated hepcidin impairs iron absorption and macrophage release, causing anemia. Whether the mild proinflammatory state of aging is associated with increased hepcidin is unknown. We characterized the relationships between urinary hepcidin, iron status, anemia, and inflammation in 582 patients 65 years or older participating in the InCHIANTI (Invecchiare in Chianti, "Aging in the Chianti Area") study, a population-based study of aging in Tuscany, Italy. Compared with nonanemic persons, urinary hepcidin (nanograms/milligram of urinary creatinine) was significantly lower in iron deficiency and inflammation anemia compared with no anemia or other anemia types. Urinary hepcidin was positively correlated with log(ferritin) and negatively correlated with the soluble transferrin receptor/log(ferritin) ratio but not correlated with markers of inflammation: interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha, and C-reactive protein (CRP). Lower iron was significantly correlated with higher IL-6 and CRP. Adjusting for confounders, IL-6 and CRP remained significantly associated with serum iron, with no evidence that such a relationship was accounted for by variability in urinary hepcidin. In conclusion, elevated proinflammatory markers were associated with anemia and low iron status, but not with higher urinary hepcidin. Future studies should test whether hepcidin production becomes up-regulated only in situations of overt inflammation.
Blood 05/2010; 115(18):3810-6. · 9.90 Impact Factor
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ABSTRACT: D-dimer is a marker of active fibrinolysis. Understanding how age-related factors affect D-dimer levels may help the interpretation of high D-dimer levels in older individuals.
776 Baltimore Longitudinal Study on Aging (BLSA) participants (mean age 68.4+/-13.9 yrs) were divided into three groups according to baseline D-dimer levels >200 ng/mL; 100-200 ng/mL and <100 ng/mL.
D-dimer level increased with age (p<0.0001). Using polychotomous logistic regression models, we found that age, cholesterol, triglycerides, creatinine, erythrocyte sedimentation rate, hemoglobin and body mass index were independently associated with D-dimer level.
Rising levels of D-dimer with age can be explained in part by the high prevalence of pro-inflammatory conditions and increasing burden of lipid abnormalities, anemia and obesity. These factors compromise the specificity of D-dimer levels as a diagnostic aid to thrombosis in older individuals.
Aging clinical and experimental research 02/2010; 22(1):20-3. · 1.55 Impact Factor
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Kushang V Patel,
Richard D Semba,
Luigi Ferrucci,
Anne B Newman,
Linda P Fried,
Robert B Wallace,
Stefania Bandinelli,
Caroline S Phillips,
Binbing Yu,
Stephanie Connelly,
Michael G Shlipak,
Paulo H M Chaves,
Lenore J Launer, William B Ershler,
Tamara B Harris,
Dan L Longo,
Jack M Guralnik
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ABSTRACT: Red cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear.
Seven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed.
Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.11-1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12-1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07-1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07-1.18). Furthermore, the RDW-mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21-1.44).
RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2009; 65(3):258-65. · 4.60 Impact Factor
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ABSTRACT: There are inevitable physiologic changes associated with advancing age, yet for some people these changes are exaggerated, and as a result a phenotype emerges recognized as "frailty." Why some people become frail and others do not remains incompletely understood. Although chronic illnesses are common among frail elderly persons, some will develop all of the phenotypic features without a diagnosed underlying disease. It has been recognized that certain proinflammatory cytokines and coagulation factors are elevated to a greater extent in those who are frail than in age-matched nonfrail individuals. In this review, we provide an overview of current research in the biology of frailty with particular emphasis on the role of inflammatory pathways and disordered coagulation in its pathogenesis.
The American journal of medicine 08/2009; 122(7):605-13. · 4.47 Impact Factor
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ABSTRACT: Life expectancy has increased considerably over the past several decades, and this most certainly relates to public health
measures, sanitation, advances in medical treatment, and lately, disease prevention strategies. Measured within an individual,
one finds evidence for aging in almost all physiological systems.
07/2009: pages 71-93;
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ABSTRACT: Mildly low haemoglobin concentration is associated with increased mortality in older adults. However, this relationship has not been well characterized in racial/ethnic minorities. Therefore, this study determined the haemoglobin threshold below which risk of death is significantly increased in older non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Data on 4089 participants of the 1988-94 US National Health and Nutrition Examination Survey who were > or =65 years of age were analyzed with mortality follow-up through December 31, 2000. Mean haemoglobin in non-Hispanic whites (n = 2686) and Mexican Americans (n = 663) was 140 g/l, while in non-Hispanic blacks (n = 740) the mean was 10 g/l lower. A total of 1944 (47.5%) participants died. Among non-Hispanic whites and Mexican Americans, age- and sex-adjusted models showed that the haemoglobin thresholds below which mortality risk was significantly increased were 4 and 2 g/l respectively, above the World Health Organization (WHO) cut-off points for anaemia. In contrast, the threshold for non-Hispanic blacks was 7 g/l below the WHO criteria. Similar threshold effects were observed when analyzing haemoglobin in categories and adjusting for multiple confounders. In conclusion, the haemoglobin threshold below which mortality rises significantly is a full g/dl lower in non-Hispanic blacks than in non-Hispanic whites and Mexican Americans.
British Journal of Haematology 03/2009; 145(4):514-23. · 4.94 Impact Factor
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ABSTRACT: The occurrence of anemia in older adults has been associated with adverse outcomes including functional decline, disability, morbidity, and mortality. It is not clear to what extent these outcomes are the result of the anemia or concurrent illness. We performed a cross-sectional, observational study to determine whether lower hemoglobin concentrations in older adults are associated with reduced health-related quality of life, functional status, depression, disability, and physical strength, independent of chronic disease. Three sites participated in this research: an academic geriatric practice, a hospital-based geriatric outpatient unit, and a community-based multispecialty internal medicine group. Health-related quality of life and functional status were measured using the Short Form-36 Health Survey (SF-36) and the Functional Assessment of Chronic Illness Therapy-Anemia (FACIT-An). Disability and depression were assessed using the Instrumental Activities of Daily Living (IADL) and the Geriatric Depression Scale (GDS) questionnaires, respectively. Handgrip strength was used as a physical performance measure. Anemia was defined as hemoglobin <13 g/dL for men or <12 g/dL for women. The mean SF-36 physical health component summary scores were 38.9 (with anemia) and 44.1 (without anemia) (p<0.001). Anemia was associated with greater fatigue (p < 0.001), lower handgrip strength (p = 0.014), increased number of disabilities (p=0.005), and more depressive symptoms (p = 0.002). Multivariate regression analysis, adjusted for demographic and clinical characteristics, demonstrated strong associations for reduced hemoglobin, even within the "normal" range, and poorer health-related quality of life across multiple domains. Thus, anemia was independently associated with clinically significant impairments in multiple domains of health-related quality of life, especially in measures of functional limitation. Mildly low hemoglobin levels, even when above the World Health Organization (WHO) anemia threshold, were associated with significant declines in quality of life among the elderly.
Medicine 03/2009; 88(2):107-14. · 4.35 Impact Factor
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ABSTRACT: Red blood cell distribution width (RDW), a component of an electronic complete blood count, is a measure of heterogeneity in the size of circulating erythrocytes. In patients with symptomatic cardiovascular disease (CVD), RDW is associated with mortality. However, it has not been demonstrated that RDW is a predictor of mortality independent of nutritional deficiencies or in the general population.
Red blood cell distribution width was measured in a national sample of 8175 community-dwelling adults 45 years or older who participated in the 1988-1994 National Health and Nutrition Examination Survey; mortality follow-up occurred through December 31, 2000. Deaths from all causes, CVD, cancer, and other causes were examined as a function of RDW.
Higher RDW values were strongly associated with an increased risk of death. Compared with the lowest quintile of RDW, the following were adjusted hazard ratios (HRs) for all-cause mortality (and 95% confidence intervals [CIs]): second quintile, HR, 1.1 (95% CI, 0.9-1.3); third quintile, HR, 1.2 (95% CI, 1.0-1.4); fourth quintile, HR, 1.4 (95% CI, 1.2-1.8); and fifth quintile, HR, 2.1 (95% CI, 1.7-2.6). For every 1% increment in RDW, all-cause mortality risk increased by 22% (HR, 1.22; 95% CI, 1.15-1.30; P < .001). Even when analyses were restricted to nonanemic participants or to those in the reference range of RDW (11%-15%) without iron, folate, or vitamin B(12) deficiency, RDW remained strongly associated with mortality. The prognostic effect of RDW was observed in both middle-aged and older adults for multiple causes of death.
Red blood cell distribution width is a widely available test that is a strong predictor of mortality in the general population of adults 45 years or older.
Archives of internal medicine 03/2009; 169(5):515-23. · 11.46 Impact Factor
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Dennis D Taub, William B Ershler,
Mark Janowski,
Andrew Artz,
Michael L Key,
Julie McKelvey,
Denis Muller,
Bernard Moss,
Luigi Ferrucci,
Patricia L Duffey,
Dan L Longo
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ABSTRACT: The threat of smallpox resulting from bioterrorist action has prompted a reassessment of the level of immunity in current populations.
We have examined the magnitude and duration of antiviral antibody immunity conferred by smallpox vaccination in 246 participants of the Baltimore Longitudinal Study of Aging. Of this population, 209 subjects were vaccinated one or more times 13 to 88 years before this evaluation, and stored serum samples were available at various intervals after vaccination. An additional 8 subjects who had documented childhood smallpox infection and 29 subjects with no history of infection or vaccination were included. We quantified the total vaccinia IgG and neutralizing antibody titers in each of these subgroups of participants over time.
Vaccinated participants maintained antivaccinia IgG and neutralizing antibody titers above 3 natural logs essentially indefinitely. The absolute titer of antivaccinia antibody was only slightly higher after multiple vaccinations. In 97% of the participants, no decrease in vaccinia-specific antibody titers was noted with age over a follow-up period of up to 88 years. Moreover, Baltimore Longitudinal Study of Aging participants who survived active smallpox infections in their youth retained antivaccinia antibody titers that were similar to the levels detected in vaccinated subjects.
These data suggest that multiple or recent vaccinations are not essential to maintain vaccinia-specific antibody responses in human subjects. Scarce vaccine supplies should be applied first to individuals who have not previously been vaccinated.
The American journal of medicine 01/2009; 121(12):1058-64. · 4.47 Impact Factor
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Journal of the American Geriatrics Society 12/2008; 56(11):2145-7. · 3.74 Impact Factor
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Journal of the American Geriatrics Society 12/2008; 56(11):2165-6. · 3.74 Impact Factor
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ABSTRACT: Among the elderly, anemia occurs with increasing frequency with each advancing decade. Unlike when anemia occurs in younger adults, the cause of anemia in the elderly is oftentimes not readily apparent or attributable to a single cause. However, this commonly observed form of anemia in the elderly (termed unexplained anemia [UA]) can generally be dissected to its root causes, which include renal insufficiency, inflammation, testosterone deficiency, and stem cell proliferative decline. Myelodysplasia (MDS) occurs commonly in this age group but can and should, for both diagnostic and therapeutic considerations, be distinguished from UA.
Seminars in Hematology 11/2008; 45(4):250-4. · 3.99 Impact Factor
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New England Journal of Medicine 06/2008; 358(22):2409-10; author reply 2410-1. · 53.30 Impact Factor
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ABSTRACT: As discussed extensively in this volume, anemia occurs with increasing frequency as people age. Curiously, a specific explanation
for anemia is less readily apparent for older patients and approximately one-third of those with anemia over 65 years of age
meet criteria for “Unexplained Anemia” (UA) as defined by Guralnik (1) and Artz (2). Although, by definition, those with kidney
disease have an explanation for anemia and would not be considered to have UA, erythropoietin (EPO) insufficiency independent
of overt renal excretory failure may be one component of this disorder. Certainly, other factors, including the coexistence
of occult inflammatory disease, age-associated cytokine dysregulation (independent of inflammation) and androgen deficiency
are also likely to contribute. In this chapter, EPO insufficiency will be considered in the context of anemia in general,
and late-life UA in particular.
10/2007: pages 115-127;
