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Objectives: There is a considerable need for support interventions for caregivers of people with dementia in developing countries, such as India. The purpose of the study was to identify the components and understand the acceptability of an online training and support program for dementia caregivers in India., Methods: Three focus group discussions were carried out with dementia caregivers (2) and health professionals (1) to understand the requirements of an online training and support program from their perspective. The commonly recurring themes were identified and defined using thematic content analysis., Results: The expectations from an online training and support program were wide-ranging from information about identification and management of dementia to support caregiver well-being. Use of simple language, cultural relevance, and an interactive design were suggestions to facilitate the use of the support program. Lack of time, difficulty in accessing the internet, lack of awareness about the portal, difficulty in reaching the rural population were anticipated as challenges in using the program., Conclusions: The study highlights the requisite components of a first of its kind online training and support program in India by integrating the experiences, motivations, challenges, and expectations of caregivers and professionals involved in dementia care., Clinical Implications: The focus group discussions in the current study provide a road map for the development of an online caregiver training and support program underlying the perspectives of the stakeholders for the consolidation of an effective dementia care program for lower resourced settings.

Background: Stroke is the leading cause of death and years of life lost in China, and this problem is growing because stroke risk factors such as hypertension and hypercholesteremia have been on the rise as China experiences the demographic transition. The Chinese government has created public health initiatives in the form of guidelines, policies and programs to combat this problem, but the dissemination and effectiveness of these policies are not well known., Aims: The aim of this study was to determine trends in stroke incidence, prevalence, and stroke-related mortality in China and to report these trends in the context of stroke initiatives that have been enacted by the Chinese government., Summary of Review: We systematically reviewed articles on stroke rates and stroke initiatives from 1980 to 2017. A meta-regression including 11 studies showed that stroke incidence remained stable at 128.3 per 100,000 per year from 1980 to 2005 and has increased by 21.3 per 100,000 per year since then to 298.7 per 100,000 per year in 2013. A meta-regression including seven studies demonstrated a gradual decline in stroke-related mortality by 6.5 per 100,000 per year since 1980 (a decline from 369.2 in 1980 to 154.7 per 100,000 per year in 2013). Average stroke prevalence was 898.4 per 100,000 over the entire time-period. Limitations included heterogeneity between the studies. We identified 12 stroke initiatives, the first of which was enacted in 2006., Conclusions: Despite numerous public health initiatives aimed at combating stroke that started in 2006, stroke incidence in China has increased over the last decade, likely as a result of aging and urbanization of the Chinese population.

Background: In acute kidney injury (AKI), medication dosing based on Cockcroft-Gault creatinine clearance (CrCl) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rates (eGFR) are not valid when serum creatinine (SCr) is not in steady state. The aim of this study was to determine the impact of a kinetic estimating equation that incorporates fluctuations in SCrs on drug dosing in critically ill patients., Methods: We used data from participants enrolled in the NIH Acute Respiratory Distress Syndrome Network Fluid and Catheters Treatment Trial to simulate drug dosing category changes with the application of the kinetic estimating equation developed by Chen. We evaluated whether kinetic estimation of renal function would change medication dosing categories (≥60, 30-59, 15-29, and <15mL/min) compared with the use of CrCl or CKD-EPI eGFR., Results: The use of kinetic CrCl and CKD-EPI eGFR resulted in a large enough change in estimated renal function to require medication dosing recategorization in 19.3% [95 CI 16.8%-21.9%] and 23.4% [95% CI 20.7%-26.1%] of participants, respectively. As expected, recategorization occurred more frequently in those with AKI. When we examined individual days for those with AKI, dosing discordance was observed in 8.5% of total days using the CG CrCl and 10.2% of total days using the CKD-EPI equation compared with the kinetic counterparts., Conclusion: In a critically ill population, use of kinetic estimates of renal function impacted medication dosing in a substantial proportion of AKI participants. Use of kinetic estimates in clinical practice should lower the incidence of medication toxicity as well as avoid subtherapeutic dosing during renal recovery., Competing Interests: The authors have declared that no competing interests exist.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

Introduction: In underserved populations, the contribution of community health workers (CHWs) is vital to the healthcare systems. Attrition of these workers causes critical breakdowns in the delivery of essential services to these populations. Literature on reasons for attrition is limited, although some have been identified in studies on sustainability of CHW programmes. These factors are, however, likely to be influenced by context. We measured CHW attrition and its predictors in a rural area in Kenya., Methods: We conducted a nested case-control study and focus group discussions among CHWs involved in a maternal and child health project. A training register of 1005 CHWs was used to sample and follow CHWs for attrition. Incidence of CHW attrition was calculated using a Poisson model. Separately, we used logistic regression to determine predictors of CHW attrition., Results: Of the 1005 CHWs, 498 (49.6%) had left the project by the time of the study. The incidence of attrition was 46.8/1000 person-years (95% CI 38.7 to 56.5). In the case-control study, lack of interest in peer organisation membership (OR 5.3; 95% CI 1.3 to 20.6) was associated with attrition. Absence of refresher training (OR 4.0; 95% CI 2.2 to 7.1) and receiving no feedback from supervisors (OR 2.0; 95% CI 1.0 to 3.9) were also associated with attrition. Discordance in expectations and perceived heavy workload were also identified as key reasons for attrition in the qualitative study., Conclusion: This study estimates high prevalence and incidence of CHW attrition in Kwale County, Kenya. Ongoing training, feedback and peer support are also important in enhancing retention of CHWs. Additionally, expectations regarding the roles and benefits of involvement in CHW work should be communicated clearly, and workload should be kept reasonable or negotiated with the CHWs., Competing Interests: Competing interests: None declared.

Background: Dementia has a huge physical, psychological, social and economic impact upon caregivers, families and societies at large. There has been a growing impetus to utilize Internet interventions given the potential scalability, and presumed cost-effectiveness and accessibility. In this paper, we describe the design of a randomized controlled trial (RCT) aiming to study the impact of online self-help programs on caregivers of people with dementia in India. The experimental group will receive an interactive training and support program and the comparison group will receive an education-only e-book. It will be among the first online support intervention RCTs for a mental health condition in a lower-middle income country., Methods and Design: Two hundred and eight participants are expected to be recruited via several strategies (email, Internet and social media, telephone and face-to-face) starting in the Bangalore region of India. The inclusion criteria for participation in the trial are: (1) being 18 years or older, (2) being a self-reported caregiver of a person with dementia, (3) self-report that a family member has a diagnosis of dementia (AD8 ≥ 2), and experience caregiver distress (≥ 4 on a 1-item burden scale ranging from 1 to 10 or ≥ 4 or < 20 on the Center for Epidemiologic Study-Depression (CES-D) scale (10-item) or ≥ 4 or < 15 on the Generalized Anxiety Disorder Scale (7-item). The intervention group will be offered iSupport, an online self-help training and support program, enabling a personalized education plan with a maximum of 23 lessons. These modules present a range of topics from "what is dementia?" to "dealing with challenging behaviors like aggression." The comparison group will receive an education-only e-book containing similar content. The outcomes of this trial are: caregiver burden as measured by the 22-item Zarit Burden Scale, depressive symptoms, anxiety symptoms (primary outcomes), quality of life, person-centered attitude, self-efficacy and mastery (secondary outcomes)., Discussion: Based on the findings of this trial, we will examine the potential use and scale up of iSupport for caregiver distress in India. This style of online self-help programs could be expanded to other regions or countries or to other suitable caregiver groups., Trial Registration: Clinical Trials Registry-India (CTRI), ID: CTRI/2017/02/007876 .

Objective: To identify incidence and prevalence of dementia in racial and ethnic populations in the United States., Methods: A systematic review of literature., Results: A total of 1215 studies were reviewed; 114 were included. Dementia prevalence rates reported for age 65+ years from a low of 6.3% in Japanese Americans, 12.9% in Caribbean Hispanic Americans, 12.2% in Guamanian Chamorro and ranged widely in African Americans from 7.2% to 20.9%. Dementia annual incidence for African American (mean = 2.6%; SD = 1%; range, 1.4%-5.5%) and Caribbean Hispanic populations were significantly higher (mean, 3.6%; SD, 1.2%; range, 2.3%-5.3%) than Mexican American and Japanese Americans and non-Latino white populations (0.8%-2.7%), P < .001., Conclusions: Data are needed for American Indian, most Asian, and Pacific Islander populations. Disaggregation of large race/ethnic classifications is warranted due to within-population heterogeneity in incidence and prevalence. African American and Caribbean Hispanic studies showed higher incidence of dementia. A nationwide approach is needed to identify communities at high risk and to tailor culturally appropriate services accordingly., (Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objectives: We investigated whether managed transportation improves outreach-based health service delivery to rural village populations., Methods: We examined systematic transportation management in a small-cluster interrupted time series field trial. In 8 districts in Southern Zambia, we followed health workers at 116 health facilities from September 2011 to March 2014. The primary outcome was the average number of outreach trips per health worker per week. Secondary outcomes were health worker productivity, motorcycle performance, and geographical coverage., Results: Systematic fleet management resulted in an increase of 0.9 (SD = 1.0) trips to rural villages per health worker per week (P < .001), village-level health worker productivity by 20.5 (SD = 5.9) patient visits, 10.2 (SD = 1.5) measles immunizations, and 5.2 (SD = 5.4) child growth assessments per health worker per week. Motorcycle uptime increased by 3.5 days per week (P < .001), use by 1.5 days per week (P < .001), and mean distance by 9.3 kilometers per trip (P < .001). Geographical coverage of health outreach increased in experimental (P < .001) but not control districts., Conclusions: Systematic motorcycle management improves basic health care delivery to rural villages in resource-poor environments through increased health worker productivity and greater geographical coverage.

Objectives: To test our hypothesis that pre-treatment executive function and brain regional activation during executive function would discriminate between responders and non-responders to cognitive behavioral therapy (CBT) in elderly depressed outpatients., Design: Clinical cohort study., Setting: University-affiliated hospital., Participants: Sixty outpatients (age 59 years and older) completed 12 weeks of CBT between July 2010 and December 2011. Forty-four completed fMRI procedures., Measurements: The main outcome consisted of a conversion from a clinical diagnosis (Mini-International Neuropsychiatric Interview) of depression to no clinical diagnosis of depression or a significant improvement in diagnostic criteria. Brain activation measured by functional magnetic resonance imaging during the Wisconsin Card Sorting task (WCST) was the primary predictor variable., Results: 67% of patients had a positive response to CBT. Decreased activation in the left inferior frontal triangle and right superior frontal gyrus as well as increased activity in the right middle frontal gyrus and left superior frontal gyrus predicted a positive response to CBT. Demographic and neurocognitive measures of WCST performance were not significant predictors of a positive CBT outcome, whereas the measure of WCST-induced activity in the prefrontal cortex was a significant predictor., Conclusions: These data are among the first to suggest that measures of prefrontal brain activation during executive functioning predict response to CBT in older adults. Further exploration of the specific underlying processes that these prefrontal cortical regions are engaging that contributes to better CBT outcomes is warranted in larger, randomized studies., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The GTPase-dependent polymerization/depolymerization dynamics of FtsZ regulate bacterial cell division in vivo. Deinococcus radiodurans is better known for its extraordinary radioresistance and therefore, the characterization of FtsZ of this bacterium (FtsZDr) would be required to understand the mechanisms underlying regulation of cell division in response to DNA damage. Recombinant FtsZDr bound to GTP and showed GTPase activity. It produced bundles of protofilaments in the presence of either GTP or Mg2+ ions. But the formation of the higher size ordered structures required both GTP and Mg2+ in vitro. It showed polymerization/depolymerization dynamics as a function of GTP and Mg2+. Interestingly, ATP interacted with FtsZDr and stimulated its GTPase activity by ∼2-fold possibly by increasing both substrate affinity and rate of reaction. FtsZDr-GFP expressing in D. radiodurans produced typical Z ring perpendicular to the plane of first cell division. These results suggested that FtsZDr is a GTPase in vitro and produces typical Z ring at the mid cell position in D. radiodurans., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Invasive lobular carcinomas (ILC) show better clinical behaviour compared with other histological types, but significantly lower pathological complete response (pCR) rates after neoadjuvant chemotherapy (NACT). We investigated whether factors influencing pCR rate in ILC after NACT can be identified and whether clinical outcome is different. 9,020 breast cancer patients from nine German neoadjuvant trials with known histological type were pooled. 11.7 % of tumours were ILC. Endpoints were: pCR rate, surgery type and survival. ILC was associated with older age, larger tumour size, lymph node negativity, lower grade and positive hormone-receptor-status (HR). Patients with ILC achieved a significantly lower pCR rate compared with non-ILC patients (6.2 vs. 17.4 %, P < 0.001). The pCR rate was 4.2 % in ILC/HR+/G1-2, 7.0 % in ILC with either HR- or G3, and 17.8 % in ILC/HR-/G3. Mastectomy rate was higher in ILC compared with non-ILC patients irrespective of response to NACT (pCR: 27.4 vs. 16.6 %, P = 0.037 and non-pCR: 41.8 % vs. 31.5 %, P < 0.0001). Age and HR independently predicted pCR in ILC. In ILC patients, pCR did not predict distant disease free (DDFS) and loco-regional disease free survival (LRFS), but overall survival (OS). Non-pCR patients with ILC had significantly better DDFS (P = 0.018), LRFS (P < 0.0001) and OS (P = 0.044) compared with non-ILC patients. Patients with ILC had a low chance of obtaining a pCR and this is not well correlated with further outcome. The mastectomy rate was considerably high in ILC patients even after obtaining a pCR. We, therefore, suggest to offer NACT mainly to ILC patients with HR-negative tumours.

Background: The proliferation marker Ki67 has been suggested as a promising cancer biomarker. As Ki67 needs an exact quantification, this marker is a prototype of a new generation of tissue-based biomarkers. In this study, we have systematically evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort., Patients and Methods: We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial. We used the standardized cutoff-finder algorithm for three end points [response to neoadjuvant chemotherapy (pCR), disease-free (DFS) and overall-survival (OS)]. The analyses were stratified for hormone receptor (HR) and HER2 status by molecular subtype radar diagrams (MSRDs)., Results: A wide range of Ki67 cut points between 3%-94% (for pCR), 6%-46% (for DFS) and 4%-58% (for OS) were significant. The three groups of Ki67 ≤ 15% versus 15.1%-35% versus >35% had pCR-rates of 4.2%, 12.8%, and 29.0% (P < 0.0005), this effect was also present in six of eight molecular subtypes. In MSRD, Ki67 was significantly linked to prognosis in uni- and multivariate analysis in the complete cohort and in HR-positive, but not triple-negative tumors., Conclusions: Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data-derived cut point optimization might not be possible. Ki67 could be used as a continuous marker; in addition, the scientific community could define standardized cut points for Ki67. Our analysis explains the variability observed for Ki67 cut points in previous studies; however, this should not be seen as weakness, but as strength of this marker. MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer. The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers.

Background: Many older adults become dependent in one or more activities of daily living (ADLs: dressing, bathing, transferring, eating, toileting) when hospitalized, and their prognosis after discharge is unclear., Objective: To develop a prognostic index to estimate one-year probabilities of recovery, dependence or death in older hospitalized patients who are discharged with incident ADL dependence., Design: Retrospective cohort study., Participants: 449 adults aged ≥ 70 years hospitalized for acute illness and discharged with incident ADL dependence., Main Measures: Potential predictors included demographics (age, sex, race, education, marital status), functional measures (ADL dependencies, instrumental activities of daily living [IADL] dependencies, walking ability), chronic conditions (e.g., congestive heart failure, dementia, cancer), reason for admission (e.g., neurologic, cardiovascular), and laboratory values (creatinine, albumin, hematocrit). Multinomial logistic regression was used to develop a prognostic index for estimating the probabilities of recovery, disability or death over 1 year. Discrimination of the index was assessed for each outcome based on the c statistic., Key Results: During the year following hospitalization, 36 % of patients recovered, 27 % remained dependent and 37 % died. Key predictors of recovery, dependence or death were age, sex, number of IADL dependencies 2 weeks prior to admission, number of ADL dependencies at discharge, dementia, cancer, number of other chronic conditions, reason for admission, and creatinine levels. The final prognostic index had good to excellent discrimination for all three outcomes based on the c statistic (recovery: 0.81, dependence: 0.72, death: 0.78)., Conclusions: This index accurately estimated the probabilities of recovery, dependence or death in adults aged 70 years or older who were discharged with incident disability following hospitalization. This tool may be useful in clinical settings to guide care discussions and inform decision-making related to post-hospitalization care.

Objectives: To determine the relationship between depressive symptoms after hospitalization and survival and functional outcomes., Design: Secondary analysis of a prospective cohort study., Setting: General medical service of two urban, teaching hospitals in Ohio., Participants: Hospitalized individuals aged 70 and older., Measurements: Ten depressive symptoms, instrumental activities of daily living (IADLs), and basic activities of daily living (ADLs) were measured at hospital discharge and 1, 3, 6, and 12 months later. Participant-specific changes in depressive symptoms (slopes) were determined using all data points. Four groups were also defined according to number of depressive symptoms (≤3 symptoms, low; 4-10 symptoms, high) at discharge and follow-up: low-low, low-high, high-low, and high-high. Mortality was measured 3, 6, and 12 months after hospital discharge., Results: Participant-specific discharge depressive symptoms and change in depressive symptoms over time (slopes) were associated (P < .05) with functional and mortality outcomes. At 1 year, more participants in the low-low depressive symptom group (49%) were alive and independent in IADLs and ADLs than in the low-high group (37%, P = .02), and more participants in the high-low group (39%) were alive and independent in IADLs and ADLs than in the high-high group (19%, P < .001)., Conclusion: Number of depressive symptoms and change in number of depressive symptoms during the year after discharge were associated with functional and mortality outcomes in hospitalized older adults. Fewer participants with persistently high or increasing depressive symptoms after hospitalization were alive and functionally independent 1 year later than participants with decreasing or persistently low symptoms, respectively., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Purpose: To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer., Patients and Methods: Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m(2)) followed by four 3-week cycles paclitaxel (175 mg/m(2)) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue., Results: Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was 96% in patients with pCR compared to 86% in patients without pCR (P = .025). pCR was the only significant prognostic factor for DFS (hazard ratio [HR] 2.5; 95% CI, 1.2 to 5.1; P = .013) and OS (HR, 4.9; 95% CI, 1.4 to 17.4; P = .012) in multivariable analysis. Cardiac toxicity was reported in eight patients (3.7%) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure., Conclusion: Neoadjuvant combination of trastuzumab and chemotherapy resulted in a high pCR rate in HER2-overexpressing primary breast cancer. Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome. Patients without a pCR had an increased risk for relapse and death.

Object naming tests are commonly included in neuropsychological test batteries. Differential item functioning (DIF) in these tests due to cultural and language differences may compromise the validity of cognitive measures in diverse populations. We evaluated 26 object naming items for DIF due to Spanish and English language translations among Latinos ( n =1,159), mean age of 70.5 years old (Standard Deviation ( SD )±7.2), using the following four item response theory -based approaches: Mplus/Multiple Indicator, Multiple Causes (Mplus/MIMIC; Muthén & Muthén, 1998-2011), Item Response Theory Likelihood Ratio Differential Item Functioning (IRTLRDIF/MULTILOG; Thissen, 1991, 2001), difwithpar/Parscale (Crane, Gibbons, Jolley, & van Belle, 2006; Muraki & Bock, 2003), and Differential Functioning of Items and Tests/MULTILOG (DFIT/MULTILOG; Flowers, Oshima, & Raju, 1999; Thissen, 1991). Overall, there was moderate to near perfect agreement across methods. Fourteen items were found to exhibit DIF and 5 items observed consistently across all methods, which were more likely to be answered correctly by individuals tested in Spanish after controlling for overall ability.

Background: Many older adults who are independent prior to hospitalization develop a new disability by hospital discharge. Early risk stratification for new-onset disability may improve care. Thus, this study's objective was to develop and validate a clinical index to determine, at admission, risk for new-onset disability among older, hospitalized adults at discharge., Design: Data analyses derived from two prospective studies., Setting: Two teaching hospitals in Ohio., Participants: Eight hundred eighty-five patients aged 70 years and older were discharged from a general medical service at a tertiary care hospital (mean age 78, 59% female) and 753 patients discharged from a separate community teaching hospital (mean age 79, 63% female). All participants reported being independent in five activities of daily living (ADLs: bathing, dressing, transferring, toileting, and eating) 2 weeks before admission., Measurements: New-onset disability, defined as a new need for personal assistance in one or more ADLs at discharge in participants who were independent 2 weeks before hospital admission., Results: Seven independent risk factors known on admission were identified and weighted using logistic regression: age (80-89, 1 point; ≥90, 2 points); dependence in three or more instrumental ADLs at baseline (2 points); impaired mobility at baseline (unable to run, 1 point; unable to climb stairs, 2 points); dependence in ADLs at admission (2-3 ADLs, 1 point; 4-5 ADLs, 3 points); acute stroke or metastatic cancer (2 points); severe cognitive impairment (1 point); and albumin less than 3.0 g/dL (2 points). New-onset disability occurred in 6%, 13%, 18%, 34%, 35%, 45%, 50%, and 87% of participants with 0, 1, 2, 3, 4, 5, 6, and 7 or more points, respectively, in the derivation cohort (area under the receiver operating characteristic curve (AUC)=0.784), and in 8%, 10%, 27%, 38%, 44%, 45%, 58%, and 83%, respectively, in the validation cohort (AUC=0.784). The risk score also predicted (P<.001) disability severity, nursing home placement, and long-term survival., Conclusion: This clinical index determines risk for new-onset disability in hospitalized older adults and may inform clinical care., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

Differential item functioning (DIF) occurs when a test item has different statistical properties in subgroups, controlling for the underlying ability measured by the test. DIF assessment is necessary when evaluating measurement bias in tests used across different language groups. However, other factors such as educational attainment can differ across language groups, and DIF due to these other factors may also exist. How to conduct DIF analyses in the presence of multiple, correlated factors remains largely unexplored. This study assessed DIF related to Spanish versus English language in a 44-item object naming test. Data come from a community-based sample of 1,755 Spanish- and English-speaking older adults. We compared simultaneous accounting, a new strategy for handling differences in educational attainment across language groups, with existing methods. Compared to other methods, simultaneously accounting for language- and education-related DIF yielded salient differences in some object naming scores, particularly for Spanish speakers with at least 9 years of education. Accounting for factors that vary across language groups can be important when assessing language DIF. The use of simultaneous accounting will be relevant to other cross-cultural studies in cognition and in other fields, including health-related quality of life.

Objectives: We evaluated mammography rates for cognitively impaired women in the context of their life expectancies, given that guidelines do not recommend screening mammography in women with limited life expectancies because harms outweigh benefits., Methods: We evaluated Medicare claims for women aged 70 years or older from the 2002 wave of the Health and Retirement Study to determine which women had screening mammography. We calculated population-based estimates of 2-year screening mammography prevalence and 4-year survival by cognitive status and age., Results: Women with severe cognitive impairment had lower rates of mammography (18%) compared with women with normal cognition (45%). Nationally, an estimated 120,000 screening mammograms were performed among women with severe cognitive impairment despite this group's median survival of 3.3 years (95% confidence interval = 2.8, 3.7). Cognitively impaired women who had high net worth and were married had screening rates approaching 50%., Conclusions: Although severe cognitive impairment is associated with lower screening mammography rates, certain subgroups with cognitive impairment are often screened despite lack of probable benefit. Given the limited life expectancy of women with severe cognitive impairment, guidelines should explicitly recommend against screening these women.

Recent studies have found that smoking is associated with an increased risk of dementia, but the effects of secondhand smoke (SHS) on dementia risk are not known to have previously been studied. The authors used Cox proportional hazards marginal structural models to examine the association between self-reported lifetime household SHS exposure and risk of incident dementia over 6 years among 970 US participants in the Cardiovascular Health Cognition Study (performed from 1991 to 1999) who were never smokers and were free of clinical cardiovascular disease (CVD), dementia, and mild cognitive impairment at baseline. In addition, because prior studies have found that SHS is associated with increased risk of CVD and that CVD is associated with increased risk of dementia, the authors tested for interactions between SHS and measures of clinical and subclinical CVD on dementia risk. Moderate (16-25 years) and high (>25 years) SHS exposure levels were not independently associated with dementia risk; however, subjects with >25 years of SHS exposure and >25% carotid artery stenosis had a 3-fold increase (hazard ratio = 3.00, 95% confidence interval: 1.03, 9.72) in dementia risk compared with subjects with no/low (0-15 years) SHS exposure and < or =25% carotid artery stenosis. High lifetime SHS exposure may increase the risk of dementia in elderly with undiagnosed CVD.

Background: A low level of formal education is becoming accepted as a risk factor for Alzheimer's disease (AD). Although increasing attention has been paid to differences in educational quality, no previous studies addressed participants' own characterizations of their overall performance in school. We examined whether self-assessed school performance is associated with AD beyond the effects of educational level alone., Methods: Participants were drawn from the population-representative Aging, Demographics, and Memory Study (ADAMS, 2000-2002). The ADAMS participants were asked about their performance in school. Possible response options included "above average," "average," or "below average." The ADAMS participants also underwent a full neuropsychological battery, and received a research diagnosis of possible or probable AD., Results: The 725 participants (mean age, 81.8 years; 59% female; 16% African-American) varied in self-assessed educational performance: 29% reported "above average," 64% reported "average," and 7% reported "below average" school performance. Participants with a lower self-assessed school performance had higher proportions of AD: 11% of participants with "above average" self-assessed performance had AD, as opposed to 12% of participants with "average" performance and 26% of participants with "below average" performance (P < 0.001). After controlling for subjects' years in school, a literacy test score (Wide-Range Achievement Test), age, sex, race/ethnicity, apolipoprotein E-epsilon4 status, socioeconomic status, and self-reported comorbidities, respondents with "below average" self-assessed school performance were four times more likely to have AD compared with those of "average" performance (odds ratio, 4.0; 95% confidence interval, 1.2-14). "Above average" and "average" self-assessed school performance did not increase or decrease the odds of having AD (odds ratio, 0.9; 95% confidence interval, 0.5-1.7)., Conclusions: We suggest an association between "below average" self-assessed school performance and AD beyond the known association with formal education. Efforts to increase cognitive reserve through better school performance, in addition to increasing the number of years of formal education in early life, may be important in reducing vulnerability throughout the life course.

Accurate neuropsychological assessment of older individuals from heterogeneous backgrounds is a major challenge. Education, ethnicity, language, and age are associated with scale level differences in test scores, but item level bias might contribute to these differences. We evaluated several strategies for dealing with item and scale level demographic influences on a measure of executive abilities defined by working memory and fluency tasks. We determined the impact of differential item functioning (DIF). We compared composite scoring strategies on the basis of their relationships with volumetric magnetic resonance imaging (MRI) measures of brain structure. Participants were 791 Hispanic, white, and African American older adults. DIF had a salient impact on test scores for 9% of the sample. MRI data were available on a subset of 153 participants. Validity in comparison with structural MRI was higher after scale level adjustment for education, ethnicity/language, and gender, but item level adjustment did not have a major impact on validity. Age adjustment at the scale level had a negative impact on relationships with MRI, most likely because age adjustment removes variance related to age-associated diseases.

Objective: Survival after Alzheimer disease (AD) is poorly understood for patients of diverse race/ethnic groups. We examined whether nonwhite AD patients (African American, Latino, Asian, American Indian) had different rates of survival compared with white AD patients., Methods: The National Alzheimer's Coordinating Center (NACC) cataloged data from more than 30 Alzheimer's Disease Centers in the United States from 1984 to 2005. Patients aged 65 years or older with a diagnosis of possible/probable AD were included (n = 30,916). Survival was calculated using Cox proportional hazards models with a primary outcome of time to death. Secondary outcomes of this study were neuropathologic characteristics on an autopsied subsample (n = 3,017)., Results: The 30,916 AD patients in the NACC were followed up for 2.4 +/- 2.9 years (mean age 77.6 +/- 6.5 years; 65% women; 19% nonwhite [12% African American, 4% Latino, 1.5% Asian, 0.5% American Indian, and 1% other]). Median survival was 4.8 years. African American and Latino AD patients had a lower adjusted hazard for mortality compared with white AD patients (African American hazard ratio [HR] 0.85, 95% CI 0.74 to 0.96; Latino HR 0.57, 95% CI 0.46 to 0.69). Asians and American Indians had similar adjusted hazards for mortality compared with white AD patients (p > 0.10 for both). African American and Latino autopsied AD patients had similar neuropathologic characteristics compared with white AD patients with similar clinical severity., Conclusions: African American and Latino Alzheimer disease (AD) patients may have longer survival compared with white AD patients. Neuropathology findings did not explain survival differences by race. Determining the underlying factors behind survival differences may lead to longer survival for AD patients of all race/ethnic backgrounds.

Background: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC., Patients and Methods: Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles)., Results: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events., Conclusion: Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxacin.

Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m(2) for 18 to 44 year old patients to 15 ml/min per 1.73 m(2) for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels <45 ml/min per 1.73 m(2) at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of >3 ml/min per 1.73 m(2). In conclusion, age is a major effect modifier among patients with an eGFR of <60 ml/min per 1.73 m(2), challenging us to move beyond a uniform stage-based approach to managing CKD.

Background: Classical hormone replacement therapy for hot flashes is contraindicated in breast cancer especially in endocrine responsive disease., Patients and Methods: In a double-blind, randomized phase III study, breast cancer patients suffering from hot flashes at least twice a day, who were not taking any medication against hypertension and depression received either clonidine 0.075 mg twice a day or venlafaxine 37.5 mg twice a day for 4 weeks. The primary end point was defined as the frequency of hot flashes after 4 weeks of treatment. A self-reported 1-week hot flash and other symptom questionnaire were kept before the start of treatment until the end of treatment course., Results: From April 2002 to October 2004, 80 patients were recruited of whom 64 were assessable for efficacy analyses. Thirty-three received clonidine and 31 venlafaxine, nine patients stopped early because of side-effects and seven withdrew consent. At the end of treatment week 4, the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes per day for those receiving clonidine (P = 0.025)., Conclusion: Venlafaxine is significantly more effective in reducing the frequency of hot flashes in breast cancer patients than clonidine.

Objective: The purpose of this study is to determine if anxiety is associated with mortality and if race moderates and depression mediates this relationship., Method: Participants are 3,015 adults aged 70-79 years., Results: Anxiety symptoms were significant predictors of all-cause, cardiovascular, and noncardiovascular mortality among blacks but not whites. Depression was not related to mortality., Conclusions: Although the mechanisms that underlie the relationship between anxiety and mortality are unknown, routine assessment of anxiety symptoms in clinical practice, particularly in black older adults, seems prudent.

Objectives: To examine the relationship between anxiety and functional decline., Design: A 5-year longitudinal cohort study of well-functioning adults., Setting: The Health, Aging and Body Composition (Health ABC) Study., Participants: Two thousand nine hundred forty adults aged 70 to 79 (48% male, 41% black), initially free of self-reported mobility difficulty., Measurements: In 1997/98, presence of three anxiety symptoms (feeling fearful, tense or keyed up, or shaky or nervous) from the Hopkins Symptom Checklist were ascertained. Physical function was examined over 5 years using the Health ABC performance battery (continuous range 0-4) consisting of chair stands, usual and narrow course gait speed, and difficulty with standing balance and self-reported mobility, defined as difficulty walking one-quarter of a mile or difficulty climbing 10 steps., Results: Participants with anxiety symptoms had similar baseline physical performance scores. After adjustment for potential confounders, subjects with anxiety symptoms had similar declines in physical performance over 5 years as participants without anxiety symptoms. Adults with anxiety symptoms were more likely to report incident mobility difficulty, with a hazard ratio of 1.4 (95% confidence interval=1.3-1.6), compared with adults without anxiety symptoms. These results persisted after adjustment for depressive symptoms, demographics, comorbidity, and use of antianxiety, depressant, and sedative hypnotic medications., Conclusion: Anxiety symptoms are not associated with declines in objectively measured physical performance over 5 years but are associated with declines in self-reported functioning. Future studies are needed to determine why anxiety has a differential effect on performance-based and self-reported measures of functioning.

Objective: Few population-based studies report cardiovascular disease (CVD) risk factor prevalence for South Asians in the United States. We examined CVD risk for South Asians in California., Design/setting/participants: We used data from two population-based surveys with South Asian participants in California, the California Health Interview Survey (CHIS) and the Cardiovascular Health among Asian Indian (CHAI) survey. The CHIS 2001 was conducted in English; 769 South Asians aged 25-83 years participated as one of many ethnic groups. The CHAI survey was population-based but focused on ethnicity-specific characteristics in 304 South Asians aged 25-80 years in English and Punjabi in 2001-2002., Main Outcome Measures: A CVD risk score included smoking, hypertension, hypercholesterolemia, diabetes, myocardial infarction, and angina. Separate logistic regression models examined the association of sociodemographics, lifestyle, medical risk, acculturation, and "any CVD risk.", Results: In CHAI, hypertension (20%), hypercholesterolemia (24%), and diabetes (10%) were high; smoking was low (12%). In CHIS, prevalence of these conditions was lower, except smoking (21%). Approximately 35% of participants in each survey had any CVD risk. Male sex, age, higher body mass index, education less than a bachelor's degree, and alcohol use were associated with CVD risk in both studies. The CHAI subjects interviewed in English had higher odds of any CVD risk than those interviewed in Punjabi (odds ratio 10.3, 95% confidence interval 2.9-36.7)., Conclusions: Data from multiple sources add crucial information about heterogeneity of risk within ethnic populations. South Asians in the CHIS had higher rates of smoking, but lower CVD risk scores than participants in the CHAI study. In CHAI, English language use was associated with increased CVD risk score. Additional research should examine if acculturation increases CVD risk.

Background: While limited literacy is common and its prevalence increases with age, no prospective study has assessed whether limited literacy is associated with mortality in older adults., Objective: To assess the association of limited literacy with mortality., Design and Setting: Five-year prospective study from 1999 to 2004 of community-dwelling elders from Memphis, TN, and Pittsburgh, PA, who were from the Health, Aging, and Body Composition study. Subjects' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into limited (0 to 8th grade reading level) or adequate literacy (> or = 9th grade reading level)., Participants: Two thousand five hundred and twelve black and white elders without baseline functional difficulties or dementia., Measurements: Time to death., Results: Participants' mean age was 75.6 years, 48% were male, 38% were black, and 24% had limited literacy; the median follow-up time was 4.2 years. Compared with those with adequate literacy, those with limited literacy had a higher risk of death (19.7% vs 10.6%) with a hazard ratio (HR) of 2.03 (95% confidence intervals [CI], 1.62 to 2.55). After adjusting for demographics and socioeconomic status, co-morbid conditions, self-rated health status, health-related behaviors, health care access measures, and psychosocial status, limited literacy remained independently associated with mortality (HR 1.75; 95% CI, 1.27 to 2.41)., Conclusions: Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly. Given the growth of the aging population and the prevalence of chronic diseases, the mechanisms by which limited literacy is associated with mortality in the elderly warrant further investigation.

Objectives: To determine the relationship between health literacy, demographics, and access to health care., Design: Cross-sectional study, Health, Aging and Body Composition data (1999/2000)., Setting: Memphis, Tennessee, and Pittsburgh, Pennsylvania., Participants: Two thousand five hundred twelve black and white community-dwelling older people who were well functioning at baseline (without functional difficulties or dementia)., Measurements: Participants' health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into 0 to sixth-, seventh- to eighth-, and ninth-grade and higher reading levels (limited health literacy defined as <9th grade). Participants' demographics, socioeconomic status, comorbidities, and three indicators of healthcare access (whether they had a doctor/regular place of medical care, an influenza vaccination within the year, or insurance for medications) were also assessed., Results: Participants' mean age was 75.6, 52% were female, 38% were black, and 24% had limited health literacy. After adjusting for sociodemographics, associations remained between limited health literacy and being male, being black, and having low income and education, diabetes mellitus, depressive symptoms, and fair/poor self-rated health (P<.02). After adjusting for sociodemographics, health status, and comorbidities, older people with a sixth-grade reading level or lower were twice as likely to have any of the three indicators of poor healthcare access (odds ratio=1.96, 95% confidence interval=1.34-2.88)., Conclusion: Limited health literacy was prevalent and was associated with low socioeconomic status, comorbidities, and poor access to health care, suggesting that it may be an independent risk factor for health disparities in older people.

Background: At present, the combination of docetaxel/doxorubicin/cyclophosphamide (TAC) is considered a treatment option for patients with node-positive primary breast cancer; however, treatment is associated with grade 1-4 anemia in up to 95% of patients (grade 2-4 in 36%)., Patients and Methods: We prospectively investigated the use of a primary prophylaxis with darbepoetin alfa once every 3 weeks in 35 patients receiving 6-8 cycles of TAC as neoadjuvant treatment for breast cancer. Darbepoetin alfa treatment was started on day 1 of a TAC cycle if hemoglobin (Hb) level was /= 14 g/dL. The primary aim was to prevent Hb levels 14 g/dL in 12 patients (34.3%) and in 13 cycles (5.4%). Hemoglobin level on day 21 of the last cycle was

Background: Black elders have a greater frequency of functional decline than do white elders. The impact of cognitive function on explaining black-white disparities in functional decline has not been extensively explored., Methods: To compare the extent to which different risk domains (comorbidity, smoking, socioeconomic status (SES), self-rated health, and cognitive function) explain more frequent functional decline in black elders, we studied 779 black and 4892 white community-dwelling adults aged 70 and older from the Assets and Health Dynamics Among the Oldest Old (AHEAD), a population-based cohort study begun in 1993. Our primary outcome was worse functional status at 2 years than at baseline. We used logistic regression to compare the unadjusted with the adjusted black-white odds ratios (ORs) after adjusting for each risk domain., Results: At baseline black participants aged 70-79 had higher rates of smoking, diabetes, and hypertension; lower SES; and worse cognitive function than did white participants (p <.05 for all). The mean cognitive score was 15.7 in black and 21.8 in white participants (p <.01). Black participants had a higher frequency of 2-year functional decline than did white participants (10.9% vs 4.7%; OR = 2.61, 95% confidence interval [CI], 1.69-4.03 adjusted for age and sex). Adjustment for comorbidity and smoking did not significantly change the black-white OR, whereas self-rated health and SES accounted for about half the risk. Adjustment for cognitive function accounted for nearly all the associated decline (OR = 1.10, 95% CI, 0.67-1.79). Among participants aged 80 and over, those who were black had significantly lower risk for functional decline after adjustment for cognitive function (OR = 0.61, 95% CI, 0.38-0.96 vs OR = 1.08, 95% CI, 0.70-1.66 adjusted for age and sex only)., Conclusions: Cognitive function mediated the higher frequency of functional decline among black elders. Efforts to understand cognitive function may enhance our understanding of black-white disparities in health outcomes.

Several studies have reported that older black and Latino adults have lower cognitive function test scores than older white adults, but few have comprehensively examined reasons for score differences. This study evaluates whether differences in health and socioeconomic indicators, including literacy level, can explain differences in cognitive function test scores between older black and white adults.

Objectives: To determine the prevalence and correlates of anxiety symptoms in the absence of depression, in older black and white people., Design: Cross-sectional study., Setting: Baseline assessment of a biracial cohort of community-resident well-functioning men and women aged 70 to 79 participating in the Health Aging and Body Composition study., Participants: Three thousand forty-one participants (mean age 74, 52% women, 58% white)., Measurements: Participants were asked about three major anxiety symptoms (feeling fearful, tense/keyed-up, or shaky/nervous) derived from the Hopkins Symptom Checklist. Participants were considered to have anxiety symptoms if they reported feeling at least two anxiety symptoms "a little" or one symptom "quite a bit" in the past week. Logistic regression models were used to identify demographic, psychosocial, and health-related correlates of anxiety symptoms., Results: Anxiety symptoms occurred in 15% of older people without depression and 43% of those with depression. Of nondepressed older people, women were more likely to have anxiety symptoms than men (P <.01), especially white women (20% prevalence). After multivariate adjustment, the chronic conditions of urinary incontinence (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-1.9), hearing impairment (OR = 1.4, 95% CI = 1.0-2.1), hypertension (OR = 1.3, 95% CI = 1.0-1.7) and poor sleep (OR = 1.7, 95% CI = 1.3-2.4) were associated with a higher prevalence of anxiety symptoms. Persons with poorer psychosocial functioning, low personal mastery (OR = 2.0, 95% CI = 1.6-2.5) and the need for more emotional support (OR = 2.2, 95% CI = 1.7-2.8), also had higher rates of anxiety symptoms., Conclusion: Anxiety symptoms are common in depressed and nondepressed older people. Given the high prevalence and coexistence with depressive symptoms, it will be important to conduct longitudinal studies that assess depressive and anxiety symptoms to clarify the direction and influence and disentangle the health-related consequences of these two conditions.

Objectives: Although cognitive impairment and depressive symptoms are associated with functional decline, it is not understood how these risk factors act together to affect the risk of functional decline. The purpose of this study is to determine the relative contributions of cognitive impairment and depressive symptoms on decline in activity of daily living (ADL) function over 2 years in an older cohort., Design: Prospective cohort study., Setting: A U.S. national prospective cohort study of older people, Asset and Health Dynamics in the Oldest Old., Participants: Five thousand six hundred ninety-seven participants (mean age 77, 64% women, 86% white) followed from 1993 to 1995., Measurements: Cognitive impairment and depressive symptoms were defined as the poorest scores: 1.5 standard deviations below the mean on a cognitive scale or 1.5 standard deviations above the mean on validated depression scales. Risk of functional decline in participants with depressive symptoms, cognitive impairment, and both, compared with neither risk factor, were calculated and stratified by baseline dependence. Analyses were adjusted for demographics and comorbidity., Results: Eight percent (n = 450) of subjects declined in ADL function. In participants who were independent in all ADLs at baseline, the relative risk (RR) of 2-year functional decline was 2.3 (95% confidence interval (CI) = 1.7-3.1) for participants with cognitive impairment, 1.9 (95% CI = 1.3-2.6) for participants with depressive symptoms, and 2.4 (95% CI = 1.4-3.7) for participants with cognitive impairment and depressive symptoms. In participants who were dependent in one or more ADLs at baseline, RR of 2-year functional decline was 1.9 (95% CI = 1.2-2.8) for participants with cognitive impairment, 0.6 (95% CI = 0.3-1.3) for participants with depressive symptoms, and 1.5 (95% CI = 0.8-2.6) for participants with cognitive impairment and depressive symptoms., Conclusions: In participants with no ADL dependence at baseline, cognitive impairment and depressive symptoms are risk factors for decline, but that, in participants with dependence in ADL at baseline, cognitive impairment, but not depressive symptoms, is a risk factor for additional decline.

Background: Light-to-moderate alcohol consumption reduces the risk of coronary heart disease and stroke. Because vascular disease is associated with cognitive impairment and dementia, we hypothesised that alcohol consumption might also affect the risk of dementia., Methods: We examined the relation between alcohol consumption and risk of dementia in individuals taking part in the Rotterdam Study--a prospective population-based study of 7983 individuals aged 55 years and older. We studied all participants who did not have dementia at baseline (1990-93) and who had complete data on alcohol consumption (n=5395). Through follow-up examinations in 1993-94 and 1997-99 and an extensive monitoring system, we obtained nearly complete follow-up (99.7%) until the end of 1999. We used proportional hazards regression analysis, adjusted for age, sex, systolic blood pressure, education, smoking, and body-mass index, to compare the risk of developing dementia between individuals who regularly consumed alcohol and individuals who did not consume alcohol., Findings: The average follow-up was 6.0 years. During this period, 197 individuals developed dementia (146 Alzheimer's disease, 29 vascular dementia, 22 other dementia). The median alcohol consumption was 0.29 drinks per day. Light-to-moderate drinking (one to three drinks per day) was significantly associated with a lower risk of any dementia (hazard ratio 0.58 [95% CI 0.38-0.90]) and vascular dementia (hazard ratio 0.29 [0.09-0.93]). We found no evidence that the relation between alcohol and dementia varied by type of alcoholic beverage., Interpretation: These findings suggest that light-to-moderate alcohol consumption is associated with a reduced risk of dementia in individuals aged 55 years or older. The effect seems to be unchanged by the source of alcohol.

The cytolytic activity of NK cells is tightly regulated by inhibitory receptors specific for MHC class I Ags. We have investigated the composition of signal transduction molecules in the supramolecular activation clusters in the MHC class I-regulated cytolytic and noncytolytic NK cell immune synapses. KIR2DL3-positive NK clones that are specifically inhibited in their cytotoxicity by HLA-Cw*0304 and polyclonal human NK cells were used for conjugate formation with target cells that are either protected or are susceptible to NK cell-mediated cytotoxicity. Polarization of talin, microtubule-organizing center, and lysosomes occurred only during cytolytic interactions. The NK immune synapses were analyzed by three-dimensional immunofluorescence microscopy, which showed two distinctly different synaptic organizations in NK cells during cytolytic and noncytolytic interactions. The center of a cytolytic synapse with MHC class I-deficient target is comprised of a complex of signaling molecules including Src homology (SH)2-containing protein tyrosine phosphatase-1 (SHP-1). Closely related molecules with overlapping functions, such as the Syk kinases, SYK, and ZAP-70, and adaptor molecules, SH2 domain-containing leukocyte protein of 76 kDa and B cell linker protein, are expressed in activated NK cells and are all recruited to the center of the cytolytic synapse. In contrast, the noncytolytic synapse contains SHP-1, but is lacking other components of the central supramolecular activation cluster. These findings indicate a functional role for SHP-1 in both the cytolytic and noncytolytic interactions. We also demonstrate, in three-cell conjugates, that a single NK cell forms a cytolytic synapse with a susceptible target cell in the presence of both susceptible and nonsusceptible target cells.

Purpose: This article provides a review of the literature on the decline of hepatitis B virus (HBV) infection in Asian and Pacific nations having universal hepatitis B immunization programs., Methods: Papers on the epidemiology of HBV infection and hepatitis B immunization programs in Asian and Pacific nations were located by searching MEDLINE and libraries for publications in English, and by contacting hepatitis B experts., Principal Findings: High endemicity for HBV in Asian and Pacific nations was partly caused by a cycle of high infectiousness, perinatal transmission, and chronic infection from early ages. Higher prevalence of infection has been found in men, some families, communities, and ethnic groups, and in people with high risk behaviors and situations, such as attending day care, getting injections, or sharing personal items. Incidence of acquisition of infection is about 2%-5% per year. Prevalence of HBV infection was declining in some nations before commencing hepatitis B immunization programs, probably because of improvements in medical practices and living conditions. Twenty-seven of 34 Pacific and East and Southeast Asian nations have attained >70% hepatitis B vaccination coverage in infants, and twelve have documented reducing infection or liver cancer to fractions of their former rates. But the immunization programs may be causing natural selection of mutant hepatitis B viruses, necessitating study of the mutants, and modification of serological tests and vaccines., Conclusions: Practical implications for U.S. health professionals are: increasing HBV screening and hepatitis B vaccination of adolescents and adults from Asian and Pacific nations can prevent many infections and disease cases; most children coming from high coverage Asian and Pacific nations will be immune and few infected; we can learn much from these successful programs; and we should still make efforts to immunize Asian and Pacific children in the United States, and help Asian and Pacific nations which do not yet have highly successful hepatitis B immunization programs.

Unlabelled: AIMS AND SUBJECTS: We investigated the prospective relationship between thyroid status and the risk of dementia and Alzheimer's disease among a random sample of 1843 participants, aged 55 years and over, from the population-based prospective Rotterdam Study., Methods: Thyroid status was measured at baseline (1990-93), through assessment of serum antibodies to thyroid peroxidase (TPO-Abs, positive: >10 IU/ml), serum TSH levels, and when TSH was abnormal (<0.4 or >4.0 mU/l), serum thyroxin levels (T4). At baseline and at follow up, after on average 2 years, participants were screened for dementia. Diagnoses were based on international criteria., Results: Persons with reduced TSH levels at baseline had a more than threefold increased risk of dementia (RR = 3.5, 95%CI: 1.2-10.0) and of Alzheimer's disease (RR = 3.5, 95%CI: 1.1-11.5), after adjustment for age and sex. Among persons with reduced TSH levels, T4 levels appeared to be positively related to the risk of dementia (RR per SD increase = 2.9, 95%CI: 0.7-12.2), although none of those who became demented had a T4 level above the normal range (>140 nmol/l). The risk of dementia was especially increased in subjects with low TSH who were positive for TPO-Abs (RR = 23.7, 95%CI: 4.0-140)., Conclusions: This is the first prospective study to suggest that subclinical hyperthyroidism in the elderly increases the risk of dementia and Alzheimer's disease.

Objective: To investigate the relation between head trauma and incidence of dementia in a prospective population-based study., Background: Whether head trauma increases the risk of dementia and AD remains controversial. It has been suggested that the risk might be particularly increased for carriers of the APOE-epsilon4 allele., Methods: The study population included 6645 participants of the prospective population-based Rotterdam Study, aged 55 years or older, who were free of dementia at baseline. Head trauma with loss of consciousness was measured at baseline by a self-report to a physician and detailed the number of head traumas, time since head trauma, and duration of loss of consciousness. The cohort was followed for incident dementia that was diagnosed according to international criteria. Logistic regression was used to calculate the risk of dementia after adjusting for age, gender, and education., Results: No increased risk of dementia or AD was found for persons with a history of head trauma with loss of consciousness (relative risk [RR] for dementia = 1.0, 95% CI, 0.5-2.0; RR for AD = 0.8, 95% CI, 0.4-1.9). Multiple head traumas, time since head trauma, and duration of unconsciousness did not significantly influence the risk of dementia. In addition, the APOE-epsilon4 allele did not modify the relationship., Conclusions: This study suggests that mild head trauma is not a major risk factor for dementia or AD in the elderly. In addition, this study does not concur with previous cross-sectional studies suggesting an interaction with the APOE genotype.