bluuebunny/crossref_metadata_2025 huggingface dataset:
Emanuel Miller Lecture: Early onset depressions – meanings, mechanisms and processes
Authors: Goodyer Ian M.
Published: November 2008

Background:  Depressive syndromes in children and adolescents constitute a serious group of mental disorders with considerable risk for recurrence. A more precise understanding of aetiology is necessary to improve treatment and management.

Methods:  Three neuroactive agents are purported to be involved in the aetiology of these disorders: serotonin, brain‐derived neurotrophic factor and cortisol. A literature review was conducted to determine their contributions to the emergence of unipolar depressions in the adolescent years.

Results:  Serotonin, brain‐derived neurotrophic factor and cortisol may operate in concert within two distinct functional frameworks: atypical early epigenesis arising in the first few years of life and resulting in the formation of a vulnerable neuronal network involving in particular the amygdala and ventral prefrontal cortex. Individuals with this vulnerability are likely to show impaired mood regulation when faced with environmental demands during adolescence and over the subsequent decades; and acquired neuroendangerment, a pathological brain process leading to reduced synaptic plasticity, in particular in the hippocampus and perhaps the nucleus accumbens and ventral tegmentum. This may result in motivational, cognitive and behavioural deficits at any point in the lifespan most apparent at times of environmental demand.

Conclusions:  The characteristics, course and outcome of a depressive episode may depend on the extent of the involvement of both atypical early neurogenesis and acquired neuroendangerment.
Personal reflections on observational and experimental research approaches to childhood psychopathology
Authors: Rapoport Judith L.
Published: November 2008

The past 50 years have seen dramatic changes in childhood psychopathology research. The goal of this overview is to contrast observational and experimental research approaches; both have grown more complex such that the boundary between these approaches may be blurred. Both are essential. Landmark observational studies with long‐term follow‐up (Robins, 1966; Yarrow, Campbell, & Burton, 1970) have had – and continue to have – unique impact on clinical research and practice. Epidemiological studies showed high rates of psychological disorder and their close tie to neurological impairment (Rutter, Tizard, & Whitemore, 1970). These studies have current impact with respect to brain imaging correlates of clinical outcome. Pharmacological studies, particularly those on stimulants and on treatment of pediatric obsessive compulsive disorder (OCD), have propelled experimental methodology and inspired translational approaches. Predicted future trends are: more informed subgrouping of our heterogeneous phenotypes, reliance on multicenter trials, and documentation of non‐conventional methods of care delivery.
How neuropsychology informs our understanding of developmental disorders
Authors: Pennington Bruce F.
Published: November 2008

This review includes 1) an explanation of what neuropsychology is, 2) a brief history of how developmental cognitive neuroscience emerged from earlier neuropsychological approaches to understanding atypical development, 3) three recent examples that illustrate the benefits of this approach, 4) issues and challenges this approach must face, and 5) a forecast for the future of this approach.
The past achievements and future promises of developmental psychopathology: the coming of age of a discipline
Authors: Cicchetti Dante , Toth Sheree L.
Published: November 2008

Over the past decades, developmental psychopathology has coalesced into a discipline that has made significant contributions toward the understanding of risk, psychopathology, and resilience in individuals across the life course. The overarching goal of the discipline has been to elucidate the interplay among biological, psychological, and social‐contextual aspects of normal and abnormal development. In addition to directing efforts toward bridging fields of study and aiding in elucidating important truths about the processes underlying adaptation and maladaptation, investigators in developmental psychopathology have been equally devoted to developing and evaluating methods for preventing and ameliorating maladaptive and psychopathological outcomes. Increasingly, efforts are being made to conduct investigations at multiple levels of analysis and to translate basic research knowledge into real‐world contexts. In this article, the contributions, challenges, and future directions of the field are highlighted.
Research Review: Crossing syndrome boundaries in the search for brain endophenotypes
Authors: Levy Yonata , Ebstein Richard P.
Published: November 2008

The inherent imprecision of behavioral phenotyping is the single most important factor contributing to the failure to discover the biological factors that are involved in psychiatric and neurodevelopmental disorders (e.g., Bearden & Freimer, 2006). In this review article we argue that in addition to an appreciation of the inherent complexity at the biological level, a rather urgent task facing behavioral scientists involves a reconsideration of the role that clinical syndromes play in psychological theorizing, as well as in research into the biological basis of cognition and personality. Syndrome heterogeneity, cross‐syndrome similarities and syndrome comorbidities question the relevance of syndromes to biological research. It is suggested that the search for brain endophenotypes, intermediate between genes and behavior, should be based on cross‐syndrome, trait classification. Cohort selection should rest on behavioral homogeneity, enabling, when necessary, syndrome heterogeneity.
Behavioural and cognitive phenotypes in idiopathic autism versus autism associated with fragile X syndrome
Authors: Dissanayake Cheryl , Bui Quang , Bulhak‐Paterson Danuta , Huggins Richard , Loesch Danuta Z.
Published: November 2008

Background:  In order to better understand the underlying biological mechanism/s involved in autism, it is important to investigate the cognitive and behavioural phenotypes associated with idiopathic autism (autism without a known cause) and comorbid autism (autism associated with known genetic/biological disorders such as fragile X syndrome). Parental effects associated with each type of autism also serve to cast light on the biological underpinnings of autism.

Method:  Forty‐nine participants with idiopathic autism (AD; Mean age: 11.16; SD: 6.08) and their parents (45 mothers; 34 fathers), and 48 participants with fragile X syndrome and co‐morbid autism (FXS/AD; Mean age: 17.30; SD: 10.22) and their parents (32 mothers; 30 fathers) were administered the ADOS‐G and the age‐appropriate Wechsler test to ascertain autism and cognitive profiles respectively.

Results:  The AD and FXS/AD groups showed a similar profile on the ADOS domains, with slightly higher scores on the Communication domain in the FXS/AD group, after adjusting for full‐scale IQ. Marked differences between the groups in their cognitive abilities were apparent, with the FXS/AD group showing significantly lower scores on all subtests except Comprehension. While no parental effects were found for the FXS/AD group, a paternal effect was apparent on the combined ADOS score for the AD group. Moreover, midparental effects were found in this group for full‐scale IQ (FSIQ) and verbal IQ (VIQ). Analyses also revealed parental effects for the subtests of Similarities, Vocabulary, and Information with predominantly maternal effect, and Digit Span with predominantly paternal effect. Both parents contributed to the midparental effect for Processing Speed.

Conclusions:  The results, together with our previous findings, suggest that the postulated combination of susceptibility genes for autism may primarily involve cognitive rather than behavioural processes.
Perception of tone and aspiration contrasts in Chinese children with dyslexia
Authors: Cheung Him , Chung Kevin K.H. , Wong Simpson W.L. , McBride‐Chang Catherine , Penney Trevor B. , Ho Connie S.H.
Published: November 2008

Background:  Previous research has shown a relationship between speech perception and dyslexia in alphabetic writing. In these studies speech perception was measured using phonemes, a prominent feature of alphabetic languages. Given the primary importance of lexical tone in Chinese language processing, we tested the extent to which lexical tone and aspiration, two fundamental dimensions of Cantonese speech not represented in writing, would distinguish dyslexic from non‐dyslexic 8‐year‐old Chinese children. Tone and aspiration were tested in addition to other phonological processing skills across groups to determine the importance of different aspects of phonological sensitivity in relation to reading disability.

Methods:  Dyslexic children and age‐matched and reading‐level controls were tested on their categorical perception of minimal pairs contrasting in tone and aspiration, phonological awareness, rapid digit naming, and Chinese reading abilities.

Results:  While performing similarly to reading‐level controls, dyslexic children perceived tone and aspiration contrasts less categorically and accurately than age‐matched controls. They also performed more poorly than the age‐matched controls on rapid digit naming and a measure of phonological awareness testing children’s sensitivity to different grain size units.

Conclusions:  Dyslexia in non‐alphabetic Chinese correlates with the categorical organization and accuracy of Cantonese speech perception, along the tone and aspiration dimensions. This association with reading is mediated by its association with phonological awareness. Therefore, dyslexia is universally at least partly a function of basic speech and phonological processes independent of whether the speech dimensions in question are coded in writing.
Low‐intensity resistance exercise with slow lifting and lowering does not increase noradrenalin and cardiovascular responses
Authors: Okamoto Takanobu , Masuhara Mitsuhiko , Ikuta Komei
Published: November 2008

The aim of this study was to investigate the effect of low‐intensity resistance exercise with slow lifting and lowering (LSL) on plasma endothelin‐1 (ET‐1) and noradrenalin concentrations in young healthy adults. Eight healthy males participated in this study (age 19·0 ± 0·5 years, mean ± SD). The LSL performed the 10 repetitions with 3 s eccentric (lowering phase) and 3 s concentric (lifting phase) muscle actions. The high‐intensity resistance exercise with normal lifting and lowering (HNL) performed the 10 repetitions with 1 s eccentric (lowering phase) and 1 s concentric (lifting phase) muscle actions. The load was set to 40% of one repetition maximal (1RM) for LSL and 80% of 1RM for HNL. Plasma ET‐1 and noradrenalin concentrations were measured before and after each type of exercise. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR) during LSL and HNL were measured. The rate‐pressure product (RPP) was calculated from SBP and HR. There were no significant differences in the plasma ET‐1 concentration between LSL and HNL. However, the plasma noradrenalin concentration was significantly increased after HNL, compared with LSL (P<0·001). SBP, DBP, PP, MAP, HR and RPP during LSL were significantly lower compared with HNL (P<0·05: PP and HR;P<0·01: RPP;P<0·001: SBP, DBP and MAP). These results suggested that LSL may suppress the increase in plasma noradrenalin concentrations and cardiovascular responses.
Seizure recurrence risk following a first seizure in neurologically normal children
Authors: Arthur Todd M. , DeGrauw Ton J. , Johnson Cynthia S. , Perkins Susan M. , Kalnin Andrew , Austin Joan K. , Dunn David W.
Published: November 2008

Purpose:  To define seizure recurrence rates in normal children who had had a single seizure and to define electroencephalography (EEG) or magnetic resonance imaging (MRI) utility in predicting seizure recurrence.

Methods:  We studied 150 children (6 to 14 years) with a first afebrile, unprovoked seizure. Inclusion criteria were: Normal physical and neurological examination, undergone EEG and MRI studies of the brain, and followed for at least 27 months. These children participated in an ongoing prospective study of new onset seizures in childhood.

Results:  The seizure recurrence rate was 66.4%. An abnormal EEG had no association with seizure recurrence at 9, 18, or 27 months (p = 0.1806, p = 0.2792, and p = 0.2379, respectively). A “significant” MRI abnormality, which occurred in 16.0% of patients, was associated with an increased seizure recurrence risk at 9 months (p = 0.0389) but not at 18 or 27 months.

Discussion:  EEG findings poorly predict recurrence after a single seizure. The high rate of MRI abnormalities suggests that MRI may need consideration as a routine test to evaluate epilepsy in normal children.
Long‐term management of the ketogenic diet: Seizure monitoring, nutrition, and supplementation
Authors: Zupec‐Kania Beth , Zupanc Mary L.
Published: November 2008

Summary

The ketogenic diet (KD) is a medical nutrition therapy (MNT) for the treatment of epilepsy. As such, it can affect the outcome of an individual's health and chronic medical condition. The components of MNT which have been established by the American Dietetic Association as core guidelines for nutrition care include a diet history, assessment, diet therapy and a follow‐up plan of care (American Dietetic Assoc 2002). We have utilized these guidelines in designing our approach to KD therapy in our pediatric population. Many of the practices described here have been adopted from our practical experience.
Cultural challenges in using the ketogenic diet in Asian countries
Authors: Seo Joo Hee , Kim Heung Dong
Published: November 2008

Summary

The ketogenic diet (KD) is a high fat, low carbohydrate diet that has been used for intractable childhood epilepsy since the early 1920s. After the resurgence of the KD since the mid 1990s in the United States, there has been a dramatic increase in its use worldwide. The increasing use of this diet in Asia is not an exception. However, since carbohydrates are considered to be a main dietary composition of Asians, there has been some limitation on the rapid adaptation of KD. This summary will give a brief review on current state, limitations, and efforts to provide a successful KD in Asia.
Neuroprotective effects of the ketogenic diet
Authors: Noh Hae Sook , Kim Yoon Sook , Choi Wan Sung
Published: November 2008

Summary

The ketogenic diet (KD) is an alternative treatment for medically refractory epilepsy. Despite numerous mechanistic hypotheses advanced to explain the anticonvulsant action of the KD, few studies to date have addressed the molecular changes in brain following KD treatment. Here, we present recent experimental results based on systemic administration of kainic acid (KA) in rodents. KA typically induces acute limbic seizures and results in cellular and molecular alterations, accompanied by neuronal death mainly in limbic structures, similar to what has been observed in surgically resected temporal lobe tissue in epileptic patients. We have reported that neuronal degeneration induced by KA is ameliorated by KD treatment via diverse protective mechanisms, including inhibition of caspase‐3‐mediated apoptosis in hippocampal neurons. Neuroprotective strategies such as the KD, if implemented early, might exert an antiepileptogenic effect, and could prevent associated learning and memory deficits.
Gamma frequency SSVEP components differentiate children with febrile seizures from normal controls
Authors: Birca Ala , Carmant Lionel , Lortie Anne , Vannasing Phetsamone , Lassonde Maryse
Published: November 2008

Gamma band electroencephalography (EEG) abnormalities have been reported in patients with epilepsy. We aimed to investigate whether patients with febrile seizures (FS) show abnormalities of the gamma frequency steady‐state visual evoked potential (SSVEP) components evoked by intermittent photic stimulation (IPS). We analyzed the magnitude and phase alignment of the 50–100 Hz SSVEP components elicited by IPS from 12 FS patients, 5 siblings of FS patients, and 15 control children between 6 and 36 months of age. Patients with FS showed significantly higher SSVEP magnitude and phase alignment values when compared to both the siblings and control groups. Detected abnormalities could either represent the direct consequence of seizures or indicate a preexisting tendency to hypersynchrony in FS patients. Future prospective studies could assess whether SSVEP abnormalities are associated with complex rather than simple FS, or have a prognostic value for the development of epilepsy following FS.
When What You See Isn’t What You Get: Alcohol Cues, Alcohol Administration, Prediction Error, and Human Striatal Dopamine
Authors: Yoder Karmen K. , Morris Evan D. , Constantinescu Cristian C. , Cheng Tee‐Ean , Normandin Marc D. , O’Connor Sean J. , Kareken David A.
Published: November 2008

Background: The mesolimbic dopamine (DA) system is implicated in the development and maintenance of alcohol drinking; however, the exact mechanisms by which DA regulates human alcohol consumption are unclear. This study assessed the distinct effects of alcohol‐related cues and alcohol administration on striatal DA release in healthy humans.

Methods: Subjects underwent 3 PET scans with [11C]raclopride (RAC). Subjects were informed that they would receive either an IV Ringer's lactate infusion or an alcohol (EtOH) infusion during scanning, with naturalistic visual and olfactory cues indicating which infusion would occur. Scans were acquired in the following sequence: (1) Baseline Scan: Neutral cues predicting a Ringer’s lactate infusion, (2) CUES Scan: Alcohol‐related cues predicting alcohol infusion in a Ringer’s lactate solution, but with alcohol infusionafterscanning to isolate the effects of cues, and (3) EtOH Scan: Neutral cues predicting Ringer's, but with alcohol infusionduringscanning (to isolate the effects of alcohol without confounding expectation or craving).

Results: Relative to baseline, striatal DA concentration decreased during CUES, but increased during EtOH.

Conclusion: While the results appear inconsistent with some animal experiments showing dopaminergic responses to alcohol’s conditioned cues, they can be understood in the context of the hypothesized role of the striatum in reward prediction error, and of animal studies showing that midbrain dopamine neurons decrease and increase firing rates during negative and positive prediction errors, respectively. We believe that our data are the first in humans to demonstrate such changes in striatal DA during reward prediction error.
Decrease in the Prevalence of Adolescent Alcohol Use and its Possible Causes in Japan: Periodical Nationwide Cross‐Sectional Surveys
Authors: Osaki Yoneatsu , Tanihata Takeo , Ohida Takashi , Kanda Hideyuki , Suzuki Kenji , Higuchi Susumu , Kaneita Yoshitaka , Minowa Masumi , Hayashi Kenji
Published: November 2008

Background:  Trends in alcohol drinking prevalence were assessed among Japanese adolescents, and possible reasons for a decrease in drinking prevalence observed in 2004.

Methods:  Cross‐sectional nationwide surveys were conducted periodically. High schools were randomly sampled from throughout Japan in 1996, 2000, and 2004. All enrolled students in sampled schools were subjects of the surveys. Self‐reporting anonymous questionnaires were collected from 115,814 students in 1996, 106,297 in 2000, and 102,451 in 2004. Questions about drinking prevalence of students and family members, proportion of students who have no friends, and sources of alcohol were included. Students who drunk at least one day of the 30 days preceding the survey were defined as the current drinkers.

Results:  The drinking prevalence in 2004 was decreased in comparison to that in 1996 and 2000 in both sexes and in all school grades. The current drinking rate (monthly drinker) among junior high school boys was 29.4% in 1996, 29.0% in 2000, and 20.5% in 2004, while that among senior high school boys was 49.7%, 48.7%, and 36.2%, respectively. The respective prevalence among junior and senior girls was 24.0%, 25.5%, and 20.0% and 40.8%, 42.1%, and 34.1%. The prevalent sources of alcohol beverages were searching in home, stores (convenience store, supermarket, or gas‐stand), liquor shops, and bars. An analysis of the reasons for this decrease identified a decrease in drinking prevalence in students’ families, especially by fathers and older brothers, and an increase in the proportion of students who had no friends.

Conclusions:  A decrease in drinking prevalence of male family members and a limitation of sources of alcoholic beverages may contribute to the decrease in adolescent drinking prevalence.
Nursing Home Assessment of Cognitive Impairment: Development and Testing of a Brief Instrument of Mental Status
Authors: Chodosh Joshua , Edelen Maria Orlando , Buchanan Joan L. , Yosef Julia Ann , Ouslander Joseph G. , Berlowitz Dan R. , Streim Joel E. , Saliba Debra
Published: November 2008

OBJECTIVES: To test the accuracy of a brief cognitive assessment of nursing home (NH) residents and to determine whether facility nurses can reliably perform this assessment.

DESIGN: Cross‐sectional, independent cognitive screening tests with NH residents.

SETTING: Six Department of Veteran Affairs nursing facilities.

PARTICIPANTS: Three hundred seventy‐four residents from six regionally distributed Veteran Affairs NHs.

MEASUREMENTS: Three cognitive assessment instruments: the Brief Interview of Mental Status (BIMS), created for this study; the Minimum Data Set (MDS) 2.0 Cognitive Performance Scale (CPS), and the Modified Mini‐Mental State Examination (3MS) as the criterion standard. The 15‐point BIMS tests memory and orientation and includes free and cued recall items. Research assistants administered the 3MS and BIMS to all subjects. Facility nurses administered the same BIMS to a subsample.

RESULTS: Three hundred seventy‐four of 417 (89.7%) residents approached completed the 3MS and research assistant–administered BIMS (BIMS‐R); 212 residents also received a facility nurse–administered BIMS (BIMS‐N). The BIMS‐R was more highly correlated with the 3MS than was the CPS (Pearson correlation coefficient (r)=0.79 vs 0.62; P<.01 for difference). For the subset who received facility assessments, the BIMS‐N was also more highly correlated with the 3MS (Pearson r=0.74 vs 0.65; P<.01 for difference). For any impairment (3MS<78), the area under the receiver operator characteristic curve (AUC) was 0.86 for the BIMS, versus 0.77 for the CPS. For severe impairment (3MS<48) the AUC was 0.94, versus 0.85 for the CPS.

CONCLUSION: In this population, a brief cognitive test is a more accurate approach to cognitive assessment than the current observational methods employed using the MDS 2.0.
Future Research: A Prospective Longitudinal Study of Elder Self‐Neglect
Authors: Dyer Carmel Bitondo , Franzini Luisa , Watson Mary , Sanchez Luis , Prati Laura , Mitchell Stacy , Wallace Robert , Pickens Sabrina
Published: November 2008

In almost every U.S. jurisdiction, elder self‐neglect is the most common allegation addressed by Adult Protective Service (APS) agencies. Not only is self‐neglect common, but this form of mistreatment is an independent risk factor for death. A lack of understanding of the precipitating factors and root causes and of the effect on social and medical systems persists in this field. Research in this area has been limited, because the needs of these vulnerable elderly people are complex and diverse. Moreover, these factors encompass interrelated medical, psychiatric, economic, social, and functional problems.

In 2004, the National Institutes of Health Interdisciplinary Roadmap Initiative provided the means for preliminary exploration of elder self‐neglect through the formation of the Consortium for Research in Elder Self‐neglect of Texas (CREST). The goals of CREST include to conduct pilot studies, form interdisciplinary working groups, convene a national research conference, and appoint a national external advisory board. CREST orchestrated the work of 35 interdisciplinary investigators to achieve these goals.

CREST researchers have begun to characterize the population of vulnerable elderly people who were reported to APS for neglecting themselves. The pilot studies provided a snapshot of 100 elderly people who had neglected themselves. A proposed next phase could involve a prospective longitudinal study of elderly people with severe self‐neglect. This study of the clinical course, the death rate, the causes of death, the occurrence of acute and chronic medical or mental illness, and the costs to the healthcare and social systems would greatly inform the field of elder mistreatment.
Conceptual Challenges and Practical Approaches to Screening Capacity for Self‐Care and Protection in Vulnerable Older Adults
Authors: Naik Aanand D. , Teal Cayla R. , Pavlik Valory N. , Dyer Carmel B. , McCullough Laurence B.
Published: November 2008

Identifying impairments in the capacity to make and execute decisions is critical to the assessment and remediation of elder self‐neglect. Few capacity assessment tools are available for use outside of healthcare settings, and none have been validated in the context of elder self‐neglect. Health and social services professionals are in need of validated tools to assess capacity for self‐care and self‐protection (SC&P) during initial evaluations of older adults with suspected self‐neglect syndrome. Currently, legal and medical declarations of incapacity and guardianship rely on clinical evaluations and instruments developed to assess only decision‐making capacity. This article first describes the conceptual and methodological challenges to assessing the capacity to make and execute decisions regarding safe and independent living. Second, the article describes the pragmatic obstacles to developing a screening tool for the capacity for SC&P. Finally, the article outlines the process for validation and field testing of the screening tool. Social services professionals can then use a valid and feasible screening tool during field assessments to screen for potential impairments in the capacity for SC&P in vulnerable older adults.
Elder Self‐Neglect: A Discussion of a Social Typology
Authors: Paveza Gregory , VandeWeerd Carla , Laumann Edward
Published: November 2008

This article presents a theoretical framework for the study of social and behavioral factors associated with elder self‐neglect. The model presented reflects the authors' beliefs that a risk–vulnerability model offers a useful framework from which to study all forms of elder mistreatment, as well as elder self‐neglect. This model has particular utility, because it can begin to define the elements of risk and vulnerability that may be addressed using preventative measures as opposed to solely addressing intervention, which is often the case when addressing elder mistreatment and self‐neglect. The authors then address a method for using the Consortium for Research in Elder Self‐neglect of Texas data as currently constructed and adding to that database to effectively study risks and vulnerabilities in the elder self‐neglect population. These additional data would greatly expand the scope of the study. The discussant adds his perspective to the ideas proposed by the authors.
Consortium for Research in Elder Self‐Neglect of Texas Research: Advancing the Field for Practitioners
Authors: Mosqueda Laura , Brandl Bonnie , Otto Joanne , Stiegel Lori , Thomas Randolph , Heisler Candace
Published: November 2008

An external advisory board consisting of members from the fields of geriatric internal medicine, family practice geriatrics, criminal prosecution, civil law, police force, adult protective services, and victims advocacy was created to advise and guide the research conducted by the Consortium for Research in Elder Self‐neglect of Texas (CREST). This panel of experts performed site visits and facilitated the research through responses to every‐other‐week fact sheets and quarterly conference calls. This paper provides the perspective of five of the board members regarding the research findings that were presented at the CREST National Conference in 2006. The discussions outline the successes of the CREST research, describe obstacles and the necessary next steps for continuance of the scientific exploration of this syndrome, and highlight the practice implications of the current and proposed research.
Ethnic Differences in Singapore's Dementia Prevalence: The Stroke, Parkinson's Disease, Epilepsy, and Dementia in Singapore Study
Authors: Sahadevan Suresh , Saw Seang Mei , Gao Wei , Tan Louis C.S. , Chin Jing Jih , Hong Ching ye , Venketasubramanian Narayanaswamy
Published: November 2008

OBJECTIVES: To study the prevalence of dementia in Singapore among Chinese, Malays, and Indians.

DESIGN: A two‐phase, cross‐sectional study of randomly selected population from central Singapore with disproportionate race stratification.

SETTING: Community‐based study. Subjects screened to have cognitive impairment at phase 1 in their homes were evaluated clinically for dementia at phase 2 in nearby community centers.

PARTICIPANTS: Fourteen thousand eight hundred seventeen subjects aged 50 and older (67% participation rate).

MEASUREMENTS: The locally validated Abbreviated Mental Test was used to screen for cognitive impairment at phase 1. Dementia was diagnosed at phase 2 as per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Possible Alzheimer's disease (AD) and possible vascular dementia (VD) were diagnosed along the National Institute of Neurological and Communicative Disorders—Alzheimer's Disease and Related Disorders Association and National Institute of Neurological Disorders and Stroke—Association Internationale pour la Recherche et l'Enseignement en Neuroscienes criteria, respectively.

RESULTS: The overall age‐ and race‐standardized dementia prevalence was 1.26% (95% confidence interval (CI)=1.10–1.45). Prevalence (in 5‐year age bands) was 0.08% (50–54), 0.08% (55–59), 0.44% (60–64), 1.16% (65–69), 1.84% (70–74), 3.26% (75–79), 8.35% (80–84), and 16.42% (≥85). From age 50 to 69, 65% of dementia cases were VD; at older ages, 60% were AD. Logistic regression (adjusted for age, sex, education) showed that Malays had twice the risk for AD as Chinese, and Indians had more than twice the risk for AD and VD than Chinese.

CONCLUSION: Singapore's dementia prevalence, primarily influenced by its Chinese majority, is lower than seen in the West. The striking interethnic differences suggest a need for a dementia incidence study and further investigation of underlying genetic and cultural differences between the three ethnic groups in relation to dementia risk.
Sensitivity of two hepatitis B virus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) nucleic acid test systems relative to hepatitis B surface antigen, anti‐HCV, anti‐HIV, and p24/anti‐HIV combination assays in seroconversion panels
Authors: Assal Azzedine , Barlet Valérie , Deschaseaux Marie , Dupont Isabelle , Gallian Pierre , Guitton Cathy , Morel P. , Van Drimmelen Harry , David Bernard , Lelie Nico , De Micco Philippe
Published: November 2008

BACKGROUND: Accurate determination of the infectious window period (IWP) that remains with individual‐donation (ID) or minipool (MP) NAT compared to those with serology assays is essential for residual risk estimations.

STUDY DESIGN AND METHODS: The relative sensitivity of the Procleix Tigris system (Gen‐Probe/Chiron) used in ID‐NAT format and cobas s 201 (Roche Molecular Systems) applied in 1:6 diluted samples to mimic six‐minipool (MP6) nucleic acid test (NAT) was assessed by quadruplicate testing of five seroconversion panels per marker. A mathematical analysis based on the log‐linear increase of viremia in the ramp‐up phase, as established with bDNA 3.0 assays enabled estimation of the IWP for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) assays.

RESULTS: The mean IWPs were Tigris HIV RNA 5.5 days, s 201 (1:6) HIV RNA 7.4 days, GenScreen Plus p24/anti‐HIV 17.8 days, PRISM anti‐HIV 19.0 days, Tigris HBV DNA 20.6 days, s 201 (1:6) HBV DNA 22.6 days, Bio‐Rad hepatitis B surface antigen (HBsAg) 37.8 days, and PRISM HBsAg 35.5 days. At estimated 50 percent NAT seroconversion rates, s 201 (1:6) and Tigris showed mean window‐period reduction times (WPRTs) of 30.5 to 35.5 days to hepatitis C virus antibody (anti‐HCV) assays, 10.4 to 13.5 days to anti‐HIV, or combination p24/anti‐HIV assays and 12.8 to 17.2 days to HBsAg assays.

CONCLUSIONS: Tigris ID‐NAT detected HIV RNA 2 days earlier than s 201 MP6‐NAT, but the difference in sensitivity between the two NAT systems was not significant in HBV seroconversion panels. Insufficient seroconversion samples were available for reliable modeling of WPRT in early HCV infection, but 1.4 to 2.0 days could be predicted by translating analytical sensitivity data. Both multiplex NAT systems demonstrate significant WPRTs compared to (combined) antigen and antibody assays.
The effects of liberal versus restrictive transfusion thresholds on ambulation after hip fracture surgery
Authors: Foss Nicolai B. , Kristensen Morten Tange , Jensen Pia Søe , Palm Henrik , Krasheninnikoff Michael , Kehlet Henrik
Published: November 2008

BACKGROUND: Perioperative anemia leads to increased morbidity and mortality and potentially inhibits rehabilitation after hip fracture surgery. As such, the optimum transfusion threshold after hip fracture surgery is unknown.

PATIENTS AND METHODS: A total of 120 elderly, cognitively intact hip fracture patients admitted from their own home were randomly assigned to receive transfusion at a hemoglobin threshold of 10.0 g per dL (liberal) versus 8.0 g per dL (restrictive) in the entire perioperative period. Patients were treated according to a well‐defined multimodal rehabilitation program. Primary outcome was postoperative functional mobility measured with the cumulated ambulation score (CAS).

RESULTS: Patients in the liberal group received transfusions more frequently than those in the restrictive group (44 patients vs. 22 patients; p < 0.01) and received more transfusions during hospitalization (median, 2 units [interquartile range, 1‐2] vs. 1 [1‐2]; p < 0.0001). There were no significant differences in postoperative rehabilitation scores (CAS: median, 9 [9‐15] vs. 9 [9‐13.5]; p = 0.46) or in length of stay (median, 18 days vs. 16 days, respectively; p = 0.46). There were fewer patients in the liberal transfusion group with cardiovascular complications (2% vs. 10%; p = 0.05) and a lower mortality (0% vs. 8%; p = 0.02).

CONCLUSION: Although a liberal transfusion trigger did not result in increased ambulation scores, restrictive transfusion thresholds should be treated with caution in elderly high‐risk hip fracture patients, until their safety has been proved in larger randomized studies.
Cost‐effectiveness of additional hepatitis B virus nucleic acid testing of individual donations or minipools of six donations in the Netherlands
Authors: Borkent‐Raven B.A. , Janssen M.P. , Van Der Poel C.L. , De Wit G.A. , Bonsel G.J. , Van Hout B.A.
Published: November 2008

BACKGROUND: To further reduce the risk of hepatitis B virus (HBV) transmission by blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this study is to estimate the incremental cost‐effectiveness ratio (ICER) in the Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection in individual donations (ID‐NAT) or in minipools of 6 donations (MP‐6‐NAT), compared to a triplex NAT assay in minipools of 24 donations (MP‐24‐NAT).

STUDY DESIGN AND METHODS: A mathematical model was made of the whole transfusion chain from donors to recipients of blood in the Netherlands. The annual number of avoided HBV transmissions was estimated with the window‐period incidence model. The natural history of a HBV infection in recipients is described by a Markov model.

RESULTS: The ICER of adding HBV MP‐6‐NAT or HBV ID‐NAT in the Netherlands is €303,218 (95% confidence interval [CI], €233,001‐€408,388) and €518,995 (95% CI, €399,359‐€699,120) per quality‐adjusted life‐year, respectively. The ICER strongly correlates with the age of transfusion recipients.

CONCLUSION: The cost‐effectiveness of additional HBV NAT is limited by the limited loss of life caused by HBV transmission. Despite a higher effectiveness, HBV ID‐NAT is less cost‐effective than MP‐6‐NAT due to higher costs. A future equivalent participation of immigrants from HBV‐endemic countries in the donor base renders HBV NAT only slightly more cost‐effective.
Clinical‐grade purification of natural killer cells in haploidentical hematopoietic stem cell transplantation
Authors: Meyer‐Monard Sandrine , Passweg Jakob , Siegler Uwe , Kalberer Christian , Koehl Ulrike , Rovó Alicia , Halter Jörg , Stern Martin , Heim Dominik , Alois Gratwohl Johannes Rischewski , Tichelli André
Published: November 2008

BACKGROUND: Because of a high risk of graft‐versus‐host disease (GVHD), donor lymphocyte infusions with unmodified lymphapheresis products are not used after haploidentical hematopoietic stem cell transplantation. Natural killer (NK) cells have antitumor activity and may consolidate engraftment without inducing GVHD. Production of NK cells under good manufacturing practice (GMP) conditions in a sufficient number is difficult.

STUDY DESIGN AND METHODS: Twenty‐four apheresis procedures and subsequent NK‐cell enrichment from 14 haploidentical donors were performed. NK‐cell enrichment was performed using a GMP suitable immunomagnetic procedure. Factors influencing the NK‐cell recovery, purity, and NK‐cell dose were analyzed.

RESULTS: A median number of 4.9 × 108 NK cells were obtained and median NK‐cell recovery was 58 percent. Median T‐cell depletion was 4.32 log. The absolute NK‐cell number in the final product after processing significantly correlated with the preharvest NK‐cell content of the peripheral blood (p = 0.002, r = 0.867). The NK‐cell recovery was inversely correlated to the absolute NK‐cell number in the apheresis product (p = 0.01, r = −0.51). The NK‐cell dose per kg of body weight of the patient was inversely correlated to the weight of the patient (p = 0.007, r = −0.533).

CONCLUSION: Donors with a high NK‐cell count in peripheral blood are likely to provide NK‐cell products with the highest cell number. However, maximal NK‐cell dose is limited and high NK‐cell doses may only be obtained for patients with a low body weight, making children and young adults the best candidates for NK‐cell therapy.
Factors affecting the frequency of red blood cell outdates: an approach to establish benchmarking targets
Authors: Heddle Nancy M. , Liu Yang , Barty Rebecca , Webert Kathryn E. , Whittaker Susan , Gagliardi Kate , Lauzon Deborah , Owens Wendy
Published: November 2008

BACKGROUND: Benchmarking is a useful tool to identify best practices and to compare an organization's performance with that of similar peers, allowing for continuous quality improvement. In this study, a provincial database of red blood cell (RBC) product inventory/disposition in hospitals was analyzed to identify factors that affected RBC outdates and to systematically establish optimal target levels for RBC outdates.

STUDY DESIGN AND METHODS: RBC inventory/disposition data for a 21‐month period from 156 hospitals were analyzed using logistic regression techniques to identify factors that affected RBC outdating (month of the year, distance from the blood supplier, monthly transfusion activity, hospital type, and provincial region). The results were used to categorize hospitals into groupings that accounted for the factors affecting wastage. Within each grouping, the lower quartile was selected as the optimal target threshold.

RESULTS: Three factors were identified as significantly affecting RBC outdating: distance from the blood supplier, mean monthly transfusion activity, and month of the year. Accounting for these variables, three hospital groupings were identified and benchmarking targets were established for mean monthly RBC outdating: There were 73 hospitals in Group 1 and their target level was 0.4 percent, 59 hospitals in Group 2 with a target of 1.1 percent, and 24 hospitals in Group 3 with a target of 20.3 percent.

CONCLUSION: A method is described for establishing evidence‐based benchmarking targets for RBC outdating that allows for hospitals to be grouped with similar peers taking into account logistic factors that impact on product outdating.
Impact of a policy to permit the return of donors repeat‐reactive to the Abbott PRISM antibody to hepatitis B core antigen assay
Authors: O'Brien Sheila F. , Yi Qi‐Long , Fan Wenli , Fearon Margaret A. , Scalia Vito , Goldman Mindy
Published: November 2008

BACKGROUND: The expected donor loss from recent implementation of antibody to hepatitis B core antigen (anti‐HBc) testing in Canada was uncertain but potentially significant based on US experience. To reduce donor loss from false‐reactive tests, repeat‐reactive donors without other evidence of infection were eligible to return. The aim was to evaluate the impact of anti‐HBc testing on donor loss and to evaluate the effectiveness of this policy.

STUDY DESIGN AND METHODS: For each donor in the first year of implementation (April 9, 2005‐April 8, 2006) repeat‐reactive for the presence of anti‐HBc only but eligible to return (screening test for hepatitis B surface antigen–negative, plus not reactive to antibody to hepatitis B surface antigen [anti‐HBs] and hepatitis B virus [HBV] DNA supplemental tests), 10 matched donors not reactive to the anti‐HBc assay were selected. Return rates over 2 years were compared using conditional logistic regression. Testing outcomes were tabulated.

RESULTS: Over the first year of testing, 412,236 donors (951,423 donations) were tested for anti‐HBc, and 4,489 donors were repeat‐reactive (1.3% of first‐time donors, 1.0% of repeat donors). Of these 85.6 percent were also reactive for the presence of anti‐HBs and/or HBV DNA supplemental tests leaving less than 15 percent eligible to return, of whom 73 percent returned (vs. 90% of controls, p < 0.001). Of the 300 anti‐HBc repeat‐reactive returning donors, 74 percent were anti‐HBc repeat‐reactive again (thus permanently deferred), 19 percent were deferred for other reasons versus 14 percent of controls (p < 0.05), and 7 percent (21 donors) did not react and were eligible to continue donating.

CONCLUSION: Most donors repeat‐reactive for the presence of anti‐HBc likely have past exposure to HBV. If eligible, most are willing to return, but likely to test anti‐HBc repeat‐reactive again.
Some Limitations of “Risk = Threat × Vulnerability × Consequence” for Risk Analysis of Terrorist Attacks
Authors: Cox, Jr Louis Anthony (Tony)
Published: November 2008

Several important risk analysis methods now used in setting priorities for protecting U.S. infrastructures against terrorist attacks are based on the formula: Risk=Threat×Vulnerability×Consequence. This article identifies potential limitations in such methods that can undermine their ability to guide resource allocations to effectively optimize risk reductions. After considering specific examples for the Risk Analysis and Management for Critical Asset Protection (RAMCAP™) framework used by the Department of Homeland Security, we address more fundamental limitations of the product formula. These include its failure to adjust for correlations among its components, nonadditivity of risks estimated using the formula, inability to use risk‐scoring results to optimally allocate defensive resources, and intrinsic subjectivity and ambiguity of Threat, Vulnerability, and Consequence numbers. Trying to directly assess probabilities for the actions of intelligent antagonists instead of modeling how they adaptively pursue their goals in light of available information and experience can produce ambiguous or mistaken risk estimates. Recent work demonstrates that two‐level (or few‐level) hierarchical optimization models can provide a useful alternative to Risk=Threat×Vulnerability×Consequence scoring rules, and also to probabilistic risk assessment (PRA) techniques that ignore rational planning and adaptation. In such two‐level optimization models, defender predicts attacker's best response to defender's own actions, and then chooses his or her own actions taking into account these best responses. Such models appear valuable as practical approaches to antiterrorism risk analysis.
Novel ICE‐Guided Registration Strategy for Integration of Electroanatomical Mapping with Three‐Dimensional CT/MR Images to Guide Catheter Ablation of Atrial Fibrillation
Authors: ROSSILLO ANTONIO , INDIANI STEFANO , BONSO ALDO , THEMISTOCLAKIS SAKIS , CORRADO ANDREA , RAVIELE ANTONIO
Published: November 2008

Introduction:
Image integration is used in AF ablation procedures. To maximize the efficacy of image integration, it is essential to obtain good alignment between the electroanatomical map and the 3D image of the heart. In the present study, we compared an ICE‐guided landmark registration with an ICE‐guided focused endocardial surface registration.

Methods and Results:
In 20 patients, registration was based on posterior landmarks acquired under ICE guidance (group A); in another 20 matched patients, a new ICE‐guided focused endocardial surface registration technique was used (group B). In these latter patients, a single landmark was acquired in the inferior part of the LIPV, and several surface points were recorded in the posterior area of the left PV antrum and around the antra of the right PVs. The mean ablation point‐to‐CT image distance was calculated in both groups. In group A, the mean landmark point‐to‐CT image distance was also calculated after adding the surface registration. The mean landmark point‐to‐CT image distance was 4.62 ± 1.65 mm and increased to 7.66 ± 2.44 mm when surface registration was added. The ablation point‐to‐CT image distance was significantly shorter in group B (1.73 ± 0.29 mm vs 3 ± 0.99 mm; P < 0.001).

Conclusions:
This ICE‐guided focused endocardial surface registration seems to be superior to landmark registration in achieving a better alignment between the CT/MR image and the electroanatomical map. The concurrent use of standard surface registration may result in rotation of the atrial chamber.
Efficacy of Medical Therapy for the Reduction of Heart Failure Events in Patients with Implanted Cardioverter Defibrillators
Authors: PIETRASIK GRZEGORZ , GOLDENBERG ILAN , McNITT SCOTT , POLONSKY BRONISLAVA , MOSS ARTHUR J. , ZAREBA WOJCIECH
Published: November 2008

Background:Prophylactic therapy with the implantable cardioverter defibrillator (ICD) reduces the mortality among patients with left ventricular dysfunction; however, life‐prolonging device therapy has been shown to be associated with an increased risk for subsequent heart failure (HF) events. There are limited data on the effect of the primary types of HF medications, angiotensin converting enzyme inhibitors (ACE‐I), and beta‐blockers on HF progression in ICD‐treated patients.

Methods:Multivariate Cox proportional hazards regression analysis was used to assess the effect of time‐dependent medical therapy with ACE‐I and beta‐blockers on the development of HF in patients with an ICD in the Multicenter Automatic Defibrillator Trail (MADIT) II.

Results:In multivariate analysis, ICD therapy was associated with a significant 39% increase in the risk of HF as compared with conventional medical therapy. ACE‐I and beta‐blockers exhibited a graded efficacy for the reduction in the risk of HF events in ICD‐treated patients: the greatest risk reduction of HF was seen in patients taking combination therapy (HR = 0.36, P < 0.001), followed by patients using beta‐blockers only (HR = 0.51, P = 0.017) and ACE‐I only (HR = 0.64, P = 0.071). Beta‐blocker subtypes (metoprolol [HR = 0.49, P = 0.001] and carvedilol [HR = 0.58, P = 0.004]) exhibited similar efficacy. Consistent results were demonstrated when the combined endpoint of HF or death was assessed.

Conclusions:ICD‐treated patients experience an increased risk for HF events that can be significantly attenuated by medical therapy with beta‐blockers and ACE‐inhibitors.