72 research outputs found

    Alzheimer’s Disease Genomics and Clinical Applications

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    Bright light therapy as part of a multicomponent management program improves sleep and functional outcomes in delirious older hospitalized adults.

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    ObjectiveDelirium is associated with poor outcomes following acute hospitalization. A specialized delirium management unit, the Geriatric Monitoring Unit (GMU), was established. Evening bright light therapy (2000-3000 lux; 6-10 pm daily) was added as adjunctive treatment, to consolidate circadian activity rhythms and improve sleep. This study examined whether the GMU program improved sleep, cognitive, and functional outcomes in delirious patients.MethodA total of 228 patients (mean age = 84.2 years) were studied. The clinical characteristics, delirium duration, delirium subtype, Delirium Rating Score (DRS), cognitive status (Chinese Mini-Mental State Examination), functional status (modified Barthel Index [MBI]), and chemical restraint use during the initial and predischarge phase of the patient's GMU admission were obtained. Nurses completed hourly 24-hour patient sleep logs, and from these, the mean total sleep time, number of awakenings, and sleep bouts (SB) were computed.ResultsThe mean delirium duration was 6.7 ± 4.6 days. Analysis of the delirium subtypes showed that 18.4% had hypoactive delirium, 30.2% mixed delirium, and 51.3% had hyperactive delirium. There were significant improvements in MBI scores, especially for the hyperactive and mixed delirium subtypes (P < 0.05). Significant improvements were noted on the DRS sleep-wake disturbance subscore, for all delirium-subtypes. The mean total sleep time (7.7 from 6.4 hours) (P < 0.05) and length of first SB (6.0 compared with 5.3 hours) (P < 0.05) improved, with decreased mean number of SBs and awakenings. The sleep improvements were mainly seen in the hyperactive delirium subtype.ConclusionThis study shows initial evidence for the clinical benefits (longer total sleep time, increased first SB length, and functional gains) of incorporating bright light therapy as part of a multicomponent delirium management program. The benefits appear to have occurred mainly in patients with hyperactive delirium, which merits further in-depth, randomized controlled studies

    A New Model of Delirium Care in the Acute Geriatric Setting: Geriatric Monitoring Unit

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    <p>Abstract</p> <p>Background</p> <p>Delirium is a common and serious condition, which affects many of our older hospitalised patients. It is an indicator of severe underlying illness and requires early diagnosis and prompt treatment, associated with poor survival, functional outcomes with increased risk of institutionalisation following the delirium episode in the acute care setting. We describe a new model of delirium care in the acute care setting, titled Geriatric Monitoring Unit (GMU) where the important concepts of delirium prevention and management are integrated. We hypothesize that patients with delirium admitted to the GMU would have better clinical outcomes with less need for physical and psychotropic restraints compared to usual care.</p> <p>Methods/Design</p> <p>GMU models after the Delirium Room with adoption of core interventions from Hospital Elder Life Program and use of evening bright light therapy to consolidate circadian rhythm and improve sleep in the elderly patients. The novelty of this approach lies in the amalgamation of these interventions in a multi-faceted approach in acute delirium management. GMU development thus consists of key considerations for room design and resource planning, program specific interventions and daily core interventions. Assessments undertaken include baseline demographics, comorbidity scoring, duration and severity of delirium, cognitive, functional measures at baseline, 6 months and 12 months later. Additionally we also analysed the pre and post-GMU implementation knowledge and attitude on delirium care among staff members in the geriatric wards (nurses, doctors) and undertook satisfaction surveys for caregivers of patients treated in GMU.</p> <p>Discussion</p> <p>This study protocol describes the conceptualization and implementation of a specialized unit for delirium management. We hypothesize that such a model of care will not only result in better clinical outcomes for the elderly patient with delirium compared to usual geriatric care, but also improved staff knowledge and satisfaction. The model may then be transposed across various locations and disciplines in the acute hospital where delirious patients could be sited.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN52323811">ISRCTN52323811</a></p

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    Utility of the Clinical Dementia Rating in Asian Populations

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    Consistent with the worldwide demographic trend of population aging, dementia is expected to become a burgeoning public health problem in Asian populations. Thus, there is a pressing need for reliable and valid methods of dementia diagnosis and staging that are applicable in heterogeneous Asian populations. The Clinical Dementia Rating (CDR) is an informant-based global assessment scale with established reliability and validity that has been widely utilized as a severity-ranking scale in many studies of Asian populations. From a diagnostic standpoint, the CDR is congruent with the Diagnostic and Statistical Manual of Mental Disorders approach of dementia diagnosis. It exhibits excellent discriminatory ability in the very mild stages of dementia, a useful property that is germane to the surging interest in mild cognitive impairment and related concepts. Limitations of the CDR include its length of administration, reliance on clinical judgment and collateral source information, and relative insensitivity as a measure of change in interventional studies. Since the exercise of clinical judgment is inherent in scoring, CDR raters should be mindful of the influence of cultural factors on premorbid lifestyle, informant reliability and performance in certain CDR test items (especially those pertaining to the categories of judgment and problem solving, community, and home and hobbies). Thus, in future studies that involve the nascent use of the CDR in Asian populations, it is recommended that any transcultural adaptation of CDR items be described in detail and appropriate validation studies be carried out before adopting the CDR as a yardstick measure of assessment. The potential of adapted versions of the CDR in chronic care settings and advanced cases should be explored. An integrative approach, combining brief informant interview in conjunction with brief objective cognitive testing, could be a viable strategy for dementia screening in the clinical and research setting that warrants further evaluation in Asian populations
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