Evidence of prostate cancer-linked virus zoonoses from biophysical genomic variations.

An ongoing double-blind examination of (mathematically) smooth functional dependences of population-based genomic distributions of single nucleotide polymorphisms (SNPs) on quantified environmental parameters has flagged a SNP that has been associated with prostate cancer for dependence on zoonotic viruses. The SNP rs13091518 is an intergenic variant near the gene/pseudo-gene COX6CP6 on chromosome 3. The risk T allele, which is the major allele in all homeostatic populations considered, clearly demonstrates a negative adaptive force of about -0.

Evidence of cancer-linked rodent zoonoses from biophysical genomic variations.

As a mechanism to explore the role of environmental adaptation in establishing the optimal distribution of single nucleotide polymophisms (SNPs) within resident homeostatic populations, relationships between quantified environmental parameters and the frequencies of the variants are being explored. We have performed sequential double-blind scans on more than 30% of chromosome 3 in an attempt to discover possible relationships using simple mathematical functions that are indicative of "adaptive forces" on the variants due to specific quantified environmental agents. We have found an association of rs13071758 with rodent zoonotic diseases.

Quantification of adaptive forces on SNP rs1010211 due to viral zoonotic pathogens.

Widespread genotyping of human populations in environmental homeostasis has created opportunities to quantify how environmental parameters affect the genomic distribution of variants in healthy populations. This represents an ongoing natural experiment upon the human species that can only be understood through developing models of adaptation. By examining the information dynamics of optimal SNP distributions within such populations, "adaptive forces" on genomic variants can be quantified through comparisons between different populations.

Predictive Factors for Conversion to Dementia in Individuals with Early-Onset Mild Cognitive Impairment.

Introduction: There is little research on factors predicting conversion to dementia in early-onset mild cognitive impairment (eoMCI), a transitional stage between healthy ageing and dementia in individuals below the age of 65. We aimed to examine whether sociodemographic and clinical factors at initial presentation predicted dementia progression in a cohort of eoMCI patients attending a memory service, at a university teaching hospital in the UK.

Methods: This is a retrospective case note study of individuals diagnosed with eoMCI between 2000 and 2013 at the Younger Person's Memory Service (YPMS) in Leicestershire, England.

Predictors of Disease Progression in Early-Onset Alzheimer's Dementia: A Retrospective Cohort Study.

Objectives: Early-onset Alzheimer's disease (EOAD), defined as onset of AD before the age of 65 years, is less common than the late-onset type, and little is known about the factors affecting disease progression. The aim of the study was to investigate factors influencing disease progression in people with EOAD.

Design: Retrospective cohort study.

Driving Cessation in Patients Attending a Young-Onset Dementia Clinic: A Retrospective Cohort Study.

Background: Although driving by persons with dementia is an important public health concern, little is known about driving cessation in younger people with dementia. We aimed to determine the prevalence and factors affecting driving cessation in individuals with and without dementia aged under 65 years attending a memory clinic in a European setting.

Methods: Subjects were consecutive patients assessed at a specialist memory service at a university teaching hospital between 2000 and 2010.

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

Objective: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients.

Methods: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial.

Screening for depression in older people on acute medical wards: the validity of the Edinburgh Depression Scale.

Background: depression is common in people with poor physical health, particularly within the acute medical in-patient setting. Co-morbid depression contributes to poor outcomes, and screening for depression in acute medical in-patients has been advocated. The Edinburgh Depression Scale (EDS) has been validated in a variety of general hospital patient groups, but not previously in older acute medical in-patients.

Screening for depression in older adults on an acute medical ward: the validity of NICE guidance in using two questions.

Background: depression is common in older people in general hospital settings and associated with poor outcomes. This study aimed to evaluate the validity of two screening questions recommended by the UK National Institute for Health and Clinical Excellence (NICE).

Methods: one hundred and eighteen patients aged over 65 years, admitted to acute medical wards at a teaching hospital, were interviewed in a standardised manner using relevant sections of the Present State Examination-Schedules for Clinical Assessment in Neuropsychiatry to identify depression according to ICD-10 criteria.

Information Dynamics of Whole Genome Adaptation.

The human genome is a complex, dynamic information system that encodes principles of life and living systems. These principles are incorporated in the structure of human genome sequence variation and are foundational for the continuity of life and human survival. Using first principles of thermodynamics and statistical physics, we have developed analogous "genodynamic tools" for population genomic studies.

Development of genodynamic metrics for exploring the biophysics of DNA polymorphisms.

Single nucleotide polymorphisms (SNPs) represent an important type of dynamic sites within the human genome. These common variants often locally correlate within more complex multi-SNP haploblocks that are maintained throughout generations in a stable population. Information encoded in the structure of SNPs and SNP haploblock variation can be characterized through a normalized information content metric.

Single Nucleotide Polymorphisms: A Window into the Informatics of the Living Genome.

Nested in the environment of the nucleus of the cell, the 23 sets of chromosomes that comprise the human genome function as one integrated whole system, orchestrating the expression of thousands of genes underlying the biological characteristics of the cell, individual and the species. The extraction of meaningful information from this complex data set depends crucially upon the lens through which the data are examined. We present a biophysical perspective on genomic information encoded in single nucleotide polymorphisms (SNPs), and introduce metrics for modeling information encoded in the genome.

The utility of the Edinburgh Depression Scale as a screening tool for depression in Parkinson's disease.

Objective: This study aimed to evaluate the Edinburgh Depression Scale (EDS) as a screening tool for use in a Parkinson's disease (PD) population. Many commonly used depression scales include items relating to somatic symptoms that also occur in PD, which could potentially result in inaccurate reporting of depressive symptoms. The EDS is a scale that incorporates no somatic items.

Review of brief cognitive tests for patients with suspected dementia.

Background: As the population ages, it is increasingly important to use effective short cognitive tests for suspected dementia. We aimed to review systematically brief cognitive tests for suspected dementia and report on their validation in different settings, to help clinicians choose rapid and appropriate tests.

Methods: Electronic search for face-to-face sensitive and specific cognitive tests for people with suspected dementia, taking ≤ 20 minutes, providing quantitative psychometric data.

Screening for depression in Parkinson's disease: the performance of two screening questions.

Background: the study objective was to evaluate the validity of the two questions recommended by the UK. National Institute for Health and Clinical Excellence for depression screening in Parkinson's disease (PD).

Methods: one hundred and twenty patients attending a PD out-patient clinic were interviewed in a standardised manner using relevant sections of the Present State Examination- Schedules for Clinical Assessment in Neuropsychiatry to identify depression according to Diagnostic and Statistical Manual (4th edition) criteria.

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial.

Background: Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes.

Aims: To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia.

Donepezil and memantine for moderate-to-severe Alzheimer's disease.

Background: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.

Methods: We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine.

Increased prevalence of insomnia and changes in hypnotics use in England over 15 years: analysis of the 1993, 2000, and 2007 National Psychiatric Morbidity Surveys.

Study Objectives: To investigate changes over 15 years in the prevalence of insomnia and its association with demographic characteristics and hypnotic medication use.

Design: Analysis of 3 cross-sectional national mental health surveys carried out in 1993, 2000, and 2007, which used comparable sampling methods and identical insomnia assessments.

Setting: Adults living in private households in England.

A new biophysical metric for interrogating the information content in human genome sequence variation: Proof of concept.

The 21 century emergence of genomic medicine is shifting the paradigm in biomedical science from the population phenotype to the individual genotype. In characterizing the biology of disease and health disparities in population genetics, human populations are often defined by the most common alleles in the group. This definition poses difficulties when categorizing individuals in the population who do not have the most common allele(s).

The meaning of reporting forgetfulness: a cross-sectional study of adults in the English 2007 Adult Psychiatric Morbidity Survey.

Objectives: we measured subjective memory impairment (SMI) across the whole adult age range in a representative, national survey. Age is the strongest risk factor for dementia and SMI may be a precursor of objective cognitive impairment. We therefore hypothesised that SMI prevalence would rise with age in a non-demented population.

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial.

Background: Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.

Methods: We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England.

Determining the minimum clinically important differences for outcomes in the DOMINO trial.

Background: Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these.

Methods: As part of the development of the Statistical Analysis Plan for the DOMINO trial, investigators met to consider expert opinion- and distribution-based values for the MCID and triangulated these to provide appropriate values for three outcome measures, the Standardised Mini-mental State Examination (sMMSE), Bristol Activities of Daily Living Scale (BADLS) and Neuropsychiatric Inventory (NPI).

Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration.