Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Atrial fibrillation in a primary care practice: prevalence and management

BACKGROUND: Atrial fibrillation is a common serious cardiac arrhythmia. Knowing the prevalence of atrial fibrillation and documentation of medical management are important in the provision of primary care. This study sought to determine the prevalence of atrial fibrillation in a primary care population and to identify and quantify the treatments being used for stroke prevention in this group of patients. METHODS: A prevalence study through chart audit was conducted in the family medicine practice at the Sunnybrook campus of the Sunnybrook and Women's College Health Sciences Centre. The main outcome measures were the prevalence of atrial fibrillation in our primary care practice and the use of warfarin for stroke prevention in this population. RESULTS: 261 patients in our practice have atrial fibrillation. The overall prevalence in our family practice unit is 3.9%. When considering patients aged 60 and over, the prevalence rises to 12.2%. 204 of our patients with atrial fibrillation (78.2%) are currently being treated with warfarin. Another 21 patients were previously treated and discontinued for a number of reasons. Of the 57 patients not currently treated with warfarin, 44 are treated with ASA, 2 with ticlopidine, and 11 are receiving no preventative treatment. CONCLUSIONS: The prevalence of atrial fibrillation in our practice is higher than the range of prevalence reported in the general literature. However, our coverage with warfarin treatment exceeds previous reports in the literature

Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans

Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted

Copy Number and Loss of Heterozygosity Detected by SNP Array of Formalin-Fixed Tissues Using Whole-Genome Amplification

The requirement for large amounts of good quality DNA for whole-genome applications prohibits their use for small, laser capture micro-dissected (LCM), and/or rare clinical samples, which are also often formalin-fixed and paraffin-embedded (FFPE). Whole-genome amplification of DNA from these samples could, potentially, overcome these limitations. However, little is known about the artefacts introduced by amplification of FFPE-derived DNA with regard to genotyping, and subsequent copy number and loss of heterozygosity (LOH) analyses. Using a ligation adaptor amplification method, we present data from a total of 22 Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an internal method control. An average of 76.5% of SNPs were called in both matched amplified and non-amplified DNA samples, and concordance was a promising 82.4%. Paired analysis for copy number, LOH, and both combined, showed that copy number changes were reduced in amplified DNA, but were 99.5% concordant when detected, amplifications were the changes most likely to be ‘missed’, only 30% of non-amplified LOH changes were identified in amplified pairs, and when copy number and LOH are combined ∼50% of gene changes detected in the unamplified DNA were also detected in the amplified DNA and within these changes, 86.5% were concordant for both copy number and LOH status. However, there are also changes introduced as ∼20% of changes in the amplified DNA are not detected in the non-amplified DNA. An integrative network biology approach revealed that changes in amplified DNA of dysplastic oral epithelium localize to topologically critical regions of the human protein-protein interaction network, suggesting their functional implication in the pathobiology of this disease. Taken together, our results support the use of amplification of FFPE-derived DNA, provided sufficient samples are used to increase power and compensate for increased error rates

Apparent Temperature and Air Pollution vs. Elderly Population Mortality in Metro Vancouver

Background: Meteorological conditions and air pollution in urban environments have been associated with general population and elderly mortality, showing seasonal variation. Objectives: This study is designed to evaluate the relationship between apparent temperature (AT) and air pollution (PM2.5) vs. mortality in elderly population of Metro Vancouver. Methods: Statistical analyses are performed on moving sum daily mortality rates vs. moving average AT and PM 2.5 in 1-, 2-, 3-, 5-, and 7-day models for all seasons, warm temperatures above 15uC, and cold temperatures below 10uC. Results: Approximately 37 % of the variation in all-season mortality from circulatory and respiratory causes can be explained by the variation in 7-day moving average apparent temperature (r 2 = 0.37, p,0.001). Although the analytical results from air pollution models show increasingly better prediction ability of longer time-intervals (r 2 = 0.012, p,0.001 in a 7-day model), a very weak negative association between elderly mortality and air pollution is observed. Conclusions: Apparent temperature is associated with mortality from respiratory and circulatory causes in elderly population of Metro Vancouver. In a changing climate, one may anticipate to observe potential health impacts from the projected high- and particularly from the low-temperature extremes

Between life and death: exploring the sociocultural context of antenatal mental distress in rural Ethiopia

The high prevalence of antenatal common mental disorders in sub-Saharan Africa compared to high-income countries is poorly understood. This qualitative study explored the sociocultural context of antenatal mental distress in a rural Ethiopian community. Five focus group discussions and 25 in-depth interviews were conducted with purposively sampled community stakeholders. Inductive analysis was used to develop final themes. Worry about forthcoming delivery and fears for the woman’s survival were prominent concerns of all participants, but only rarely perceived to be pathological in intensity. Sociocultural practices such as continuing physical labour, dietary restriction, prayer and rituals to protect against supernatural attack were geared towards safe delivery and managing vulnerability. Despite strong cultural norms to celebrate pregnancy, participants emphasised that many pregnancies were unwanted and an additional burden on top of pre-existing economic and marital difficulties. Short birth interval and pregnancy out of wedlock were both seen as shameful and potent sources of mental distress. The notion that pregnancy in traditional societies is uniformly a time of joy and happiness is misplaced. Although antenatal mental distress may be self-limiting for many women, in those with enduring life difficulties, including poverty and abusive relationships, poor maternal mental health may persist

A unified approach to molecular epidemiology investigations: tools and patterns in California as a case study for endemic shigellosis

<p>Abstract</p> <p>Background</p> <p>Shigellosis causes diarrheal disease in humans from both developed and developing countries, and multi-drug resistance is an emerging problem. The objective of this study is to present a unified approach that can be used to characterize endemic and outbreak patterns of shigellosis using use a suite of epidemiologic and molecular techniques. The approach is applied to a California case study example of endemic shigellosis at the population level.</p> <p>Methods</p> <p>Epidemiologic patterns were evaluated with respect to demographics, multi-drug resistance, antimicrobial resistance genes, plasmid profiles, and pulsed-field gel electrophoresis (PFGE) fingerprints for the 43 <it>Shigella </it>isolates obtained by the Monterey region health departments over the two year period from 2004-2005.</p> <p>Results</p> <p>The traditional epidemiologic as well as molecular epidemiologic findings were consistent with endemic as compared to outbreak shigellosis in this population. A steady low level of cases was observed throughout the study period and high diversity was observed among strains. In contrast to most studies in developed countries, the predominant species was <it>Shigella flexneri </it>(51%) followed closely by <it>S. sonnei </it>(49%). Over 95% of <it>Shigella </it>isolates were fully resistant to three or more antimicrobial drug subclasses, and 38% of isolates were resistant to five or more subclasses. More than half of <it>Shigella </it>strains tested carried the <it>tetB</it>, <it>catA</it>, or <it>bla</it>_TEMgenes for antimicrobial resistance to tetracycline, chloramphenicol, and ampicillin, respectively.</p> <p>Conclusion</p> <p>This study shows how epidemiologic patterns at the host and bacterial population levels can be used to investigate endemic as compared to outbreak patterns of shigellosis in a community. Information gathered as part of such investigations will be instrumental in identifying emerging antimicrobial resistance, for developing treatment guidelines appropriate for that community, and to provide baseline data with which to compare outbreak strains in the future.</p