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Emily Herrett, Elizabeth Williamson, Danielle Beaumont, Danielle Prowse, Nabila Youssouf, Kieran Brack, Jane Armitage, Ben Goldacre, Thomas MacDonald, Tjeerd van Staa, Ian Roberts, Haleema Shakur-Still, Liam Smeeth
INTRODUCTION: Statins are effective at preventing cardiovascular disease, widely prescribed and their use is growing. Uncertainty persists about whether they cause symptomatic muscle adverse effects, such as pain and weakness, in the absence of statin myopathy. Discrepancies between data from observational studies, which suggest statins are associated with excess muscle symptoms, and from randomised trials, which suggest no such excess, have caused confusion. N-of-1 trials offer the opportunity to establish whether muscle symptoms during statin use are caused by statins in particular individuals...
December 1, 2017: BMJ Open
Roaa Hani Fairoozy, Jackie Cooper, Jon White, Claudia Giambartolomei, Lasse Folkersen, S Goya Wannamethee, Barbara J Jefferis, Peter Whincup, Yoav Ben-Shlomo, Meena Kumari, Mika Kivimaki, Andrew Wong, Rebecca Hardy, Diana Kuh, Tom R Gaunt, J P Casas, Stela McLachlan, Jackie F Price, Aroon Hingorani, Anders Franco-Cereceda, Thomas Grewal, Anastasia Z Kalea, Steve E Humphries
BACKGROUND AND AIMS: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulate low-density lipoprotein cholesterol (LDL-C) levels. Here we identify variants in ANXA2 influencing LDL-C levels and we determine the molecular mechanisms of their effects. RESULTS: The ANXA2 single nucleotide polymorphism (SNP) genotype-phenotype association was examined using the Second-Northwick-Park Heart Study (NPHSII) (n∼2700) and the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium (n∼14,600)...
June 2017: Atherosclerosis
Pimphen Charoen, Dorothea Nitsch, Jorgen Engmann, Tina Shah, Jonathan White, Delilah Zabaneh, Barbara Jefferis, Goya Wannamethee, Peter Whincup, Amy Mulick Cassidy, Tom Gaunt, Ian Day, Stela McLachlan, Jacqueline Price, Meena Kumari, Mika Kivimaki, Eric Brunner, Claudia Langenberg, Yoav Ben-Shlomo, Aroon Hingorani, John Whittaker, Juan Pablo Casas, Frank Dudbridge
Impaired kidney function, as measured by reduced estimated glomerular filtration rate (eGFR), has been associated with increased risk of coronary heart disease (CHD) in observational studies, but it is unclear whether this association is causal or the result of confounding or reverse causation. In this study we applied Mendelian randomisation analysis using 17 genetic variants previously associated with eGFR to investigate the causal role of kidney function on CHD. We used 13,145 participants from the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium and 194,427 participants from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus Coronary Artery Disease (CARDIoGRAMplusC4D) consortium...
June 24, 2016: Scientific Reports
Rebecca C Harris, Mishal S Khan, Laura J Martin, Victoria Allen, David A J Moore, Katherine Fielding, Louis Grandjean
BACKGROUND: In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. With limited options for medical treatment, surgery has re-emerged as an adjuvant therapeutic strategy. We conducted a systematic review and meta-analysis to assess the evidence for the effect of surgery as an adjunct to chemotherapy on outcomes of adults treated for MDR-TB. METHODS: Databases and grey literature sources were searched using terms incorporating surgery and MDR-TB...
June 10, 2016: BMC Infectious Diseases
Stela McLachlan, Claudia Giambartolomei, Jon White, Pimphen Charoen, Andrew Wong, Chris Finan, Jorgen Engmann, Tina Shah, Micha Hersch, Clara Podmore, Alana Cavadino, Barbara J Jefferis, Caroline E Dale, Elina Hypponen, Richard W Morris, Juan P Casas, Meena Kumari, Yoav Ben-Shlomo, Tom R Gaunt, Fotios Drenos, Claudia Langenberg, Diana Kuh, Mika Kivimaki, Rico Rueedi, Gerard Waeber, Aroon D Hingorani, Jacqueline F Price, Ann P Walker
Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms...
2016: PloS One
Suerie Moon, Devi Sridhar, Muhammad A Pate, Ashish K Jha, Chelsea Clinton, Sophie Delaunay, Valnora Edwin, Mosoka Fallah, David P Fidler, Laurie Garrett, Eric Goosby, Lawrence O Gostin, David L Heymann, Kelley Lee, Gabriel M Leung, J Stephen Morrison, Jorge Saavedra, Marcel Tanner, Jennifer A Leigh, Benjamin Hawkins, Liana R Woskie, Peter Piot
No abstract text is available yet for this article.
November 28, 2015: Lancet
Ernest D Benavente, Francesc Coll, Nick Furnham, Ruth McNerney, Judith R Glynn, Susana Campino, Arnab Pain, Fady R Mohareb, Taane G Clark
BACKGROUND: Phylogenetic-based classification of M. tuberculosis and other bacterial genomes is a core analysis for studying evolutionary hypotheses, disease outbreaks and transmission events. Whole genome sequencing is providing new insights into the genomic variation underlying intra- and inter-strain diversity, thereby assisting with the classification and molecular barcoding of the bacteria. One roadblock to strain investigation is the lack of user-interactive solutions to interrogate and visualise variation within a phylogenetic tree setting...
May 13, 2015: BMC Bioinformatics
Julia Blau, Céline Hoestlandt, Andrew D Clark, Louise Baxter, Ana Gabriela Felix Garcia, Bérénice Mounaud, Liudmila Mosina
BACKGROUND: For many years, low- and middle-income countries have made efforts to strengthen national decision-making on immunization. The Pan American Health Organization (PAHO) ProVac Initiative was established to help expedite the use of evidence-based decision-making around new vaccine introduction. This initiative provides training in user-friendly cost-effectiveness models and supports the development of country-led economic evaluations. Due to the success of the ProVac Initiative in the Americas, and following requests from countries from outside the Americas, the Bill & Melinda Gates Foundation funded a two-year pilot effort to expand the initiative to other world regions...
May 7, 2015: Vaccine
Jovin Kitau, Richard Oxborough, Angela Kaye, Vanessa Chen-Hussey, Evelyn Isaacs, Johnson Matowo, Harparkash Kaur, Stephen M Magesa, Franklin Mosha, Mark Rowland, James Logan
BACKGROUND: Long-lasting insecticide treated blankets (LLIBs) may provide additional protection against malaria where use of long lasting insecticidal nets (LLIN) is low or impractical such as in disaster or emergency situations. METHODS: Initial efficacy testing of a new candidate LLIB was carried out at LSHTM and KCMUCo, before and after washing, in cone and ball bioassays and arm-in-cage tests against pyrethroid susceptible Anopheles gambiae. A small scale field trial was conducted using veranda-trap experimental huts in northern Tanzania against wild An...
2014: Parasites & Vectors
Francesc Coll, Mark Preston, José Afonso Guerra-Assunção, Grant Hill-Cawthorn, David Harris, João Perdigão, Miguel Viveiros, Isabel Portugal, Francis Drobniewski, Sebastien Gagneux, Judith R Glynn, Arnab Pain, Julian Parkhill, Ruth McNerney, Nigel Martin, Taane G Clark
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second major cause of death from an infectious disease worldwide. Recent advances in DNA sequencing are leading to the ability to generate whole genome information in clinical isolates of M. tuberculosis complex (MTBC). The identification of informative genetic variants such as phylogenetic markers and those associated with drug resistance or virulence will help barcode Mtb in the context of epidemiological, diagnostic and clinical studies...
May 2014: Tuberculosis
Michael P Barrett, Simon L Croft
The need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs...
January 2014: Parasitology
I Roberts, H Shakur, T Coats, B Hunt, E Balogun, L Barnetson, L Cook, T Kawahara, P Perel, D Prieto-Merino, M Ramos, J Cairns, C Guerriero
BACKGROUND: Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed...
March 2013: Health Technology Assessment: HTA
John Kepros
QUESTION: Does a prognostic model accurately estimate risk for early death in patients with traumatic bleeding? METHODS: HASH(0x3847718) DESIGN: 2 cohort studies: Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial (derivation) and Trauma Audit and Research Network (TARN) dataset (validation). SETTING: 274 hospitals in 40 countries (derivation cohort) and 60% of hospitals that received trauma patients in England and Wales and some hospitals in Europe (validation cohort)...
November 20, 2012: Annals of Internal Medicine
Francesc Coll, Kim Mallard, Mark D Preston, Stephen Bentley, Julian Parkhill, Ruth McNerney, Nigel Martin, Taane G Clark
SUMMARY: Spoligotyping is a well-established genotyping technique based on the presence of unique DNA sequences in Mycobacterium tuberculosis (Mtb), the causal agent of tuberculosis disease (TB). Although advances in sequencing technologies are leading to whole-genome bacterial characterization, tens of thousands of isolates have been spoligotyped, giving a global view of Mtb strain diversity. To bridge the gap, we have developed SpolPred, a software to predict the spoligotype from raw sequence reads...
November 15, 2012: Bioinformatics
Mark D Preston, Magnus Manske, Neil Horner, Samuel Assefa, Susana Campino, Sarah Auburn, Issaka Zongo, Jean-Bosco Ouedraogo, Francois Nosten, Tim Anderson, Taane G Clark
SUMMARY: There is an immediate need for tools to both analyse and visualize in real-time single-nucleotide polymorphisms, insertions and deletions, and other structural variants from new sequence file formats. We have developed VarB software that can be used to visualize variant call format files in real time, as well as identify regions under balancing selection and informative markers to differentiate user-defined groups (e.g. populations). We demonstrate its utility using sequence data from 50 Plasmodium falciparum isolates comprising two different continents and confirm known signals from genomic regions that contain important antigenic and anti-malarial drug-resistance genes...
November 15, 2012: Bioinformatics
Pablo Perel, David Prieto-Merino, Haleema Shakur, Tim Clayton, Fiona Lecky, Omar Bouamra, Rob Russell, Mark Faulkner, Ewout W Steyerberg, Ian Roberts
OBJECTIVE: To develop and validate a prognostic model for early death in patients with traumatic bleeding. DESIGN: Multivariable logistic regression of a large international cohort of trauma patients. SETTING: 274 hospitals in 40 high, medium, and low income countries PARTICIPANTS: Prognostic model development: 20,127 trauma patients with, or at risk of, significant bleeding, within 8 hours of injury in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial...
August 15, 2012: BMJ: British Medical Journal
Taane G Clark, Susana G Campino, Elisa Anastasi, Sarah Auburn, Yik Y Teo, Kerrin Small, Kirk A Rockett, Dominic P Kwiatkowski, Christopher C Holmes
MOTIVATION: Quantifying differences in linkage disequilibrium (LD) between sub-groups can highlight genetic regions or sites under selection and/or associated with disease, and may have utility in trans-ethnic mapping studies. RESULTS: We present a novel pseudo Bayes factor (PBF) approach that assess differences in covariance of genotype frequencies from single nucleotide polymorphism (SNP) data from a genome-wide study. The magnitude of the PBF reflects the strength of evidence for a difference, while accounting for the sample size and number of SNPs, without the requirement for permutation testing to establish statistical significance...
August 15, 2010: Bioinformatics
D D Chadee
The diel oviposition periodicity of females of the LSHTM strain of Aedes aegypti was studied, under laboratory conditions, using one female/cage and monitoring, by changing the substrate, every 1, 2, 4 or 24 h. The individual females monitored at hourly intervals showed peak oviposition at 18.00-19.00 hours (a period when 44% of the eggs observed were laid) whereas the individuals monitored at two-hourly intervals showed peak oviposition between 16.00-18.00 hours (38% of eggs). The four-hourly monitoring gave a result that was similar to that of the two-hourly monitoring, with 79% of eggs laid between 14...
April 2008: Annals of Tropical Medicine and Parasitology
D D Chadee
The diel oviposition periodicities of the LSHTM and Trinidad strains of Aedes aegypti were studied under laboratory conditions, using different mosquito densities in the cages and monitoring at 2-h intervals. With both strains, the peak in oviposition occurred earlier in the day when there was only one female in a test cage (16.00-18.00 hours) than when 25 or 500 females were held in a cage (18.00-20.00 hours). It therefore appears that the numbers of females in the cages can affect the diel oviposition periodicity of Ae...
June 2007: Annals of Tropical Medicine and Parasitology
Elizabeth Smith, Fiona Ross, Sheila Donovan, Jill Manthorpe, Sally Brearley, John Sitzia, Peter Beresford
OBJECTIVES: In the UK policy recommends that service users (patients, carers and the public) should be involved in all publicly funded health and social care research. However, little is known about which approaches work best in different research contexts and why. The purpose of this paper is to explain some of the theoretical limitations to current understandings of service user involvement and to provide some suggestions for theory and methods development. This paper draws upon findings from a review of the research 'evidence' and current practice on service user involvement in the design and undertaking of nursing, midwifery and health visiting research...
February 2008: International Journal of Nursing Studies
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