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https://www.readbyqxmd.com/read/29396385/how-knowledge-is-constructed-and-exchanged-in-virtual-communities-of-physicians-qualitative-study-of-mindlines-online
#1
Sietse Wieringa, Eivind Engebretsen, Kristin Heggen, Trisha Greenhalgh
BACKGROUND: As a response to the criticisms evidence-based practice currently faces, groups of health care researchers and guideline makers have started to call for the appraisal and inclusion of different kinds of knowledge in guideline production (other than randomized controlled trials [RCTs]) to better link with the informal knowledge used in clinical practice. In an ethnographic study, Gabbay and Le May showed that clinicians in everyday practice situations do not explicitly or consciously use guidelines...
February 2, 2018: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29386252/tumour-risks-and-genotype-phenotype-correlations-associated-with-germline-variants-in-succinate-dehydrogenase-subunit-genes-sdhb-sdhc-and-sdhd
#2
Katrina A Andrews, David B Ascher, Douglas Eduardo Valente Pires, Daniel R Barnes, Lindsey Vialard, Ruth T Casey, Nicola Bradshaw, Julian Adlard, Simon Aylwin, Paul Brennan, Carole Brewer, Trevor Cole, Jackie A Cook, Rosemarie Davidson, Alan Donaldson, Alan Fryer, Lynn Greenhalgh, Shirley V Hodgson, Richard Irving, Fiona Lalloo, Michelle McConachie, Vivienne P M McConnell, Patrick J Morrison, Victoria Murday, Soo-Mi Park, Helen L Simpson, Katie Snape, Susan Stewart, Susan E Tomkins, Yvonne Wallis, Louise Izatt, David Goudie, Robert S Lindsay, Colin G Perry, Emma R Woodward, Antonis C Antoniou, Eamonn R Maher
BACKGROUND: Germline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers. METHODS: A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma...
January 31, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29384470/the-uk-endovascular-aneurysm-repair-evar-randomised-controlled-trials-long-term-follow-up-and-cost-effectiveness-analysis
#3
Rajesh Patel, Janet T Powell, Michael J Sweeting, David M Epstein, Jessica K Barrett, Roger M Greenhalgh
BACKGROUND: Short-term survival benefits of endovascular aneurysm repair (EVAR) compared with open repair (OR) of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival benefit is soon lost. Survival benefit of EVAR was unclear at follow-up to 10 years. OBJECTIVE: To assess the long-term efficacy of EVAR against OR in patients deemed fit and suitable for both procedures (EVAR trial 1; EVAR-1); and against no intervention in patients unfit for OR (EVAR trial 2; EVAR-2)...
January 2018: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/29382705/discovery-of-potent-and-selective-mrck-inhibitors-with-therapeutic-effect-on-skin-cancer
#4
Mathieu Unbekandt, Simone Belshaw, Justin Bower, Maeve Clarke, Jacqueline Cordes, Diane Crighton, Daniel R Croft, Martin J Drysdale, Mathew J Garnett, Kathryn Gill, Christopher Gray, David A Greenhalgh, James Am Hall, Jennifer Konczal, Sergio Lilla, Duncan McArthur, Patricia McConnell, Laura McDonald, Lynn McGarry, Heather McKinnon, Carol McMenemy, Mokdad Mezna, Nicholas A Morrice, June Munro, Gregory Naylor, Nicola Rath, Alexander W Schüttelkopf, Mairi Sime, Michael F Olson
The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character...
January 30, 2018: Cancer Research
https://www.readbyqxmd.com/read/29378576/economic-evaluation-of-type-2-diabetes-prevention-programmes-markov-model-of-low-and-high-intensity-lifestyle-programmes-and-metformin-in-participants-with-different-categories-of-intermediate-hyperglycaemia
#5
Samantha Roberts, Dawn Craig, Amanda Adler, Klim McPherson, Trisha Greenhalgh
BACKGROUND: National guidance on preventing type 2 diabetes mellitus (T2DM) in the UK recommends low-intensity lifestyle interventions for individuals with intermediate categories of hyperglycaemia defined in terms of impaired fasting glucose (IFG) or 'at-risk' levels of HbA1c. In a recent systematic review of economic evaluations of such interventions, most studies had evaluated intensive trial-based lifestyle programmes in participants with impaired glucose tolerance (IGT). This study examines the costs and effects of different intensity lifestyle programmes and metformin in participants with different categories of intermediate hyperglycaemia...
January 30, 2018: BMC Medicine
https://www.readbyqxmd.com/read/29374007/a-web-based-course-on-public-health-principles-in-disaster-and-medical-humanitarian-response-survey-among-students-and-faculty
#6
Greta Tam, Emily Ying Yang Chan, Sida Liu
BACKGROUND: Web-based public health courses are becoming increasingly popular. "Public Health Principles in Disaster and Medical Humanitarian Response" is a unique Web-based course in Hong Kong. This course aimed to fill a public health training gap by reaching out to postgraduates who are unable to access face-to-face learning. OBJECTIVE: The aim of this paper was to use a structured framework to objectively evaluate the effectiveness of a Web-based course according to Greenhalgh et al's quality framework and the Donabedian model to make recommendations for program improvement...
January 26, 2018: JMIR Medical Education
https://www.readbyqxmd.com/read/29329500/c-o-isothiouronium-interaction-dictates-enantiodiscrimination-in-acylative-kinetic-resolution-of-tertiary-heterocyclic-alcohols
#7
Mark Greenhalgh, Samuel Smith, Daniel Walden, James Taylor, Zamira Brice, Emily Robinson, Charlene Fallan, David Cordes, Alexandra Slawin, Hannah Camille Richardson, Markas Grove, Paul Cheong, Andrew David Smith
A combination of experimental and computational studies have identified a C=O***isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s up to > 200). The reaction proceeds at low catalyst loadings (generally 1 mol%) using either isobutyric or acetic anhydride as the acylating agent under mild conditions...
January 12, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29325407/the-bright-elusive-butterfly-of-value-in-health-technology-development-comment-on-providing-value-to-new-health-technology-the-early-contribution-of-entrepreneurs-investors-and-regulatory-agencies
#8
Trisha Greenhalgh, Nick Fahy, Sara Shaw
The current system of health technology development is characterised by multiple misalignments. The "supply" side (innovation policy-makers, entrepreneurs, investors) and the "demand" side (health policy-makers, regulators, health technology assessment, purchasers) operate under different - and conflicting - logics. The system is less a "pathway" than an unstable ecosystem of multiple interacting sub-systems. "Value" means different things to each of the numerous actors involved. Supply-side dynamics are built on fictions; regulatory checks and balances are designed to assure quality, safety and efficacy, not to ensure that technologies entering the market are either desirable or cost-effective...
May 29, 2017: International Journal of Health Policy and Management
https://www.readbyqxmd.com/read/29325217/neutrophil-infiltration-to-the-brain-is-platelet-dependent-and-is-reversed-by-blockade-of-platelet-gpib%C3%AE
#9
James A Giles, Andrew D Greenhalgh, Adam Denes, Bernhard Nieswandt, Graham Coutts, Barry W McColl, Stuart M Allan
Neutrophils are key components of the innate immune response, providing host defence against infection and being recruited to non-microbial injury sites. Platelets act as a trigger for neutrophil extravasation to inflammatory sites but mechanisms and tissue-specific aspects of these interactions are currently unclear. Here, we use bacterial endotoxin in mice to trigger an innate inflammatory response in different tissues and measure neutrophil invasion with or without platelet reduction. We show that platelets are essential for neutrophil infiltration to the brain, peritoneum and skin, neutrophil numbers returning to basal levels in the peritoneum and skin and being decreased (~60%) in the brain when platelets are reduced...
January 11, 2018: Immunology
https://www.readbyqxmd.com/read/29301143/prostate-specific-antigen-velocity-in-a-prospective-prostate-cancer-screening-study-of-men-with-genetic-predisposition
#10
Christos Mikropoulos, Christina G Hutten Selkirk, Sibel Saya, Elizabeth Bancroft, Emily Vertosick, Tokhir Dadaev, Charles Brendler, Elizabeth Page, Alexander Dias, D Gareth Evans, Jeanette Rothwell, Lovise Maehle, Karol Axcrona, Kate Richardson, Diana Eccles, Thomas Jensen, Palle J Osther, Christi J van Asperen, Hans Vasen, Lambertus A Kiemeney, Janneke Ringelberg, Cezary Cybulski, Dominika Wokolorczyk, Rachel Hart, Wayne Glover, Jimmy Lam, Louise Taylor, Monica Salinas, Lidia Feliubadaló, Rogier Oldenburg, Ruben Cremers, Gerald Verhaegh, Wendy A van Zelst-Stams, Jan C Oosterwijk, Jackie Cook, Derek J Rosario, Saundra S Buys, Tom Conner, Susan Domchek, Jacquelyn Powers, Margreet Gem Ausems, Manuel R Teixeira, Sofia Maia, Louise Izatt, Rita Schmutzler, Kerstin Rhiem, William D Foulkes, Talia Boshari, Rosemarie Davidson, Marielle Ruijs, Apollonia Tjm Helderman-van den Enden, Lesley Andrews, Lisa Walker, Katie Snape, Alex Henderson, Irene Jobson, Geoffrey J Lindeman, Annelie Liljegren, Marion Harris, Muriel A Adank, Judy Kirk, Amy Taylor, Rachel Susman, Rakefet Chen-Shtoyerman, Nicholas Pachter, Allan Spigelman, Lucy Side, Janez Zgajnar, Josefina Mora, Carole Brewer, Neus Gadea, Angela F Brady, David Gallagher, Theo van Os, Alan Donaldson, Vigdis Stefansdottir, Julian Barwell, Paul A James, Declan Murphy, Eitan Friedman, Nicola Nicolai, Lynn Greenhalgh, Elias Obeid, Vedang Murthy, Lucia Copakova, John McGrath, Soo-Hwang Teo, Sara Strom, Karin Kast, Daniel A Leongamornlert, Anthony Chamberlain, Jenny Pope, Anna C Newlin, Neil Aaronson, Audrey Ardern-Jones, Chris Bangma, Elena Castro, David Dearnaley, Jorunn Eyfjord, Alison Falconer, Christopher S Foster, Henrik Gronberg, Freddie C Hamdy, Oskar Johannsson, Vincent Khoo, Jan Lubinski, Eli Marie Grindedal, Joanne McKinley, Kylie Shackleton, Anita V Mitra, Clare Moynihan, Gad Rennert, Mohnish Suri, Karen Tricker, Sue Moss, Zsofia Kote-Jarai, Andrew Vickers, Hans Lilja, Brian T Helfand, Rosalind A Eeles
BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values...
January 4, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29260592/how-do-aggregated-patient-reported-outcome-measures-data-stimulate-health-care-improvement-a-realist-synthesis
#11
Joanne Greenhalgh, Sonia Dalkin, Elizabeth Gibbons, Judy Wright, Jose Maria Valderas, David Meads, Nick Black
Objectives Internationally, there has been considerable debate about the role of data in supporting quality improvement in health care. Our objective was to understand how, why and in what circumstances the feedback of aggregated patient-reported outcome measures data improved patient care. Methods We conducted a realist synthesis. We identified three main programme theories underlying the use of patient-reported outcome measures as a quality improvement strategy and expressed them as nine 'if then' propositions...
January 1, 2017: Journal of Health Services Research & Policy
https://www.readbyqxmd.com/read/29228966/estimating-the-prevalence-of-infectious-diseases-from-under-reported-age-dependent-compulsorily-notification-databases
#12
Marcos Amaku, Marcelo Nascimento Burattini, Eleazar Chaib, Francisco Antonio Bezerra Coutinho, David Greenhalgh, Luis Fernandez Lopez, Eduardo Massad
BACKGROUND: National or local laws, norms or regulations (sometimes and in some countries) require medical providers to report notifiable diseases to public health authorities. Reporting, however, is almost always incomplete. This is due to a variety of reasons, ranging from not recognizing the diseased to failures in the technical or administrative steps leading to the final official register in the disease notification system. The reported fraction varies from 9 to 99% and is strongly associated with the disease being reported...
December 12, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/29146638/preventing-type-2-diabetes-systematic-review-of-studies-of-cost-effectiveness-of-lifestyle-programmes-and-metformin-with-and-without-screening-for-pre-diabetes
#13
Samantha Roberts, Eleanor Barry, Dawn Craig, Mara Airoldi, Gwyn Bevan, Trisha Greenhalgh
OBJECTIVE: Explore the cost-effectiveness of lifestyle interventions and metformin in reducing subsequent incidence of type 2 diabetes, both alone and in combination with a screening programme to identify high-risk individuals. DESIGN: Systematic review of economic evaluations. DATA SOURCES AND ELIGIBILITY CRITERIA: Database searches (Embase, Medline, PreMedline, NHS EED) and citation tracking identified economic evaluations of lifestyle interventions or metformin alone or in combination with screening programmes in people at high risk of developing diabetes...
November 15, 2017: BMJ Open
https://www.readbyqxmd.com/read/29142896/sodium-variability-is-associated-with-increased-mortality-in-severe-burn-injury
#14
Soman Sen, Nam Tran, Brian Chan, Tina L Palmieri, David G Greenhalgh, Kiho Cho
Background: Dysnatremias are associated with increased mortality in critically ill patients. Hypernatremia in burn patients is also associated with poor survival. Based on these findings, we hypothesized that high plasma sodium variability is a marker for increased mortality in severely burn-injured patients. Methods: We performed a retrospective review of adult burn patients with a burn injury of 15% total body surface area (TBSA) or greater from 2010 to 2014. All patients included in the study had at least three serum sodium levels checked during admission...
2017: Burns and Trauma
https://www.readbyqxmd.com/read/29097444/razor-a-phase-ii-open-randomized-trial-of-screening-plus-goserelin-and-raloxifene-versus-screening-alone-in-pre-menopausal-women-at-increased-risk-of-breast-cancer
#15
Anthony Howell, Linda Ashcroft, Lesley Fallowfield, Diana M Eccles, Rosalind A Eeles, Ann Ward, Adam R Brentnall, Mitchell Dowsett, Jack M Cuzick, Rosemary Greenhalgh, Caroline Boggis, Jamie Motion, Jamie C Sergeant, Judith Adams, D Gareth R Evans
BACKGROUND: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the LHRH analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention. METHODS: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone(C-Control) or screening in addition to monthly subcutaneous injections of 3...
November 2, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29092808/beyond-adoption-a-new-framework-for-theorizing-and-evaluating-nonadoption-abandonment-and-challenges-to-the-scale-up-spread-and-sustainability-of-health-and-care-technologies
#16
Trisha Greenhalgh, Joseph Wherton, Chrysanthi Papoutsi, Jennifer Lynch, Gemma Hughes, Christine A'Court, Susan Hinder, Nick Fahy, Rob Procter, Sara Shaw
BACKGROUND: Many promising technological innovations in health and social care are characterized by nonadoption or abandonment by individuals or by failed attempts to scale up locally, spread distantly, or sustain the innovation long term at the organization or system level. OBJECTIVE: Our objective was to produce an evidence-based, theory-informed, and pragmatic framework to help predict and evaluate the success of a technology-supported health or social care program...
November 1, 2017: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29061963/%C3%AE-v-integrins-on-mesenchymal-cells-regulate-skeletal-and-cardiac-muscle-fibrosis
#17
I R Murray, Z N Gonzalez, J Baily, R Dobie, R J Wallace, A C Mackinnon, J R Smith, S N Greenhalgh, A I Thompson, K P Conroy, D W Griggs, P G Ruminski, G A Gray, M Singh, M A Campbell, T J Kendall, J Dai, Y Li, J P Iredale, H Simpson, J Huard, B Péault, N C Henderson
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRβ) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRβ(+) cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRβ(+) cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29044179/the-effect-of-insecticide-synergist-treatment-on-genome-wide-gene-expression-in-a-polyphagous-pest
#18
Simon Snoeck, Robert Greenhalgh, Luc Tirry, Richard M Clark, Thomas Van Leeuwen, Wannes Dermauw
Synergists can counteract metabolic insecticide resistance by inhibiting detoxification enzymes or transporters. They are used in commercial formulations of insecticides, but are also frequently used in the elucidation of resistance mechanisms. However, the effect of synergists on genome-wide transcription in arthropods is poorly understood. In this study we used Illumina RNA-sequencing to investigate genome-wide transcriptional responses in an acaricide resistant strain of the spider mite Tetranychus urticae upon exposure to synergists such as S,S,S-tributyl phosphorotrithioate (DEF), diethyl maleate (DEM), piperonyl butoxide (PBO) and cyclosporin A (CsA)...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29034449/nitrous-oxide-based-vs-nitrous-oxide-free-general-anaesthesia-and-accidental-awareness-in-surgical-patients-an-abridged-cochrane-systematic-review
#19
REVIEW
J Hounsome, J Greenhalgh, O J Schofield-Robinson, S R Lewis, T M Cook, A F Smith
Accidental awareness during general anaesthesia can arise from a failure to deliver sufficient anaesthetic agent, or from a patient's resistance to an expected sufficient dose of such an agent. Awareness is 'explicit' if the patient is subsequently able to recall the event. We conducted a systematic review into the effect of nitrous oxide used as part of a general anaesthetic on the risk of accidental awareness in people over the age of five years undergoing general anaesthesia for surgery. We included 15 randomised controlled trials, 14 of which, representing a total of 3439 participants, were included in our primary analysis of the frequency of accidental awareness events...
October 16, 2017: Anaesthesia
https://www.readbyqxmd.com/read/29017005/early-planned-removal-of-umbilical-venous-catheters-to-prevent-infection-in-newborn-infants
#20
REVIEW
Adrienne Gordon, Mark Greenhalgh, William McGuire
BACKGROUND: Lengthy duration of use may be a risk factor for umbilical venous catheter-associated bloodstream infection in newborn infants. Early planned removal of umbilical venous catheters (UVCs) is recommended to reduce the incidence of infection and associated morbidity and mortality. OBJECTIVES: To compare the effectiveness of early planned removal of UVCs (up to two weeks after insertion) versus an expectant approach or a longer fixed duration in preventing bloodstream infection and other complications in newborn infants...
October 10, 2017: Cochrane Database of Systematic Reviews
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