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Vinay Prasad - there is overdiagnosis in clinical trials

We want clinical trials to be thorough - but Vinay Prasad, assistant professor of medicine at Oregon Health Science University, argues that the problem of overdiagnosis may be as prevalent, in the way we measure disease in our research, as our practice. In this podcast he joins us to discuss the problem, and why he thinks what qualifies as...




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HIV - everything you wanted to know about PeP and PreP

We have had two articles published recently on bmj.com, looking at drug prevention of HIV; PeP - Post-exposure Prophylaxis and PreP - Pre-exposure Prophylaxis, neither prevent the virus from entering the body, but they do prevent the infection from taking hold. There are lots of questions that doctors have about these - what are the risk...




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Nuffield 2019 - How can the NHS provide a fulfilling lifelong career

More doctors are choosing to retire early, doctors who take career breaks find it hard to return to practice, and doctors at all stages of their careers are frustrated by the lack of support given to training and development in today’s NHS. Each year the BMJ holds a roundtable discussion at the Nuffield Summit - where health leaders come...




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Social prescribing

Non-medical interventions are increasingly being proposed to address wider determinants of health and to help patients improve health behaviours and better manage their conditions - this is known as social prescribing. In England, the NHS Long Term Plan states that nearly one million people will qualify for referral to social prescribing schemes...




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Talk evidence - cancer causing food, prostate cancer and disease definitions

Helen Macdonald and Carl Heneghan are back again talking about what's happened in the world of evidence this month. (1.05) Carl rants about bacon causing cancer (7.10) Helen talks about prostate cancer, and we hear from the author of the research paper which won Research Paper Of The Year at the BMJ awards. We also cover disease definition and...




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Fertility awareness based methods for pregnancy prevention

Fertility awareness based methods of contraception are increasingly being used for pregnancy prevention. In the US, the proportion of contraceptive users who choose such methods has grown from 1% in 2008 to approximately 3% in 2014.  Relative to other methods of pregnancy prevention, however, substantial misinformation exists around fertility...




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Cancer drug trials used for regulatory approval are at risk of bias

Around half of trials that supported new cancer drug approvals in Europe between 2014 and 2016 were judged to be at high risk of bias, in a new study. Huseyin Naci,assistant professor of health policy a the London School of Economics joins us to talk about why potential bias may mean potential exaggeration of treatment effects, and could be...




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Climate change will make universal health coverage precarious

The BMJ in partnership with The Harvard Global Health Institute has launched a collection of articles exploring how to achieve effective universal health coverage (UHC). The collection highlights the importance of quality in UHC, potential finance models, how best to incentivise stakeholders, and some of the barriers to true UHC. One of those...




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Minimum unit pricing in Scotland

On the 1st of May, 2018 Scotland was the first country to try a new way of reducing alcohol consumption in its population. It introduced a minimum unit prices for alcohol. Now new research just published on BMJ.com is looking at the effect of that price increase - and measuring how well it has achieved the goal of reducing drinking in...




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Talk Evidence - eating less, drinking less, drug approval data

Talk Evidence is back, with your monthly take on the world of EBM with Duncan Jarvies and GPs Carl Heneghan (also director for the Centre of Evidence Based Medicine at the University of Oxford) and Helen Macdonald (also The BMJ's UK research Editor). This month Carl talks about evidence that restricting your diet might improve health at a...




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How Blockchain could improve clinical trial transparency

Blockchain is the digital technology that underpins cryptocurrencies such as bitcoin, and has been proposed as the digital panacea of our times. But Leeza Osipenko, from the London School of Economics, has thought about how it could actually be used in clinical trials, and what else would need to change in our regulatory environment to make that...




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Statins for primary prevention - How good is the evidence

Statins are now the most commonly used drug in the UK and one of the most commonly used medicines in the world, but debate remains about their use for primary prevention for people without cardiovascular disease. Paula Byrne from the National University of Ireland Galway, joins us to talk about the evidence of benefit for low risk individuals,...




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Talk Evidence - aggravating acronyms, a time to prescribe, and screening (again)

Talk Evidence is back, with your monthly take on the world of EBM with Duncan Jarvies and GPs Carl Heneghan (also director for the Centre of Evidence Based Medicine at the University of Oxford) and Helen Macdonald (also The BMJ's UK research Editor). This month Helen talks about the messy business of colon cancer screening - which modality is...




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Reversing our preconceptions about where innovation comes from

Reverse innovation may sound like some attempt to return to the dark ages - but it has a specific meaning, especially when it comes to med-tech. It’s about where we look for innovation - and overturning our preconceived ideas of where new ideas come from. Mark Skopec, and Matthew Harris - both from Imperial College London are two of the authors...




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Behind the campaign promises - GP numbers, and appointment slots

A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week has...




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Behind the campaign promises - Health and social care spending

A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week...




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Behind the campaign promises - Health beyond the NHS

A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week...




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Behind the campaign promises - what the NHS means for the election

UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week we're...




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Behind the campaign promises - Doctors in parliament

The UK general election is happening this week, and you’ve probably made your mind up which MP you’re voting for already - and maybe the NHS has influenced that decision. This year has seen an increase in the number of doctors running for parliament, and in this podcast we find out what motivates doctors to step away from clinical practice, and...




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From dance class to social prescription - starting and evaluating an idea

If you read the Christmas BMJ in the last few weeks, you might have noticed a lot around art and health - the way in which engagement in arts can help in prevention and treatment, but can also affect those more nebulous things which really matter to patients - loneliness, self expression, being connected to the wider community. That obviously...




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Is it possible to have fair pricing for medicines

Is it possible to have a fair price for medicines? Yes, according to a new collection just published on bmj.com. The authors set out to evaluate how we could improve the functioning of the market for medicines, to honestly compensate industry for innovation, whilst allowing the poorest to afford them. Suerie Moon, co-director of global health at...




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Prevalence and treatment of precocious puberty

Precocious puberty, that is puberty that starts before age 8 in girls and 9 in boys seems to be on the rise, but whether that’s because of an increase in incidence, or greater attention is unknown - what we do know that precocious puberty in girls is commonly idiopathic, while in boys is a red flag for pathology. But either way ther first point of...




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QI and improvement are not synonyms

In October 2019, Mary Dixon-Woods, director of the THIS Institute, dedicated to healthcare improvement. In that she explained how she believed healthcare improvement could be improved. The essay took the position that "Quality Improvement" isn't necessarily the best way to improve healthcare, and that more rigour needs to be brought to the field....




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David Williams - everyday discrimination is an independent predictor of mortality

There comes a tipping point in all campaigns when the evidence is overwhelming and the only way to proceed is with action. According to David Williams, it’s time to tackle the disproportionate effects of race on patients in the UK. David Williams, from Harvard University, developed the Everyday Discrimination Scale that, in 1997, launched a new...




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Talk Evidence - testing under the microscope and opioid prescription

This edition of talk evidence was recorded before the big increase in covid-19 infections in the UK, and then delayed by some self isolation. We'll be back with more evidence on the pandemic very soon. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford...




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Talk Evidence covid-19 update - pneumonia, guidelines, preprints and testing

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...




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Talk Evidence covid-19 update - hydroxy/chloroquinine, prognostic models and facemaskss

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...




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Prospective Analysis of The Insulin-Resistance Syndrome (Syndrome X)

Steven M Haffner
Jun 1, 1992; 41:715-722
Original Article




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C-Reactive Protein Is an Independent Predictor of Risk for the Development of Diabetes in the West of Scotland Coronary Prevention Study

Dilys J. Freeman
May 1, 2002; 51:1596-1600
Complications




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5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle

EJ Kurth-Kraczek
Aug 1, 1999; 48:1667-1671
Articles




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Endothelial Progenitor Cell Dysfunction: A Novel Concept in the Pathogenesis of Vascular Complications of Type 1 Diabetes

Cindy J.M. Loomans
Jan 1, 2004; 53:195-199
Complications




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Relation Between Antioxidant Enzyme Gene Expression and Antioxidative Defense Status of Insulin-Producing Cells

Markus Tiedge
Nov 1, 1997; 46:1733-1742
Original Article




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Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes: Results of the Prospective Population-Based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology




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Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles




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NCEP-Defined Metabolic Syndrome, Diabetes, and Prevalence of Coronary Heart Disease Among NHANES III Participants Age 50 Years and Older

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications




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Evidence for 5'AMP-Activated Protein Kinase Mediation of the Effect of Muscle Contraction on Glucose Transport

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications




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High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells

T Inoguchi
Nov 1, 2000; 49:1939-1945
Articles




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Protein kinase C activation and the development of diabetic complications

D Koya
Jun 1, 1998; 47:859-866
Articles




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Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and I{kappa}B-{alpha}

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications




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Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats

G Xu
Dec 1, 1999; 48:2270-2276
Articles




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Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications




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The Relationship of Glycemic Exposure (HbA1c) to the Risk of Development and Progression of Retinopathy in the Diabetes Control and Complications Trial

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article




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A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans

David E. Cummings
Aug 1, 2001; 50:1714-1719
Rapid Publications




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PPAR{gamma} Ligands Increase Expression and Plasma Concentrations of Adiponectin, an Adipose-Derived Protein

Norikazu Maeda
Sep 1, 2001; 50:2094-2099
Pathophysiology




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Preservation of Pancreatic {beta}-Cell Function and Prevention of Type 2 Diabetes by Pharmacological Treatment of Insulin Resistance in High-Risk Hispanic Women

Thomas A. Buchanan
Sep 1, 2002; 51:2796-2803
Pathophysiology




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Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles




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U.K. Prospective Diabetes Study 16: Overview of 6 Years' Therapy of Type II Diabetes: A Progressive Disease

U.K. Prospective Diabetes Study Group
Nov 1, 1995; 44:1249-1258
Perspectives in Diabetes




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Assessment of MTNR1B Type 2 Diabetes Genetic Risk Modification by Shift Work and Morningness-Eveningness Preference in the UK Biobank

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (n = 5,042 cases) and HbA1c levels (n = 175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk allele associated with type 2 diabetes and HbA1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that MTNR1B risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.




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Clinical and Molecular Prevalence of Lipodystrophy in an Unascertained Large Clinical Care Cohort

Lipodystrophies are a group of disorders characterized by absence or loss of adipose tissue and abnormal fat distribution, commonly accompanied by metabolic dysregulation. Although considered rare disorders, their prevalence in the general population is not well understood. We aimed to evaluate the clinical and genetic prevalence of lipodystrophy disorders in a large clinical care cohort. We interrogated the electronic health record (EHR) information of >1.3 million adults from the Geisinger Health System for lipodystrophy diagnostic codes. We estimate a clinical prevalence of disease of 1 in 20,000 individuals. We performed genetic analyses in individuals with available genomic data to identify variants associated with inherited lipodystrophies and examined their EHR for comorbidities associated with lipodystrophy. We identified 16 individuals carrying the p.R482Q pathogenic variant in LMNA associated with Dunnigan familial partial lipodystrophy. Four had a clinical diagnosis of lipodystrophy, whereas the remaining had no documented clinical diagnosis despite having accompanying metabolic abnormalities. We observed a lipodystrophy-associated variant carrier frequency of 1 in 3,082 individuals in our cohort with substantial burden of metabolic dysregulation. We estimate a genetic prevalence of disease of ~1 in 7,000 in the general population. Partial lipodystrophy is an underdiagnosed condition. and its prevalence, as defined molecularly, is higher than previously reported. Genetically guided stratification of patients with common metabolic disorders, like diabetes and dyslipidemia, is an important step toward precision medicine.




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Predictive Modeling of Type 1 Diabetes Stages Using Disparate Data Sources

This study aims to model genetic, immunologic, metabolomics, and proteomic biomarkers for development of islet autoimmunity (IA) and progression to type 1 diabetes in a prospective high-risk cohort. We studied 67 children: 42 who developed IA (20 of 42 progressed to diabetes) and 25 control subjects matched for sex and age. Biomarkers were assessed at four time points: earliest available sample, just prior to IA, just after IA, and just prior to diabetes onset. Predictors of IA and progression to diabetes were identified across disparate sources using an integrative machine learning algorithm and optimization-based feature selection. Our integrative approach was predictive of IA (area under the receiver operating characteristic curve [AUC] 0.91) and progression to diabetes (AUC 0.92) based on standard cross-validation (CV). Among the strongest predictors of IA were change in serum ascorbate, 3-methyl-oxobutyrate, and the PTPN22 (rs2476601) polymorphism. Serum glucose, ADP fibrinogen, and mannose were among the strongest predictors of progression to diabetes. This proof-of-principle analysis is the first study to integrate large, diverse biomarker data sets into a limited number of features, highlighting differences in pathways leading to IA from those predicting progression to diabetes. Integrated models, if validated in independent populations, could provide novel clues concerning the pathways leading to IA and type 1 diabetes.