Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial

<br>Background: Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes.</br> <br>Methods: We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307.</br> <br>Findings: We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI −0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI −0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5).</br> <br>Interpretation: Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population.</br&gt

Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial

<br>Background: Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes.</br> <br>Methods: We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307.</br> <br>Findings: We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI −0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI −0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5).</br> <br>Interpretation: Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population.</br&gt

Ten Years of Experience Training Non-Physician Anesthesia Providers in Haiti.

Surgery is increasingly recognized as an effective means of treating a proportion of the global burden of disease, especially in resource-limited countries. Often non-physicians, such as nurses, provide the majority of anesthesia; however, their training and formal supervision is often of low priority or even non-existent. To increase the number of safe anesthesia providers in Haiti, Médecins Sans Frontières has trained nurse anesthetists (NAs) for over 10 years. This article describes the challenges, outcomes, and future directions of this training program. From 1998 to 2008, 24 students graduated. Nineteen (79%) continue to work as NAs in Haiti and 5 (21%) have emigrated. In 2008, NAs were critical in providing anesthesia during a post-hurricane emergency where they performed 330 procedures. Mortality was 0.3% and not associated with lack of anesthesiologist supervision. The completion rate of this training program was high and the majority of graduates continue to work as nurse anesthetists in Haiti. Successful training requires a setting with a sufficient volume and diversity of operations, appropriate anesthesia equipment, a structured and comprehensive training program, and recognition of the training program by the national ministry of health and relevant professional bodies. Preliminary outcomes support findings elsewhere that NAs can be a safe and effective alternative where anesthesiologists are scarce. Training non-physician anesthetists is a feasible and important way to scale up surgical services resource limited settings

Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes

The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience

The association between sleeping time and metabolic syndrome features among older adults living in Mediterranean region. The MEDIS study.

Background: Metabolic Syndrome (MetS) as a combination of features has been known to significantly increase Cardiovascular Disease (CVD) risk, whilst MetS presence is linked to lifestyle parameters including physical activity and dietary habits; recently, the potential impact of sleeping habits has also become an issue under consideration. The aim of this study was to investigate the role of sleep quantity in several MetS components. Methods: Design:Cross-sectional observational study. Setting: 26 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece. Participants: during 2005-2017, 3130 older (aged 65-100 years) Mediterranean residents were voluntarily enrolled. Measurements: Dietary habits (including MedDietScore assessment), physical activity status, socio-demographic characteristics, lifestyle parameters (sleeping and smoking habits) and clinical profile aspects including Metabolic Syndrome (MetS) components (i.e., waist circumference, systolic and diastolic blood pressure, fasting glucose, triglycerides, LDL and HDL-cholesterol) were derived through standard procedures. Results: The number of daily hours of sleep was independently associated with greater waist circumference (b coefficient per 1 hour=0.91, 95% Confidence Interval (CI); 0.34, 1.49), higher LDL-cholesterol levels (b per 1 hour=3.84, 95%CI; 0.63, 7.05) and lower diastolic blood pressure levels (b per 1 hour=-0.98, 95%CI; - 1.57, -0.39) after adjusting for participants’ age, gender, body mass index, daily walking time, level of adherence to Mediterranean diet and smoking status. No association was revealed between hours of sleep per day and fasting glucose, triglycerides, HDL-cholesterol and systolic blood pressure. Conclusions: Increased hours of sleep is an indicator of metabolic disorders among elderly inviduals, and further research is needed to identify the paths through which sleep quantity is linked to MetS features in different age-groups

The Security imaginary: Explaining military isomorphism

This article proposes the notion of a security imaginary as a heuristic tool for exploring military isomorphism (the phenomenon that weapons and military strategies begin to look the same across the world) at a time when the US model of defence transformation is being adopted by an increasing number of countries. Built on a critical constructivist foundation, the security-imaginary approach is contrasted with rationalist and neo-institutionalist ways of explaining military diffusion and emulation. Merging cultural and constructivist themes, the article offers a ‘strong cultural’ argument to explain why a country would emulate a foreign military model and how this model is constituted in and comes to constitute a society’s security imaginary.Web of Scienc

Council tax valuation bands, socio-economic status and health outcome: a cross-sectional analysis from the Caerphilly Health and Social Needs Study

Council tax valuation bands (CTVBs) are a categorisation of household property value in Great Britain. The aim of the study was to assess the CTVB as a measure of socio-economic status by comparing the strength of the associations between selected health and lifestyle outcomes and CTVBs with two measures of socio-economic status: the National Statistics Socio-Economic Classification (NS-SEC) and the 2001 UK census-based Townsend deprivation index. METHODS: Cross-sectional analysis of data on 12,092 respondents (adjusted response 62.7%) to the Caerphilly Health and Social Needs Study, a postal questionnaire survey undertaken in Caerphilly county borough, south-east Wales, UK. The CTVB was assigned to each individual by matching the sampling frame to the local authority council tax register. Crude and age-gender adjusted odds ratios for each category of CTVB, NS-SEC and fifth of the ward distribution of Townsend scores were estimated for smoking, poor diet, obesity, and limiting long-term illness using logistic regression. Mean mental (MCS) and physical (PCS) component summary scores of the Short-Form SF-36 health status questionnaire were estimated in general linear models. RESULTS: There were significant trends in odds ratios across the CTVB categories for all outcomes, most marked for smoking and mental and physical health status. The adjusted odds ratio for being a smoker in the lowest versus highest CTVB category was 3.80 (95% CI: 3.06, 4.71), compared to 3.00 (95% CI: 2.30, 3.90) for the NS-SEC 'never worked and long-term unemployed' versus 'higher managerial and professional' categories, and 1.61 (95% CI: 1.42, 1.83) for the most deprived versus the least deprived Townsend fifth. The difference in adjusted mean MCS scores was 5.9 points on the scale for CTVB, 9.2 for NS-SEC and 3.2 for the Townsend score. The values for the adjusted mean PCS scores were 6.3 points for CTVB, 11.3 for NS-SEC, and 2.5 for the Townsend score. CONCLUSION: CTVBs assigned to individuals were strongly associated with the health and lifestyle outcomes modelled in this study. CTVBs are readily available for all residential properties and deserve further consideration as a proxy for socio-economic status in epidemiological studies in Great Britain

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

OSSOS. IV. DISCOVERY OF A DWARF PLANET CANDIDATE IN THE 9 : 2 RESONANCE WITH NEPTUNE

We report the discovery and orbit of a new dwarf planet candidate, 2015 RR245, by the Outer Solar System Origins Survey (OSSOS). The orbit of 2015 RR245 is eccentric (e = 0.586), with a semimajor axis near 82 au, yielding a perihelion distance of 34 au. 2015 RR245 has g - r = 0.59 +/- 0.11 and absolute magnitude H-r = 3.6 +/- 0.1; for an assumed albedo of p(V) = 12%, the object has a diameter of similar to 670. km. Based on astrometric measurements from OSSOS and Pan-STARRS1, we find that 2015 RR245 is securely trapped on ten-megayear timescales in the 9: 2 mean-motion resonance with Neptune. It is the first trans-Neptunian object (TNO) identified in this resonance. On hundred-megayear. timescales, particles in 2015 RR245-like orbits depart and sometimes return to the resonance, indicating that 2015 RR245 likely forms part of the long-lived metastable population of distant TNOs that drift between resonance sticking and actively scattering via gravitational encounters with Neptune. The discovery of a 9: 2 TNO stresses the role of resonances in the long-term evolution of objects in the scattering disk. and reinforces the view that distant resonances are heavily populated in the current solar system. This object further motivates detailed modeling of the transient sticking population.Peer reviewe

Phamerator: a bioinformatic tool for comparative bacteriophage genomics

Background: Bacteriophage genomes have mosaic architectures and are replete with small open reading frames of unknown function, presenting challenges in their annotation, comparative analysis, and representation.Results: We describe here a bioinformatic tool, Phamerator, that assorts protein-coding genes into phamilies of related sequences using pairwise comparisons to generate a database of gene relationships. This database is used to generate genome maps of multiple phages that incorporate nucleotide and amino acid sequence relationships, as well as genes containing conserved domains. Phamerator also generates phamily circle representations of gene phamilies, facilitating analysis of the different evolutionary histories of individual genes that migrate through phage populations by horizontal genetic exchange.Conclusions: Phamerator represents a useful tool for comparative genomic analysis and comparative representations of bacteriophage genomes. © 2011 Cresawn et al; licensee BioMed Central Ltd