Non-osteoporotic post-menopausal women do not have elevated concentrations of autoantibodies against osteoprotegerin

Introduction: Osteoprotegerin (OPG) plays a protective role in bone remodelling as it provides a ‘decoy’ binding site for RANKL, preventing the stimulation of osteoclasts. Autoantibodies to OPG allow a sustained reaction between RANKL and RANK which in turn increase bone degradation. Autoantibodies against Osteoprotegerin (-OPGAb) first isolated in patients with autoimmune conditions associated with high bone turnover have been shown to be present in 14% of a healthy young adult population. Bone degradation is more prominent in the oldest population, particularly in women. Objective: To define a reference range for OPG autoantibodies in non-osteoporotic post-menopausal women. Method: Using a previously developed sandwich ELISA assay we were able to detect OPG autoantibody in serum samples taken from non-osteoporotic post-menopausal women (ANSAVID study - 60-65yrs). Briefly, -OPGAb are captured by the use of an immobilized full-length human recombinant OPG and detected by the sequential addition of a biotinylated antibody and a horseradish-peroxidase-labelled streptavidin. The concentration of human α-OPGAb in the samples is determined directly from a 4PL-fit standard curve. Results: We established that the population of post-menopausal women who do not present osteoporosis do not have elevated concentration of -OPGAb as compared to a younger healthy population (17-32yrs). This suggest that -OPGAb is not normally occurring with age suggesting that the production of -OPGAb is solely related to pathologic conditions in which the bone is heavily degraded. Conclusion: Comparison of osteoporotic patient samples to the non-osteoporotic post-menopausal women would be interesting to determine whether -OPGAb can be used to identify appropriate treatment options for this particular subgroup of patients

Drug coated balloons for coronary artery bifurcation lesions: a systematic review and focused meta-analysis

Objectives We sought to systematically review the evidence supporting the role of drug coated balloons (DCBs) in the treatment of coronary bifurcation lesions. Background DCBs are emerging as an attractive alternative treatment strategy for treating coronary bifurcations due to simplifying the approach and reducing rates of stent related complications. We systematically reviewed the evidence for DCB use in coronary bifurcations and conducted a focused meta-analysis on late lumen loss in the side branch comparing DCB and plain old balloon angioplasty (POBA). Methods This study was conducted in line with the PRISMA statement. All studies (including both RCTs and observational studies, excluding case reports) using DCB as part of a bifurcation strategy were included in this review. A literature search identified a total of ten studies for inclusion. A focused meta-analysis was undertaken for the use of DCB in side-branch compared with POBA. Mean late lumen loss was used with a random effects model due to heterogeneity. Results DCB was found to be superior to POBA for side branch treatment in bifurcations (p = 0.01). There are four studies that investigated the use of DCB for main branch treatment in a bifurcation, with evidence supporting its safety in main branches of bifurcation lesions, while prospective observational studies have demonstrated favourable target lesion revascularisation rates. Conclusion Although there is a lack of robust RCTs comparing DCBs with current generation DES, DCBs appear safe in main branch bifurcation lesions with improved side branch late lumen loss when compared with DES or POBA

Clinical translation of three-dimensional scar, diffusion tensor imaging, four-dimensional flow, and quantitative perfusion in cardiac MRI: a comprehensive review

Cardiovascular magnetic resonance (CMR) imaging is a versatile tool that has established itself as the reference method for functional assessment and tissue characterisation. CMR helps to diagnose, monitor disease course and sub-phenotype disease states. Several emerging CMR methods have the potential to offer a personalised medicine approach to treatment. CMR tissue characterisation is used to assess myocardial oedema, inflammation or thrombus in various disease conditions. CMR derived scar maps have the potential to inform ablation therapy—both in atrial and ventricular arrhythmias. Quantitative CMR is pushing boundaries with motion corrections in tissue characterisation and first-pass perfusion. Advanced tissue characterisation by imaging the myocardial fibre orientation using diffusion tensor imaging (DTI), has also demonstrated novel insights in patients with cardiomyopathies. Enhanced flow assessment using four-dimensional flow (4D flow) CMR, where time is the fourth dimension, allows quantification of transvalvular flow to a high degree of accuracy for all four-valves within the same cardiac cycle. This review discusses these emerging methods and others in detail and gives the reader a foresight of how CMR will evolve into a powerful clinical tool in offering a precision medicine approach to treatment, diagnosis, and detection of disease

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

The impact of extracorporeal membrane oxygenation on mortality in patients with cardiogenic shock post-acute myocardial infarction: a systematic review and meta-analysis

Funder: NIHR; DOI: https://doi.org/10.13039/501100000272Funder: Academic Clinical FellowsFunder: Wellcome Trust PhD FellowshipAbstract Aims Cardiogenic shock remains the leading cause of death in patients hospitalized with acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in the treatment of infarct-related cardiogenic shock. However, there is limited evidence regarding its beneficial impact on mortality. The aim of this study was to systematically review studies reporting the impact of VA-ECMO on mortality in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and results A comprehensive search of medical databases (Cochrane Register and PubMed) was conducted. Studies that reported mortality outcomes in patients treated with VA-ECMO for infarct-related cardiogenic shock were included. The database search yielded 1194 results, of which 11 studies were included in the systematic review. Four of these studies, with a total of 586 patients, were randomized controlled trials and were included in the meta-analysis. This demonstrated that there was no significant difference in 30-day all-cause mortality with the use of VA-ECMO compared with standard medical therapy [odds ratio (OR) 0.91; 95% confidence interval (CI) 0.65–1.27]. Meta-analysis of two studies showed that VA-ECMO was associated with a significant reduction in 12-month all-cause mortality (OR 0.31; 95% CI 0.11–0.86). Qualitative synthesis of the observational studies showed that age, serum creatinine, serum lactate, and successful revascularization are independent predictors of mortality. Conclusion Veno-arterial extracorporeal membrane oxygenation does not improve 30-day all-cause mortality in patients with cardiogenic shock following acute myocardial infarction; however, there may be significant reduction in all-cause mortality at 12 months. Further studies are needed to delineate the potential benefit of VA-ECMO in long-term outcomes. Registration The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42023461740). </jats:sec

The impact of extracorporeal membrane oxygenation on mortality in patients with cardiogenic shock post-acute myocardial infarction: a systematic review and meta-analysis

Funder: NIHR; DOI: https://doi.org/10.13039/501100000272Funder: Academic Clinical FellowsFunder: Wellcome Trust PhD FellowshipAims: Cardiogenic shock remains the leading cause of death in patients hospitalized with acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in the treatment of infarct-related cardiogenic shock. However, there is limited evidence regarding its beneficial impact on mortality. The aim of this study was to systematically review studies reporting the impact of VA-ECMO on mortality in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and results: A comprehensive search of medical databases (Cochrane Register and PubMed) was conducted. Studies that reported mortality outcomes in patients treated with VA-ECMO for infarct-related cardiogenic shock were included. The database search yielded 1194 results, of which 11 studies were included in the systematic review. Four of these studies, with a total of 586 patients, were randomized controlled trials and were included in the meta-analysis. This demonstrated that there was no significant difference in 30-day all-cause mortality with the use of VA-ECMO compared with standard medical therapy [odds ratio (OR) 0.91; 95% confidence interval (CI) 0.65–1.27]. Meta-analysis of two studies showed that VA-ECMO was associated with a significant reduction in 12-month all-cause mortality (OR 0.31; 95% CI 0.11–0.86). Qualitative synthesis of the observational studies showed that age, serum creatinine, serum lactate, and successful revascularization are independent predictors of mortality. Conclusion: Veno-arterial extracorporeal membrane oxygenation does not improve 30-day all-cause mortality in patients with cardiogenic shock following acute myocardial infarction; however, there may be significant reduction in all-cause mortality at 12 months. Further studies are needed to delineate the potential benefit of VA-ECMO in long-term outcomes. Registration: The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42023461740)

The impact of extracorporeal membrane oxygenation on mortality in patients with cardiogenic shock post-acute myocardial infarction: a systematic review and meta-analysis

Funder: NIHR; DOI: https://doi.org/10.13039/501100000272Funder: Academic Clinical FellowsFunder: Wellcome Trust PhD FellowshipAims: Cardiogenic shock remains the leading cause of death in patients hospitalized with acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in the treatment of infarct-related cardiogenic shock. However, there is limited evidence regarding its beneficial impact on mortality. The aim of this study was to systematically review studies reporting the impact of VA-ECMO on mortality in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and results: A comprehensive search of medical databases (Cochrane Register and PubMed) was conducted. Studies that reported mortality outcomes in patients treated with VA-ECMO for infarct-related cardiogenic shock were included. The database search yielded 1194 results, of which 11 studies were included in the systematic review. Four of these studies, with a total of 586 patients, were randomized controlled trials and were included in the meta-analysis. This demonstrated that there was no significant difference in 30-day all-cause mortality with the use of VA-ECMO compared with standard medical therapy [odds ratio (OR) 0.91; 95% confidence interval (CI) 0.65–1.27]. Meta-analysis of two studies showed that VA-ECMO was associated with a significant reduction in 12-month all-cause mortality (OR 0.31; 95% CI 0.11–0.86). Qualitative synthesis of the observational studies showed that age, serum creatinine, serum lactate, and successful revascularization are independent predictors of mortality. Conclusion: Veno-arterial extracorporeal membrane oxygenation does not improve 30-day all-cause mortality in patients with cardiogenic shock following acute myocardial infarction; however, there may be significant reduction in all-cause mortality at 12 months. Further studies are needed to delineate the potential benefit of VA-ECMO in long-term outcomes. Registration: The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42023461740)