6 research outputs found
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Mitochondrial Dysfunction Increases Arrhythmic Triggers and Substrates; Potential Anti-arrhythmic Pharmacological Targets.
Incidence of cardiac arrhythmias increases significantly with age. In order to effectively stratify arrhythmic risk in the aging population it is crucial to elucidate the relevant underlying molecular mechanisms. The changes underlying age-related electrophysiological disruption appear to be closely associated with mitochondrial dysfunction. Thus, the present review examines the mechanisms by which age-related mitochondrial dysfunction promotes arrhythmic triggers and substrate. Namely, via alterations in plasmalemmal ionic currents (both sodium and potassium), gap junctions, cellular Ca2+ homeostasis, and cardiac fibrosis. Stratification of patients' mitochondrial function status permits application of appropriate anti-arrhythmic therapies. Here, we discuss novel potential anti-arrhythmic pharmacological interventions that specifically target upstream mitochondrial function and hence ameliorates the need for therapies targeting downstream changes which have constituted traditional antiarrhythmic therapy
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 2Â years which mostly contained basic medical science content and the later 3Â years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2Â 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
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
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Prosthesis-Patient Mismatch and Aortic Root Enlargement: Indications, Techniques and Outcomes.
Peer reviewed: TrueAcknowledgements: The authors would like to thank Khadeeja Mafaz for illustrating Figure 1 and Figure 2.Prosthesis-patient mismatch (PPM) is defined as implanting a prosthetic that is insufficiently sized for the patient receiving it. PPM leads to high residual transvalvular gradients post-aortic valve replacement and consequently results in left ventricular dysfunction, morbidity and mortality in both the short and long term. Younger patients and patients with poor preoperative left ventricular function are more vulnerable to increased mortality secondary to PPM. There is debate over the measurement of valvular effective orifice area (EOA) and variation exists in how manufacturers report the EOA. The most reliable technique is using in vivo echocardiographic measurements to create tables of predicted EOAs for different valve sizes. PPM can be prevented surgically in patients at risk through aortic root enlargement (ARE). Established techniques include the posterior enlargement through Nicks and Manouguian procedures, and aortico-ventriculoplasty with the Konno-Rastan procedure, which allows for a greater enlargement but carries increased surgical risk. A contemporary development is the Yang procedure, which uses a Y-shaped incision created through the non- and left-coronary cusp commissure, undermining the nadirs of the non- and left-coronary cusps. Early results are promising and demonstrate an ability to safely increase the aortic root by up to two to three sizes. Aortic root enlargement thus remains a valuable and safe tool in addressing PPM, and should be considered during surgical planning
Prosthesis–Patient Mismatch and Aortic Root Enlargement: Indications, Techniques and Outcomes
Prosthesis–patient mismatch (PPM) is defined as implanting a prosthetic that is insufficiently sized for the patient receiving it. PPM leads to high residual transvalvular gradients post-aortic valve replacement and consequently results in left ventricular dysfunction, morbidity and mortality in both the short and long term. Younger patients and patients with poor preoperative left ventricular function are more vulnerable to increased mortality secondary to PPM. There is debate over the measurement of valvular effective orifice area (EOA) and variation exists in how manufacturers report the EOA. The most reliable technique is using in vivo echocardiographic measurements to create tables of predicted EOAs for different valve sizes. PPM can be prevented surgically in patients at risk through aortic root enlargement (ARE). Established techniques include the posterior enlargement through Nicks and Manouguian procedures, and aortico-ventriculoplasty with the Konno–Rastan procedure, which allows for a greater enlargement but carries increased surgical risk. A contemporary development is the Yang procedure, which uses a Y-shaped incision created through the non- and left-coronary cusp commissure, undermining the nadirs of the non- and left-coronary cusps. Early results are promising and demonstrate an ability to safely increase the aortic root by up to two to three sizes. Aortic root enlargement thus remains a valuable and safe tool in addressing PPM, and should be considered during surgical planning
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Anti-malarial drugs: Mechanisms underlying their proarrhythmic effects.
Malaria remains the leading cause of parasitic death in the world. Artemisinin resistance is an emerging threat indicating an imminent need for novel combination therapy. Given the key role of mass drug administration, it is pivotal that the safety of anti-malarial drugs is investigated thoroughly prior to widespread use. Cardiotoxicity, most prominently arrhythmic risk, has been a concern for anti-malarial drugs. We clarify the likely underlying mechanisms by which anti-malarial drugs predispose to arrhythmias. These relate to disruption of (1) action potential upstroke due to effects on the sodium currents, (2) action potential repolarisation due to effects on the potassium currents, (3) cellular calcium homeostasis, (4) mitochondrial function and reactive oxygen species production and (5) cardiac fibrosis. Together, these alterations promote arrhythmic triggers and substrates. Understanding these mechanisms is essential to assess the safety of these drugs, stratify patients based on arrhythmic risk and guide future anti-malarial drug development