Enhancing the connection between the classroom and the clinical workplace:A systematic review

Introduction Although medical students are increasingly exposed to clinical experiences as part of their training, these often occur parallel with, rather than connected to, their classroom-based learning experiences. Additionally, students seem to struggle with spontaneously making the connection between these spheres of their training themselves. Therefore, this systematic review synthesized the existing evidence about educational interventions that aim to enhance the connection between learning in the classroom and its application in the workplace. Methods Electronic databases (AMED, CINAHL, EMBASE, ERIC, Medline, RDRB, PsycINFO and WoS) were screened for quantitative and qualitative studies investigating educational interventions that referenced a connection between the classroom and workplace-based experiences within undergraduate, graduate or postgraduate medical education. Results Three types of interventions were identified: classroom to workplace interventions, workplace to classroom interventions, and interventions involving multiple connections between the two settings. Most interventions involved a tool (e.g. video, flow chart) or a specific process (e.g. linking patient cases with classroom-based learning content, reflecting on differences between what was learned and how it works in practice) which aimed to enhance the connection between the two settings. Discussion Small-scale interventions can bring classroom learning and workplace practice into closer alignment. Such interventions appear to be the necessary accompaniments to curricular structures, helping bridge the gap between classroom learning and workplace experience. This paper documents examples that may serve to assist medical educators in connecting the classroom and the workplace

Estimating daily yield and content of major fatty acids from single milking

Reducing the frequency of milk recording and the number of recorded samples per test-day could be a solution in order to reduce costs of official milk recording. However, fewer samples lead to a decrease in the accuracy of predicted daily yields. Unfortunately, the current published equations use the milking interval that is often not available and/or reliable in practice. The first objective of this study was to propose models using easily available traits. Therefore the milking interval was replaced by a combination of data easily recorded by milk recording. The second objective of this study was to enlarge the previous investigations to milk fatty acids (FA) in order to propose a practical method for estimating accurate daily milk, fat and major FA yields from single milking. The fit goodness of proposed models was evaluated based on the correlation values between the estimated and observed daily yields in addition to the calculation of the mean square error. Obtained results are promising. Correlation values were comprised between 96.4% and 97.6% when daily yield were estimated from morning milking, and from 96.9% to 98.3% when daily yield were estimated from evening milking. The combination of records related to lactation stage, month of test, milk yield, and fat could replace the milking interval effect. Because of their simplicity, proposed models would be easy to implement

Pseudo Identities Based on Fingerprint Characteristics

This paper presents the integrated project TURBINE which is funded under the EU 7th research framework programme. This research is a multi-disciplinary effort on privacy enhancing technology, combining innovative developments in cryptography and fingerprint recognition. The objective of this project is to provide a breakthrough in electronic authentication for various applications in the physical world and on the Internet. On the one hand it will provide secure identity verification thanks to fingerprint recognition. On the other hand it will reliably protect the biometric data through advanced cryptography technology. In concrete terms, it will provide the assurance that (i) the data used for the authentication, generated from the fingerprint, cannot be used to restore the original fingerprint sample, (ii) the individual will be able to create different "pseudo-identities" for different applications with the same fingerprint, whilst ensuring that these different identities (and hence the related personal data) cannot be linked to each other, and (iii) the individual is enabled to revoke an biometric identifier (pseudo-identity) for a given application in case it should not be used anymore

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

OBJECTIVE To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN Network meta-analysis. DATA SOURCES Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk

Clinical decision support improves the appropriateness of laboratory test ordering in primary care without increasing diagnostic error : the ELMO cluster randomized trial

Background: Inappropriate laboratory test ordering poses an important burden for healthcare. Clinical decision support systems (CDSS) have been cited as promising tools to improve laboratory test ordering behavior. The objectives of this study were to evaluate the effects of an intervention that integrated a clinical decision support service into a computerized physician order entry (CPOE) on the appropriateness and volume of laboratory test ordering, and on diagnostic error in primary care. Methods: This study was a pragmatic, cluster randomized, open-label, controlled clinical trial. Setting: Two hundred eighty general practitioners (GPs) from 72 primary care practices in Belgium. Patients: Patients aged >= 18 years with a laboratory test order for at least one of 17 indications: cardiovascular disease management, hypertension, check-up, chronic kidney disease (CKD), thyroid disease, type 2 diabetes mellitus, fatigue, anemia, liver disease, gout, suspicion of acute coronary syndrome (ACS), suspicion of lung embolism, rheumatoid arthritis, sexually transmitted infections (STI), acute diarrhea, chronic diarrhea, and follow-up of medication. Interventions: The CDSS was integrated into a computerized physician order entry (CPOE) in the form of evidence-based order sets that suggested appropriate tests based on the indication provided by the general physician. Measurements: The primary outcome of the ELMO study was the proportion of appropriate tests over the total number of ordered tests and inappropriately not-requested tests. Secondary outcomes of the ELMO study included diagnostic error, test volume, and cascade activities. Results: CDSS increased the proportion of appropriate tests by 0.21 (95% CI 0.16-0.26, p < 0.0001) for all tests included in the study. GPs in the CDSS arm ordered 7 (7.15 (95% CI 3.37-10.93, p = 0.0002)) tests fewer per panel. CDSS did not increase diagnostic error. The absolute difference in proportions was a decrease of 0.66% (95% CI 1.4% decrease-0.05% increase) in possible diagnostic error. Conclusions: A CDSS in the form of order sets, integrated within the CPOE improved appropriateness and decreased volume of laboratory test ordering without increasing diagnostic error

PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations.

CLINICAL QUESTION In adults with low density lipoprotein (LDL) cholesterol levels >1.8 mmol/L (>70 mg/dL) who are already taking the maximum dose of statins or are intolerant to statins, should another lipid-lowering drug be added, either a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor or ezetimibe, to reduce the risk of major cardiovascular events? If so, which drug is preferred? Having decided to use one, should we add the other lipid-lowering drug? CURRENT PRACTICE Most guidelines emphasise LDL cholesterol targets in their recommendations for prescribing PCSK9 inhibitors and/or ezetimibe in adults at high risk of experiencing a major adverse cardiovascular event. However, to achieve these goals in very high risk patients with statins alone is almost impossible, so physicians are increasingly considering other lipid-lowering drugs solely for achieving LDL cholesterol treatment goals rather than for achieving important absolute cardiovascular risk reduction. Most guidelines do not systematically assess the cardiovascular benefits of adding PCSK9 inhibitors and/or ezetimibe for all risk groups across primary and secondary prevention, nor do they report, in accordance with explicit judgments of assumed patients' values and preferences, absolute benefits and harms and potential treatment burdens. RECOMMENDATIONS The guideline panel provided mostly weak recommendations, which means we rely on shared decision making when applying these recommendations. For adults already using statins, the panel suggests adding a second lipid-lowering drug in people at very high and high cardiovascular risk but recommends against adding it in people at low cardiovascular risk. For adults who are intolerant to statins, the panel recommends using a lipid-lowering drug in people at very high and high cardiovascular risk but against adding it in those at low cardiovascular risk. When choosing to add another lipid-lowering drug, the panel suggests ezetimibe in preference to PCSK9 inhibitors. The panel suggests further adding a PCSK9 inhibitor to ezetimibe for adults already taking statins at very high risk and those at very high and high risk who are intolerant to statins. HOW THIS GUIDELINE WAS CREATED An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified four risk groups of patients (low, moderate, high, and very high cardiovascular risk) and primarily applied an individual patient perspective in moving from evidence to recommendations, though societal issues were a secondary consideration. The panel considered the balance of benefits and harms and burdens of starting a PCSK9 inhibitor and/or ezetimibe, making assumptions of adults' average values and preferences. Interactive evidence summaries and decision aids accompany multi-layered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that also allows re-use and adaptation. THE EVIDENCE A linked systematic review and network meta-analysis (14 trials including 83 660 participants) of benefits found that PCSK9 inhibitors or ezetimibe probably reduce myocardial infarctions and stroke in patients with very high and high cardiovascular risk, with no impact on mortality (moderate to high certainty evidence), but not in those with moderate and low cardiovascular risk. PCSK9 inhibitors may have similar effects to ezetimibe on reducing non-fatal myocardial infarction or stroke (low certainty evidence). These relative benefits were consistent, but their absolute magnitude varied based on cardiovascular risk in individual patients (for example, for 1000 people treated with PCSK9 inhibitors in addition to statins over five years, benefits ranged from 2 fewer strokes in the lowest risk to 21 fewer in the highest risk). Two systematic reviews on harms found no important adverse events for these drugs (moderate to high certainty evidence). PCSK9 inhibitors require injections that sometimes result in injection site reactions (best estimate 15 more per 1000 in a 5 year timeframe), representing a burden and harm that may matter to patients. The MATCH-IT decision support tool allows you to interact with the evidence and your patients across the alternative options: https://magicevidence.org/match-it/220504dist-lipid-lowering-drugs/. UNDERSTANDING THE RECOMMENDATIONS The stratification into four cardiovascular risk groups means that, to use the recommendations, physicians need to identify their patient's risk first. We therefore suggest, specific to various geographical regions, using some reliable risk calculators that estimate patients' cardiovascular risk based on a mix of known risk factors. The largely weak recommendations concerning the addition of ezetimibe or PCSK9 inhibitors reflect what the panel considered to be a close balance between small reductions in stroke and myocardial infarctions weighed against the burdens and limited harms.Because of the anticipated large variability of patients' values and preferences, well informed choices warrant shared decision making. Interactive evidence summaries and decision aids linked to the recommendations can facilitate such shared decisions. The strong recommendations against adding another drug in people at low cardiovascular risk reflect what the panel considered to be a burden without important benefits. The strong recommendation for adding either ezetimibe or PCSK9 inhibitors in people at high and very high cardiovascular risk reflect a clear benefit.The panel recognised the key uncertainty in the evidence concerning patient values and preferences, namely that what most people consider important reductions in cardiovascular risks, weighed against burdens and harms, remains unclear. Finally, availability and costs will influence decisions when healthcare systems, clinicians, or people consider adding ezetimibe or PCSK9 inhibitors

Stress rotations and the long-term weakness of the Median Tectonic Line and the Rokko-Awaji Segment

International audienceWe used a field analysis of rock deformation microstructures and mesostructures to reconstructthe long-term orientation of stresses around two major active fault systems in Japan, the Median TectonicLine and the Rokko-Awaji Segment. Our study reveals that the dextral slip of the two fault systems, activesince the Plio-Quaternary, was preceded by fault normal extension in the Miocene and sinistral wrenching inthe Paleogene. The two fault systems deviated the regional stress field at the kilometer scale in their vicinityduring each of the three tectonic regimes. The largest deviation, found in the Plio-Quaternary, is a more faultnormal rotation of the maximum horizontal stress to an angle of 79° with the fault strands, suggesting anextremely low shear stress on the Median Tectonic Line and the Rokko-Awaji Segment. Possible causes of thislong-term stress perturbation include a nearly total release of shear stress during earthquakes, a low staticfriction coefficient, or lowelastic properties of the fault zones comparedwith the country rock. Independently ofthe preferred interpretation, the nearly fault normal orientation of the direction of maximum compressionsuggests that the mechanical properties of the fault zones are inadequate for the buildup of a pore fluidpressure sufficiently elevated to activate slip. The long-term weakness of the Median Tectonic Line and theRokko-Awaji Segment may reside in low-friction/low-elasticity materials or dynamic weakening rather than inpreearthquake fluid overpressures

Deep crustal earthquakes in North Tanzania, East Africa: Interplay between tectonic and magmatic processes in an incipient rift

International audienceIn this study, we explore the origin of lower crustal seismicity and the factors controlling rift propagation using seismological data recorded within the youngest part of the East African Rift System, the North Tanzanian Divergence (NTD). Most earthquakes below Lake Manyara occur at depth ranging between 20 and 40 km and have a swarm-like distribution. Focal mechanisms of 26 events indicate a combination of strike-slip and normal faulting involving Archaean basement structures and forming a relay zone. The derived local stress regime is transtensive and the minimum principal stress is oriented N110°E. Crustal seismic tomography reveals low-velocity anomalies below the rifted basins in the NTD, interpreted as localized thermomechanical perturbations promoting fluid release and subsequent seismicity in the lower crust. SKS splitting analysis in the NTD indicates seismic anisotropy beneath 17 stations most likely due to aligned magma lenses and/or dikes beneath the rift and to the lithospheric fabrics. Our results favor a strain pattern intermediate between purely mechanical and purely magmatic. We suggest that melt products arising from a large asthenospheric thermal anomaly enhance lithospheric weakening and facilitate faulting and creeping on critically oriented inherited structures of the Precambrian lower crust. Although the crust is unlikely weakened at a point comparable to other parts of the East African Rift System, this deep-seated thermomechanical process is efficient enough to allow slow rift propagation within the eastern Tanzanian cratonic edge

Gout and pseudo-gout-related crystals promote GLUT1-mediated glycolysis that governs NLRP3 and interleukin-1β activation on macrophages

Objective Macrophage activation by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals mediates an interleukin (IL)-1β-dependent inflammation during gout and pseudo-gout flare, respectively. Since metabolic reprogramming of macrophages goes along with inflammatory responses dependently on stimuli and tissue environment, we aimed to decipher the role of glycolysis and oxidative phosphorylation in the IL-1β-induced microcrystal response. Methods Briefly, an in vitro study (metabolomics and real-time extracellular flux analysis) on MSU and CPP crystal-stimulated macrophages was performed to demonstrate the metabolic phenotype of macrophages. Then, the role of aerobic glycolysis in IL-1β production was evaluated, as well in vitro as in vivo using 18F-fluorodeoxyglucose positron emission tomography imaging and glucose uptake assay, and molecular approach of glucose transporter 1 (GLUT1) inhibition. Results We observed that MSU and CPP crystals led to a metabolic rewiring toward the aerobic glycolysis pathway explained by an increase in GLUT1 plasma membrane expression and glucose uptake on macrophages. Also, neutrophils isolated from human synovial fluid during gout flare expressed GLUT1 at their plasma membrane more frequently than neutrophils isolated from bloodstream. Both glucose deprivation and treatment with either 2-deoxyglucose or GLUT1 inhibitor suppressed crystal-induced NLRP3 activation and IL-1β production, and microcrystal inflammation in vivo. Conclusion In conclusion, we demonstrated that GLUT1-mediated glucose uptake is instrumental during the inflammatory IL-1β response induced by MSU and CPP crystals. These findings open new therapeutic paths to modulate crystal-related inflammation