Is Cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney anomalies?

Assessment of neonatal renal function remains a challenge. This study by Paloma et al. suggest that low-molecular weight proteins may indeed serve as promising markers of renal function at birth and in neonates prenatally diagnosed with congenital kidney anomalie

Does Prevalence Matter to Physicians in Estimating Post-test Probability of Disease? A Randomized Trial

ABSTRACT: BACKGROUND: The probability of a disease following a diagnostic test depends on the sensitivity and specificity of the test, but also on the prevalence of the disease in the population of interest (or pre-test probability). How physicians use this information is not well known. OBJECTIVE: To assess whether physicians correctly estimate post-test probability according to various levels of prevalence and explore this skill across respondent groups. DESIGN: Randomized trial. PARTICIPANTS: Population-based sample of 1,361 physicians of all clinical specialties. INTERVENTION: We described a scenario of a highly accurate screening test (sensitivity 99% and specificity 99%) in which we randomly manipulated the prevalence of the disease (1%, 2%, 10%, 25%, 95%, or no information). MAIN MEASURES: We asked physicians to estimate the probability of disease following a positive test (categorized as 99.9%). Each answer was correct for a different version of the scenario, and no answer was possible in the "no information” scenario. We estimated the proportion of physicians proficient in assessing post-test probability as the proportion of correct answers beyond the distribution of answers attributable to guessing. KEY RESULTS: Most respondents in each of the six groups (67%-82%) selected a post-test probability of 95-99.9%, regardless of the prevalence of disease and even when no information on prevalence was provided. This answer was correct only for a prevalence of 25%. We estimated that 9.1% (95% CI 6.0-14.0) of respondents knew how to assess correctly the post-test probability. This proportion did not vary with clinical experience or practice setting. CONCLUSIONS: Most physicians do not take into account the prevalence of disease when interpreting a positive test result. This may cause unnecessary testing and diagnostic error

Antenatal and postnatal ultrasound in the evaluation of the risk of vesicoureteral reflux

Antenatal hydronephrosis (ANH) is a frequent anomaly detected on fetal ultrasound scans. There is no consensus recommendation for the postnatal follow-up and/or the necessity to perform a voiding cystourethrography (VCUG) to diagnose vesicoureteral reflux (VUR). We conducted a cohort/non-randomized trial of 121 patients with ANH, defined as an anterior posterior diameter (APD) ≥5mm after the 20th week of gestation, to evaluate the ability of the antenatal and postnatal ultrasonography results to predict VUR. All infants had two successive ultrasounds at 5days and 1month, respectively, after birth. A VCUG was performed at 6weeks in children with a persistent APD ≥5mm and/or an ureteral dilatation observed on at least one of two postnatal ultrasounds. In total, 88 patients had VCUG and nine had VUR, with five having high-grade reflux (>grade II). The risk of VUR increased significantly with the degree of APD detected on the postnatal ultrasound scan (p = 0.03). The odds ratios were 5.0 [95% confidence interval (CI) 0.5-51.2] for APD = 7-9mm and 9.1 (95% CI 1.0-80.9) for APD ≥10mm. The results of this study show that among our patient cohort antenatal ultrasound was not predictive of reflux. There was, however, a relation between the importance of the postnatal renal pelvis diameter and the risk of VUR. A cut-off of 7mm showed a fair ability of ultrasonography to predict VUR and a cut-off of 10mm enabled all severe refluxes in the 88 patients who had a VCUG to be diagnose

Diffusion-weighted imaging findings in Perthes disease with dynamic gadolinium-enhanced subtracted (DGS) MR correlation: a preliminary study

Background: Legg-Calvé-Perthes disease (LCP) is necrosis of the proximal femoral epiphysis of vascular origin. Clinical course and outcome in LCP disease varies considerably between different patients. Earlier prognostic criteria than those offered by conventional radiography are necessary to identify children who require prompt surgical treatment. Objective: To assess the significance of signal alteration on diffusion-weighted MR imaging (DWI MR) in LCP. Materials and methods: Twelve boys with unilateral LCP disease (Catterall grade 2 and 3), at the initial sclerotic stage and early fragmentation phase, underwent dynamic gadolinium-enhanced subtracted (DGS) and DWI MR. For DGS MR, the lateral pillar enhancement was recorded. For DWI imaging, we measured ADC values in the diseased and the unaffected epiphyses and metaphyses. Receiver operating characteristic curves were performed to analyze the performance of DWI in establishing agreement with the results of DGS MR, which is the gold standard for prognosis. Results: Femoral epiphysis increased diffusivity was observed in the affected hip in all cases. Increased metaphysis diffusivity in the affected side was observed in all cases with absent lateral pillar enhancement at DGS MR. Conclusion: DWI seems to be a noninvasive means of distinguishing between Perthes disease with favourable and unfavourable prognosi

Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis

Aim Thrombolytic therapy induces faster clot dissolution than anticoagulation in patients with acute pulmonary embolism (PE) but is associated with an increased risk of haemorrhage. We reviewed the risks and benefits of thrombolytic therapy in the management of patients with acute PE. Methods and results We systematically reviewed randomized controlled studies comparing systemic thrombolytic therapy plus anticoagulation with anticoagulation alone in patients with acute PE. Fifteen trials involving 2057 patients were included in our meta-analysis. Compared with heparin, thrombolytic therapy was associated with a significant reduction of overall mortality (OR; 0.59, 95% CI: 0.36-0.96). This reduction was not statistically significant after exclusion of studies including high-risk PE (OR; 0.64, 95% CI: 0.35-1.17). Thrombolytic therapy was associated with a significant reduction in the combined endpoint of death or treatment escalation (OR: 0.34, 95% CI: 0.22-0.53), PE-related mortality (OR: 0.29; 95% CI: 0.14-0.60) and PE recurrence (OR: 0.50; 95% CI: 0.27-0.94). Major haemorrhage (OR; 2.91, 95% CI: 1.95-4.36) and fatal or intracranial bleeding (OR: 3.18, 95% CI: 1.25-8.11) were significantly more frequent among patients receiving thrombolysis. Conclusions Thrombolytic therapy reduces total mortality, PE recurrence, and PE-related mortality in patients with acute PE. The decrease in overall mortality is, however, not significant in haemodynamically stable patients with acute PE. Thrombolytic therapy is associated with an increase of major and fatal or intracranial haemorrhag

Tolerance and Safety of Nifurtimox in Patients with Chronic Chagas Disease

Background. Nifurtimox has been used to treat Chagas disease for 40 years, but tolerance and safety data in adults are scarce. We aimed to evaluate nifurtimox tolerance and safety in a cohort of Trypanosoma cruzi-infected adult patients in a country of nonendemicity. Methods. This observational study included all consecutive adults patients who were given a diagnosis of T. cruzi infection from June through December 2008. Eligible patients received nifurtimox at 10 mg/kg/day for 60 days, with regular medical and biological follow-up. Adverse events (AEs) were recorded according to Common Terminology Criteria for Adverse Events, version 3.0. Results. Eighty-one patients received nifurtimox. Eight were lost to follow-up during treatment, and 41 (56.2%) completed the 60-day course. All premature treatment terminations were caused by AEs; 97.5% of patients suffered from AEs, mostly expected (90.5%) and not severe. Gastrointestinal symptoms predominated. Six (7.4%) patients presented with a suspected unexpected serious adverse reaction: drug reaction with eosinophilia and systemic symptoms (n = 3), Quincke edema (n = 1), acute myocarditis (n = 1), and anaphylaxis (n = 1). Patients with 3 or more AEs had an increased risk of premature treatment termination (hazard ratio, 8.42; 95% confidence interval, 1.6-45.5). Conclusion. Nifurtimox is poorly tolerated among adults with chronic Chagas disease, resulting in a low treatment completion rate. Considering the significant risk of serious AEs, close monitoring is required, which may be difficult to implement in poor rural areas of countries of endemicity. The safety and efficacy of nifurtimox and benznidazole should be compared to improve current therapeutic recommendations, and pharmacovigilance systems should be enhance

Accuracy of Computational Soft Tissue Predictions in Orthognathic Surgery From Three-Dimensional Photographs 6 Months After Completion of Surgery: A Preliminary Study of 13 Patients

Background: This study aimed at a preliminary evaluation of the accuracy of computed three-dimensional (3D) predictions in orthognathic surgery by comparing predicted and real postoperative results. Methods: Pre- and postoperative 3D photographs and time-matching computed tomography (CT) and cone-beam CT scans of the face of 13 patients with dentofacial deformities were analyzed. Three-dimensional photographs were fused with preoperative CT data using dedicated software (3dMDvultus, version 2.2.0.8). Postoperative CT data were superposed on the preoperative skull. With an activated rendering function, the osteotomies were simulated in the preoperative CT data and the bony segments moved to their real postoperative position, resulting in a textured soft tissue prediction. This computed skin surface was compared with the real postoperative result by dividing the face into a surgically treated lower half and an untreated upper half. A statistical quantitative analysis of the surfaces was performed. Results: The mean differences between surfaces were +0.27mm for the untreated upper half and -0.64mm for the surgically treated lower half (p<0.001). Averaged distributions of absolute errors showed more discrepancies between predicted and real postoperative results in the lower half of the face. Errors exceeding 3mm were encountered in 4% of the upper halves versus 29.8% of the lower halves (p<0.001). Conclusions: The accuracy of a specific software platform for predicting 3D soft tissue changes after surgery was insufficient. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266

Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel. Systematic review and meta-analysis of individual patient data.

Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. The role and usefulness of PR with regard to levels of cardiovascular risk are unclear. We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischaemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20 µM ADP. Thirteen prospective studies totaled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5 %) during a median follow-up of 12 months. The strength of the association between the risk of MACE and PR increased significantly (p=0.04) with the number of risk factors present (age> 75 years, ACS at inclusion, diabetes, and hypertension). No association was detected in patients with no risk factor (p=0.48). In patients presenting one risk factor, only high-PR was associated with an increased risk of MACE (HR 3.2, p=0.001). In patients presenting ≥ 2 risk factors, the increase of risk started from medium-PR (medium-PR: HR=2.9, p=0.0004; high-PR: HR=3.7, p=0.0003). PR allowed the reclassification of 44 % of the total population to a different risk level for the outcome of MACE, mostly in intermediate or high risk patients. In conclusion, the magnitude of the association between PR and MACE risk is strongly dependent on the level of cardiovascular risk faced by patients on clopidogrel

Prediction and numerical simulation of droplet impact erosion on metallic structure

Hydraulic turbines can undergo severe damage during operation, because of low quality water or detrimental flow conditions. Damage induces maintenance costs and power production losses, and can also endanger safety of installations. Hydropower plants operators and turbine manufacturers are interested in extending overhaul periods by reducing damage intensity and protecting turbine components with surface treatments, but accurate and reliable prediction of damage is however missing. The present work is related to the erosion arising from repeated impacts of high speed water droplets on specific parts of Pelton turbines. Indeed for high head Pelton units, the jet of water is composed of a liquid core surrounded by droplets. Observations show that regions of impact of these droplets exhibit specific erosion patterns. The aim of the work consists in understanding the corresponding erosion mechanisms through detailed numerical simulation (micro-scale) of the impacts of high speed liquid droplets on turbine components. These results will then be transposed at the machine level (macro-scale) in order to predict the damage along the life cycle of the turbine. When a high velocity water droplet with small diameter impacts a rigid surface, the ``water-hammer'' pressure due to inertial effect appears in the water droplet at the central contact zone, though the maximum pressure occurs on the envelope of the contact area and may be far higher than water-hammer pressure. The impact causes the traveling of a shock wave across the droplet, and lateral jetting occurs by compression when the wave front overtakes the contact area. Concerning the structure, erosion has been found to be due to fatigue cracking. First, material grains are weakened during an ``incubation'' phase. After a large number of impacts, micro-cracks emerge and lead to ejection or fracture of grains, what is called ``amplification'' phase. Numerical simulations are performed subsequently to understand and get a more detailed analysis. The entire simulation is modeled in explicit dynamics with a strong 2-way coupler which is energy conservative at the interface. The solid domain is computed by the finite elements method with Europlexus code, and the fluid one is discretized by Smoothed Particle Hydrodynamics with an Arbitrary Lagrangien-Eulerian description by an in-house software. Thanks to these simulations, the pressure peak on the contact surface can be found. Results are in line with literature and the impulse of the impact allows to locate the most loaded zones of the area. The fatigue-based mechanism is validated by observing the change of sign of hydrostatic stress. Finally, a post-processing erosion program developed with a simple damage criterion provides the location of the most eroded zones of the structure during a loading cycle. The stress range of the transient simulation is computed and gives a number of cycles to failure by a S-N curve for each Gauss point of the solid mesh. A number of cycles is chosen, which allows to make some elements eroded then removed from the mesh for further droplet impact simulations. This post-processing makes some strong assumptions for the number of cycles: every droplet falls with the same velocity, angle, diameter, density at the same place and water is cleaned between each impact. Moreover we assume that geometry does not change during the chosen number of cycles. These first results will be a strong basis for a sensitivity analysis on main impact parameters (droplets diameter and velocity). It is also planned to investigate the influence of a thin water layer set on the solid surface to mimic the wet environment, and a multi-layer material to take into account the coated surface of Pelton buckets