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

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

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

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

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

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

Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders

Background Microalbuminuria (MA) has been shown to be an early biomarker of renal damage. It is postulated that MA is the early result of hyperfiltration, which could evolve into glomerular sclerosis and renal failure if hyperfiltration is left untreated. We hypothesized that MA is a good indicator of hyperfiltration in children with kidney disorders, obviating the need to calculate the filtration fraction (FF). Methods A total of 155 children or young adults were prospectively included [42 single kidney (SK), 61 vesico-ureteral reflux, 23 obstructive uropathies, 29 other kidney diseases]. We measured inulin, para-aminohippuric acid clearances, FF and MA. Prediction of hyperfiltration was explored by studying the association between the FF and other variables such as urinary albumin (Alb), urinary albumin-creatinine ratio (ACR) and creatinine clearance. Results A significant but weak association between urinary Alb or ACR and FF was found in subjects with an SK (Spearman correlation coefficients 0.32 and 0.19, respectively). Multivariate analysis also showed that urinary Alb and ACR significantly predict FF only in subjects with an SK (r2 = 0.17, P = 0.01 and r2 = 0.13, P = 0.02, respectively). This holds true only in subjects with an SK and inulin clearance >90 mL/min/1.73 m2 (r2 = 0.41, P < 0.001). There was no association between creatinine clearance and FF. Conclusions MA is not associated with FF in our subjects with nephro-urological disorders, except in those with an SK, where the association is weak, indicating that MA is due to other mechanisms than high FF and cannot predict hyperfiltration in such group

Medico-economic evaluation of infliximab in rheumatoid arthritis—prospective French study of a cohort of 635 patients monitored for two years

Objectives. To perform, in real conditions of prescription, the medico-economic evaluation of infliximab in severe RA. Methods. A cost-effectiveness analysis of the annual costs was done with a comparison between the previous and the following year under infliximab. The effectiveness, determined from the HAQ, was expressed in clinically significant units and in quality-adjusted life years (QALYs). The incremental net benefit (INB), defined as willingness to pay (λ), was used to express the results. Results. A cohort of 635 patients was formed. Before the use of infliximab, after 1 and 2 years, the mean annual cost per patient for the care of RA was €9832, 27 723 and 46 704, respectively. Among the direct costs, infliximab accounts for €21 182 for the first year. The distribution of the different costs was similar after 2 years. By using the INB, the difference before and after 1 year under infliximab is significant, on average by 1.86 (s.e.m. = 0.76) when the effectiveness is expressed in clinically significant units. For severe HAQ, λ is €9841 (18 593 for all HAQ). When it is expressed in QALYs, also for severe HAQ, λ >€100 000. This can be explained by a short follow-up although severe complication of RA appears later. Conclusion. An evaluation of the more long-term costs is required in order to determine whether there are any full economic benefits with this treatmen