European union regulation of health technology assessment: what is required for it to succeed?

The European Journal of Health Economics -     

Modelling,Bayesian inference,and model assessment for nosocomial pathogens using whole-genome-sequence data

Whole-genome sequencing of pathogens in outbreaks of infectious disease provides the potential to reconstruct transmission pathways and enhance the information contained in conventional epidemiological data. In recent years, there have been numerous new methods and models developed to exploit such high-resolution genetic data. However, corresponding methods for model assessment have been largely overlooked. In this article, we develop both new modelling methods and new model assessment methods, specifically by building on the work of Worby et al. Although the methods are generic in nature, we focus specifically on nosocomial pathogens and analyze a dataset collected during an outbreak of MRSA in a hospital setting.     

An eHealth decision-support tool to prioritize referral practices for genetic evaluation of patients with Wilms tumor

Over 10% of children with Wilms tumor (WT) have an underlying cancer predisposition syndrome (CPS). Cognizant of increasing demand for genetic evaluation and limited resources across health care settings, there is an urgent need to rationalize genetic referrals for this population. The McGill Interactive Pediatric OncoGenetic Guidelines study, a Canadian multi-institutional initiative, aims to develop an eHealth tool to assist physicians in identifying children at elevated risk of having a CPS. As part of this project, a decisional algorithm specific to WT consisting of five tumor-specific criteria (age <2 years, bilaterality/multifocality, stromal-predominant histology, nephrogenic rests, and overgrowth features) and universal criteria including features of family history suspicious for CPS and congenital anomalies, was developed. Application of the algorithm generates a binary recommendation—for or against genetic referral for CPS evaluation. To evaluate the algorithm's sensitivity for CPS identification, we retrospectively applied the tool in consecutive pediatric patients (n = 180) with WT, diagnosed and/or treated at The Hospital for Sick Children (1997–2016). Odds ratios were calculated to evaluate the strengths of associations between each criterion and specific CPS subtypes. Application of the algorithm identified 100% of children with WT and a confirmed CPS (n = 27). Age <2 years, bilaterality/multifocality, and congenital anomalies were strongly associated with pathogenic variants in WT1. Presence of >1 overgrowth feature was strongly associated with Beckwith-Wiedemann syndrome. Stromal-predominant histology did not contribute to CPS identification. We recommend the incorporation of the WT algorithm in the routine assessment of children with WT to facilitate prioritization of genetic referrals in a sustainable manner.     

Neurocardiogenic syncope and epilepsy in pediatric age: the diagnostic value of electroencephalogram-electrocardiogram holter

Neurocardiogenic syncope is induced by a hyperrecruitment of parasympathetic nerve tone elicited by emotional stress or pain. The presence of a transient loss of consciousness associated with involuntary motor activity or with urinary incontinence and the misinterpretation of anamnestic data or of electroencephalogram (EEG) abnormalities often leads to wrong diagnosis of epilepsy in children with this disorder.Careful and systematic history taking, pressure measurement, electrocardiogram (ECG), and, in selected cases, head-up tilt table testing are generally enough to rule out a cardiogenic or a neurocardiogenic syncope. Simultaneous EEG-ECG Holter represents a useful instrument for differential diagnosis between neurocardiogenic syncope and epilepsy.We report 3 case reports to demonstrate how simultaneous EEG-ECG Holter can contribute to characterize functional heart-brain interactions and the exact sequence of the physiopathologic events leading to the loss of consciousness in cases in which the clinical borders with epileptic disorders are particularly subtle.     

Residual platelet reactivity is an independent predictor of myocardial injury in acute myocardial infarction patients on antiaggregant therapy

In this study we sought to evaluate if platelet function measured after percutaneous coronary intervention (PCI) affects the severity of myocardial infarction (MI), measured by markers of cardiac necrosis. We measured platelet function by both a point-of-care assay (PFA-100) and platelet-rich plasma aggregation by two agonists (arachidonic acid -AA- and 2 and 10 microM ADP) in 367 patients with MI after PCI (200 patients on dual antiplatelet agents - group A- and 167 on dual antiplatelet agents plus GpIIb/IIIa inhibitors - group B). One hundred twenty-one (32.9%) patients were found to have a residual platelet reactivity (RPR) by PFA (CT/EPI <203 sec): 74/200 (37%) in group A and 47/167 (28.1%) in group B (p = 0.07). In 129 (35.1%) patients we found a RPR by AA-PA: 80/200 (40%) in group A and 49/167 (29.3%) in group B (p < 0.05). Seventeen out of 367 (4.6%) were found to have a RPR by ADP2-PA [15/200 (7.5%) in group A and 2/167 (1.2%) in group B; p < 0.005] and 88/367 (23.9%) by ADP10-PA [64/200 (32%) in group A and 24/167 (14.4%) in group B, p < 0.0001]. CK-MB and cTnI mean peak values were significantly higher in the first tertile of CT/ADP and CT/EPI distribution with respect to the other tertiles and they were significantly higher in patients with RPR by CT/EPI in both group A and group B patients. CK-MB and cTnI peak values were significantly higher in the third tertile of AA-PA, ADP 2 microM-PA and ADP 10 microM-PA distribution with respect to the other tertiles and were significantly higher in patients with RPR by AA-PA and by ADP 10-PA in both group A and group B patients. Multivariate analysis revealed platelet function as an independent predictor of CK-MB and cTnI peak values in both groups of patients independently of clinical, laboratory ad procedural parameters. In conclusion, we found that the severity of MI in patients with MI undergoing primary PCI is influenced by a persistent platelet activation on multiple antiplatelet therapy.