Feasibility and interpretation of FENO measurements in asthma patients in general practice

n/

Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

BACKGROUND: Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. METHODS: The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using χ(2). RESULTS: Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4). The degree of improvement was also larger with desferrioxamine. CONCLUSIONS: This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis – despite its limitations – should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients

Antihypertensive efficacy of spironolactone: what about sex?

[No abstract available

Glucose-6-phosphate dehydrogenase deficiency associated hemolysis in COVID-19 patients treated with hydroxychloroquine/chloroquine: New case reports coming out.

Afra TP et al comment our recent report entitled: \u201cacute hemolysis by hydroxychloroquine (HCQ) was observed in G6PD-deficient patient with severe COVID-19 related lung injury\u201d [1,2]. Afra et al. underlight \u201dconfounding factors and inconsistencies\u201d in our conclusion, linking acute drop in Hb in COVID-19 patient with suspected G6PD and HCQ treatment. We respectfully disagree with comments from Afra et al. Our case report was the first one of a series, linking G6PD deficiency with HCQ/CQ treatment for COVID19 infection such as Kuiper ME et al. or Beauverd Y et al. or Maillart et al. [3\u20135]. In our case, we observed an acute drop of Hb values associated with the appearance of hemoglo-binuria and abnormalities in red cell morphology at the blood smear within 48 h after patient hospital admission and the introduction of HCQ treatment. Our patient was transfused and HCQ was withdrawn with stabilization of Hb values. Thus, this was not a spontaneous re-covery of Hb values as suspected by Afra et al. (see Fig. 1 in De Fran-ceschi L et al 2020) [2]. In addition, hemoglobinuria is a hallmark of intravascular hemolysis, which characterizes drug induced acute he-molysis in G6PD patients [6]. Otherwise, drug induced hemolytic an-emia in patients with healthy red cells is general an extravascular he-molysis without hemoglobinuria. Italy is an endemic area for G6PD deficiency [6]. Our patient was suspected for G6PD deficiency based on previous hemolytic events re-corded in patient history. To fully answer the question raised by Afra et al., we have evaluated G6PD activity in our patients at 8 weeks after hospital discharge. As expected we found G6PD deficiency with normal complete blood count analysis and normal reticulocyte count (43.500 retics/uL). Collectively our results and the post-recovery determination of G6PD support the link between acute hemolysis and HCQ/CQ treatment in COVID-19 patient

Acute hemolysis by hydroxycloroquine was observed in G6PD-deficient patient with severe COVD-19 related lung injury.

Our patient might be affected by Mediterannean variant of G6PD deficiency, which is more sensitive to pro-oxidant drugs compared to African G6PD A variant. No conclusive data are available on the possible pro-hemolytic impact of CQ/HCQ on patient with G6PD deficiency [3\u20135]. In COVID-19 emergency we believe it is important to warning the possible hemolytic effects of CQ/HCQ in patients with G6PD deficiency. Thus, the acute drop in Hb levels in the early days of CQ/HCQ treatment of COVID19 symptomatic patient should be considere

Improved workflow for quantification of left ventricular volumes and mass using free-breathing motion corrected cine imaging.

BACKGROUND: Traditional cine imaging for cardiac functional assessment requires breath-holding, which can be problematic in some situations. Free-breathing techniques have relied on multiple averages or real-time imaging, producing images that can be spatially and/or temporally blurred. To overcome this, methods have been developed to acquire real-time images over multiple cardiac cycles, which are subsequently motion corrected and reformatted to yield a single image series displaying one cardiac cycle with high temporal and spatial resolution. Application of these algorithms has required significant additional reconstruction time. The use of distributed computing was recently proposed as a way to improve clinical workflow with such algorithms. In this study, we have deployed a distributed computing version of motion corrected re-binning reconstruction for free-breathing evaluation of cardiac function. METHODS: Twenty five patients and 25 volunteers underwent cardiovascular magnetic resonance (CMR) for evaluation of left ventricular end-systolic volume (ESV), end-diastolic volume (EDV), and end-diastolic mass. Measurements using motion corrected re-binning were compared to those using breath-held SSFP and to free-breathing SSFP with multiple averages, and were performed by two independent observers. Pearson correlation coefficients and Bland-Altman plots tested agreement across techniques. Concordance correlation coefficient and Bland-Altman analysis tested inter-observer variability. Total scan plus reconstruction times were tested for significant differences using paired t-test. RESULTS: Measured volumes and mass obtained by motion corrected re-binning and by averaged free-breathing SSFP compared favorably to those obtained by breath-held SSFP (r = 0.9863/0.9813 for EDV, 0.9550/0.9685 for ESV, 0.9952/0.9771 for mass). Inter-observer variability was good with concordance correlation coefficients between observers across all acquisition types suggesting substantial agreement. Both motion corrected re-binning and averaged free-breathing SSFP acquisition and reconstruction times were shorter than breath-held SSFP techniques (p \u3c 0.0001). On average, motion corrected re-binning required 3 min less than breath-held SSFP imaging, a 37 % reduction in acquisition and reconstruction time. CONCLUSIONS: The motion corrected re-binning image reconstruction technique provides robust cardiac imaging that can be used for quantification that compares favorably to breath-held SSFP as well as multiple average free-breathing SSFP, but can be obtained in a fraction of the time when using cloud-based distributed computing reconstruction

Phase Transition in Ferromagnetic Ising Models with Non-Uniform External Magnetic Fields

In this article we study the phase transition phenomenon for the Ising model under the action of a non-uniform external magnetic field. We show that the Ising model on the hypercubic lattice with a summable magnetic field has a first-order phase transition and, for any positive (resp. negative) and bounded magnetic field, the model does not present the phase transition phenomenon whenever $\liminf h_i> 0$, where ${\bf h} = (h_i)_{i \in \Z^d}$ is the external magnetic field.Comment: 11 pages. Published in Journal of Statistical Physics - 201

Thrombosis and sickle cell disease

Sickle cell disease (SCD) is characterized by the presence of sickle hemoglobin, which has the unique property of polymerizing when deoxygenated. The pathophysiology of acute and chronic clinical manifestations of SCD have shown the central role of dense, dehydrated red cells in acute and chronic clinical manifestations of this pathology. Recent studies have indicated that SCD is characterized by a hypercoagulable state that contributes to the vaso-occlusive events in microcirculation, leading to acute and chronic sickle cell-related organ damage. This review discusses, in the context of SCD, (1) abnormalities in the coagulation system, (2) perturbation of platelet activation and aggregation, (3) vascular endothelial dysfunction, (4) the contribution of cell inflammatory responses, and (5) the connection with nitric oxide metabolism. We also review the available studies on the therapeutic approaches in clinical management of hypercoagulability in SCD

Metastability and Nucleation for the Blume-Capel Model. Different mechanisms of transition

We study metastability and nucleation for the Blume-Capel model: a ferromagnetic nearest neighbour two-dimensional lattice system with spin variables taking values in -1,0,+1. We consider large but finite volume, small fixed magnetic field h and chemical potential "lambda" in the limit of zero temperature; we analyze the first excursion from the metastable -1 configuration to the stable +1 configuration. We compute the asymptotic behaviour of the transition time and describe the typical tube of trajectories during the transition. We show that, unexpectedly, the mechanism of transition changes abruptly when the line h=2*lambda is crossed.Comment: 96 pages, 44 tex-figures, 7 postscript figure

Abrupt Convergence and Escape Behavior for Birth and Death Chains

We link two phenomena concerning the asymptotical behavior of stochastic processes: (i) abrupt convergence or cut-off phenomenon, and (ii) the escape behavior usually associated to exit from metastability. The former is characterized by convergence at asymptotically deterministic times, while the convergence times for the latter are exponentially distributed. We compare and study both phenomena for discrete-time birth-and-death chains on Z with drift towards zero. In particular, this includes energy-driven evolutions with energy functions in the form of a single well. Under suitable drift hypotheses, we show that there is both an abrupt convergence towards zero and escape behavior in the other direction. Furthermore, as the evolutions are reversible, the law of the final escape trajectory coincides with the time reverse of the law of cut-off paths. Thus, for evolutions defined by one-dimensional energy wells with sufficiently steep walls, cut-off and escape behavior are related by time inversion.Comment: 2 figure