Do drugs interact together in cardiovascular prevention? A meta-analysis of powerful or factorial randomized controlled trials.

To explore whether preventive cardiovascular drugs (antihypertensive, antiplatelet, lipid lowering and hypoglycemic agents) interact together in cardiovascular prevention. We searched PubMed®, Web of science™, Embase and Cochrane library for powerful randomized placebo-controlled trials (>1000 patients). We explored whether drug effect on major vascular events changed according to cross-exposure to other drug classes or to cardiovascular risk factors (hypertension or type 2 diabetes), through a meta-analysis of relative odds ratio computed by trial subgroups. A significant interaction was suggested from confidence intervals of the ratio of odds ratios, when they excluded neutral value of 1. In total, 14 trials with 178,398 patients were included. No significant interaction was observed between co-prescribed drugs or between these medications and type 2 diabetes/hypertension status. Our meta-analysis is the first one to evaluate drug-drug and drug-hypertension/type 2 diabetes status interactions in terms of cardiovascular risks: we did not observe any significant interaction. This indirectly reinforces the rationale of using several contrasted mechanisms to address cardiovascular prevention; and allows the combination effect prediction by a simple multiplication of their odds ratios. The limited availability of data reported or obtained from authors is a strong argument in favor of data sharing

Impact of Combined Clenbuterol and Metoprolol Therapy on Reverse Remodelling during Mechanical Unloading

Clenbuterol (Cl), a β2 agonist, is associated with enhanced myocardial recovery during left ventricular assist device (LVAD) support, and exerts beneficial remodelling effects during mechanical unloading (MU) in rodent heart failure (HF). However, the specific effects of combined Cl+β1 blockade during MU are unknown.We studied the chronic effects (4 weeks) of β2-adrenoceptor (AR) stimulation via Cl (2 mg/kg/day) alone, and in combination with β1-AR blockade using metoprolol ((Met), 250 mg/kg/day), on whole heart/cell structure, function and excitation-contraction (EC) coupling in failing (induced by left coronary artery (LCA) ligation), and unloaded (induced by heterotopic abdominal heart transplantation (HATx)) failing rat hearts. Combined Cl+Met therapy displayed favourable effects in HF: Met enhanced Cl's improvement in ejection fraction (EF) whilst preventing Cl-induced hypertrophy and tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MU-induced myocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+ transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Met mono-therapy, but these benefits, together with Cl's enhancement of sarcomeric contraction speed, and MU-induced recovery of Ca2+ spark frequency, disappeared during combined therapy.Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appears inferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined β2-AR simulation +β1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective as mono-therapy in enhancing myocardial recovery during LVAD support

Septal ablation versus surgical myomectomy for hypertrophic obstructive cardiomyopathy

Patients with hypertrophic cardiomyopathy (HCM) who have left ventricular outflow tract obstruction (LVOTO) often experience severe symptoms and functional limitation. Relief of LVOTO can be achieved by two invasive interventions, i.e., surgery myectomy and alcohol septal ablation (ASA), leading in experienced hands to a dramatic improvement in clinical status. Despite extensive research, however, the choice of the best option in individual patients remains challenging and poses numerous clinical dilemmas

Tumeurs primitives de l’orbite traitement chirurgical

Les tumeurs primitives de l’orbite sont des affections rares, leurs  manifestation cliniques sont tardives et variées pouvant êtres trompeuses. L’imagerie TDM et surtout IRM est capitale pour le diagnostic et la prise en charge. Le traitement est souvent chirurgical, le choix de la technique dépend de la taille et la topographie tumorale. Nous rapportons 13 cas de tumeurs orbitaires colligés entre 2004 et 2010. L’âge moyen de nos patients est de 36 ans, l’exophtalmie a été le maitre symptôme. Tous nos patients ont été opérés. Après étude histologique de la pièce d’exérèse opératoire il s’agissait de: 5 hémangiomes caverneux, 4 tumeurs mixtes, 2 neurinomes, 1 kyste hydatique et 1 angiome. Un seul cas de récidive tumorale a été noté.Mots clés : tumeur de l’orbite, hémangiome caverneux, shwannome, chirurgie

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation

Patients with breakthrough reactions to iodinated contrast media have low incidence of positive skin tests

BACKGROUND: The term "breakthrough reactions" designates repeated hypersensitivity reactions to iodinated contrast media (ICM) despite premedication with glucocorticoids and antihistamines. We aimed to retrospectively evaluate the rate of positive skin test (STs) in our cohort of patients with previous breakthrough reactions to different ICMs. METHODS: A series of 35 patients, who experienced at least one breakthrough reaction to ICM and who underwent STs within 6 months from the reaction were studied, and results were compared to a control group of patients with a first hypersensitivity reaction occurred without premedication. Skin prick tests (SPT), intradermal tests (IDT) and patch tests (PT) at different dilutions, with a set of three to four ICM were performed. RESULTS: Of the 35 patients with prior breakthrough reactions, 57% had an immediate reaction (IR) and 43% had a non-immediate reaction (NIR). Patients who experienced the first hypersensitivity IR or NIR, later had one or more breakthrough IR or NIR, respectively. Overall, 29% (10/35) of patients with prior breakthrough reactions resulted positive to STs compared to 57% (16/28) of the control group (p < 0.05). No significant difference in allergy history, age, sex, other clinical / demographic features nor chronic use of ACE-inhibitor, beta-blockers or NSAIDs was observed. CONCLUSION: This preliminary finding suggests that patients with prior breakthrough reactions have significantly lower immunologically proven ICM reactions (positive STs) if compared to non-breakthrough patients. According to that, a considerable number of breakthrough reactions seems to be non-allergic hypersensitivity reactions or reactions which could be mostly prevented by a proper, well-timed skin testing. Larger prospective studies are needed to confirm these results, with a more careful analysis of patients' risk factors, a laboratory assessment that includes an in vitro allergy diagnostics, and hopefully a drug provocation test for selected cases

Drug induced exfoliative dermatitis: State of the art

Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Overall, T cells are the central player of these immune-mediated drug reactions. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED

Global burden of human brucellosis : a systematic review of disease frequency

BACKGROUND: This report presents a systematic review of scientific literature published between 1990-2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis.METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden.CONCLUSIONS: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understand of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources

Log-moment estimators of the Nakagami-lognormal distribution

[EN] In this paper, estimators of the Nakagami-lognormal (NL) distribution based on the method of log-moments have been derived and thoroughly analyzed. Unlike maximum likelihood (ML) estimators, the log-moment estimators of the NL distribution are obtained using straightforward equations with a unique solution. Also, their performance has been evaluated using the sample mean, confidence regions and normalized mean square error (NMSE). The NL distribution has been extensively used to model composite small-scale fading and shadowing in wireless communication channels. This distribution is of interest in scenarios where the small-scale fading and the shadowing processes cannot be easily separated such as the vehicular environment.This work has been funded in part by the Programa de Estancias de Movilidad de Profesores e Investigadores en Centros Extranjeros de Ensenanza Superior e Investigacion of the Ministerio de Educacion, Cultura y Deporte, Spain, PR2015-00151 and by the Ministerio de Economia, Industria y Competitividad of the Spanish Government under the national project TEC2017-86779-C2-2-R, through the Agencia Estatal de Investigacion (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER).Reig, J.; Brennan, C.; Rodrigo Peñarrocha, VM.; Rubio Arjona, L. (2019). Log-moment estimators of the Nakagami-lognormal distribution. EURASIP Journal on Wireless Communications and Networking. 1-10. https://doi.org/10.1186/s13638-018-1328-6S110J. M. Ho, G. L. Stüber, in Co-channel interference of microcellular systems on shadowed Nakagami fading channels. Proc. IEEE 43rd Vehicular Technology Conference, 1993 (VTC 93) (IEEESecaucus, 1993), pp. 568–571.A. A. Abu-Dayya, N. C. Beaulieu, Micro- and macrodiversity NCFSK (DPSK) on shadowed Nakagami-fading channels. IEEE Trans. Commun.42(9), 2693–2702 (1994).X. Wang, W. Wang, Z. Bu, Fade statistics for selection diversity in Nakagami-lognormal fading channels. Electron. Lett.42(18), 1046–1047 (2006).D. T. Nguyen, Q. T. Nguyen, S. C. Lam, Analysis and simulation of MRC diversity reception in correlated composite Nakagami-lognormal fading channels. REV J. Electron. Commun.4(1–2), 44–51 (2014).P. Xu, X. Zhou, D. Hu, in Performance evaluations of adaptive modulation over composite Nakagami-lognormal fading channels. 2009 15th Asia-Pacific Conference on Communications (IEEEShanghai, 2009), pp. 467–470.G. C. Alexandropoulos, A. Conti, P. T. Mathiopoulos, in Adaptive M-QAM systems with diversity in correlated Nakagami-m fading and shadowing. IEEE Global Telecommunications Conference (GLOBECOM 2010) (IEEEMiami, 2010), pp. 1–5.Ö. Bulakci, A. B. Saleh, J. Hämäläinen, S. Redana, Performance analysis of relay site planning over composite fading/shadowing channels with cochannel interference. IEEE Trans. Veh. Technol.62(4), 1692–1706 (2013).W. Cheng, Y. Huang, On the performance of adaptive SC/MRC cooperative systems over composite fading channels. Chin. J. Electron.25(3), 533–540 (2016).M. G. Kibria, G. P. Villardi, W. Liao, K. Nguyen, K. Ishizu, F. Kojima, Outage analysis of offloading in heterogeneous networks: Composite fading channels. IEEE Trans. Veh. Technol.66(10), 8990–9004 (2017).K. Cho, J. Lee, C. G. Kang, Stochastic geometry-based coverage and rate analysis under Nakagami & log-normal composite fading channel for downlink cellular networks. IEEE Commun. Lett.21(6), 1437–1440 (2017).R. Singh, M. Rawat, Closed-form distribution and analysis of a combined Nakagami-lognormal shadowing and unshadowing fading channel. J Telecommun. Inf. Technol.4:, 81–87 (2016).J. Reig, L. Rubio, Estimation of the composite fast fading and shadowing distribution using the log-moments in wireless communications. IEEE Trans. Wireless. Commun.12(8), 3672–3681 (2013).S. Atapattu, C. Tellambura, H. Jiang, A mixture gamma distribution to model the SNR of wireless channels. IEEE Trans. Wireless Commun.10(12), 4193–4203 (2011).Q. Wang, H. Lin, P. Kam, Tight bounds and invertible average error probability expressions over composite fading channels. J. Commun. Netw.18(2), 182–189 (2016).J. M. Holtzmann, On using perturbation analysis to do sensitivity analysis: derivatives versus differences. IEEE Trans. Autom. Control. 37(2), 243–247 (1992).H. Suzuki, A statistical model for urban radio propagation. IEEE Trans. Commun.25(7), 673–680 (1977).M. D. Yacoub, The α- μ distribution: a physical fading model for the Stacy distribution. IEEE Trans. Veh. Technol.56(1), 122–124 (2007).P. M. Shankar, Error rates in generalized shadowed fading channels. Wirel. Pers. Commun.28(3), 233–238 (2004).J. -M. Nicolas, Introduction aux statistiques de deuxième espèce: applications des logs-moments et des logs-cumulants à l’analyse des lois d’images radar. Traitement du Signal. 19(3), 139–167 (2002). Translation to English by S. N. Anfinsen.C. Withers, S. Nadarajah, A generalized Suzuki distribution. Wirel. Pers. Commun.62(4), 807–830 (2012).M. Abramowitz, Handbook of Mathematical Functions, with Formulas, Graphs, and Mathematical Tables, 9th edn. (Dover, New York, NY, 1972).M. K. Simon, M. S. Alouini, Digital Communication over Fading Channels, 2nd edn. (Wiley, Hoboken, NY, 2005).Z. Sun, J. Du, in Proc. 10th International Conference, ICIC 2014, ed. by D. -S. Huang, V. Bevilacqua, and P. Premaratne. Log-cumulant parameter estimator of log-normal distribution. Intelligent computing theory (SpringerNew York, NY, 2014), pp. 668–674.S. Zhang, J. M. Jin, Computation of Special Functions (Wiley, New York, 1996).G. Casella, R. L. Berger, Statistical Inference (Duxbury Thomson Learning, Pacific Grove, CA, 2002).C. Kleiber, S. Kotz, Statistical Size Distributions in Economics and Actuarial Sciences (Wiley, Hoboken, NJ, 2003).L. Devroye, Non-uniform Random Variate Generation (Springer, New York,1986).A. Abdi, M. Kaveh, Performance comparison of three different estimators for the Nakagami m parameter using Monte Carlo simulation. IEEE Commun. Lett.4(4), 119–121 (2000).L. Rubio, J. Reig, N. Cardona, Evaluation of Nakagami fading behaviour based on measurements in urban scenarios. Int. J. Electron. Commun. (AEÜ). 61(2), 135–138 (2007)