The circulation of substandard medicines in the developing world is a serious clinical and public health concern. Problems include under or over concentration of ingredients, contamination, poor ...quality ingredients, poor stability and inadequate packaging. There are multiple causes. Drugs manufactured for export are not regulated to the same standard as those for domestic use, while regulatory agencies in the less-developed world are poorly equipped to assess and address the problem. A number of recent initiatives have been established to address the problem, most notably the WHO pre-qualification programme. However, much more action is required. Donors should encourage their partners to include more explicit quality requirements in their tender mechanisms, while purchasers should insist that producers and distributors supply drugs that comply with international quality standards. Governments in rich countries should not tolerate the export of substandard pharmaceutical products to poor countries, while developing country governments should improve their ability to detect substandard medicines.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Over the past decade, a large number of jet substructure observables have been proposed in the literature, and explored at the LHC experiments. Such observables attempt to utilize the internal ...structure of jets in order to distinguish those initiated by quarks, gluons, or by boosted heavy objects, such as top quarks and
W
bosons. This report, originating from and motivated by the BOOST2013 workshop, presents original particle-level studies that aim to improve our understanding of the relationships between jet substructure observables, their complementarity, and their dependence on the underlying jet properties, particularly the jet radius and jet transverse momentum. This is explored in the context of quark/gluon discrimination, boosted
W
boson tagging and boosted top quark tagging.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over the past decade, a large number of jet substructure observables have been proposed in the literature, and explored at the LHC experiments. Such observables attempt to utilize the internal ...structure of jets in order to distinguish those initiated by quarks, gluons, or by boosted heavy objects, such as top quarks and W bosons. This report, originating from and motivated by the BOOST2013 workshop, presents original particle-level studies that aim to improve our understanding of the relationships between jet substructure observables, their complementarity, and their dependence on the underlying jet properties, particularly the jet radius and jet transverse momentum. This is explored in the context of quark/gluon discrimination, boosted W boson tagging and boosted top quark tagging.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
La prévalence des complications cardiaques varie au cours du syndrome de Churg-Strauss, essentiellement en fonction des moyens diagnostiques utilisés pour les dépister. Leur diagnostic précoce est ...indispensable car elles constituent un facteur pronostique péjoratif de la maladie.
Il s’agit d’une étude rétrospective de trois patients qui ont développé des atteintes cardiaques, révélatrices d’un syndrome de Churg-Strauss et décelées par l’imagerie par résonance magnétique (IRM) cardiaque.
Il s’agissait de deux hommes et d’une femme. Les signes d’appel clinique étaient une insuffisance cardiaque (
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1) et des douleurs thoraciques (
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2). La biologie montrait une éosinophilie importante (6000 à 11 000 par millimètre cube). Les anticorps anticytoplasme des polynucléaires neutrophiles étaient détectés chez un seul patient. L’IRM cardiaque objectivait : (1) un rehaussement tardif après injection de gadolinium touchant des territoires non systématisés à une artère coronaire (
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3) ; (2) des troubles de la fonction systolique du ventricule gauche (
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2), la fraction d’éjection du ventricule gauche étant estimée en moyenne à 51 % et (3) un épanchement péricardique (
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3). L’évolution clinique et biologique était favorable sous prednisone et cyclophosphamide (
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2) ; chez un patient, le recours aux échanges plasmatiques était nécessaire.
Nos observations ont l’intérêt de souligner que l’IRM constitue un outil précieux au diagnostic des localisations cardiaques au cours du syndrome de Churg-Strauss. Elles incitent à s’interroger sur la place de cet examen dans le cadre du dépistage systématique des atteintes cardiaques chez ces patients ; de fait, les atteintes cardiaques constituent un paramètre de mauvais pronostic, justifiant l’initiation d’un traitement médical d’emblée plus agressif chez les patients.
The reported prevalence of cardiac complications is variable in patients with Churg-Strauss syndrome (15–92%) and depends on diagnostic tools. Diagnosis at early stage of heart involvement is crucial, resulting in appropriate management.
We report three patients who developed cardiac manifestations, revealing Churg-Strauss syndrome. The diagnosis of cardiac involvement was obtained using cardiac magnetic resonance imaging (MRI).
Two patients were males and the remaining one was a female. Presenting clinical manifestations were: cardiac failure (
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1) and retrosternal pain (
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2). Laboratory findings disclosed: high blood count of eosinophils (range: 6000–11 000/mm
3); antineutrophil cytoplasmic antibodies were positive in a single patient. Cardiac MRI demonstrated: (1) late gadolinium enhancement (
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3), involving mainly the apical and mid-cavity left ventricular segments; (2) impaired left ventricular function (
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2), mean left ventricular ejection fraction being: 51%; and (3) pericardial effusion (
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3). Outcome was favourable after institution of combined therapy with prednisone and cyclophosphamide (
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2); one patient also underwent plasma exchanges.
Our case series underlines that MRI is a helpful tool in the diagnosis of Churg-Strauss syndrome-related cardiac complications. We further suggest that clinical assessment of patients with Churg-Strauss syndrome should include cardiac MRI, in order to detect cardiac involvement at an early stage; indeed, because cardiac manifestations are predictive factors of poor prognosis, diagnosis at early stages of cardiac involvement may result in improvement of patients management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To evaluate intra- and inter-observer variability of multidetector computed tomography (MDCT) sizing of the aortic annulus before transcatheter aortic valve replacement (TAVR) and the effect of ...observer experience, aortic valve calcification and image quality.
MDCT examinations of 52 consecutive patients with tricuspid aortic valve (30 women, 22 men) with a mean age of 83±7 (SD) years (range: 64–93 years) were evaluated retrospectively. The maximum and minimum diameters, area and circumference of the aortic annulus were measured twice at diastole and systole with a standardized approach by three independent observers with different levels of experience (expert observer 1; resident with intensive 6 months practice observer 2; trained resident with starting experience observer 3). Observers were requested to recommend the valve prosthesis size. Calcification volume of the aortic valve and signal to noise ratio were evaluated.
Intra- and inter-observer reproducibility was excellent for all aortic annulus dimensions, with an intraclass correlation coefficient ranging respectively from 0.84 to 0.98 and from 0.82 to 0.97. Agreement for selection of prosthesis size was almost perfect between the two most experienced observers (k=0.82) and substantial with the inexperienced observer (k=0.67). Aortic valve calcification did not influence intra-observer reproducibility. Image quality influenced reproducibility of the inexperienced observer.
Intra- and inter-observer variability of aortic annulus sizing by MDCT is low. Nevertheless, the less experienced observer showed lower reliability suggesting a learning curve.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The purpose of this study was to quantify the distribution of trabeculated (T) and compact (C) left ventricular (LV) myocardium masses in a healthy Caucasian population against age, gender and LV ...parameters, and to provide normal values for T, C and T/C.
One hundred and forty healthy subjects were prospectively recruited and underwent cardiac MRI at 1.5T with a stack of short-axis cine sequences covering the entire LV. End-diastolic volume (EDV), C and T masses were quantified using a semi-automatic method. Ejection fraction (EF) and T/C ratio were computed.
We included 70 men and 70 women with a mean age of 44±14 (SD) years (range: 20–69 years). The mean EF was 63.7±6.3 (SD) % (range: 50.7–82.0%), the mean EDV was 75.9±16.2 (SD) mL/m2 (range: 36.4–112.2mL/m2), the mean C mass was 53.9±11.2 (SD) g/m2 (range: 26.5–93.4g/m2) and the mean T mass was 4.9±2.4 (SD) g/m2 (range: 1.1–11.4g/m2). The T/C ratio was 9.2±4.5% (range: 2.0–29.4%). Multivariate ANOVA test showed that the compact mass was influenced by EDV (P<0.0001), EF (P=0.001) and gender (P<0.0001), and the trabeculated mass depended on EDV (P<0.0001), gender (P=0.002) and age (P<0.0001), while the T/C ratio was only influenced by age (P=0.0003). Spearman test showed a correlation between EDV and C (r=0.60; P<0.0001),T (r=0.46; P<0.0001) and T/C ratio (r=0.26; P=0.0023).T and T/C ratio correlated with EF (r=−0.18, P=0.0373; r=−0.18, P=0.0321, respectively).
While the compact and trabeculated myocardium masses appear to relate separately to the cardiac function, age and gender, their ratio T/C appears to only decrease with age. Furthermore, we propose here normal values for T, C and T/C in a cohort of healthy Caucasians subjects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multidrug-resistant tuberculosis (MDR-TB) is caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin, the two most powerful first-line antituberculosis (anti-TB) ...drugs. Although drug resistance in TB is not a new phenomenon, several factors--including irrational antibiotic use, poor-quality anti-TB drugs, the collapse of public health infrastructures, the HIV epidemic, war, famine, and increasing inequality and poverty--have all contributed to the increasing incidence of TB. In recent years, outbreaks of MDR-TB in public institutions (hospitals, prisons, and homeless shelters) in the United States, Europe, and Latin America have caused many deaths and have raised concerns about epidemic transmission of drug-resistant strains of M. tuberculosis.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
ObjectiveIn today's context of globalisation of pharmaceutical production and distribution, international and national procurement agencies play a de facto key role in defining the quality of ...medicines available in sub-Saharan Africa. We evaluated the compliance of a sample of pharmaceutical distributors active in sub-Saharan Africa with the standards of the WHO guideline ‘Model Quality Assurance System (WHO MQAS) for procurement agencies’, and we investigated factors favouring or hindering the adequate implementation of the guideline.MethodsWe used mixed-methods methodology to analyse quantitative and qualitative data. The quantitative study consisted of a retrospective secondary analysis of data collected by QUAMED (Quality Medicines for all), a partnership that pleads for universal access to quality-assured medicines. The qualitative survey consisted of formal and informal interviews with key informants. We adopted an embedded multiple-case study design.FindingsOur analysis suggests that international distributors based in Europe perform, on average, better than sub-Saharan African distributors. However, some weaknesses are ubiquitous and concern critical processes, such as the initial selection of the products and the ongoing reassessment of their quality. This is due to several different factors: weak regulatory oversight, insufficient human/financial resources, weak negotiating power, limited judicial autonomy and/or lack of institutional commitment to quality.ConclusionsOur findings suggest that pharmaceutical distributors active in sub-Saharan Africa generally do not apply stringent criteria for selecting products and suppliers. Therefore, product quality is not consistently assured but depends on the requirements of purchasers. While long-term solutions are awaited, the WHO MQAS guideline should be used as an evaluation and training tool to upgrade current standards.
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