[Fixed combination of budesonide, formoterol, glycopyrronium for the treatment of severe COPD : Trixeo Aerosphere®]. / Le médicament du mois. Combinaison fixe budésonide, formotérol, glycopyronium pour le traitement de la BPCO modérée à sévère : Trixeo Aerosphère®.

Here we present pharmacological and clinical properties of a new fixed triple inhaled combination including an inhaled corticoid, a long acting ?2 agonist and a long acting anticholinergic for the treatment of severe chronic obstructive pulmonary disease (COPD). Trixeo Aerosphere® is the name of this triple combination which contains 160 µg budesonide, 4,8 µg formoterol and 9 µg glycopyrronium delivered by a pMDI. As compared to a budesonide/formoterol combination, Trixeo Aerosphere® improves forced expiratory volume in the first second (FEV1). As compared to glycopyrronium/formoterol combination, Trixeo Aerosphere® reduces exacerbation rate, improved quality of life and most importantly reduces mortality with a benefit increasing with blood eosinophil count. Trixeo Aerosphere® 320/18/9.6 is delivered twice daily 2 inhalations and is indicated in moderate to severe COPD insufficiently controlled by LABA/LAMA (long-acting ?2-adrenergic receptor agonist/ long-acting ?2-muscarinic receptor agonist) or ICS/LABA (inhaled corticosteroid/long-acting ?2-adrenergic receptor agonist).

Nous présentons dans cet article les propriétés pharmacologiques et les effets cliniques d'une nouvelle triple combinaison fixe inhalée comprenant un corticoïde inhalé, un ?2 mimétique à longue durée d'action et un anticholinergique à longue durée d'action, destinée au traitement de la bronchopneumopathie chronique obstructive (BPCO) sévère. Cette combinaison qui porte le nom de Trixeo Aerosphere® regroupe, dans le même dispositif, 160 µg de budésonide, 4,8 µg de formotérol et 18 µg de glycopyrronium. Par rapport à une combinaison budésonide/formotérol, le Trixeo Aerosphere® améliore la valeur du volume expiratoire maximum par seconde (VEMS). Par rapport à une combinaison formotérol/glycopyrronium, le Trixeo Aerosphere® réduit la fréquence des exacerbations et réduit la mortalité avec un bénéfice qui augmente avec le taux des éosinophiles circulants. Le Trixeo Aerosphere®, à la dose de 2X2 bouffées/24h, est indiqué dans le traitement des patients BPCO modérés à sévères insuffisamment contrôlés par une bithérapie LABA/LAMA (long-acting ?2-adrenergic receptor agonist/ long-acting ?2-muscarinic receptor agonist) ou ICS/LABA (inhaled corticosteroid/long-acting ?2-adrenergic receptor agonist).

[Feasibility and effectiveness study of a simplified mobile self-education and self-monitoring application for patients with severe chronic obstructive pulmonary disease]. / Étude de faisabilité et d'efficacité d'une application mobile simplifiée d'auto-éducation et d'auto-surveillance pour des patients atteints d'une broncho-pneumopathie chronique obstructive sévère.

Chronic obstructive pulmonary disease (COPD) and its exacerbations cause a deterioration in quality of life and a significant consumption of medical resources. Patient empowerment supported by education and self-monitoring practices can improve quality of life and reduce the number of hospital admissions. With the development of telemedicine, a lot of digital applications have been studied. Many are considered too complicated to use. So, we partnered with an IT company in Liège named «COMUNICARE¼ to develop a simplified application that is managed autonomously, without the support of a health professional. In addition, we conducted a prospective pilot study including patients with severe COPD with exacerbations. We observed an excellent rate of use despite low comfort with a smartphone. The primary objective of reducing the number of hospitalizations was not achieved. Nevertheless, we observed interesting results concerning the symptomatology, overall satisfaction and help with therapeutic compliance.

La bronchopneumopathie chronique obstructive (BPCO) et ses exacerbations engendrent une dégradation de la qualité de vie ainsi qu'une consommation importante des ressources médicales. L'autonomisation du patient appuyée par des pratiques d'éducation et d'auto-surveillance permet d'améliorer la symptomatologie et de diminuer le nombre d'hospitalisations. Avec le développement de la télémédecine, de nombreuses applications digitales ont été étudiées. Beaucoup sont jugées trop compliquées d'utilisation. Par conséquent, nous nous sommes associés à la société informatique liégeoise «COMUNICARE¼ pour développer une application simplifiée gérée de façon autonome, sans l'appui d'un professionnel de santé. En complément, nous avons réalisé une étude pilote prospective incluant des patients atteints d'une BPCO sévère à caractère exacerbateur. On observe un excellent taux d'utilisation malgré une faible aisance avec un smartphone. L'objectif primaire d'une diminution du nombre d'hospitalisations n'est pas atteint. Néanmoins, nous observons des résultats intéressants concernant la symptomatologie, la satisfaction globale et l'aide à l'observance thérapeutique.

[Telemonitoring of severe COPD patients]. / Expérience liégeoise dans le télé-monitoring de patients BPCO sévères.

Following a solicitation of INAMI in 2016, a team of the CHU Liège pneumology department has proposed a telemonitoring pilot project in severe chronic obstructive pulmonary disease (COPD) patients. The main objective of the study was to reduce the number of hospitalizations for COPD exacerbation. The patients included in the study had been at least hospitalized once in 12 months before the beginning of the telemonitoring. A close collaboration with the general practitioner was required. Patients were educated in the manipulation of the application and connected objects. The numerous technical difficulties encountered limited the number of patients studied within the short time allowed by INAMI. However, some interesting observations could be made and a first experience in the field acquired. A project on a large scale seems necessary.

Suite à un appel lancé par l'INAMI en 2016, une équipe de soins du Service de Pneumologie du CHU de Liège a proposé un projet pilote de télé-monitoring de patients souffrant de bronchopneumopathie chronique obstructive (BPCO) sévère dont l'objectif principal était de réduire le nombre de ré-hospitalisations pour exacerbation de BPCO. Les patients sélectionnés étaient des patients sévèrement atteints et ayant été au moins hospitalisés une fois dans les 12 mois précédant la mise en place de la surveillance à distance. Une collaboration étroite avec le médecin généraliste était requise. Les patients ont été éduqués à la manipulation de l'application et des objets connectés proposés. Les nombreuses difficultés techniques rencontrées ont limité le nombre de patients étudiés dans les délais courts autorisés par l'INAMI. Cependant, quelques observations intéressantes ont pu être faites et une première expérience dans le domaine a été acquise. Un projet à plus grande échelle paraît nécessaire.

[Long-term oxygen therapy: mortality rate, short-term predictive mortality factors]. / Oxygénothérapie de longue durée : survie à 1 an, facteurs prédictifs de mortalité.

OBJECTIVES: The aims of this study were to assess the survival rate at one year of patients receiving long-term oxygen therapy (LTOT) as prescribed by the National Institute for Health and Disability Insurance's imposed criteria based on international recommendations, to search for short-term predictive factors for mortality and to measure the impact of LTOT on the frequency of hospitalization due to COPD exacerbations. METHODS: We conducted a retrospective analysis of 416 patients suffering from chronic respiratory insufficiency and started on long-term oxygen therapy between 2012 and 2014. The survival curves were estimated by the Kaplan-Meier method. Cox regression models were used to estimate the impact of the variables on survival. The evolution of patients hospitalized for COPD exacerbation was analysed by the McNemar test. RESULTS: The average age of our cohort was 70±10 years. It included 57% women and 78% patients with COPD. The one-year survival rate (n=416) under LTOT was 75%. Identified predictive mortality factors were coronary insufficiency [HR (95% CI): 1.8 (1.2-2.8); P=0.0083], reduction of the left ventricular ejection fraction [HR (95% CI): 2.5 (1.3-4.9); P=0.0080], the presence of osteoporosis [HR (95% CI): 1.7 (1.0-2.9); P=0.040]. There was a 28% reduction in the frequency of hospitalization for exacerbations of COPD during the year after starting LTOT. CONCLUSIONS: Mortality at one year with LTOT was about 25%. Factors predictive of mortality at one year included coronary insufficiency, reduction of the left ventricular ejection fraction and osteoporosis. LTOT seems to reduce hospitalizations due to exacerbations of COPD.

[Update in non-union treatment]. / Actualités dans le traitement des pseudarthroses aseptiques.

Non-union of long bones is still a dreadfull complication. Depending on the type and location of the non-union, we describe current treatment options including various types of bone fixation, isolated or vascularised bone grafts, biophysical enhancement and newer developments with biological bone inducers (BMP).

Effects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivo.

Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis. Both the follicular and luteal phases of the menstrual cycle are characterized by proliferation, whereas apoptosis occurs only at the end of the latter phase. In this study, we observed that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but not continuous treatment with it, induced apoptosis of normal human breast epithelial cells in vitro and in women who applied NOMAC gel to their breasts. Furthermore, this apoptotic response was specific to normal breast cells, since withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of fibroadenoma cells in women. These observations open up new perspectives in the prevention of hyperplasia and breast cancer.

Progesterone receptor activation. an alternative to SERMs in breast cancer.

Data regarding the effects of progesterone and a progestagen on human normal breast epithelial cell proliferation and apoptosis are presented here. In postmenopausal women, adding progesterone to percutaneously administrated oestradiol significantly reduces the proliferation induced by oestradiol. In vitro and in premenopausal women, stopping the administration of nomegestrol acetate triggers a peak of apoptosis. Fibro-adenoma and cancerous cells do not show this regulation of apoptosis. Progesterone seems to be important in normal breast homeostasis.

Hypertension and left ventricular hypertrophy.

In response to high blood pressure, left ventricular hypertrophy develops. But in hypertension, the myocardial hypertrophied structure is abnormal. The prevalence of this hypertrophy is influenced by age, gender, weight, race, genetics and the severity of high blood pressure. By echocardiography, it has been possible to detect non invasively and more precisely this hypertrophy and its anatomical pattern which is not uniform. This cardiac response is influenced by hemodynamic but also by non hemodynamic factors, but the exact mechanisms are not yet well understood. The humoral and tropic factors particularly affect the cardiac remodeling. Left ventricular hypertrophy has been noted by itself to be an independent risk factor for sudden death, ventricular arrhythmias, myocardial ischemia, and heart failure. Very early hypertension, diastolic dysfunction is noted. The progression to systolic failure in moderate hypertension usually occurs over several decades. According to the worse prognosis of left ventricular hypertrophy, it has been suggested that the reversibility of this anatomical modification by antihypertensive treatment is beneficial. Preliminary data support this idea.

Comparative study of tilidine-naloxone and pentazocine in knee and hip osteoarthritis.

Fifty patients, twenty-five suffering from severe knee osteoarthritis and twenty-five from acute hip osteoarthritis, received pentazocine or a new preparation of tilidine-naloxone for a period of 2 weeks, in a double-blind study. The two drugs were found to have the same efficacy and tolerance in both diseases with a minor but not statistically significant superiority for tilidine-naloxone. Similar quantities of drugs were taken over the study period, while patients were allowed to take as many as 8 capsules per day to relieve pain. There were quite equivalent side-effects and no marked changes in laboratory tests.

Metabolic and circulatory evaluation of cerebral ischemic accident in humans by positron emission tomography: a pilot study with almitrine-raubasine.

Positron emission tomography and oxygen-15 were used to evaluate the effect of almitrine-raubasine combination on cerebral blood flow and oxidative metabolism in patients with cerebral ischemia. In five patients aged between 58 and 74 years, with a cerebral ischemic accident in the territory of the middle cerebral artery, blood flow rate, oxygen metabolic rate, and cerebral oxygen extraction were measured before and after a 90-min intravenous perfusion of almitrine bismesilate 15 mg and raubasine 5 mg. Investigations were performed from day 2 to day 7 after stroke occurred. One patient showed evidence of initial relative luxury perfusion, the degree of which was reduced by such combined treatment. The other four patients had a focal reduction in cerebral blood flow and oxygen consumption prior to treatment. The statistical analysis of three cerebral areas (epicenter of lesion, anterior and posterior juxtalesional areas, and homologous heterolateral areas) showed a 3.6% increase in oxygen metabolic rate at the epicenter, when both hemispheres were taken together, and a significant increase in cerebral blood flow in all three areas (3% on the healthy hemisphere, 13% on the injured hemisphere). These changes were greater in some patients than in others. This suggests that heterogeneity of drug responses may correspond to the heterogeneity of the initial status.

[Metabolic and blood circulation evaluation of acute ischemic cerebral accident in humans using positron emission tomography]. / Evaluation métabolique et circulatoire de l'accident cérébral ischémique aigu chez l'homme par tomographie d'émission positonique.

Positron emission tomography and oxygen-15 were used to evaluate the effects of an almitrine-raubasine combination on cerebral blood flow and oxydation metabolism in patients with acute cerebral ischaemia. In 5 patients, aged between 58 and 74 years, with cerebral ischaemic accident in the territory of the middle cerebral artery, blood flow rate, oxygen consumption and brain oxygen extraction were measured before and after a 90-min intravenous infusion of almitrine bismesilate 15 mg and raubasine 5 mg. Only one patient presented with initial relative luxury perfusion, the intensity of which was reduced by the combined treatment. The other 4 patients had focal reduction of cerebral blood flow and oxygen consumption prior to treatment. Statistical analysis conducted on three cerebral areas (epicentre of the lesion, anterior and posterior juxtalesional areas and homologous heterolateral areas) showed a significant 3.6% increase of oxygen consumption in the epicentre, both hemispheres included, and a significant increase of cerebral blood flow in all three areas (3% on the healthy side, 13% on the diseased side). No significant change in oxygen extraction was demonstrated. The authors conclude that acute almitrine-raubasine treatment has beneficial effects on the brain immediately after a cerebral vascular accident, reflecting respect of the circulation-metabolism couple.

[The role of plasma alpha 1-glycoprotein acid in the binding of aminopyrine]. / Rôle de l' alpha 1-glycoprotéine acide plasmatique dans la fixation de l'aminopyrine.

Under certain pathological conditions the binding of various substances by serum proteins is altered. The plasma concentrations of alpha 1-acid glycoprotein, also known as orosomucoid are reported to be elevated in stressful situation and in certain disease states like acute myocardial infarction. The binding of aminopyrine to serum proteins and alpha 1-acid glycoprotein was determined using equilibrium dialysis. It appears that alpha 1-acid glycoprotein has specific binding sites for aminopyrine. Aminopyrine was also bound to other serum proteins. On addition the results indicate that an increase of alpha 1-acid glycoprotein to concentrations such as those seen in some pathological states does not really alter the percent of aminopyrine bind to serum proteins.

[Free salivary steroids and plasma hormones in women]. / Stéroïdes salivaires et hormones plasmatiques libres chez la femme.

The use and limitations of steroid assay in saliva are presented and discussed. Salivary cortisol was well correlated with unbound cortisol plasma, the only biological active fraction of total cortisol. Assay of salivary cortisol is particularly useful in patients taking oral contraceptives or during pregnancy. Indeed, in these patients, because of the marked increase in plasma cortisol binding globulin concentration (from 41 to 100 mg% or more), plasma total cortisol concentration increases from 18 +/- 4 micrograms% to 40 +/- 10 micrograms% whereas plasma unbound cortisol usually remains within the normal range. During the menstrual cycle, salivary progesterone rises from 5.4 +/- 1.8 to 15.1 +/- 3.6 ng%. As it is well correlated with plasma unbound progesterone concentration, salivary progesterone may be considered as a convenient and reliable index of luteal function. Because of its very low concentration, salivary estradiol is difficult to assay with routinely available techniques and, at present, is of limited interest for clinical investigation.