Benfluorex and Unexplained Valvular Heart Disease: A Case-Control Study

BACKGROUND: Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation. METHODS: We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1(st) 2003 and June 30(th) 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051). Patients with either a primary cause (degenerative, known rheumatic heart disease, infectious endocarditis, congenital, radiation-induced valvular disease, associated connective and/or vasculitis disease, trauma, tumor) or a secondary (functional) cause were considered as having an "explained" mitral regurgitation. Other patients were considered as having an "unexplained" mitral regurgitation and were included as cases. For each case, two controls were matched for gender and for the closest date of birth, among a list of patients with an "explained" mitral regurgitation. Drug exposures were assessed blindly regarding the case or control status, through contacts with patients, their family and/or their physicians. RESULTS: Out of the 682 eligible patients, 27 cases and 54 matched controls were identified. The use of benfluorex was reported in 22 patients: 19 of the 27 cases, versus 3 of the 54 controls, odds-ratio 17.1 (3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use. CONCLUSION: The use of benfluorex is associated with unexplained mitral regurgitation

Comorbidities of COPD

International audienceBy 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately. Extrapulmonary comorbidities are common in COPD and influence prognosis; we propose an exhaustive comorbidities revie

Transposition of a triphosgene-based process for pharmaceutical development: from mg·h-1 to kg·h-1 of an unsymmetrical urea

A two reaction synthesis of a urea, using triphosgene, was studied. The objective was to transpose the process from laboratory scale to pre-industrial plant. The whole study was performed in a continuous process, adapting the characteristic dimensions and length of the reactor. In this paper, the development of the process is presented, and the choices about safety and operating conditions constraints are discussed. The final operation allows a 70% global yield in a 7 week study. Furthermore, the use of microreactors not only permits an exhaustive study of the process operating parameters, but also provides feedback on the developed chemistry itself. The results obtained are a demonstration of the use of continuous processes in small scale reactors for complex molecule development. The mg·h-1 to kg·h-1 is a key transposition in the pharmaceutical industries project development, as it can help to accelerate the first lot production used in toxicological or pre-clinic stages

Paléoenvironnements tardiglaciaires en Aquitaine : la séquence alluviale de la Brunetière (Bergerac, France)

Des dépôts alluviaux datant du Tardiglaciaire et du début de l’Holocène ont été découverts dans la plaine du Caudeau, petit affluent de la Dordogne, à La Brunetière sur la commune de Pombonne (Dordogne) à l’occasion de travaux d’archéologie préventive. Leur analyse permet de renouveler nos connaissances sur l’évolution des cours d’eau en Aquitaine pendant cette période charnière. Ils montrent en particulier que les principales phases de métamorphose alluviale décrites dans le nord de l’Europe se sont également produites dans cette région de manière à peu près synchrone, pour autant que l’on puisse en juger d’après les dates disponibles. Deux phases majeures d’incision aux dépens de la nappe alluviale à galets pléniglaciaire sont identifiables. La première intervient pendant une phase très précoce du Bølling, soit avant 12 700 ± 45 BP, dans un environnement steppique. L’abandon rapide du chenal, associé à du soutirage karstique, permet ensuite l’installation d’un petit lac colmaté par des argiles avec quelques intercalations tourbeuses riches en macrorestes végétaux (bouleau nain, saule). L’image de la végétation donnée aussi bien par les pollens que par la faune de mollusques et d’insectes est celle d’une steppe encore très ouverte à armoise et genévriers, alors que les paléotempératures estivales indiquées par les insectes sont déjà proches de celles connues actuellement dans la région. Des paléotempératures hivernales sensiblement plus froides que les actuelles (-20 à 5 °C) renvoient cependant l’image d’un climat à caractère plus continental. Les dépôts lacustres sont ensuite recouverts par une couche de sables d’inondation attribués au Dryas moyen et/ou récent. L’assèchement du chenal et le développement d’un sol hydromorphe pourrait correspondre respectivement soit à l’Allerød, soit au tout début de l’Holocène. La seconde phase d’incision est attribuée au Préboréal et tronque la séquence tardiglaciaire; elle est associée à un style alluvial à chenaux anastomosés. L’abandon de la majorité des chenaux pendant le Boréal marque la réduction du lit à un chenal unique sinueux, comparable à celui qui caractérise le Caudeau actuel. Une industrie lithique de type Magdalénien supérieur a également été découverte sur la berge du chenal tardiglaciaire. L’industrie recueillie est exclusivement taillée dans le silex local maestrichtien. Elle comprend environ 200 éclats et 800 petits restes de taille, pour seulement 15 lames de plein débitage et 6 outils (sans aucun microlithe). L’utilisation exclusive d’un percuteur minéral tendre, la morphologie du nucléus laminaire, la rectitude des petites lames, les 2 lames appointées sont autant de caractères qui évoquent le stade ultime du Magdalénien supérieur, tel qu’il est connu plus en amont le long de la Dordogne sur les sites de la Gare de Couze et du Moulin du Roc.Late-glacial to Holocene alluvial deposits have been discovered along a small tributary of the Dordogne river at “La Brunetière” near Bergerac (Dordogne, southwestern France) and yield novel information on the evolution of rivers at the end of the Weichselian. The deposits show that the main alluvial changes described in Northern Europe occurred simultaneously at “La Brunetière”. Two major phases of channel incision in the basal Pleniglacial gravel body have been identified. The first channels developed at the very onset of the Bølling, i.e. before 12,700 ± 45 BP, in a steppic landscape. Rapid channel abandonment allowed development of a small lake, filled in with alternating peat and clay layers rich in vegetal debris. Pollen data as well as molluscs and insects point to an open Artemisia steppe with juniper trees, together with a local component of riparian shrubs (willow and dwarf birch). Palaeotemperatures reconstructed from coleopteran assemblages indicate larger-than-today yearly thermal amplitude with cold winters and warm summers. The lacustrine clays and peats are buried by sandy overbank deposits that are attributed to the Older and/or the Upper Dryas. Channel drying and subsequent hydromorphic soil development relate respectively to the Allerød or the early Holocene. The second phase of incision corresponds to the Preboreal and is typified by stable anastomosed channel formation. Most of these were abandoned during the Boreal and filled by organicclay. An Upper Magdalenian lithic industry has been discovered in a paleosol on the bank of the Late-glacial channel. It includes ca. 200 flakes and 800 small debris of local Maestrichtian flint, and only 15 full-debitage blades and 6 tools. Exclusive use of soft hammer, laminar core morphology, straightness of the small blades, and the 2 pointed blades indicate an ultimate stage of the Upper Magdalenian

Complications of Peripherally Inserted Central Venous Catheters: A Retrospective Cohort Study

Background and Aim The use of venous catheters is a widespread practice, especially in oncological and oncohematological units. The objective of this study was to evaluate the complications associated with peripherally inserted central catheters (PICCs) in a cohort of patients. Materials and Methods In this retrospective cohort study, we included all patient carrying PICCs (n = 603) inserted at our institute between October 2010 and December 2013. The main variables collected were medical diagnosis, catheter care, location, duration of catheterization, reasons for catheter removal, complications, and nursing care. Complications were classified as infection, thrombosis, phlebitis, migration, edema, and/or ecchymosis. Results All patients were treated according to the same “nursing care” protocol. The incidence rate of complications was two cases per 1000 days of catheter duration. The most relevant complications were infection and thrombosis, both with an incidence of 0.17 cases per 1000 days of the total catheterization period. The total average duration of catheterization was 170 days [SD 6.06]. Additionally to “end of treatment” (48.42%) and “exitus”, (22.53%) the most frequent cause of removal was migration (displacement towards the exterior) of the catheter (5.80%). Conclusions PICCs are safe devices that allow the administration of long-term treatment and preserve the integrity of the venous system of the patient. Proper care of the catheter is very important to improve the quality life of patients with oncologic and hematologic conditions. Therefore, correct training of professionals and patients as well as following the latest scientific recommendations are particularly relevant

Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial

Background Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. Methods Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. Results There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). Conclusions We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma

"I think my body has become addicted to those tablets" Chronic heart failure patients' understanding of and beliefs about their illness and its treatment: a qualitative longitudinal study from Uganda

Patients with heart failure in Uganda present for health care with advanced structural heart disease, have repeated hospitalizations and poorly controlled disease symptoms. The reasons for these are unclear. Literature from other settings shows that patients' understanding of their illness and their beliefs influence their health related behaviour. The study aimed to explore the beliefs of patients with heart failure, their understanding of their illness and its treatment, and how this influenced their health related behaviour to inform future health education programs, information and palliative care services.Serial qualitative in-depth interviews were conducted with Heart Failure patients who were purposively sampled and recruited in Mulago National Referral Hospital until thematic saturation was reached. In-depth interviews were conducted at three time points over the course of their illness with intervals of 3 months between interviews. A grounded theory approach was used in data analysis. The University of Edinburgh ethics committee, Mulago Hospital Research Ethics committee and the Uganda National Council of Science and Technology (Reference numbers D/GC/178; MREC 33, SS 3083 respectively) approved the research.A total of 40 face to face qualitative longitudinal interviews (36-patient alone, 4 paired-patient and family carer), were conducted with 21 patients. The findings revealed that heart failure patients were unaware of the symptoms of the illness and their definition of illness differed from that of health professionals. Patients understood their diagnosis, cause of illness, prognosis and the importance of the medicines differently from health professionals, and had insufficient information on self-care. Lay beliefs were used to explain many aspects of the illness and treatments. All these influenced where patients sought care and their adherence to treatment, self-care and follow up leading to uncontrolled disease.There is a high level of health illiteracy among heart failure patients in Uganda. Patients rely on lay beliefs to make health decisions and medical information is often miscomprehended. There is an urgent need for health education using culturally appropriate information

Wellbeing and chronic lung disease incidence: The Survey of Health, Ageing and Retirement in Europe

Judith A. Okely and Catharine R. Gale are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

De l'intérêt de la mise en place de la télésurveillance des insuffisants cardiaques vue par le médecin généraliste en Basse-Normandie en 2010

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF