Indicateurs sécurité en obstétrique : une étude Delphi [Patient safety indicators for obstetrics: a Delphi based study]

OBJECTIVE: Clinical indicators are increasingly used to assess safety of patient care. In obstetrics, only a few indicators have been validated to date and none is used across specialties. The purpose of this study was to identify and assess for face and content validity a group of safety indicators that could be used by anaesthetists, obstetricians and neonatologists involved in labour and delivery units. MATERIALS AND METHODS: We first conducted a systematic review of the literature to identify potential measures. Indicators were then validated by a panel of 30 experts representing all specialties working in labour and delivery units. We used the Delphi method, an iterative questionnaire-based consensus seeking technique. Experts determined on a 7-point Likert scale (1=most representative/7=less representative) the soundness of each indicator as a measure of safety and their possible association with errors and complications caused by medical management. RESULTS: We identified 44 potential clinical indicators from the literature. Following the Delphi process, 13 indicators were considered as highly representative of safety during obstetrical care (mean score</=2.3). Experts ranked 6 of these indicators as being strongly associated to potential errors and complications. CONCLUSIONS: We identified and validated for face and content, a group of six clinical indicators to measure potentially preventable iatrogenic complications in labour and delivery units.

Beta-adrenoceptor stimulation increases neuropeptide Y release from sympathetic nerves in intact rats.

This study was undertaken to assess in conscious normotensive rats the effects of beta-adrenoceptor stimulation on plasma neuropeptide Y (NPY) levels. Wistar rats were subjected to adrenal demedullation on the right side and were either adrenalectomized or sham-operated on the left side. Eleven days later, the conscious rats were infused i.v. for 30 min with either isoproterenol (10 ng/min) or its vehicle. Plasma NPY levels were significantly lower (23.8 +/- 2.6 pM, means +/- S.E.M., n = 12, P < 0.01) in vehicle-treated medullectomized rats than in corresponding sham-operated controls (36.7 +/- 4.1 pM, n = 12). The medullectomized rats infused with isoproterenol showed plasma NPY levels (36.7 +/- 3.3 pM, n = 11) comparable to those of sham-operated rats having received the vehicle. These data therefore demonstrate that plasma NPY levels are lower in rats without adrenal medulla and that in these animals isoproterenol increases NPY release, most likely by activating pre-synaptic beta-adrenoceptors.

Lifetime of an ocean island volcano feeder zone: constraints from U-Pb dating on coexisting zircon and baddeleyite, and 40Ar/39Ar age determinations, Fuerteventura, Canary Islands

High-precision isotope dilution - thermal ionization mass spectrometry (ID-TIMS) U-Pb zircon and baddeleyite ages from the PX1 vertically layered mafic intrusion Fuerteventura, Canary Islands, indicate initiation of magma crystallization at 22.10 +/- 0.07 Ma. The magmatic activity lasted a minimum of 0.52 Ma. Ar-40/Ar-39 amphibole dating yielded ages from 21.9 +/- 0.6 to 21.8 +/- 0.3, identical within errors to the U-Pb ages, despite the expected 1% theoretical bias between Ar-40/Ar-39 and U-Pb dates. This overlap could result from (i) rapid cooling of the intrusion (i. e., less than the 0.3 to 0.6 Ma 40Ar/39Ar age uncertainties) from closure temperatures (T-c) of zircon (699-988 degrees C) to amphibole (500-600 degrees C); (ii) lead loss affecting the youngest zircons; or (iii) excess argon shifting the plateau ages towards older values. The combination of the Ar-40/Ar-39 and U/Pb datasets implies that the maximum amount of time PX1 intrusion took to cool below amphibole T-c is 0.8 Ma, suggesting PX1 lifetime of 520 000 to 800 000 Ma. Age disparities among coexisting baddeleyite and zircon (22.10 +/- 0.07/0.08/0.15 Ma and 21.58 +/- 0.15/0.16/0.31 Ma) in a gabbro sample from the pluton margin suggest complex genetic relationships between phases. Baddeleyite is found preserved in plagioclase cores and crystallized early from low silica activity magma. Zircon crystallized later in a higher silica activity environment and is found in secondary scapolite and is found close to calcite veins, in secondary scapolite that recrystallised from plagioclase. close to calcite veins. Oxygen isotope delta O-18 values of altered plagioclase are high (+7.7), indicating interaction with fluids derived from host-rock carbonatites. The coexistence of baddeleyite and zircon is ascribed to interaction of the PX1 gabbro with CO2-rich carbonatite-derived fluids released during contact metamorphism.

Multicenter Study on the Clinical Effectiveness, Pharmacokinetics, and Pharmacogenetics of Mirtazapine in Depression.

ABSTRACT: Pharmacogenetic tests and therapeutic drug monitoring may considerably improve the pharmacotherapy of depression. The aim of this study was to evaluate the relationship between the efficacy of mirtazapine (MIR) and the steady-state plasma concentrations of its enantiomers and metabolites in moderately to severely depressed patients, taking their pharmacogenetic status into account. Inpatients and outpatients (n = 45; mean age, 51 years; range, 19-79 years) with major depressive episode received MIR for 8 weeks (30 mg/d on days 1-14 and 30-45 mg/d on days 15-56). Mirtazapine treatment resulted in a significant improvement in mean Hamilton Depression Rating Scale total score at the end of the study (P < 0.0001). There was no evidence for a significant plasma concentration-clinical effectiveness relationship regarding any pharmacokinetic parameter. The enantiomers of MIR and its hydroxylated (OH-MIR) and demethylated (DMIR) metabolites in plasma samples on days 14 and 56 were influenced by sex and age. Nonsmokers (n = 28) had higher mean MIR plasma levels than smokers (n = 17): S(+)-enantiomer of MIR, 9.4 (SD, 3.9) versus 6.2 (SD, 5.5) ng/mL (P = 0.005); R(-)-enantiomer of MIR, 24.4 (SD, 6.5) versus 18.5 (SD, 4.1) ng/mL (P = 0.003). Only in nonsmokers, plasma levels of S(+)-enantiomer of MIR and metabolites depended on the CYP2D6 genotype. Therefore, high CYP1A2 activity seen in smokers seems to mask the influence of the CYP2D6 genotype. In patients presenting the CYP2B6 *6/*6 genotype (n = 8), S-OH-MIR concentrations were higher those in the other patients (n = 37). Although it is not known if S-OH-MIR is associated with the therapeutic effect of MIR, the reduction of the Hamilton scores was significantly (P = 0.016) more pronounced in the CYP2B6 *6/*6-genotyped patients at the end of the study. The role of CYP2B6 in the metabolism and effectiveness of MIR should be further investigated.

Bacterial biofilms and capsular contracture in patients with breast implants.

BACKGROUND: It has been hypothesized that bacterial biofilms on breast implants may cause chronic inflammation leading to capsular contracture. The association between bacterial biofilms of removed implants and capsular contracture was investigated. METHODS: Breast implants explanted between 2006 and 2010 at five participating centres for plastic and reconstructive surgery were investigated by sonication. Bacterial cultures derived from sonication were correlated with patient, surgical and implant characteristics, and the degree of capsular contracture. RESULTS: The study included 121 breast implants from 84 patients, of which 119 originated from women and two from men undergoing gender reassignment. Some 50 breast prostheses were implanted for reconstruction, 48 for aesthetic reasons and 23 implants were used as temporary expander devices. The median indwelling time was 4·0 (range 0·1-32) years for permanent implants and 3 (range 1-6) months for temporary devices. Excluding nine implants with clinical signs of infection, sonication cultures were positive in 40 (45 per cent) of 89 permanent implants and in 12 (52 per cent) of 23 temporary devices. Analysis of permanent implants showed that a positive bacterial culture after sonication correlated with the degree of capsular contracture: Baker I, two of 11 implants; Baker II, two of ten; Baker III, nine of 23; and Baker IV, 27 of 45 (P < 0·001). The most frequent organisms were Propionibacterium acnes (25 implants) and coagulase-negative staphylococci (21). CONCLUSION: Sonication cultures correlated with the degree of capsular contracture, indicating the potential causative role of bacterial biofilms in the pathogenesis of capsular contracture. Registration number: NCT01138891 (http://www.clinicaltrials.gov).

Genotypic variability in seed accumulation of foliar-applied molybdenum to common bean

The genotypic variability in molybdenum (Mo) accumulation in common bean seeds has been demonstrated in cases in which soil is the main Mo source, but this variability is yet unknown when Mo is foliar-applied. Therefore, seed Mo concentrations (SMoCc) and seed Mo contents (SMoCt) of 12 genotypes were determined in four experiments in the Zona da Mata, Minas Gerais, Brazil, in which plants were sprayed with 600 g ha-1 Mo. For comparison, two additional experiments without external Mo were conducted. Without Mo application, the average SMoCc was undetectable or 2.83 µg g-1, without significant differences among genotypes. On average, with Mo applications, SMoCc ranged from 14.7 to 25.0 µg g-1 and SMoCt, from 3.94 to 6.84 µg. 'Majestoso' was among the genotypes with the highest SMoCc in the four experiments. However, the large-seeded 'Jalo MG-65' and 'Carnaval' generally had higher SMoCt than the small-seeded 'Majestoso'. 'Ouro Negro' and especially 'Valente' were among the genotypes with the lowest SMoCc and SMoCt. The values of these variables were 61 and 90 %, respectively, higher for 'Majestoso' than those for 'Valente'. Our results suggest that common bean genotypes differ in their capacity to accumulate foliar-applied Mo in the seeds. Mo-rich seeds of large-seeded genotypes or of small-seeded of small-seeded genotypes with good capacity to accumulate Mo in seeds can be produced with relatively less Mo fertilizer.

Pharmacokinetic variability of extended interval tobramycin in burn patients.

BACKGROUND: Aminoglycosides are mandatory in the treatment of severe infections in burns. However, their pharmacokinetics are difficult to predict in critically ill patients. Our objective was to describe the pharmacokinetic parameters of high doses of tobramycin administered at extended intervals in severely burned patients. METHODS: We prospectively enrolled 23 burned patients receiving tobramycin in combination therapy for Pseudomonas species infections in a burn ICU over 2 years in a therapeutic drug monitoring program. Trough and post peak tobramycin levels were measured to adjust drug dosage. Pharmacokinetic parameters were derived from two points first order kinetics. RESULTS: Tobramycin peak concentration was 7.4 (3.1-19.6)microg/ml and Cmax/MIC ratio 14.8 (2.8-39.2). Half-life was 6.9 (range 1.8-24.6)h with a distribution volume of 0.4 (0.2-1.0)l/kg. Clearance was 35 (14-121)ml/min and was weakly but significantly correlated with creatinine clearance. CONCLUSION: Tobramycin had a normal clearance, but an increased volume of distribution and a prolonged half-life in burned patients. However, the pharmacokinetic parameters of tobramycin are highly variable in burned patients. These data support extended interval administration and strongly suggest that aminoglycosides should only be used within a structured pharmacokinetic monitoring program.

Extensive circumferential endoscopic mucosal resection with a new rigid esophagoscope: an animal study

RÉSUME Les techniques de résection muqueuse endoscopique utilisées actuellement ne permettent pas d'effectuer une résection circonférentielle d'un long segment de muqueuse oesophagienne. Une telle résection permettrait le traitement de foyers multicentriques de dysplasies de haut grade (HGIN) ou d'adénocarcinomes précoces (AC) développés sur oesophage de Barrett. Sachant que la prévalence des métastases ganglionnaires régionales est d'environ 7 % pour les adénocarcinomes intra-muqueux (Tis,T1a), les méthodes de traitement non-chirurgicales et moins invasives sont actuellement préférées à une oesophagectomie, dont la morbidité et la mortalité restent élevées en comparaison avec les mucosectomies endoscopiques. Un oesophagoscope rigide modifié a été développé à Lausanne en collaboration avec la maison Karl Storz GmbH, de façon à permettre des résections muqueuses étendues dans l'oesophage. Cette étude animale pilote a investigué la faisabilité et la fiabilité des résections muqueuses circonférentielles de différentes longueurs dans l'oesophage du mouton. Des résections circonférentielles de 2,2 cm (n=6), 3,3 cm (n=6), 4,4 cm (n=7) et 5,5 cm (n=5) de longueur ont été effectuées dans l'oesophage de 24 moutons. Elles consistaient en 2 mucosectomies hémi-circonférentielles opposées. Les animaux ont été suivis par des examens endoscopiques à une semaine puis chaque mois pendant 6 mois ou jusqu'à réépithélialisation complète sans sténose. Au cours du processus de guérison, les sténoses cicatricielles ont été traitées par une ou plusieurs dilatations avec les bougies de Savary. Des résections circonférentielles de 2,2 à 5,5 cm de longueur ont été réalisées avec succès dans 23/24 des cas. Une seule perforation, secondaire à une erreur de manipulation, est survenue directement après la mucosectomie. A l'analyse histologique, une profondeur de résection précise à travers la sousmuq Tyrp1ueuse a été obtenue dans 85% des specimens. Les sténoses cicatricielles ont été contrôlées dans 95% des cas par dilatations avec les bougies de Savary. L'oesophagoscope rigide modifié a permis de réaliser des résections muqueuses circonférentielles et étendues en une seule séance endoscopique d'une durée de moins d'une demi-heure. L'utilisation de ce résectoscope chez l'homme devrait permettre l'éradication complète de l'oesophage de Barrett avec HGIN et/ou AC précoce dans un avenir très proche.

Soil fertility, nutrition and yield of maize and barley with gypsum application on soil surface in no-till

Annual crop yield and nutrition have shown differentiated responses to modifications in soil chemical properties brought about by gypsum application. The aim of this study was to evaluate the effect of gypsum application rates on the chemical properties of a Latossolo Bruno (Clayey Oxisol), as well as on the nutrition and yield of a maize-barley succession under no-till. The experiment was set up in November 2009 in Guarapuava, Parana, Brazil, applying gypsum rates of 0.0, 1.5, 3.0, 4.5, and 6.0 Mg ha-1 to the soil surface upon sowing maize, with crop succession of barley. Gypsum application decreased the levels of Al3+ and Mg2+ in the 0.0-0.1 m layer and increased soil pH in the layers from 0.2-0.6 m depth. Gypsum application has increased the levels of Ca2+ in all soil layers up to 0.6 m, and the levels of S-SO4(2-) up to 0.8 m. In both crops, the leaf concentrations of Ca and S were increased while Mg concentrations have decreased as a function of gypsum rates. There was also an effect of gypsum rates on grain yield, with a quadratic response of maize and a linear increase for barley. Yield increases were up to 11 and 12 % in relation to control for the maximum technical efficiency (MTE) rates of 3.8 and 6.0 Mg ha-1 of gypsum, respectively. Gypsum application improved soil fertility in the profile, especially in the subsurface, as well as plant nutrition, increasing the yields of maize and barley.

Cardiorenal end points in a trial of aliskiren for type 2 diabetes.

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

ASSESSMENT OF BIOAVAILABILITY OF HEAVY METALS AFTER VERMICOMPOSTING IN THE PRESENCE OF ELECTRONIC WASTE

ABSTRACT Heavy metals contained in electronic waste, if discarded improperly, can become bioavailable after vermicomposting, posing a risk to the environment. Small-scale vermicomposting experiments were carried out with printed circuit boards (PCBs) to investigate the migration of heavy metals (Cu, Pb, Zn, Ni, and Sn) to the final compost, as well as the mobility and bioavailability of these metals. High total levels of Pb, Sn and Cu in samples of manure with electronic waste (MEW) and vegetables with electronic waste (VEW) were detected. Based on the initial metal levels in the PCBs and their concentration in the resulting compost, the order of migration of these metals to the MEW and VEW samples was Sn (23.1 %)>Pb (18.4 %)>Ni (4.63 %)>Zn (0.46 %)>Cu (0.14 %) and Sn (24.3 %)>Pb (23.6 %)>Ni (11.33 %)>Zn (1.76 %)>Cu (0.60 %), respectively. Mobility and bioavailability of these metals in the compost were evaluated by three-stage sequential extraction, where F1 was the exchangeable fraction, F2 the organic fraction and F3 the residual fraction. The bioavailability factor (BF) was calculated by the ratio of the sum of fractions F1 and F2 divided by the total sum of the fractions (F1 + F2 + F3). The highest bioavailability factor (BF = 0.92) was found for Pb, the heavy metal considered the greatest environmental concern in this study, indicating the high mobility and the possibility of becoming bioavailable of this metal.

Isolation of a novel monkey adenovirus reveals a new phylogenetic clade in the evolutionary history of simian adenoviruses

Adenoviruses of primates include human (HAdV) and simian (SAdV) isolates classified into 8 species (Human Adenovirus A to G, and Simian Adenovirus A). In this study, a novel adenovirus was isolated from a colony of cynomolgus macaques (Macaca fascicularis) and subcultured in VERO cells. Its complete genome was purified and a region encompassing the hexon gene, the protease gene, the DNA binding protein (DBP) and the 100 kDa protein was amplified by PCR and sequenced by primer walking. Sequence analysis of these four genes showed that the new isolate had 80% identity to other primate adenoviruses and lacked recombination events. The study of the evolutionary relationships of this new monkey AdV based on the combined sequences of the four genes supported a close relationship to SAdV-3 and SAdV-6, lineages isolated from Rhesus monkeys. The clade formed by these three types is separated from the remaining clades and establishes a novel branch that is related to species HAdV-A, F and G. However, the genetic distance corresponding to the newly isolated monkey AdV considerably differs from these as to belong to a new, not yet established species. Results presented here widen our knowledge on SAdV and represents an important contribution to the understanding of the evolutionary history of primate adenoviruses.