9 resultados para More

em Université de Lausanne, Switzerland


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Ornament expression fluctuates with age in many organisms. Whether these changes are adaptively plastic is poorly known. In order to understand the ultimate function of melanin-based ornaments, we studied their within-individual fluctuations and their covariation with fitness-related traits. In barn owls (Tyto alba), individuals vary from reddish-brown pheomelanic to white and from immaculate to marked with black eumelanic spots, males being less reddish and less spotted than females. During the first molt, both sexes became less pheomelanic, females displayed larger spots and males fewer spots, but the extent of these changes was not associated with reproduction. At subsequent molts, intra-individual changes in melanin-based traits covaried with simultaneous reproduction changes. Adult females bred earlier in the season and laid larger eggs when they became scattered with larger spots, while adults of both sexes produced larger broods when they became whiter. These results suggest that the production of melanin pigments and fitness-related life history traits are concomitantly regulated in a sex-specific way.

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BACKGROUND: Hypotension, a common intra-operative incident, bears an important potential for morbidity. It is most often manageable and sometimes preventable, which renders its study important. Therefore, we aimed at examining hospital variations in the occurrence of intra-operative hypotension and its predictors. As secondary endpoints, we determined to what extent hypotension relates to the risk of post-operative incidents and death. METHODS: We used the Anaesthesia Databank Switzerland, built on routinely and prospectively collected data on all anaesthesias in 21 hospitals. The three outcomes were assessed using multi-level logistic regression models. RESULTS: Among 147,573 anaesthesias, hypotension ranged from 0.6% to 5.2% in participating hospitals, and from 0.3% up to 12% in different surgical specialties. Most (73.4%) were minor single events. Age, ASA status, combined general and regional anaesthesia techniques, duration of surgery and hospitalization were significantly associated with hypotension. Although significantly associated, the emergency status of the surgery had a weaker effect. Hospitals' odds ratios for hypotension varied between 0.12 and 2.50 (P < or = 0.001), even after adjusting for patient and anaesthesia factors, and for type of surgery. At least one post-operative incident occurred in 9.7% of the procedures, including 0.03% deaths. Intra-operative hypotension was associated with a higher risk of post-operative incidents and death. CONCLUSION: Wide variations remain in the occurrence of hypotension among hospitals after adjustment for risk factors. Although differential reporting from hospitals may exist, variations in anaesthesia techniques and blood pressure maintenance may also have contributed. Intra-operative hypotension is associated with morbidities and sometimes death, and constant vigilance must thus be advocated.

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Rapport de Synthése : Introducfíon : la maladie diverticulaire est devenue un problème majeur de santé communautaire et occupe la cinquième place en termes de coûts des maladies digestives. La diverticulite représente sa complication la plus fréquente chez environ 20-25% des patients avec une maladie diverticulaire. Son taux de récidive après un premier épisode de diverticulite est estimé à 20%. Historiquement, il était accepté que le taux de complications et d'échec du traitement conservateur de la diverticulite soient plus élevés lors de récidive qu'après un épisode initial. Ceci a amené la communauté médicale ä un consensus qui est de proposer une sigmoidectomie élective suite à un 2ème épisode de diverticulite. De nouvelles données et réinterprétations de travaux antérieurs ont remis en question ce consensus. Par ces faits, les dernières recommandations de la société américaine de chirurgie colorectale restent encore évasives dues au manque d'évidence. Le but de cette thèse est de déterminer si la récidive de diverticulite a une présentation clinique et radiologique différente d'un épisode initiale et si le risque d'échec du traitement est réellement plus élevé. Méthode : étude rétrospective .de 271 patients consécutifs admis dans le service. de chirurgie viscérale CHUV pour diverticulite, confirmée par CT-scan, de 2001 à 2004. 202 patients présentaient un épisode initial (groupe I), et 69 une récidive (groupe R). Au total 20 paramètres cliniques et 15 radiologiques ont été analysés et comparés entre les 2 groupes, dont le taux de prise en charge chirurgicale, la présentation clinique initiale, la réponse au traitement, les complications, les paramètres de laboratoires, la présence de liquide libre, d'abcès ou de pneumopéritoine au scanner. Une analyse statistique univariée a été effectuée. Résultats : aucun des paramètres cliniques ou radiologiques n'étaient différents entre les deux groupes. Concernant la chirurgie, 15.8% des patients dans le groupe I ont nécessité une prise en charge chirurgicale à l'admission comparé à 5.8% dans le groupe R (p=0.04). Le taux d'échec du traitement conservateur dans les deux groupes était similaire (10.7% vs 10.0% ; p=0.84). Le taux de mortalité à 30 jours était de 3% dans le groupe I et 0% dans le groupe R (p= 0.34). Conclusion : selon les résultats de cette étude, la récidive de diverticulite n'entraîne pas plus de complications ni d'échec du traitement conservateur. De plus, le taux de prise en charge chirurgicale à l'admission du patient est moins fréquent en cas de récidive. Ces résultats remettent en questions le consensus actuel de prise en charge chirurgicale élective.

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Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.

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There is little information regarding the prevalence of thinness in European adolescents. This was assessed in a convenience sample of children and adolescents from the Lisbon area (Portugal). Cross-sectional study including 2494 boys and 2519 girls aged 10-18 years. Body mass index (BMI), waist and hip were measured using standardized methods; thinness was defined using international criteria. Body fat was assessed by bioelectrical impedance. In girls, prevalence of thinness, overweight and obesity were 5.6%, 19.7% and 4.7%, respectively, whereas the corresponding numbers in boys were 3.9%, 17.4% and 5.3%. Prevalence of thinness increased whereas obesity decreased with age: from 1.5% to 7.6% for thinness and from 9.2% to 3.8% for obesity in girls aged 10 and 18, respectively. In boys, the corresponding trends were from 0% to 7.3% for thinness and from 10.6% to 3% for obesity. After adjusting for age, differences were found between BMI groups for weight, body fat percentage, fat mass, lean mass, waist and hip, while no differences regarding height were found between thin and normal weight participants. The prevalence of thinness is more frequent than obesity after age 14 in girls and 16 years in boys. Thinness is associated with a decreased body weight and body fat, whereas no consistent effect on height was noted.

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QUESTIONS UNDER STUDY: Iron deficiency with or without anaemia is the most common deficiency in the world. Its prevalence is higher in developing countries and in low socioeconomic populations. We aimed at determining and comparing the prevalence of iron deficiency in an immigrant and non-immigrant population. METHODS: Every child scheduled for a routine check-up at 12 months of age was allowed to participate in the study. Haemoglobin, ferritin, anthropometric data, familial and nutritional status were measured. RESULTS: 586 infants were eligible and 463 were included in the study as they had assessment data at 12 months. Children were divided into two groups: immigrants' children and non-immigrants' children. The global prevalence of iron deficiency was 5.7% at 12 months. A significant difference for iron deficiency was noticed between the groups at 12 months (p = 0.01). Among risk factors, immigration (odds ratio 2.91; 95% CI 1.05-8.04) and unemployment (odds ratio 6.08; 95% CI 1.18-31.30) had the higher odds in the multivariable analysis. CONCLUSION: The prevalence of iron deficiency in the immigrant population is higher than in non-immigrants. Immigration and the category of employment are risk factors for iron deficiency, as starting baby cereals before 9 months is a protective factor. Good socioeconomic conditions in Switzerland, the quality of food for pregnant women and young infants may be the explanation. A study up to five years of age is necessary before drawing general conclusions on infancy.

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BACKGROUND: Intensification of pharmacotherapy in persons with poorly controlled chronic conditions has been proposed as a clinically meaningful process measure of quality. OBJECTIVE: To validate measures of treatment intensification by evaluating their associations with subsequent control in hypertension, hyperlipidemia, and diabetes mellitus across 35 medical facility populations in Kaiser Permanente, Northern California. DESIGN: Hierarchical analyses of associations of improvements in facility-level treatment intensification rates from 2001 to 2003 with patient-level risk factor levels at the end of 2003. PATIENTS: Members (515,072 and 626,130; age >20 years) with hypertension, hyperlipidemia, and/or diabetes mellitus in 2001 and 2003, respectively. MEASUREMENTS: Treatment intensification for each risk factor defined as an increase in number of drug classes prescribed, of dosage for at least 1 drug, or switching to a drug from another class within 3 months of observed poor risk factor control. RESULTS: Facility-level improvements in treatment intensification rates between 2001 and 2003 were strongly associated with greater likelihood of being in control at the end of 2003 (P < or = 0.05 for each risk factor) after adjustment for patient- and facility-level covariates. Compared with facility rankings based solely on control, addition of percentages of poorly controlled patients who received treatment intensification changed 2003 rankings substantially: 14%, 51%, and 29% of the facilities changed ranks by 5 or more positions for hypertension, hyperlipidemia, and diabetes, respectively. CONCLUSIONS: Treatment intensification is tightly linked to improved control. Thus, it deserves consideration as a process measure for motivating quality improvement and possibly for measuring clinical performance.

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Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

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INTRODUCTION: Dendritic cells (DCs) are the most important antigen-presenting cell population for activating antitumor T-cell responses; therefore, they offer a unique opportunity for specific targeting of tumors. AREAS COVERED: We will discuss the critical factors for the enhancement of DC vaccine efficacy: different DC subsets, types of in vitro DC manufacturing protocol, types of tumor antigen to be loaded and finally different adjuvants for activating them. We will cover potential combinatorial strategies with immunomodulatory therapies: depleting T-regulatory (Treg) cells, blocking VEGF and blocking inhibitory signals. Furthermore, recommendations to incorporate these criteria into DC-based tumor immunotherapy will be suggested. EXPERT OPINION: Monocyte-derived DCs are the most widely used DC subset in the clinic, whereas Langerhans cells and plasmacytoid DCs are two emerging DC subsets that are highly effective in eliciting cytotoxic T lymphocyte responses. Depending on the type of tumor antigens selected for loading DCs, it is important to optimize a protocol that will generate highly potent DCs. The future aim of DC-based immunotherapy is to combine it with one or more immunomodulatory therapies, for example, Treg cell depletion, VEGF blockage and T-cell checkpoint blockage, to elicit the most optimal antitumor immunity to induce long-term remission or even cure cancer patients.