Study of the effectiveness of first-line treatment in renal cell carcinoma.

The emergence of novel drugs corresponds with the determination of the effectiveness of the current treatments used in clinical practice. A retrospective observational study was conducted to evaluate the effectiveness of first-line treatments and to test the influence of the prognostic factors established using the Memorial Sloan-Kettering Cancer Center (MSKCC) and the analysis of Mekhail's study for two or more metastatic sites. The primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS) times. A total of 65 patients were enrolled and the mPFS and mOS of the patients treated with sunitinib (n=51) were 9.0 and 20.1 months, respectively, and for the patients treated with temsirolimus (n=14) these were 3.0 and 6.2 months, respectively. In the poor-prognosis (PP) group, a difference of 1.2 months (P=0.049) was found in mPFS depending on the first-line treatment. A difference of 4.1 months (P=0.023) was also found in mPFS when classified by histology (clear verses non-clear cell) in the sunitinib-treatment group. When stratified by the prognostic group, differences of >7 months (P<0.001) were found between the groups. Therefore, it was concluded that the effectiveness of the treatments was reduced compared to previous studies and differences were found in the PP group when classified by first-line drug and histology. Additionally, the influence of prognostic factors on OS and the value of stratifying patients using these factors have been confirmed.

Guía farmacoterapéutica de hospital : Sistema Sanitario Público de Andalucía 2014

Actualización enero de 2015. Esta guía se ha realizado en virtud de un convenio de colaboración entre el Servicio Andaluz de Salud y la Sociedad Andaluza de Famacéuticos de Hospital. Grupo hospitalario para la evaluación de medicamentos en Andalucía (GHEMA).

Normal weight obesity: relationship with lipids, glycaemic status, liver enzymes and inflammation

BACKGROUND AND AIMS: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI) and has been associated with early inflammation, but its relationship with cardiovascular risk factors await investigation. METHODS AND RESULTS: Cross-sectional study including 3213 women and 2912 men aged 35-75 years to assess the clinical characteristics of NWO in Lausanne, Switzerland. Body fat was assessed by bioimpedance. NWO was defined as a BMI<25 kg/m(2) and a % body fat ≥66(th) gender-specific percentiles. The prevalence of NWO was 5.4% in women and less than 3% in men, so the analysis was restricted to women. NWO women had a higher % of body fat than overweight women. After adjusting for age, smoking, educational level, physical activity and alcohol consumption, NWO women had higher blood pressure and lipid levels and a higher prevalence of dyslipidaemia (odds-ratio=1.90 [1.34-2.68]) and fasting hyperglycaemia (odds-ratio=1.63 [1.10-2.42]) than lean women, whereas no differences were found between NWO and overweight women. Conversely, no differences were found between NWO and lean women regarding levels of CRP, adiponectin and liver markers (alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase). Using other definitions of NWO led to similar conclusions, albeit some differences were no longer significant. CONCLUSION: NWO is almost nonexistent in men. Women with NWO present with higher cardiovascular risk factors than lean women, while no differences were found for liver or inflammatory markers. Specific screening of NWO might be necessary in order to implement cardiovascular prevention.

Addiction and arousal: the hypocretin connection

The hypocretins, also known as orexins, are two neuropeptides now commonly described as critical components to maintain and regulate the stability of arousal. Several lines of evidence have raised the hypothesis that hypocretin-producing neurons are part of the circuitries that mediate the hypothalamic response to acute stress. Intracerebral administration of hypocretin leads to a dose-related reinstatement of drug and food seeking behaviors. Furthermore, stress-induced reinstatement can be blocked with hypocretin receptor 1 antagonism. These results, together with recent data showing that hypocretin is critically involved in cocaine sensitization through the recruitment of NMDA receptors in the ventral tegmental area, strongly suggest that activation of hypocretin neurons play a critical role in the development of the addiction process. The activity of hypocretin neurons may affect addictive behavior by contributing to brain sensitization or by modulating the brain reward system. Hypocretinergic cells, in coordination with brain stress systems may lead to a vulnerable state that facilitates the resumption of drug seeking behavior. Hence, the hypocretinergic system is a new drug target that may be used to prevent relapse of drug seeking

Two cases of "cannabis acute psychosis" following the administration of oral cannabis.

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

Excessive alcohol consumption in young men: is there an association with their earlier family situation? A baseline-analysis of the C-SURF-study (Cohort Study on Substance Use Risk Factors).

AIMS: To determine whether parental factors earlier in life (parenting, single parent family, parental substance use problem) are associated with patterns of alcohol consumption among young men in Switzerland. METHODS: This analysis of a population based sample from the Cohort Study on Substance Use Risk Factors (C-SURF) included 5,990 young men (mean age 19.51 years), all attending a mandatory recruitment process for the army. These conscripts reported on parental monitoring and rule-setting, parental behaviour and family structure. The alcohol use pattern was assessed through abstention, risky single occasion drinking (RSOD), volume drinking and dependence. Furthermore, the impact of age, family socio-economic status, educational level of the parents, language region and civil status was analysed. RESULTS: A parental substance use problem was positively associated with volume drinking and alcohol dependence in young Swiss men. Active parenting corresponded negatively with RSOD, volume drinking and alcohol dependence. Single parent family was not associated with a different alcohol consumption pattern compared to standard family. CONCLUSION: Parental influences earlier in life such as active parenting (monitoring, rule-setting and knowing the whereabouts) and perceived parental substance use problem are associated with alcohol drinking behaviour in young male adults. Therefore, health professionals should stress the importance of active parenting and parental substance use prevention in alcohol prevention strategies.

Multifunctional ligands for application in Alzheimer’s Disease: molecular modelling and biological evaluation

Projecte de recerca elaborat a partir d’una estada a la University of British Columbia, Canadà, entre 2010 i 2012 La malaltia d'Alzheimer (MA) representa avui la forma més comuna de demència en la població envellida. Malgrat fa 100 anys que va ser descoberta, encara avui no existeix cap tractament preventiu i/o curatiu ni cap agent de diagnòstic que permeti valorar quantitativament l'evolució d'aquesta malaltia. L'objectiu en el que s'emmarca aquest treball és contribuir a aportar solucions al problema de la manca d'agents terapèutics i de diagnosi, unívocs i rigorosos, per a la MA. Des del camp de la química bioinorgànica és fàcil fixar-se en l'excessiva concentració d'ions Zn(II) i Cu(II) en els cervells de malalts de MA, plantejar-se la seva utilització com a dianes terapèutica i, en conseqüència, cercar agents quelants que evitin la formació de plaques senils o contribueixin a la seva dissolució. Si bé aquest va ser el punt de partida d’aquest projecte, els múltiples factors implicats en la patogènesi de la MA fan que el clàssic paradigma d’ ¨una molècula, una diana¨ limiti la capacitat de la molècula de combatre aquesta malaltia tan complexa. Per tant, un esforç considerable s’ha dedicat al disseny d’agentsmultifuncionals que combatin els múltiples factors que caracteritzen el desenvolupament de la MA. En el present treball s’han dissenyat agents multifuncionals inspirats en dos esquelets moleculars ben establers i coneguts en el camp de la química medicinal: la tioflavina-T (ThT) i la deferiprona (DFP). La utilització de tècniques in silico que inclouen càlculs farmacocinètics i modelatge molecular ha estat un procés cabdal per a l’avaluació dels millors candidats en base als següents requeriments: (a) compliment de determinades propietats farmacocinètiques que estableixin el seu possible ús com a fàrmac (b) hidrofobicitat adequada per travessar la BBB i (c) interacció amb el pèptid Aen solució.

Sustainable Development and Concrete Technology, May 2004

For a variety of reasons, the concrete construction industry is not sustainable. First, it consumes huge quantities of virgin materials. Second, the principal binder in concrete is portland cement, the production of which is a major contributor to greenhouse gas emissions that are implicated in global warming and climate change. Third, many concrete structures suffer from lack of durability which has an adverse effect on the resource productivity of the industry. Because the high-volume fly ash concrete system addresses all three sustainability issues, its adoption will enable the concrete construction industry to become more sustainable. In this paper, a brief review is presented of the theory and construction practice with concrete mixtures containing more than 50% fly ash by mass of the cementitious material. Mechanisms are discussed by which the incorporation of high volume of fly ash in concrete reduces the water demand, improves the workability, minimizes cracking due to thermal and drying shrinkage, and enhances durability to reinforcement corrosion, sulfate attack, and alkali-silica expansion. For countries like China and India, this technology can play an important role in meeting the huge demand for infrastructure in a sustainable manner.

Smoking and adolescence: Exploring tobacco consumption and related attitudes in three different age groups in Switzerland

The present study constitutes an investigation of tobacco consumption, related attitudes and individual differences in smoking or non-smoking behaviors in a sample of adolescents of different ages in the French-speaking part of Switzerland. We investigated three school-age groups (7th-grade, 9th-grade, and the second-year of high school) for differences in attitude and social and cognitive dimensions. We present both descriptive and inferential statistics. On an inferential level, we present a binary logistic regression-based model predicting risk of smoking. The resulting model most importantly suggests a strong relationship between smoking and alcohol consumption (both regular and sporadic). We interpret this result in terms of both the impact of the actual campaigns and the cognitive processes associated with adolescence.

Computerunterstützte Rigiditätsmessung zur Differenzierung psychopathologischer Gruppen [Computer-assisted determination of rigidity in the differentiation of psychopathologic groups]

The measurement of rigidity and perseveration respectively gets increasing importance in clinical psychodiagnostics. Recently we have developed a computer-assisted technique which allows to get information about inadequate persisting in psychic processes and behaviour within shortest time and to differentiate between psychopathological groups. 257 patients of both sexes who came for elucidation of their disorders to the department of clinical psychodiagnostics were investigated. The most significant differences between the groups were found in redundance of second degree (the patient has to press 10 buttons indiscriminately according to the beat of a metronom--standard condition) and in personal speed (the patient has to press 10 buttons as fast as possible--speed condition). Furthermore the psychopathological groups were ranged in the particular variables of rigidity according to their mean values and their average ranges the schizophrenics and effective psychoses were characterized by a high tendency of perseveration while the neurotics, patients with organic brain syndrome and alcohol and drug dependents showed more flexibility.

Nursing concepts and theories

The theory framework of nursing science is built in a dynamic process that arises from practice and is reproduced through research, mainly by analysis and development of concepts and theories. This study presents a theory reflection on nursing knowledge construction and points out subsidies for future studies in the area. The interrelation among theory, research, and clinical practice is required for continuous development of nursing as a profession and science. Ideally, the practice must be based on theory that is validated by research. Therefore, theory, research, and practice affect each other reciprocally and continuously.

Adherence To Diabetes Mellitus Treatments In Family Health Strategy Units

This cross-sectional study aimed to analyze the adherence to drug and non-drug treatments in 17 Family Health Strategy units. A total of 423 patients with type 2 diabetes mellitus were selected through stratified random sampling in Family Health Strategy units of a city in the state of Minas Gerais, Brazil, in 2010. The results showed that the prevalence rate of adherence to drug therapy was higher than 60% in the 17 units investigated; in relation to physical activity, adherence was higher than 60% in 58.8% units; and for the diet plan, there was no adherence in 52.9% units. Therefore, we concluded that adherence to drug therapy in most units was high and the practice of physical activity was heterogeneous, and in relation to diet adherence, it was low in all units. We recommend strengthening of institutional guidelines and educational strategies, in line with SUS guidelines, so that, professionals may face the challenges imposed by the lack of adherence.



Lost in translation : euro-compatibility, legal security, and the autonomous implementation of EU law in Switzerland

This article presents the legislative and judicial practice relating to the "autonomous implementation" of EU law in Switzerland. Given that "euro-compatibility" is the central consideration behind this legislative policy, one would expect Swiss authorities to have devised legislative and hermeneutical techniques guaranteeing high fidelity to EU "mother law". That is not the case, however, and as this article shows much is lost in the translation from EU to Swiss Law

Dietary folates and cancer risk in a network of case-control studies.

Background Folate deficiency leads to DNA damage and inadequate repair, caused by a decreased synthesis of thymidylate and purines. We analyzed the relationship between dietary folate intake and the risk of several cancers. Patients and methods The study is based on a network of case-control studies conducted in Italy and Switzerland in 1991-2009. The odds ratios (ORs) for dietary folate intake were estimated by multiple logistic regression models, adjusted for major identified confounding factors. Results For a few cancer sites, we found a significant inverse relation, with ORs for an increment of 100 μg/day of dietary folate of 0.65 for oropharyngeal (1467 cases), 0.58 for esophageal (505 cases), 0.83 for colorectal (2390 cases), 0.72 for pancreatic (326 cases), 0.67 for laryngeal (851 cases) and 0.87 for breast (3034 cases) cancers. The risk estimates were below unity, although not significantly, for cancers of the endometrium (OR = 0.87, 454 cases), ovary (OR = 0.86, 1031 cases), prostate (OR = 0.91, 1468 cases) and kidney (OR = 0.88, 767 cases), and was 1.00 for stomach cancer (230 cases). No material heterogeneity was found in strata of sex, age, smoking and alcohol drinking. Conclusions Our data support a real inverse association of dietary folate intake with the risk of several common cancers.

Cannabis use as a means of socialization?: new consumption patterns among heavy users

Purpose: After tobacco and alcohol, cannabis is the most used substance among adolescents in Switzerland. Our aim is to assess whether cannabis use has become an ordinary means of socialization. We hypothesize that cannabis consumption has become a normative, although still illegal, behavior. Methods: As part of a larger qualitative study aimed at assessing new ways [patterns] of cannabis consumption, 16 daily cannabis consumers (11 males) and 2 former heavy consumers (both females), aged 15 to 20 years, participated in interviews and focus groups. Data were transcribed verbatim and analyzed using Atlas.ti qualitative analysis software. Results: Most consumers define the beginning of their consumption as a moment when they made new friends. They commonly use cannabis in group settings, which encourages the belief that all adolescents use cannabis. Thus, cannabis is mainly identified as an everyday social act. Joints are smoked like cigarettes: at all times of the day, during or after school or work with peers, often starting at lunch break, and mostly in public places. Friends offer a joint in a group setting, much like beer in a bar, as a means of making contact. Consumption invariably increases while socializing on vacation: "During vacation, we smoke up to 10-15 joints a day; at the end we're just dead." Additionally, in order to obtain cannabis, consumers have to be part of the right networks; they generally have several dealers to assure their supply, buy and sell themselves, or practice group-buying. As a result, all friends or acquaintances of consumers are themselves cannabis users. For instance, 4 boys, who say they are best friends, always smoke together and that, in order to quit, "All four of us should say to ourselves, 'Okay, now, let's all stop smoking'. That would be the only solution. . .but it would be impossible!" The 2 former consumers state that when they started using cannabis, "I found myself little by little in a vicious circle where I saw only people who also smoked". When they quit, they separated from their group of friends: "Either you make new friends who don't smoke or you smoke." Conclusions: Discussions with consumers demonstrate a normative facet of cannabis consumption as part of teenage socialization. Consequently, cannabis consumers develop a significant dependency since a majority of their friends use cannabis and their consumption involves most of their daily social life. Our study highlights the need for clear messages about the harmful aspects of using this substance while also suggesting that cessation efforts should include helping users separate from their consumption milieu. Sources of Support: Dept. of Public Health of the canton of Vaud.