Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication.

The importance of direct and indirect alcohol markers to evaluate alcohol consumption in clinical and forensic settings is increasingly recognized. While some markers are used to prove abstinence from ethanol, other markers are suitable for detection of alcohol misuse. Phosphatidyl ethanol (PEth) is ranked among the latter. There is only little information about the correlation between PEth and other currently used markers (ethyl glucuronide, ethyl sulfate, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, and methanol) and about their decline during detoxification. To get more information, 18 alcohol-dependent patients in withdrawal therapy were monitored for these parameters in blood and urine for up to 19 days. There was no correlation between the different markers. PEth showed a rapid decrease at the beginning of the intervention, a slow decline after the first few days, and could still be detected after 19 days of abstinence from ethanol.

Swiss adolescents' and adults' perceptions of cannabis use : a qualitative study

Abstract Few studies have attempted to investigate the nature of adolescents' and adults' conceptions and perceptions of cannabis use. Our objectives were to explore adolescent and adult perception of use and misuse of cannabis, and their opinions and beliefs about the current legal context and preventive strategies. We used focus group dis¬cussions with four categories of stakeholders: younger (12-15 year old) adolescents, older (16-19 year old) adolescents, parents of teen¬agers and professionals working with young people. In some areas (legal framework, role of the media, importance of early preventive inter¬ventions), we found consensual attitudes and beliefs across the four groups of participants. In all four groups, participants did not have any consensual vision of the risks of cannabis use or the definition of misuse. In the area of the prevention of cannabis use/misuse, while parents focused on the potential role of professionals and the media, thus minimizing their own educa¬tional and preventive role, professionals stressed the importance of parental control and educa¬tion. Within the Swiss context, we conclude there exists an urgent need for information and clari¬fication of the issues linked with cannabis use and misuse directed at parents and professionals.

Estudio piloto sobre el manejo de la fluidoterapia intravenosa en pacientes adultos de un hospital de tercer nivel.

The purpose of intravenous fluid therapy (IFT) is to maintain or restore internal equilibrium by administering fluids and/or different electrolyte components. Its correct use and the prevention of complications arising from their misuse depend on the knowledge of the medical team on this subject. We analyzed this issue in different clinical areas of a tertiary hospital. MATERIAL AND METHODS We performed a descriptive cross-sectional pilot study via a questionnaire given to physicians specializing in internal medicine (IM) and digestive system surgery (SDS) who perform clinical practice in hospital units with unit dose drug dispensing system. We designed an anonymous questionnaire with 25 questions relative to knowledge of theory and practices, as well as the opinion of physicians regarding IFT. We evaluated the association between nominal qualitative variables with the Chi-square or Fisher's exact test. The behavior of the quantitative variables was assessed using the t-student test. The analysis of the data was generated using SAS/STAT, Version 9. RESULTS 28 questionnaires were collected from 13 surgeons and 15 digestive interns. Over 40% of specialists considered further education in IFT a necessity , especially regarding its prescription (SDS: 61.54%, IM: 71.43%). No statistically significant differences were found between the specialties in terms of perceived frequency of complications associated with IFT or in the frequency indication with the exception of hypovolemic shock, which is considered to be more prevalent in gastrointestinal surgery (p = 0.046). 90% of professionals prefer an individualized prescription. Statistically significant differences in terms of scores in the area of knowledge, with IM physicians achieving the highest scores (p = 0.014). There were also differences in attitude but they are not significant (p = 0.162). Knowledge of intravenous fluid increases with years of clinical experience (Spearman correlation coefficient = 0.386, p = 0.047). CONCLUSIONS The professionals who prescribe IFT perceive the need to design IFT training programs, together with the production of guides and consensus protocols.

Statistical discrimination of steroid profiles in doping control with support vector machines.

Due to their performance enhancing properties, use of anabolic steroids (e.g. testosterone, nandrolone, etc.) is banned in elite sports. Therefore, doping control laboratories accredited by the World Anti-Doping Agency (WADA) screen among others for these prohibited substances in urine. It is particularly challenging to detect misuse with naturally occurring anabolic steroids such as testosterone (T), which is a popular ergogenic agent in sports and society. To screen for misuse with these compounds, drug testing laboratories monitor the urinary concentrations of endogenous steroid metabolites and their ratios, which constitute the steroid profile and compare them with reference ranges to detect unnaturally high values. However, the interpretation of the steroid profile is difficult due to large inter-individual variances, various confounding factors and different endogenous steroids marketed that influence the steroid profile in various ways. A support vector machine (SVM) algorithm was developed to statistically evaluate urinary steroid profiles composed of an extended range of steroid profile metabolites. This model makes the interpretation of the analytical data in the quest for deviating steroid profiles feasible and shows its versatility towards different kinds of misused endogenous steroids. The SVM model outperforms the current biomarkers with respect to detection sensitivity and accuracy, particularly when it is coupled to individual data as stored in the Athlete Biological Passport.

Some conceptual difficulties regarding "net" multipliers

Multipliers are routinely used for impact evaluation of private projects and public policies at the national and subnational levels. Oosterhaven and Stelder (2002) correctly pointed out the misuse of standard 'gross' multipliers and proposed the concept of 'net' multiplier as a solution to this bad practice. We prove their proposal is not well founded. We do so by showing that supporting theorems are faulty in enunciation and demonstration. The proofs are flawed due to an analytical error but the theorems themselves cannot be salvaged as generic, non-curiosum counterexamples demonstrate. We also provide a general analytical framework for multipliers and, using it, we show that standard 'gross' multipliers are all that is needed within the interindustry model since they follow the causal logic of the economic model, are well defined and independent of exogenous shocks, and are interpretable as predictors for change.

The association between alcohol screening scores and health status in male veterans.

OBJECTIVES: Alcohol use is associated with self-reported health status. However, little is known about the concurrent association between alcohol screening scores and patient perception of health. We evaluated this association in a sample of primarily older male veterans.METHODS: This secondary, cross-sectional analysis included male general medicine outpatients from 7 VA medical centers who returned mailed questionnaires. Screening scores from the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire were divided into 6 categories (0, 1­3, 4­5, 6­7, 8­9, and 10­12). Outcomes included scores on the 8 subscales and 2 component scores of the 36-item Short Form Health Survey (SF-36). Unadjusted and adjusted linear regression models were fit to characterize the association between AUDIT-C categories and SF-36 scores. Models were adjusted for demographic characteristics, smoking, and site?both alone and in combination with 14 self-reported comorbid conditions.RESULTS: Male respondents (n = 24,531; mean age = 63.6 years) represented 69% of those surveyed with the SF-36. After adjustment, a quadratic (inverted U-shaped) relationship was demonstrated between AUDIT-C categories and all SF-36 scores such that patients with AUDIT-C scores 4­5 or 6­7 reported the highest health status, and patients with AUDIT-C scores 0, 8­9, and =10 reported the lowest health status.CONCLUSIONS: Across all measures of health status, patients with the most severe alcohol misuse had significantly poorer health status than those who screened positive for alcohol misuse at mild or moderate levels of severity. The relatively good health status reported by patients with mild-moderate alcohol misuse might interfere with clinicians' acceptance and adoption of guidelines recommending that they counsel these patients about their drinking.

Effectiveness of interventions targeting frequent users of emergency departments: a systematic review.

STUDY OBJECTIVE: Frequent users of emergency departments (EDs) are a relatively small group of vulnerable patients accounting for a disproportionally high number of ED visits. Our objective is to perform a systematic review of the type and effectiveness of interventions to reduce the number of ED visits by frequent users. METHODS: We searched MEDLINE, EMBASE, CINAHL, PsychINFO, the Cochrane Library, and ISI Web of Science for randomized controlled trials, nonrandomized controlled trials, interrupted time series, and controlled and noncontrolled before-and-after studies describing interventions targeting adult frequent users of EDs. Primary outcome of interest was the reduction in ED use. We also explored costs analyses and various clinical (alcohol and drug use, psychiatric symptoms, mortality) and social (homelessness, insurance status, social security support) outcomes. RESULTS: We included 11 studies (3 randomized controlled trials, 2 controlled and 6 noncontrolled before-and-after studies). Heterogeneity in both study designs and definitions of frequent users precluded meta-analyses of the results. The most studied intervention was case management (n=7). Only 1 of 3 randomized controlled trials showed a significant reduction in ED use compared with usual care. Six of the 8 before-and-after studies reported a significant reduction in ED use, and 1 study showed a significant increase. ED cost reductions were demonstrated in 3 studies. Social outcomes such as reduction of homelessness were favorable in 3 of 3 studies, and clinical outcomes trended toward positive results in 2 of 3 studies. CONCLUSION: Interventions targeting frequent users may reduce ED use. Case management, the most frequently described intervention, reduced ED costs and seemed to improve social and clinical outcomes. It appears to be beneficial to patients and justifiable for hospitals to implement case management for frequent users in the framework of a clear and consensual definition of frequent users and standardized outcome measures.

Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module.

Steroid profiles of professional soccer players: an international comparative study.

BACKGROUND AND OBJECTIVES: Urinary steroid profiling is used in doping controls to detect testosterone abuse. A testosterone over epitestosterone (T/E) ratio exceeding 4.0 is considered as suspicious of testosterone administration, irrespectively of individual heterogeneous factors such as the athlete's ethnicity. A deletion polymorphism in the UGT2B17 gene was demonstrated to account for a significant part of the interindividual variability in the T/E between Caucasians and Asians. Here, the variability of urinary steroid profiles was examined in a widely heterogeneous cohort of professional soccer players. Method: The steroid profile of 57 Africans, 32 Asians, 50 Caucasians and 32 Hispanics was determined by gas chromatography-mass spectrometry. RESULTS: Significant differences have been observed between all ethnic groups. After estimation of the prevalence of the UGT2B17 deletion/deletion genotype (African: 22%; Asian: 81%; Caucasian: 10%; Hispanic: 7%), ethnic-specific thresholds were developed for a specificity of 99% for the T/E (African: 5.6; Asian: 3.8; Caucasian: 5.7; Hispanic: 5.8). Finally, another polymorphism could be hypothesised in Asians based on specific concentration ratio of 5alpha-/5beta-androstane-3alpha,17beta-diol in urine. CONCLUSION: These results demonstrate that a unique and non-specific threshold to evidence testosterone misuse is not fit for purpose. An athlete's endocrinological passport consisting of a longitudinal follow-up together with the ethnicity and/or the genotype would strongly enhance the detection of testosterone abuse. Finally, additional genotyping studies should be undertaken to determine whether the remaining unexplained disparities have an environmental or a genetic origin.

Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study.

BACKGROUND/AIMS: Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. METHODS: IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres. RESULTS: A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. CONCLUSION: The subset of IMPROVE data presented gives a present-day, real-life overview of the OMT landscape in Switzerland. It represents a valuable resource for policy makers, key opinion leaders and drug addiction researchers and will be a useful basis for improving the current Swiss OMT model.

Health risk behaviors in adolescents with chronic conditions

OBJECTIVE: The objective of this study was to compare the frequency of risk behaviors and to measure the extent of co-occurrence of these behaviors in chronically ill and healthy adolescents. METHODS: Data were drawn from the 2002 Swiss Multicenter Adolescent Survey on Health database, a nationally representative survey of 7548 adolescents in postmandatory school aged 16 to 20 years. There were 760 subjects who reported a chronic illness and/or a disability. The comparison group consisted of 6493 subjects who answered negatively to both questions. We defined 8 risk behaviors: daily smoking, alcohol misuse, current cannabis use, current use of any other illegal drug, early sexual debut, eating disorder, violent acts, and antisocial acts. We analyzed each behavior and the sum of behaviors, controlling for age, gender, academic track, parents' education level, depression, and health status. Results are given as adjusted odds ratios using the comparison group as the reference category. RESULTS: Youth with a chronic condition were more likely to smoke daily, to be current cannabis users, and to have performed violent or antisocial acts. Youth with a chronic condition were also more likely to report 3 or >or=4 risk behaviors. CONCLUSIONS: These results indicate that having a chronic condition carries additional risks for engaging in health risk behaviors and emphasize the importance of health risk screening and preventive counseling for young people in general and among those suffering from chronic conditions in particular.

On a series of Goldbach and Euler

Theorem 1 of Euler s paper of 1737 'Variae Observationes Circa Series Infinitas', states the astonishing result that the series of all unit fractions whose denominators are perfect powers of integers minus unity has sum one. Euler attributes the Theorem to Goldbach. The proof is one of those examples of misuse of divergent series to obtain correct results so frequent during the seventeenth and eighteenth centuries. We examine this proof closelyand, with the help of some insight provided by a modern (and completely dierent) proof of the Goldbach-Euler Theorem, we present a rational reconstruction in terms which could be considered rigorous by modern Weierstrassian standards. At the same time, with a few ideas borrowed from nonstandard analysis we see how the same reconstruction can be also be considered rigorous by modern Robinsonian standards. This last approach, though, is completely in tune with Goldbach and Euler s proof. We hope to convince the reader then how, a few simple ideas from nonstandard analysis, vindicate Euler's work.

Drug use and suicide attempts: the role of personality factors.

This study on suicide attempts is part of a large research project on dependent behavior in adolescents and young adults. 228 subjects aged 14-25 (107 "drug abusers," 121 controls) from the French speaking part of Switzerland were evaluated on the basis of a semi-structured interview (Mini International Neuropsychiatric Interview), enabling a DSM-IV diagnosis, and self-reports (SSS by Zuckermann, MMPI-2, IDI by Hirschfeld). 31.5% of "drug abuser" males and 41.2% of "drug abuser" females committed one or more suicide attempts. The results of a logistic regression show that the significant factor explaining suicide attempts in drug users is emotional reliance for males and experience-seeking for females.

Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009

Different types of cell death are often defined by morphological criteria, without a clear reference to precise biochemical mechanisms. The Nomenclature Committee on Cell Death (NCCD) proposes unified criteria for the definition of cell death and of its different morphologies, while formulating several caveats against the misuse of words and concepts that slow down progress in the area of cell death research. Authors, reviewers and editors of scientific periodicals are invited to abandon expressions like 'percentage apoptosis' and to replace them with more accurate descriptions of the biochemical and cellular parameters that are actually measured. Moreover, at the present stage, it should be accepted that caspase-independent mechanisms can cooperate with (or substitute for) caspases in the execution of lethal signaling pathways and that 'autophagic cell death' is a type of cell death occurring together with (but not necessarily by) autophagic vacuolization. This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including 'entosis', 'mitotic catastrophe', 'necrosis', 'necroptosis' and 'pyroptosis'.

Human growth hormone doping in sport.

BACKGROUND AND OBJECTIVES: Recombinant human growth hormone (rhGH) has been on the list of forbidden substances since availability of its recombinant form improved in the early 1990s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products (androgens, erythropoietin, etc.). The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: the indirect method, which measures a combination of several factors in the biological cascade affected by administration of GH; and the direct method, which measures the difference between the circulating and the recombinant (represented by the unique 22 kD molecule) forms of GH. This article gives an overview of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated. METHODS: Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. RESULTS AND CONCLUSION: The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed. Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. hGH doping is a major challenge in the fight against doping. The effect of exercise on hGH and its short half-life are still presenting difficulties during doping analysis. To date the most promising method appears to be the direct approach utilising immunoassays.