Antidoping programme and biological monitoring before and during the 2014 FIFA World Cup Brazil.

BACKGROUND: The FIFA has implemented an important antidoping programme for the 2014 FIFA World Cup. AIM: To perform the analyses before and during the World Cup with biological monitoring of blood and urine samples. METHODS: All qualified players from the 32 teams participating in the World Cup were tested out-of-competition. During the World Cup, 2-8 players per match were tested. Over 1000 samples were collected in total and analysed in the WADA accredited Laboratory of Lausanne. RESULTS: The quality of the analyses was at the required level as described in the WADA technical documents. The urinary steroid profiles of the players were stable and consistent with previously published papers on football players. During the competition, amphetamine was detected in a sample collected on a player who had a therapeutic use exemption for attention deficit hyperactivity disorder. The blood passport data showed no significant difference in haemoglobin values between out-of-competition and postmatch samples. CONCLUSIONS: Logistical issues linked to biological samples collection, and the overseas shipment during the World Cup did not impair the quality of the analyses, especially when used as the biological passport of football players.

Monitoring de la problématique du cannabis en Suisse: étude sentinelle: panels 2008 = Monitoring der Cannabisproblematik in der Schweiz: Sentinella-Studie: Panels 2008

A l'heure actuelle, le monitoring de la problématique du cannabis en Suisse constitue un ensemble de travaux qui permettent le suivi de la situation au niveau national et qui sont mis en oeuvre par un consortium d'instituts. Ce monitoring comprend l'étude présentée dans ce rapport, l'étude sentinelle. Elle s'intéresse à l'évolution de la situation en matière de cannabis ainsi qu'à la gestion de cette situation au niveau local. Ainsi, les observations relevées par des professionnels de terrain dans différents domaines (santé/social, école/formation professionnelle, police/justice) et dans quatre cantons suisses (St Gall, Tessin, Vaud, Zurich), dits "sentinelle", sont récoltées et analysées annuellement.

Household-based malaria control in a highly endemic area of Africa (Tanzania): determinants of transmission and disease and indicators for monitoring - Kilombero Malaria Project

The Kilombero Malaria Project (KMP) attemps to define opperationally useful indicators of levels of transmission and disease and health system relevant monitoring indicators to evaluate the impact of disease control at the community or health facility level. The KMP is longitudinal community based study (N = 1024) in rural Southern Tanzania, investigating risk factors for malarial morbidity and developing household based malaria control strategies. Biweekly morbidity and bimonthly serological, parasitological and drug consumption surveys are carried out in all study households. Mosquito densities are measured biweekly in 50 sentinel houses by timed light traps. Determinants of transmission and indicators of exposure were not strongly aggregated within households. Subjective morbidity (recalled fever), objective morbidity (elevated body temperature and high parasitaemia) and chloroquine consumption were strongly aggregated within a few households. Nested analysis of anti-NANP40 antibody suggest that only approximately 30% of the titer variance can explained by household clustering and that the largest proportion of antibody titer variability must be explained by non-measured behavioral determinants relating to an individual's level of exposure within a household. Indicators for evaluation and monitoring and outcome measures are described within the context of health service management to describe control measure output in terms of community effectiveness.

Monographies on drugs, which are frequently analysed in the course of Therapeutic Drug Monitoring

In 1995 the working group "Drug Monitoring" of the Swiss Society of Clinical Chemistry (SSCC) has already published a printed version of drug monographs, which are now newly compiled and presented in a standardised manner. The aim of these monographs is to give an overview on the most important informations that are necessary in order to request a drug analysis or is helpful to interpret the results. Therefore, the targeted audience are laboratory health professionals or the receivers of the reports. There is information provided on the indication for therapeutic drug monitoring, protein binding, metabolic pathways and enzymes involved, elimination half life time and elimination routes as well as information on therapeutic or toxic concentrations. Because preanalytical considerations are of particular importance for therapeutic drug monitoring, there is also information given at which time the determination of the drug concentration is reasonable and when steady-state concentrations are reached after changing the dose. Furthermore, the stability of the drug and its metabolite(s), respectively, after blood sampling is described. For readers with a specific interest, references to important publications are given. The number of the monographs will be continuously enlarged. The updated files are presented on the homepage of the SSCC (www.sscc.ch).

Robotic, fluoroscopic or EMG assisted pedicle screw insertion. A CT based comparative study

Introduction: In order to improve safety of pedicle screw placement several techniques have been developed. More recently robotically assisted pedicle insertion has been introduced aiming at increasing accuracy. The aim of this study was to compare this new technique with the two main pedicle insertion techniques in our unit namely fluoroscopically assisted vs EMG aided insertion. Material and methods: A total of 382 screws (78 thoracic,304 lumbar) were introduced in 64 patients (m/f = 1.37, equally distributed between insertion technique groups) by a single experienced spinal surgeon. From those, 64 (10 thoracic, 54 lumbar) were introduced in 11 patients using a miniature robotic device based on pre operative CT images under fluoroscopic control. 142 (4 thoracic, 138 lumbar) screws were introduced using lateral fluoroscopy in 27 patients while 176 (64 thoracic, 112 lumbar) screws in 26 patients were inserted using both fluoroscopy and EMG monitoring. There was no difference in the distribution of scoliotic spines between the 3 groups (n = 13). Screw position was assessed by an independent observer on CTs in axial, sagittal and coronal planes using the Rampersaud A to D classification. Data of lumbar and thoracic screws were processed separately as well as data obtained from axial, sagittal and coronal CT planes. Results: Intra- and interobserver reliability of the Rampersaud classification was moderate, (0.35 and 0.45 respectively) being the least good on axial plane. The total number of misplaced screws (C&D grades) was generally low (12 thoracic and 12 lumbar screws). Misplacement rates were same in straight and scoliotic spines. The only difference in misplacement rates was observed on axial and coronal images in the EMG assisted thoracic screw group with a higher proportion of C or D grades (p <0.05) in that group. Recorded compound muscle action potentials (CMAP) values of the inserted screws were 30.4 mA for the robot and 24.9mA for the freehand technique with a CI of 3.8 of the mean difference of 5.5 mA. Discussion: Robotic placement did improve the placement of thoracic screws but not that of lumbar screws possibly because our misplacement rates in general near that of published navigation series. Robotically assisted spine surgery might therefore enhance the safety of screw placement in particular in training settings were different users at various stages of their learning curve are involved in pedicle instrumentation.

Review of therapeutic drug monitoring of anticancer drugs part one - Cytotoxics.

Most anticancer drugs are characterised by a steep dose-response relationship and narrow therapeutic window. Inter-individual pharmacokinetic (PK) variability is often substantial. The most relevant PK parameter for cytotoxic drugs is the area under the plasma concentration versus time curve (AUC). Thus it is somewhat surprising that therapeutic drug monitoring (TDM) is still uncommon for the majority of agents. Goals of the review were to assess the rationale for more widely used TDM of cytotoxics in oncology. There are several reasons why TDM has never been fully implemented into daily oncology practice. These include difficulties in establishing appropriate concentration target ranges, common use of combination chemotherapies for many tumour types, analytical challenges with prodrugs, intracellular compounds, the paucity of published data from pharmacological trials and 'Day1=Day21' administration schedules. There are some specific situations for which these limitations are overcome, including high dose methotrexate, 5-fluorouracil infusion, mitotane and some high dose chemotherapy regimens. TDM in paediatric oncology represents an important challenge. Established TDM approaches includes the widely used anticancer agents carboplatin, busulfan and methotrexate, with 13-cis-retinoic acid also recently of interest. Considerable effort should be made to better define concentration-effect relationships and to utilise tools such as population PK/PD models and comparative randomised trials of classic dosing versus pharmacokinetically guided adaptive dosing. There is an important heterogeneity among clinical practices and a strong need to promote TDM guidelines among the oncological community.

Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring

OBJECTIVE: To reach a consensus on the clinical use of ambulatory blood pressure monitoring (ABPM). METHODS: A task force on the clinical use of ABPM wrote this overview in preparation for the Seventh International Consensus Conference (23-25 September 1999, Leuven, Belgium). This article was amended to account for opinions aired at the conference and to reflect the common ground reached in the discussions. POINTS OF CONSENSUS: The Riva Rocci/Korotkoff technique, although it is prone to error, is easy and cheap to perform and remains worldwide the standard procedure for measuring blood pressure. ABPM should be performed only with properly validated devices as an accessory to conventional measurement of blood pressure. Ambulatory recording of blood pressure requires considerable investment in equipment and training and its use for screening purposes cannot be recommended. ABPM is most useful for identifying patients with white-coat hypertension (WCH), also known as isolated clinic hypertension, which is arbitrarily defined as a clinic blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic. Some experts consider a daytime blood pressure below 130 mmHg systolic and 80 mmHg diastolic optimal. Whether WCH predisposes subjects to sustained hypertension remains debated. However, outcome is better correlated to the ambulatory blood pressure than it is to the conventional blood pressure. Antihypertensive drugs lower the clinic blood pressure in patients with WCH but not the ambulatory blood pressure, and also do not improve prognosis. Nevertheless, WCH should not be left unattended. If no previous cardiovascular complications are present, treatment could be limited to follow-up and hygienic measures, which should also account for risk factors other than hypertension. ABPM is superior to conventional measurement of blood pressure not only for selecting patients for antihypertensive drug treatment but also for assessing the effects both of non-pharmacological and of pharmacological therapy. The ambulatory blood pressure should be reduced by treatment to below the thresholds applied for diagnosing sustained hypertension. ABPM makes the diagnosis and treatment of nocturnal hypertension possible and is especially indicated for patients with borderline hypertension, the elderly, pregnant women, patients with treatment-resistant hypertension and patients with symptoms suggestive of hypotension. In centres with sufficient financial resources, ABPM could become part of the routine assessment of patients with clinic hypertension. For patients with WCH, it should be repeated at annual or 6-monthly intervals. Variation of blood pressure throughout the day can be monitored only by ABPM, but several advantages of the latter technique can also be obtained by self-measurement of blood pressure, a less expensive method that is probably better suited to primary practice and use in developing countries. CONCLUSIONS: ABPM or equivalent methods for tracing the white-coat effect should become part of the routine diagnostic and therapeutic procedures applied to treated and untreated patients with elevated clinic blood pressures. Results of long-term outcome trials should better establish the advantage of further integrating ABPM as an accessory to conventional sphygmomanometry into the routine care of hypertensive patients and should provide more definite information on the long-term cost-effectiveness. Because such trials are not likely to be funded by the pharmaceutical industry, governments and health insurance companies should take responsibility in this regard.

A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues.

Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during sport practice (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide, cotinine-N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3% amongst athletes. While this number may appear lower than the worldwide smoking prevalence of around 25%, focusing the study on selected sports highlighted more alarming findings. Indeed, active nicotine consumption in ice hockey, skiing, biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American football, wrestling and gymnastics was found to range between 19.0 and 55.6%. Therefore, considering the adverse effects of smoking on the respiratory tract and numerous health threats detrimental to sport practice at top level, likelihood of smokeless tobacco consumption for performance enhancement is greatly supported.

Evaluation of the impact of a therapeutic drug monitoring program in a Swiss University Hospital

Background and objective: Therapeutic Drug Monitoring (TDM) has been introduced early 1970 in our hospital (CHUV). It represents nowadays an important routine activity of the Division of Clinical Pharmacology and Toxicology (PCL), and its impact and utility for clinicians required assessment. This study thus evaluated the impact of TDM recommendations in terms of dosage regimen adaptation. Design: A prospective observational study was conducted over 5 weeks. The primary objective was to evaluate the application of our TDM recommendations and to identify potential factors associated to variations in their implementation. The secondary objective was to identify pre-analytical problems linked to the collection and processing of blood samples. Setting: Four representative clinical units at CHUV. Main outcome measure: Clinical data, drug related data (intake, collection and processing) and all information regarding the implementation of clinical recommendations were collected and analyzed by descriptive statistics. Results: A total of 241 blood measurement requests were collected, among which 105 triggered a recommendation. 37% of the recommendations delivered were applied, 25 % partially applied and 34% not applied. In 4% it was not applicable. The factors determinant for implementation were the clinical unit and the mode of transmission of the recommendation (written vs oral). No clear difference between types of drugs could be detected. Pre-analytical problems were not uncommon, mostly related to completion of request forms and delays in blood sampling (equilibration or steady-state not reached). We have identified 6% of inappropriate and unusable drug level measurements that could cause a substantial cost for the hospital. Conclusion: This survey highlighted a better implementation of TDM recommendations in clinical units where this routine is well integrated and understood by the medical staff. Our results emphasize the importance of communication with the nurse or the physician in charge, either to transmit clinical recommendations or to establish consensual therapeutic targets in specific conditions. Development of strong partnerships between clinical pharmacists or pharmacologists and clinical units would be beneficial to improve the impact of this clinical activity.

Sintonización dinámica de aplicaciones MPI

En la actualidad, la computación de altas prestaciones está siendo utilizada en multitud de campos científicos donde los distintos problemas estudiados se resuelven mediante aplicaciones paralelas/distribuidas. Estas aplicaciones requieren gran capacidad de cómputo, bien sea por la complejidad de los problemas o por la necesidad de solventar situaciones en tiempo real. Por lo tanto se debe aprovechar los recursos y altas capacidades computacionales de los sistemas paralelos en los que se ejecutan estas aplicaciones con el fin de obtener un buen rendimiento. Sin embargo, lograr este rendimiento en una aplicación ejecutándose en un sistema es una dura tarea que requiere un alto grado de experiencia, especialmente cuando se trata de aplicaciones que presentan un comportamiento dinámico o cuando se usan sistemas heterogéneos. En estos casos actualmente se plantea realizar una mejora de rendimiento automática y dinámica de las aplicaciones como mejor enfoque para el análisis del rendimiento. El presente trabajo de investigación se sitúa dentro de este ámbito de estudio y su objetivo principal es sintonizar dinámicamente mediante MATE (Monitoring, Analysis and Tuning Environment) una aplicación MPI empleada en computación de altas prestaciones que siga un paradigma Master/Worker. Las técnicas de sintonización integradas en MATE han sido desarrolladas a partir del estudio de un modelo de rendimiento que refleja los cuellos de botella propios de aplicaciones situadas bajo un paradigma Master/Worker: balanceo de carga y número de workers. La ejecución de la aplicación elegida bajo el control dinámico de MATE y de la estrategia de sintonización implementada ha permitido observar la adaptación del comportamiento de dicha aplicación a las condiciones actuales del sistema donde se ejecuta, obteniendo así una mejora de su rendimiento.

Predictive and distributed routing balancing (PR-DRB): high speed interconnection networks

Current parallel applications running on clusters require the use of an interconnection network to perform communications among all computing nodes available. Imbalance of communications can produce network congestion, reducing throughput and increasing latency, degrading the overall system performance. On the other hand, parallel applications running on these networks posses representative stages which allow their characterization, as well as repetitive behavior that can be identified on the basis of this characterization. This work presents the Predictive and Distributed Routing Balancing (PR-DRB), a new method developed to gradually control network congestion, based on paths expansion, traffic distribution and effective traffic load, in order to maintain low latency values. PR-DRB monitors messages latencies on intermediate routers, makes decisions about alternative paths and record communication pattern information encountered during congestion situation. Based on the concept of applications repetitiveness, best solution recorded are reapplied when saved communication pattern re-appears. Traffic congestion experiments were conducted in order to evaluate the performance of the method, and improvements were observed.