Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance.

Therapeutic drug monitoring (TDM) and pharmacogenetic tests play a major role in minimising adverse drug reactions and enhancing optimal therapeutic response. The response to medication varies greatly between individuals, according to genetic constitution, age, sex, co-morbidities, environmental factors including diet and lifestyle (e.g. smoking and alcohol intake), and drug-related factors such as pharmacokinetic or pharmacodynamic drug-drug interactions. Most adverse drug reactions are type A reactions, i.e. plasma-level dependent, and represent one of the major causes of hospitalisation, in some cases leading to death. However, they may be avoidable to some extent if pharmacokinetic and pharmacogenetic factors are taken into consideration. This article provides a review of the literature and describes how to apply and interpret TDM and certain pharmacogenetic tests and is illustrated by case reports. An algorithm on the use of TDM and pharmacogenetic tests to help characterise adverse drug reactions is also presented. Although, in the scientific community, differences in drug response are increasingly recognised, there is an urgent need to translate this knowledge into clinical recommendations. Databases on drug-drug interactions and the impact of pharmacogenetic polymorphisms and adverse drug reaction information systems will be helpful to guide clinicians in individualised treatment choices.

Apport de la pH-impédancemétrie au diagnostic du reflux gastro- oesophagien et de la dysphagie [Advantages of pH-impedance monitoring in gastroesophageal reflux and dysphagia investigations]

Les manifestations ORL du reflux gastro-œsophagien sont fréquentes. La pH-impédancemétrie permet d’évaluer des reflux acides ou non acides et de déterminer leur extension proximale. A la lumière de deux patients de notre collectif, nous observons une corrélation entre reflux non acide et symptômes ORL dans le premier cas et une suppression acide insuffisante dans le deuxième cas. Ces résultats nous orientent vers un traitement spécifique complémentaire aux inhibiteurs de la pompe à protons. La pH-impédancemétrie détecte les reflux aussi bien acides que non acides, et analyse la concordance entre les symptômes et les épisodes de reflux. Elle permet ainsi une meilleure compréhension des manifestations ORL du reflux gastro-œsophagien et une prise en charge thérapeutique mieux adaptée. ENT symptoms of gastro-esophageal reflux are frequent. pH-impedance can detect acid and non-acid reflux and measure their proximal extension. The technique identifies the refluxate by changes in impedance. We discuss 2 clinical situations where correlation of symptoms could be explained by a non-acid reflux in the first case, and a lack of acid suppression in the second case, respectively. These results lead to a specific additional treatment to proton pump inhibitors (PPI). This technology provides a better understanding of the pathogenesis of reflux laryngitis, and affords the prescription of PPI on a proven diagnosis. Detection of non-acid reflux leads to an optimized medical treatment.

Monitoring and failure mechanism interpretation of an unstable slope in Southern Switzerland based on terrestrial laser scanner

We present the application of terrestrial laser scanning (TLS) for the monitoring and characterization of an active landslide area in Val Canaria (Ticino, Southern Swiss Alps). At catchment scale, the study area is affected by a large Deep Seated Gravitational Slope Deformation (DSGSD) area presenting, in the lower boundary, several retrogressive landslides active since the 1990s. Due to its frequent landslide events this area was periodically monitored by TLS since 2006. Periodic acquisitions provided new information on 3D displacements at the bottom of slope and the detection of centimetre to decimetre level scale changes (e.g. rockfall and pre-failure deformations). In October 2009, a major slope collapse occured at the bottom of the most unstable area. Based on the comparison between TLS data before and after the collapse, we carried out a detailed failure mechanism analysis and volume calculation.

Effect of Video Camera-Based Remote Roadway Condition Monitoring on Snow Removal-Related Maintenance Operations. 2014

Remote monitoring through the use of cameras is widely utilized for traffic operation, but has not been utilized widely for roadway maintenance operations. The Utah Department of Transportation (UDOT) has implemented a new remote monitoring system, referred to as a Cloud-enabled Remote Video Streaming (CRVS) camera system for snow removal-related maintenance operations in the winter. The purpose of this study was to evaluate the effectiveness of the use of the CRVS camera system in snow removal-related maintenance operations. This study was conducted in two parts: opinion surveys of maintenance station supervisors and an analysis on snow removal-related maintenance costs. The responses to the opinion surveys mostly displayed positive reviews of the use of the CRVS cameras. On a scale of 1 (least effective) to 5 (most effective), the average overall effectiveness given by the station supervisors was 4.3. An expedition trip for this study was defined as a trip that was made to just check the roadways if snow-removal was necessary. The average of the responses received from surveys was calculated to be a 33 percent reduction in expedition trips. For the second part of this study, an analysis was performed on the snow removal-related maintenance cost data provided by UDOT to see if the installation of a CRVS camera had an effect in reducing expedition trips. This expedition cost comparison was performed for 10 sets of maintenance stations within Utah. It was difficult to make any definitive inferences from the comparison of expedition costs over the years for which precipitation and expedition cost data were available; hence a statistical analysis was performed using the Mixed Model ANOVA. This analysis resulted in an average of 14 percent higher ratio of expedition costs at maintenance stations with a CRVS camera before the installation of the camera compared to the ratio of expedition costs after the installation of the camera. This difference was not proven to be statistically significant at the 95 percent confident level, but indicated that the installation of CRVS cameras was on the average helpful in reducing expedition costs and may be considered practically significant. It is recommended that more detailed and consistent maintenance cost records be prepared for accurate analysis of cost records for this type of study in the future.

Ambulatory blood pressure monitoring in the elderly hypertensive patient.

In this retrospective analysis, we assessed the usefulness of ambulatory blood pressure monitoring in the evaluation of elderly hypertensive patients. Thirty-eight untreated and 31 treated hypertensives aged 70 years or more had a systolic blood pressure greater than or equal to 160 mmHg and/or a diastolic blood pressure greater than or equal to 95 mmHg in the clinic. All 69 patients underwent blood pressure monitoring during their customary daily activities using a portable semi-automatic blood pressure recorder (Remier M2000). The mean of all blood pressures obtained with this device was taken as the ambulatory recorded blood pressure. Recorded blood pressures were greater than or equal to 160 mmHg systolic and greater than or equal to 90 mmHg diastolic in 17 untreated and 17 treated patients. In these patients, the introduction of antihypertensive therapy, or its modification, markedly reduced blood pressure during a 4-8 month follow-up. A further 21 untreated and 14 treated patients had recorded blood pressures of less than 160/90 mmHg. The treatment status of these patients was left unchanged for 4-8 months of follow-up. Nevertheless, office blood pressure in these groups, with no change in treatment, decreased significantly during the observation period. At the last visit to the outpatient clinic, there was no significant difference in blood pressure between the four subgroups of patients. Thus, ambulatory blood pressure monitoring appears to be useful in the elderly hypertensive patient in detecting those patients whose blood pressure is elevated only in the clinic. Blood pressure profiles obtained outside the clinic may therefore be useful in making therapeutic decisions in the aged hypertensive.

Parental monitoring: an easy way to decrease adolescent substance use?

Objective: To examine whether the level of parental monitoring is associated with substance use among Swiss adolescents, and to assess whether this effect remains when these adolescents have consuming peers. Methods: Nationally representative sample from the Swiss participation in the 2007 European School Project on Alcohol and Other Drugs (ESPAD) survey, which included 7611 adolescents issued from public schools (8th-10th grades). Four levels of parental control were created and four substances (tobacco, alcohol, cannabis and ecstasy) were analyzed. All significant variables at the bivariate level were included in the multivariate analysis. Results: Most adolescents had a high level of parental monitoring and that was associated with younger age, being female, high socioeconomic status, intact family structure and a satisfactory relationship with mother, father and peers. Globally, substance use decreased as parental monitoring increased and high parental monitoring decreased having consuming peers. Results remained essentially the same when consuming peers were added in the analysis. Conclusions: Parental monitoring has positive effects on adolescent substance use with a reduction of consumption and a lower association with consuming peers, which seems to protect adolescents against their potential negative influence. Encouraging parents to monitor their adolescents' activities and friendships by establishing rules about what is allowed or not are simple ways to limit the negative influence of consuming peers on adolescent substance use.

Soluble MHC-peptide complexes: tools for the monitoring of T cell responses in clinical trials and basic research.

Soluble MHC-peptide complexes, commonly known as tetramers, allow the detection and isolation of antigen-specific T cells. Although other types of soluble MHC-peptide complexes have been introduced, the most commonly used MHC class I staining reagents are those originally described by Altman and Davis. As these reagents have become an essential tool for T cell analysis, it is important to have a large repertoire of such reagents to cover a broad range of applications in cancer research and clinical trials. Our tetramer collection currently comprises 228 human and 60 mouse tetramers and new reagents are continuously being added. For the MHC II tetramers, the list currently contains 21 human (HLA-DR, DQ and DP) and 5 mouse (I-A(b)) tetramers. Quantitative enumeration of antigen-specific T cells by tetramer staining, especially at low frequencies, critically depends on the quality of the tetramers and on the staining procedures. For conclusive longitudinal monitoring, standardized reagents and analysis protocols need to be used. This is especially true for the monitoring of antigen-specific CD4+ T cells, as there are large variations in the quality of MHC II tetramers and staining conditions. This commentary provides an overview of our tetramer collection and indications on how tetramers should be used to obtain optimal results.

Automated Traffic/Truck Weight Monitoring Equipment (Weigh-in-Motion), HR-282, 1988

This report documents work undertaken in the demonstration of a low-cost Automatic Weight and Classification System (AWACS). An AWACS procurement specification and details of the results of the project are also included. The intent of the project is to support and encourage transferring research knowledge to state and local agencies and manufacturers through field demonstrations. Presently available, Weigh-in-Motion and Classification Systems are typically too expensive to permit the wide deployment necessary to obtain representative vehicle data. Piezo electric technology has been used in the United Kingdom and Europe and is believed to be the basic element in a low-cost AWACS. Low-cost systems have been installed at two sites, one in Portland Cement Concrete (PCC) pavement in Iowa and the other in Asphaltic Cement Concrete (ACC) pavement in Minnesota to provide experience with both types of pavement. The systems provide axle weights, gross vehicle weight, axle spacing, vehicle classification, vehicle speed, vehicle count, and time of arrival. In addition, system self-calibration and a method to predict contact tire pressure is included in the system design. The study has shown that in the PCC pavement, the AWACS is capable of meeting the needs of state and federal highway agencies, producing accuracies comparable to many current commercial WIM devices. This is being achieved at a procurement cost of substantially less than currently available equipment. In the ACC pavement the accuracies were less than those observed in the PCC pavement which is concluded to result from a low pavement rigidity at this site. Further work is needed to assess the AWACS performance at a range of sites in ACC pavements.