Thorax, pelvis and hip pattern in the frontal plane during walking in unilateral transtibial amputees: biomechanical analysis.

BACKGROUND Lower limb amputees exhibit postural control deficits during standing which can affect their walking ability. OBJECTIVES The primary purpose of the present study was to analyze the thorax, pelvis, and hip kinematics and the hip internal moment in the frontal plane during gait in subjects with Unilateral Transtibial Amputation (UTA). METHOD The participants included 25 people with UTA and 25 non-amputees as control subjects. Gait analysis was performed using the Vicon(r) Motion System. We analyzed the motion of the thorax, pelvis, and hip (kinematics) as well as the hip internal moment in the frontal plane. RESULTS The second peak of the hip abductor moment was significantly lower on the prosthetic side than on the sound side (p=.01) and the control side (right: p=.01; left: p=.01). During middle stance, the opposite side of the pelvis was higher on the prosthetic side compared to the control side (right: p=.01: left: p=.01). CONCLUSIONS The joint internal moment at the hip in the frontal plane was lower on the prosthetic side than on the sound side or the control side. Thorax and pelvis kinematics were altered during the stance phase on the prosthetic side, presumably because there are mechanisms which affect postural control during walking.

Modèle et application pour la génération automatique de parcours d'apprentissage personnalisés à partir de sources de confiance

Résumé Lors d'une recherche d'information, l'apprenant est très souvent confronté à des problèmes de guidage et de personnalisation. Ceux-ci sont d'autant plus importants que la recherche se fait dans un environnement ouvert tel que le Web. En effet, dans ce cas, il n'y a actuellement pas de contrôle de pertinence sur les ressources proposées pas plus que sur l'adéquation réelle aux besoins spécifiques de l'apprenant. A travers l'étude de l'état de l'art, nous avons constaté l'absence d'un modèle de référence qui traite des problématiques liées (i) d'une part aux ressources d'apprentissage notamment à l'hétérogénéité de la structure et de la description et à la protection en terme de droits d'auteur et (ii) d'autre part à l'apprenant en tant qu'utilisateur notamment l'acquisition des éléments le caractérisant et la stratégie d'adaptation à lui offrir. Notre objectif est de proposer un système adaptatif à base de ressources d'apprentissage issues d'un environnement à ouverture contrôlée. Celui-ci permet de générer automatiquement sans l'intervention d'un expert pédagogue un parcours d'apprentissage personnalisé à partir de ressources rendues disponibles par le biais de sources de confiance. L'originalité de notre travail réside dans la proposition d'un modèle de référence dit de Lausanne qui est basé sur ce que nous considérons comme étant les meilleures pratiques des communautés : (i) du Web en terme de moyens d'ouverture, (ii) de l'hypermédia adaptatif en terme de stratégie d'adaptation et (iii) de l'apprentissage à distance en terme de manipulation des ressources d'apprentissage. Dans notre modèle, la génération des parcours personnalisés se fait sur la base (i) de ressources d'apprentissage indexées et dont le degré de granularité en favorise le partage et la réutilisation. Les sources de confiance utilisées en garantissent l'utilité et la qualité. (ii) de caractéristiques de l'utilisateur, compatibles avec les standards existants, permettant le passage de l'apprenant d'un environnement à un autre. (iii) d'une adaptation à la fois individuelle et sociale. Pour cela, le modèle de Lausanne propose : (i) d'utiliser ISO/MLR (Metadata for Learning Resources) comme formalisme de description. (ii) de décrire le modèle d'utilisateur avec XUN1 (eXtended User Model), notre proposition d'un modèle compatible avec les standards IEEE/PAPI et IMS/LIP. (iii) d'adapter l'algorithme des fourmis au contexte de l'apprentissage à distance afin de générer des parcours personnalisés. La dimension individuelle est aussi prise en compte par la mise en correspondance de MLR et de XUM. Pour valider notre modèle, nous avons développé une application et testé plusieurs scenarii mettant en action des utilisateurs différents à des moments différents. Nous avons ensuite procédé à des comparaisons entre ce que retourne le système et ce que suggère l'expert. Les résultats s'étant avérés satisfaisants dans la mesure où à chaque fois le système retourne un parcours semblable à celui qu'aurait proposé l'expert, nous sommes confortées dans notre approche.

Protocolo de investigación del atlas de mortalidad de las capitales de provincia de Andalucía y Cataluña (Proyecto AMCAC).

The aim of this work is to make known the multicentric project AMCAC, whose objective is to describe the geographical distribution of mortality from all causes in census groups of the provincial capitals of Andalusia and Catalonia during 1992-2002 and 1994-2000 respectively, and to study the relationship between the sociodemographic characteristics of the census groups and mortality. This is an ecological study in which the analytical unit is the census group. The data correspond to 298,731 individuals (152,913 men and 145,818 women) who died during the study periods in the towns of Almeria, Barcelona, Cadiz, Cordoba, Girona, Granada, Huelva, Jaen, Lleida, Malaga, Seville and Tarragona during the study periods. The dependent variable is the number of deaths observed per census group. The independent variables are the percentage of unemployment, illiteracy and manual workers. Estimation of the moderated relative risk and the study of the associations among the sociodemographic characteristics of the census groups and the mortality will be done for each town and each sex using the Besag-York-Mollie model. Dissemination of the results will help to improve and broaden knowledge about the population's health, and will provide an important starting point to establish the influence of contextual variables on the health of urban populations.

Características de la familia de origen y de la familia formada por las médicas y los médicos de familia de Andalucía.

BACKGROUND The origin and formed family characteristics are related to physician's professional career. The purpose of this study was to know and compare by sex the characteristics of the origin family and formed family of women and men family physician in Andalusia. METHODS Cross sectional and multicenter study. SETTING Urban primary health care centres from Andalusian province capitals. PARTICIPANTS Physician of primary health care centres. INCLUSION CRITERIA at least one year using computerized medical history with the same quota patients. Multistage random sample, 88 primary health care centres and 500 physicians, 50% of both sexes (alpha=5%, power=90%, precision=15%). Postal auto administrated questionnaire. VARIABLES sex, age, tutor of resident in family medicine, last father's activity, last mother's activity, number of brothers or sisters, family situation, last couple's activity (if any), to have or not children. RESULTS 73.6 % responses. In no responses there weren't differences of sex neither tutor of resident in family medicine. Mean age: women physicians 49.5 +/- 4.3 and men physician 51.3 +/- 4.9 (p= or < 0.005). Postgraduate formation in family medicine: 42.2% of women and 33.3% of men (p=0.016). Live alone: 6.1% of women physician and 2.7% men physician (p=0.005). Live alone with children 9.9% of women and 2.2% of men (p=0.005). 16.5% of women and 10.2% of men don t have children (p=0.077). 21.1% of men physician s couples work only at home vs. 0.1% of women physician s couples (p= or < 0.005). 46% of women physician s couples is also physician vs. 22% of men physician s couples (p= or < 0.005). No significant differences registered in parent s activities neither in the number of brother or sisters. CONCLUSION There are no significant differences in physician s origin family. However important differences in the characteristics of formed family are observed in both sexes.

Participación social en salud: conceptos de usuarios, líderes comunitarios, gestores y formuladores de políticas en Colombia. Una mirada cualitativa.

BACKGROUND Health sector reforms taking place in Colombia during the Nineties included policies to promote social participation in the health system, which is considered essential to its functioning. The aim of this article is to analyse the meaning and the significance of participation in health for the different social actors involved in implementing policies in Colombia. METHODS A qualitative, descriptive, exploratory study was carried out using focal groups (FG) and semi-structured individual interviews (I) of the different social actors: 210 users (FG), 40 community leaders (FG), 3 policy makers (E) and 36 healthcare professionals (E). A carried out analysis was content up of the contents. The study area corresponded to the municipalities of Tulua and Palmira in Colombia. RESULTS The concept of participation was interpreted differently depending on the actor studied: for users and leaders the concept referred to contributing ideas, presence in social spaces, solidarity and frequently, and use of the health services. Healthcare professionals considered the activities carried out by institutions together with the community as social participation, the use of services and affiliation to the health system. Policy markers considered participation to concern evaluation and control of the health services by the community, to improve its quality. CONCLUSIONS The different concepts of participation reveal dif ferences between the content of the policy and how it is understood and interpreted by the different social actors in their interaction with the health services. These different perspectives must be taken into account to develop a link between society and the health services.

Revisión de los trabajos publicados sobre promoción de la salud en jóvenes españoles.

The objective of this study is to review the health promotion interventions on spanish youths published in Spanish in the 1995-2000 period and to describe them in accordance with the scope within which they have been carried out, the topics addressed, the methodology, the evaluation design used and the results obtained. Two hundred and fourteen intervention were identified. Illegal drugs were the topic on which the largest number of interventions were focused (29.8%), followed by alcohol (15.9%), the risk-related sexual behaviours (14.6%) and leisure time (12.6%). The activities carried out most often were: participation-based educational methods (30.7%), explanatory education methods (11.5%) and the preparation of educational materials (11%). In 80.8% of the cases, some evaluation of the health promotion activities was found. The type of evaluation employed most often was the process evaluation (73.7%), and the medium-long term results evaluation being those employed the least (2.2%). The evaluation methodologies used most often were questionnaires (28.2%). A combination of qualitative and quantitative methods was employed in 13.2% of the cases. The four interventions in which the medium-long term impact was gauged had the purpose of preventing and reducing cigarette smoking and/or drinking and or marijuana smoking, all of these initiatives achieving a reduction in cigarette smoking. In conclusion, it seems necessary to improve the design of the evaluations of the health promotion initiatives addressed to young people in Spain and to increase the dissemination of the same by way of their publication.

El proyecto EMECAM: Estudio Multicéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad. Antecedentes, participantes, objetivos y métodología.

In recent years, a growing number of studies suggests that increases in air pollution levels may have short-term impact on human health, even at pollution levels similar to or lower than those which have been considered to be safe to date. The different methodological approaches and the varying analysis techniques employed have made it difficult to make a direct comparison among all of the findings, preventing any clear conclusions from being drawn. This has led to multicenter projects such as the APHEA (Short-Term Impact of Air Pollution on Health. A European Approach) within a European Scope. The EMECAM Project falls within the context of the aforesaid multicenter studies and has a wide-ranging projection nationwide within Spain. Fourteen (14) cities throughout Spain were included in this Project (Barcelona, Metropolitan Area of Bilbao, Cartagena, Castellón, Gijón, Huelva, Madrid, Pamplona, Seville, Oviedo, Valencia, Vigo, Vitoria and Saragossa) representing different sociodemographic, climate and environmental situations, adding up to a total of nearly nine million inhabitants. The objective of the EMECAM project is that to asses the short-term impact of air pollution throughout all of the participating cities on the mortality for all causes, on the population and on individuals over age 70, for respiratory and cardiovascular design causes. For this purpose, with an ecological, the time series data analyzed taking the daily deaths, pollutants, temperature data and other factors taken from records kept by public institutions. The period of time throughout which this study was conducted, although not exactly the same for all of the cities involved, runs in all cases from 1990 to 1996. The degree of relationship measured by means of an autoregressive Poisson regression. In the future, the results of each city will be combined by means of a meta-analysis.

Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars.

While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA). In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29%) softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids). The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..

Efectividad comparativa del seguimiento remoto a personas con marcapasos cardíacos frente al convencional: calidad de vida a los 6 meses.

BACKGROUND The use of remote follow-up (RF) of people with pacemakers (PM) is limited in comparison to the hospital modality (HS), being still poor the scientific evidence that shows their comparative effectiveness. The aim of this study was to compare the quality of life in individuals with different modalities of follow-up. METHODS Controlled, not randomized nor masked clinical trial, with data collection at pre and post-implantation of pacemakers during the 6 months follow-up. All patients over 18 years-old who were implanted a PM during the study period were selected (n = 83), and they were assigned to RF (n = 30) or HF (n = 53) groups according to their personal characteristics and patient's preferences. Baseline characteristics and number of visits to the hospital were analysed, the EuroQol-5D (EQ5D) questionnaire was administered to evaluate the health-related quality of life, and Duke Activity Status Index (DASI) to assess the functional capacity. RESULTS There were no significant differences between both groups in relation to the baseline analysis, EQ5D (RF:0.7299; HF:0.6769) and DASI (RF:21.41; HF:19.99). At 6 months the quality of life was improved in both groups (EQ5D RF:0.8613; HF:0.8175; p = 0,439) still without significant differences between them. DASI score was similar to baseline (20.51 vs 21.80). RF group performed less transmissions/visits per patient (1.57) than hospital group (1.96; relative reduction 31%; p = 0.015). CONCLUSIONS Remote follow-up of people with pacemakers might be considered as an equivalent option to the hospital follow-up in relation to the quality of life and it reduces the number of hospital visits.

Estudio de las subpoblaciones linfocitarias y secreción intratecal en pacientes con esclerosis múltiple defnida

Multiple sclerosis is an infammatory demyelinating autoimmune disease that affects the brain and spinal cord. The aim of the study was to quantify lym-phocyte subpopulations in cerebrospinal fuid and blood of patients diagnosed with multiple sclerosis and in patients whit degenerative diseases not (control) in order to fnd some relationships between them that make it possible to differentiate the immune status of patients in each group. This work was jointly carried out with Hospital Universitario Virgen Macarena in Seville during 2008, 2009 and 2010. It is a descriptive, transversal and cohort study. The selected population is composed of 142 subjects who were subjected to lumbar puncture and a blood sample. Group 1 (n=70), control, Group 2 (n=53), patients with relapsing remitting multiple sclerosis, Group 3 (n=5), patients with primary type progressive multiple sclerosis, and Group 4 (n=14) patients with isolated neurological syndrome. The results show an increase in CSF B cells in MS patients suggesting an increase in focal infammatory activity in the CNS. Regarding NKCD8, reduced total levels of NK and NKCD8 regard-ing controls were observed, and it showed an increased IgG index value in patients with RRMS.

O to Z flaps in facial reconstructions.

Local flaps are the standard procedure to reconstruct facial defects. As it occurs in any surgical procedure, the incision should be planned so that scars are located in the minimum skin tension lines. We report two cases of O to Z flaps in the supra and infraciliary regions. One of them is a hatchet flap.

A professor on a mission

How the INTERNORM project can be a way to influence the development of international standards and reinforce the commitment of academia to support a greater participation of civil society to transnational regulatory processes remote from the public.

Pooling of dentin microtensile bond strength data improves clinical correlation.

Purpose: To evaluate whether the correlation between in vitro bond strength data and estimated clinical retention rates of cervical restorations after two years depends on pooled data obtained from multicenter studies or single-test data. Materials and Methods: Pooled mean data for six dentin adhesive systems (Adper Prompt L-Pop, Clearfil SE, OptiBond FL, Prime & Bond NT, Single Bond, and Scotchbond Multipurpose) and four laboratory methods (macroshear, microshear, macrotensile and microtensile bond strength test) (Scherrer et al, 2010) were correlated to estimated pooled two-year retention rates of Class V restorations using the same adhesive systems. For bond strength data from a single test institute, the literature search in SCOPUS revealed one study that tested all six adhesive systems (microtensile) and two that tested five of the six systems (microtensile, macroshear). The correlation was determined with a database designed to perform a meta-analysis on the clinical performance of cervical restorations (Heintze et al, 2010). The clinical data were pooled and adjusted in a linear mixed model, taking the study effect, dentin preparation, type of isolation and bevelling of enamel into account. A regression analysis was carried out to evaluate the correlation between clinical and laboratory findings. Results: The results of the regression analysis for the pooled data revealed that only the macrotensile (adjusted R2 = 0.86) and microtensile tests (adjusted R2 = 0.64), but not the shear and the microshear tests, correlated well with the clinical findings. As regards the data from a single-test institute, the correlation was not statistically significant. Conclusion: Macrotensile and microtensile bond strength tests showed an adequate correlation with the retention rate of cervical restorations after two years. Bond strength tests should be carried out by different operators and/or research institutes to determine the reliability and technique sensitivity of the material under investigation.

A non-invasive assessment of hepatic glycogen kinetics and post-absorptive gluconeogenesis in man.

A novel approach to the study of hepatic glycogen kinetics and fractional gluconeogenesis in vivo is described. Ten healthy female subjects were fed an iso-caloric diet containing 55% carbohydrate energy with a 13C abundance of 1.083 atom percent for a 3-day baseline period; then, a diet of similar composition, but providing carbohydrate with a 13C abundance of 1.093 atom percent was started and continued for 5 days. Resting respiratory gas exchanges, urinary nitrogen excretion, breath 13CO2 and plasma 13C glucose were measured every morning in the fasting state. The enrichment in 13C of hepatic glycogen was calculated from these measured data. 13C glycogen enrichment increased after switching to a 13C enriched carbohydrate diet, and was identical to the 13C enrichment of dietary carbohydrates after 3 days. The time required to renew 50% of hepatic glycogen, as determined from the kinetics of 13C glycogen enrichment, was 18.9 +/- 3.6 h. Fractional gluconeogenesis, as determined from the difference between the enrichments of glucose oxidized originating from hepatic glycogen and plasma glucose 13C was 50.8 +/- 5.3%. This non-invasive method will allow the study of hepatic glycogen metabolism in insulin-resistant patients.

Tools in pharmacovigilance in psychiatry: therapeutic drug monitoring, pharmacogenetic tests and drug-drug interactions databases

SUMMARYIn order to increase drug safety we must better understand how medication interacts with the body of our patients and this knowledge should be made easily available for the clinicians prescribing the medication. This thesis contributes to how the knowledge of some drug properties can increase and how to make information readily accessible for the medical professionals. Furthermore it investigates the use of Therapeutic drug monitoring, drug interaction databases and pharmacogenetic tests in pharmacovigilance.Two pharmacogenetic studies in the naturalistic setting of psychiatric in-patients clinics have been performed; one with the antidepressant mirtazapine, the other with the antipsychotic clozapine. Forty-five depressed patients have been treated with mirtazapine and were followed for 8 weeks. The therapeutic effect was as seen in other previous studies. Enantioselective analyses could confirm an influence of age, gender and smoking in the pharmacokinetics of mirtazapine; it showed a significant influence of the CYP2D6 genotype on the antidepressant effective S-enantiomer, and for the first time an influence of the CYP2B6 genotype on the plasma concentrations of the 8-OH metabolite was found. The CYP2B6*/*6 genotype was associated to better treatment response. A detailed hypothesis of the metabolic pathways of mirtazapine is proposed. In the second pharmacogenetic study, analyses of 75 schizophrenic patients treated with clozapine showed the influence of CYP450 and ABCB1 genotypes on its pharmacokinetics. For the first time we could demonstrate an in vivo effect of the CYP2C19 genotype and an influence of P-glycoprotein on the plasma concentrations of clozapine. Further we confirmed in vivo the prominent role of CYP1A2 in the metabolism of clozapine.Identifying risk factors for the occurrence of serious adverse drug reactions (SADR) would allow a more individualized and safer drug therapy. SADR are rare events and therefore difficult to study. We tested the feasibility of a nested matched case-control study to examine the influence of high drug plasma levels and CYP2D6 genotypes on the risk to experience an SADR. In our sample we compared 62 SADR cases with 82 controls; both groups were psychiatric patients from the in-patient clinic Königsfelden. Drug plasma levels of >120% of the upper recommended references could be identified as a risk factor with a statistically significant odds ratio of 3.5, a similar trend could be seen for CYP2D6 poor metaboliser. Although a matched case-control design seems a valid method, 100% matching is not easy to perform in a relative small cohort of one in-patient clinic. However, a nested case-control study is feasible.On the base of the experience gained in the AMSP+ study and the fact that we have today only sparse data indicating that routine drug plasma concentration monitoring and/or pharmacogenetic testing in psychiatry are justified to minimize the risk for ADR, we developed a test algorithm named "TDM plus" (TDM plus interaction checks plus pharmacogenetic testing).Pharmacovigilance programs such as the AMSP project (AMSP = Arzneimittelsicherheit in der Psychiatrie) survey psychiatric in-patients in order to collect SADR and to detect new safety signals. Case reports of such SADR are, although anecdotal, valuable to illustrate rare clinical events and sometimes confirm theoretical assumptions of e.g. drug interactions. Seven pharmacovigilance case reports are summarized in this thesis.To provide clinicians with meaningful information on the risk of drug combinations, during the course of this thesis the internet based drug interaction program mediQ.ch (in German) has been developed. Risk estimation is based on published clinical and pharmacological information of single drugs and alimentary products, including adverse drug reaction profiles. Information on risk factors such as renal and hepatic insufficiency and specific genotypes are given. More than 20'000 drug pairs have been described in detail. Over 2000 substances with their metabolic and transport pathways are included and all information is referenced with links to the published scientific literature or other information sources. Medical professionals of more than 100 hospitals and 300 individual practitioners do consult mediQ.ch regularly. Validations with comparisons to other drug interaction programs show good results.Finally, therapeutic drug monitoring, drug interaction programs and pharmacogenetic tests are helpful tools in pharmacovigilance and should, in absence of sufficient routine tests supporting data, be used as proposed in our TDM plus algorithm.RESUMEPour améliorer la sécurité d'emploi des médicaments il est important de mieux comprendre leurs interactions dans le corps des patients. Ensuite le clinicien qui prescrit une pharmacothérapie doit avoir un accès simple à ces informations. Entre autres, cette thèse contribue à mieux connaître les caractéristiques pharmacocinétiques de deux médicaments. Elle examine aussi l'utilisation de trois outils en pharmacovigilance : le monitorage thérapeutique des taux plasmatiques des médicaments (« therapeutic drug monitoring »), un programme informatisé d'estimation du risque de combinaisons médicamenteuses, et enfin des tests pharmacogénétiques.Deux études cliniques pharmacogénétiques ont été conduites dans le cadre habituel de clinique psychiatrique : l'une avec la mirtazapine (antidépresseur), l'autre avec la clozapine (antipsychotique). On a traité 45 patients dépressifs avec de la mirtazapine pendant 8 semaines. L'effet thérapeutique était semblable à celui des études précédentes. Nous avons confirmé l'influence de l'âge et du sexe sur la pharmacocinétique de la mirtazapine et la différence dans les concentrations plasmatiques entre fumeurs et non-fumeurs. Au moyen d'analyses énantiomères sélectives, nous avons pu montrer une influence significative du génotype CYP2D6 sur l'énantiomère S+, principalement responsable de l'effet antidépresseur. Pour la première fois, nous avons trouvé une influence du génotype CYP2B6 sur les taux plasmatiques de la 8-OH-mirtazapine. Par ailleurs, le génotype CYP2B6*6/*6 était associé à une meilleure réponse thérapeutique. Une hypothèse sur les voies métaboliques détaillées de la mirtazapine est proposée. Dans la deuxième étude, 75 patients schizophrènes traités avec de la clozapine ont été examinés pour étudier l'influence des génotypes des iso-enzymes CYP450 et de la protéine de transport ABCB1 sur la pharmacocinétique de cet antipsychotique. Pour la première fois, on a montré in vivo un effet des génotypes CYP2C19 et ABCB1 sur les taux plasmatiques de la clozapine. L'importance du CYP1A2 dans le métabolisme de la clozapine a été confirmée.L'identification de facteurs de risques dans la survenue d'effets secondaire graves permettrait une thérapie plus individualisée et plus sûre. Les effets secondaires graves sont rares. Dans une étude de faisabilité (« nested matched case-control design » = étude avec appariement) nous avons comparé des patients avec effets secondaires graves à des patients-contrôles prenant le même type de médicaments mais sans effets secondaires graves. Des taux plasmatiques supérieurs à 120% de la valeur de référence haute sont associés à un risque avec « odds ratio » significatif de 3.5. Une tendance similaire est apparue pour le génotype du CYP2D6. Le « nested matched case-control design » semble une méthode valide qui présente cependant une difficulté : trouver des patients-contrôles dans le cadre d'une seule clinique psychiatrique. Par contre la conduite d'une « nested case-control study » sans appariement est recommandable.Sur la base de notre expérience de l'étude AMSP+ et le fait que nous disposons que de peux de données justifiant des monitorings de taux plasmatiques et/ou de tests pharmacogénétiques de routine, nous avons développé un test algorithme nommé « TDMplus » (TDM + vérification d'interactions médicamenteuses + tests pharmacogénétique).Des programmes de pharmacovigilances comme celui de l'AMSP (Arzneimittelsicherheit in der Psychiatrie = pharmacovigilance en psychiatrie) collectent les effets secondaires graves chez les patients psychiatriques hospitalisés pour identifier des signaux d'alertes. La publication de certains de ces cas même anecdotiques est précieuse. Elle décrit des événements rares et quelques fois une hypothèse sur le potentiel d'une interaction médicamenteuse peut ainsi être confirmée. Sept publications de cas sont résumées ici.Dans le cadre de cette thèse, on a développé un programme informatisé sur internet (en allemand) - mediQ.ch - pour estimer le potentiel de risques d'une interaction médicamenteuse afin d'offrir en ligne ces informations utiles aux cliniciens. Les estimations de risques sont fondées sur des informations cliniques (y compris les profils d'effets secondaires) et pharmacologiques pour chaque médicament ou substance combinés. Le programme donne aussi des informations sur les facteurs de risques comme l'insuffisance rénale et hépatique et certains génotypes. Actuellement il décrit en détail les interactions potentielles de plus de 20'000 paires de médicaments, et celles de 2000 substances actives avec leurs voies de métabolisation et de transport. Chaque information mentionne sa source d'origine; un lien hypertexte permet d'y accéder. Le programme mediQ.ch est régulièrement consulté par les cliniciens de 100 hôpitaux et par 300 praticiens indépendants. Les premières validations et comparaisons avec d'autres programmes sur les interactions médicamenteuses montrent de bons résultats.En conclusion : le monitorage thérapeutique des médicaments, les programmes informatisés contenant l'information sur le potentiel d'interaction médicamenteuse et les tests pharmacogénétiques sont de précieux outils en pharmacovigilance. Nous proposons de les utiliser en respectant l'algorithme « TDM plus » que nous avons développé.