Optical Coherence Tomography for the Monitoring of Neovascular Age-Related Macular Degeneration: A Systematic Review

Topic

To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition.

Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests.

Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias.

We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias.

There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland

Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16-93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche^® linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n=684) and 5.1% for HPV-18 (n=93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n=283), 34.1% CIN II (n=145), 18.7% of CIN III (n=146), 7.8% of SCC (n=5), and 35.7% of AC (n=5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines.

Estimating the size of the population of persons who inject drugs in the island of Montréal, Canada, using a six-source capture-recapture model

BACKGROUND: To plan and implement services to persons who inject drugs (PWID), knowing their number is essential. For the island of Montréal, Canada, the only estimate, of 11,700 PWID, was obtained in 1996 through a capture-recapture method. Thirteen years later, this study was undertaken to produce a new estimate. METHODS: PWID were defined as individuals aged 14-65 years, having injected recently and living on the island of Montréal. The study period was 07/01/2009 to 06/30/2010. An estimate was produced using a six-source capture-recapture log-linear regression method. The data sources were two epidemiological studies and four drug dependence treatment centres. Model selection was conducted in two steps, the first focusing on interactions between sources and the second, on age group and gender as covariates and as modulators of interactions. RESULTS: A total of 1480 PWID were identified in the six capture sources. They corresponded to 1132 different individuals. Based on the best-fitting model, which included age group and sex as covariates and six two-source interactions (some modulated by age), the estimated population was 3910 PWID (95% confidence intervals (CI): 3180-4900) which represents a prevalence of 2.8 (95% CI: 2.3-3.5) PWID per 1000 persons aged 14-65 years. CONCLUSIONS: The 2009-2010 estimate represents a two-third reduction compared to the one for 1996. The multisource capture-recapture method is useful to produce estimates of the size of the PWID population. It is of particular interest when conducted at regular intervals thus allowing for close monitoring of the injection phenomenon.

Stepwise evaluation of unexplained syncope in a large ambulatory population.

BACKGROUND: Up to 60% of syncopal episodes remain unexplained. We report the results of a standardized, stepwise evaluation of patients referred to an ambulatory clinic for unexplained syncope. METHODS AND RESULTS: We studied 939 consecutive patients referred for unexplained syncope, who underwent a standardized evaluation, including history, physical examination, electrocardiogram, head-up tilt testing (HUTT), carotid sinus massage (CSM) and hyperventilation testing (HYV). Echocardiogram and stress test were performed when underlying heart disease was initially suspected. Electrophysiological study (EPS) and implantable loop recorder (ILR) were used only in patients with underlying structural heart disease or major unexplained syncope. We identified a cause of syncope in 66% of patients, including 27% vasovagal, 14% psychogenic, 6% arrhythmias, and 6% hypotension. Noninvasive testing identified 92% and invasive testing an additional 8% of the causes. HUTT yielded 38%, CSM 28%, HYV 49%, EPS 22%, and ILR 56% of diagnoses. On average, patients with arrhythmic causes were older, had a lower functional capacity, longer P-wave duration, and presented with fewer prodromes than patients with vasovagal or psychogenic syncope. CONCLUSIONS: A standardized stepwise evaluation emphasizing noninvasive tests yielded 2/3 of causes in patients referred to an ambulatory clinic for unexplained syncope. Neurally mediated and psychogenic mechanisms were behind >50% of episodes, while cardiac arrhythmias were uncommon. Sudden syncope, particularly in older patients with functional limitations or a prolonged P-wave, suggests an arrhythmic cause.

Benchmarking therapeutic drug monitoring software: A review of available computer tools

Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare settings. Each software tool must therefore be regarded with respect to the individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Computer-assisted TDM is gaining growing interest and should further improve, especially in terms of information system interfacing, user friendliness, data storage capability and report generation.

Monitoring of human CD4 T cell responses in metastatic melanoma and arthritic patients

SUMMARY : Detailed knowledge of the different components of the immune system is required for the development of new immunotherapeutic strategies. CD4 T lymphocytes represent a highly heterogeneous group of cells characterized by various profiles of cytokine production and effector vs. regulatory functions. They are central players in orchestrating adaptive immune responses: unbalances between the different subtypes can lead either to aggressive autoimmune disorders or can favour the uncontrolled growth of malignancies. In this study we focused on the characterization of human CD4 T cells in advanced stage melanoma patients as well as in patients affected by various forms of autoimmune inflammatory spondyloarthropathies. In melanoma patients we report that a population of FOXP3 CD4 T cells, known as regulatory T cells, is overrepresented in peripheral blood, and even more in tumor-infitrated lymph nodes as well as at tumor sites, as compared to healthy donors. In tumor-infiltrated lymph nodes, but not in normal lymph nodes or in peripheral blood, FOXP3 CD4 T cells feature a highly differentiated phenotype (CD45RA-CCR7+/-), which suggests for a recent encounter with their cognate antigen. FOXP3 CD4 T cells have been described to be an important component of the several known immune escape mechanisms. We demonstrated that FOXP3 CD4 T cells isolated from melanoma patients exert an in vitro suppressive action on autologous CD4 T cells, thus possibly inhibiting an efficient anti-tumor response. Next, we aimed to analyse CD4 T cells at antigen-specific level. In advanced stage melanoma patients, we identified for the first time, using pMHCII multimers, circulating CD4 T cells specific for the melanoma antigen Melan-A, presented by HLA-DQB1 *0602. Interestingly, in a cohort of melanoma patients enrolled in an immunotherapy trails consisting of injection of a Melan-A derived peptide, we did not observe signif cant variations in the ex vivo frequencies of Melan-A specific CD4 T cells, but important differences in the quality of the specific CD4 T cells. In fact, up to 50% of the ex vivo Melan-A/DQ6 specific CD4 T cells displayed a regulatory phenotype and were hypoproliferative before vaccination, while more effector, cytokine-secreting Melan-A/DQ6 specific CD4 T cells were observed after immunization. These observations suggest that peptide vaccination may favourably modify the balance between regulatory and effector tumor-specific CD4 T cells. Finally, we identified another subset of CD4 T cells as possible mediator of pathology in a group of human autoimmune spondyloarthropathies, namely Th17 cells. These cells were recently described to play a critical role in the pathogenesis of some marine models of autommunity. We document an elevated presence of circulating Th17 cells in two members of seronegative spondyloarthropathies, e.g. psoriatic arthritis and ankylosing spondylitis, while we do not observe increased frequencies of Th17 cells in peripheral blood of rheumatoid arthritic patients. In addition, Th17 cells with a more advanced differentiation state (CD45RA-CCR7-CD27-) and polyfunctionality (concomitant secretion of IL-17, IL-2 and TNFα) were observed exclusively in patients with seronegative spondylarthropathies. Together, our observations emphasize the importance of CD4 T cells in various diseases and suggest that immunotherapeutic approaches considering CD4 T cells as targets should be evaluated in the future.

Persistent unequal sex ratio in a population of grayling (salmonidae) and possible role of temperature increase.

In some fishes, water chemistry or temperature affects sex determination or creates sex-specific selection pressures. The resulting population sex ratios are hard to predict from laboratory studies if the environmental triggers interact with other factors, whereas in field studies, singular observations of unusual sex ratios may be particularly prone to selective reporting. Long-term monitoring largely avoids these problems. We studied a population of grayling (Thymallus thymallus) in Lake Thun, Switzerland, that has been monitored since 1948. Samples of spawning fish have been caught about 3 times/week around spawning season, and water temperature at the spawning site has been continuously recorded since 1970. We used scale samples collected in different years to determine the average age of spawners (for life-stage specific analyses) and to identify the cohort born in 2003 (an extraordinarily warm year). Recent tissue samples were genotyped on microsatellite markers to test for genetic bottlenecks in the past and to estimate the genetically effective population size (N(e) ). Operational sex ratios changed from approximately 65% males before 1993 to approximately 85% males from 1993 to 2011. Sex ratios correlated with the water temperatures the fish experienced in their first year of life. Sex ratios were best explained by the average temperature juvenile fish experienced during their first summer. Grayling abundance is declining, but we found no evidence of a strong genetic bottleneck that would explain the apparent lack of evolutionary response to the unequal sex ratio. Results of other studies show no evidence of endocrine disruptors in the study area. Our findings suggest temperature affects population sex ratio and thereby contributes to population decline. Persistencia de Proporción de Sexos Desigual en una Población de Tímalos (Salmonidae) y el Posible Papel del Incremento de la Temperatura.

Population pharmacokinetic study to evaluate dosing strategies of imipenem in neonates and infants

Objective: Imipenem is a broad spectrum antibiotic used to treat severe infections in critically ill patients. Imipenem pharmacokinetics (PK) was evaluated in a cohort of neonates treated in the Neonatal Intensive Care Unit of the Lausanne University Hospital. The objective of our study was to identify key demographic and clinical factors influencing imipenem exposure in this population. Method: PK data from neonates and infants with at least one imipenem concentration measured between 2002 and 2013 were analyzed applying population PK modeling methods. Measurement of plasma concentrations were performed upon the decision of the physician within the frame of a therapeutic drug monitoring (TDM) programme. Effects of demographic (sex, body weight, gestational age, postnatal age) and clinical factors (serum creatinine as a measure of kidney function; co-administration of furosemide, spironolactone, hydrochlorothiazide, vancomycin, metronidazole and erythromycin) on imipenem PK were explored. Model-based simulations were performed (with a median creatinine value of 46 μmol/l) to compare various dosing regimens with respect to their ability to maintain drug levels above predefined minimum inhibitory concentrations (MIC) for at least 40 % of the dosing interval. Results: A total of 144 plasma samples was collected in 68 neonates and infants, predominantly preterm newborns, with median gestational age of 27 weeks (24 - 41 weeks) and postnatal age of 21 days (2 - 153 days). A two-compartment model best characterized imipenem disposition. Actual body weight exhibited the greatest impact on PK parameters, followed by age (gestational age and postnatal age) and serum creatinine on clearance. They explain 19%, 9%, 14% and 9% of the interindividual variability in clearance respectively. Model-based simulations suggested that 15 mg/kg every 12 hours maintain drug concentrations over a MIC of 2 mg/l for at least 40% of the dosing interval during the first days of life, whereas neonates older than 14 days of life required a dose of 20 mg/kg every 12 hours. Conclusion: Dosing strategies based on body weight and post-natal age are recommended for imipenem in all critically ill neonates and infants. Most current guidelines seem adequate for newborns and TDM should be restricted to some particular clinical situations.

Incidence of resistance to benzimidazole fungicides in a field population of Venturia inaequalis /

The allele-specific polymerase chain reaction (PCR) was used to screen for the presence of benomyl resistance, and to characterize their levels and frequencies in field populations of Venturia inaequalis during two seasons. Three hundred isolates of V. inaequalis were collected each season from infected leaves of MalusX domestica. Borkh c.v. Mcintosh. The trees used were sprayed in the year prior to collection with five applications of benomyl, its homologue Azindoyle, or water. Monoconidial isolates of V. inaequalis were grown on 2% potato dextrose agar (PDA) for four weeks. Each isolate was taken from a single lesion from a single leaf. Total genomic DNA was extracted from the four week old colonies of V. inaequalis, prepared and used as a template in PCR reactions. PCR reactions were achieved by utilizing allele-specific primers. Each primer was designed to amplify fragments from a specific allele. Primer Vin was specific for mutations conferring the ben^^"^ phenotype. It was expected to amplify a 171 bp. DNA fragment from the ben^"^ alleles only. Primers BenHR and BenMR were specific for mutations conferring the ben"" and ben'^'' phenotypes, respectively. They were expected to amplify 172 bp. and 165 bp. DNA fragments from the ben"" and ben"^" alleles, respectively. Of the 953 isolates tested, 414 (69.9%) were benomyl sensitive (ben^) and 179 (30.1%) were benomyl resistant. All the benomyl resistant alleles were ben^"", since neither the ben"" nor the ben"" alleles were detected. Frequencies of benomyl resistance were 23%, 24%, and 23% for the 1997 collections, and were 46%, 26% and 38% for the 1998 collections for benomyl, Azindoyle and water treatments, respectively. Growth assay was performed to evaluate the applicability of using PCR in monitoring benomyl resistance in fungal field populations. Tests were performed on 14 isolates representing the two phenotypes (ben^ and ben^"'' alleles) characterized by PCR. Results of those tests were in agreement with PCR results. Enzyme digestion was also used to evaluate the accuracy and reliability of PCR products. The mutation associated with the ben^"'' phenotype creates a unique site for the endonuclease enzyme Bsh^236^ allowing the use of enzyme digestion. Isolates characterized by PCR as ben^'^'^ alleles had this restriction site for the SsA7l2361 enzyme. The most time consuming aspect of this study was growing fungal isolates on culture media for DNA extraction. In addition, the risk of contamination or losing the fungus during growth processes was relatively high. A technique for extracting DNA directly from lesions on leaves has been used (Luck and Gillings 1 995). In order to apply this technique in experiments designed to monitor fungicide resistance, a lesion has to be homogeneous for fungicide sensitivity. For this purpose, PCR protocol was used to determine lesion homogeneity. One hundred monoconidial isolates of V. inaequalis from 10 lesions (10-conidia/ lesion) were tested for their phenotypes with respect to benomyl sensitivity. Conidia of six lesions were homogeneous, while conidia of the remaining lesions were mixtures of ben^ and ben^ phenotypes. Neither the ben" nor the ben' phenotype was detected.

The effectiveness of a health versus appearance message on pregnant women's intentions to exercise postpartum : the moderating role of self-monitoring

Despite the confimied health benefits of exercise during the postpartum period, many new mothers are not sufficiently active. The present research aimed to examine the effectiveness of 2 types of messages on intention to exercise after giving birth on 2 groups of pregnant women (low and high self-monitors) using the Theory of Planned Behavior as a theoretical basis. Participants were 2 1 8 pregnant women 1 8 years of age and older (Mean age = 27.9 years, SD = 5.47), and in their second or third trimester. Women completed a demographics questionnaire, a self-monitoring (SM) scale and the Godin Leisure Time Exercise Questionnaire for current and pre-pregnancy exercise levels. They then read one of two brochures, describing either the health or appearance benefits of exercise for postpartum women. Women's attitudes, social norms, perceived behavioral control, and intentions to exercise postpartum were then assessed to determine whether one type of message (health or appearance) was more effective for each group. A MANOVA found no significant effect (p>0.05) for message type, SM, or their interaction. Possible reasons include the fact that the two messages may have been too similar, reading any message about exercise may result in intentions to exercise, or lack of attention given to the brochure. Given the lack of research in this area, more studies are necessary to confirm the present results. Two additional exploratory analyses were conducted. Pearson correlations found higher levels of pre-pregnancy exercise and current exercise to be associated with more positive attitudes, more positive subjective norms, higher perceived behavioral control, and higher intention to exercise postpartum. A hierarchical regression was conducted to determine the predictive utility of attitudes, subjective norms, and perceived behavioral control on intention for each self-monitoring group. Results of the analysis demonstrated the three independent variables significantly predicted intention (p < .001) in both groups, accounting for 58-62% of the variance in intention. For low self-monitors, attitude was the strongest predictor of intention, followed by perceived behavioral control and subjective norm. For high self-monitors, perceived behavioral control was the strongest predictors, followed by attitudes and subjective norm. The present study has practical and real world implications by contributing to our understanding of what types of messages, in a brochure format, are most effective in changing pregnant women's attitudes, subjective norm, perceived behavioral control and intention to exercise postpartum and provides ftirther support for the use of the Theory of Planned Behavior with this population.

L'association entre la psychopathie et les pratiques parentales dans une population non criminelle

La présente thèse avait pour but d’étudier les liens qui existaient entre la psychopathie du parent et les pratiques parentales utilisées. L’échantillon était composé de 65 parents francophones, hommes ou femmes, ayant au moins un enfant âgé entre 6 et 10 ans. Les parents ont été rencontrés à leur domicile, à l’école de leur enfant ou dans un organisme communautaire. Le Self Report Psychopathy Scale R12-III (Paulhus, Hemphill & Hare, sous presse) a été traduit en français pour la présente étude afin de mesurer la psychopathie du parent. La version francophone de l’Alabama Parenting Questionnaire (Pauzé & al., 2004) a été utilisée pour mesurer cinq pratiques parentales : les pratiques éducatives positives, le manque de supervision, l’engagement, la discipline incohérente et les punitions corporelles. La version francophone de l’échelle de désirabilité sociale abrégée de Marlowe-Crowe (Crowe-Marlowe, 1960) a été jointe aux deux autres questionnaires (Bergeron, Valla & Breton, 1992). Des régressions simples ont été effectuées entre le score global de psychopathie et chacune des cinq pratiques parentales énumérées ci-dessus. Ensuite, des régressions multiples ont été exécutées afin de vérifier quel était le meilleur facteur de la psychopathie pouvant prédire chaque pratique parentale. Les résultats ont montré que la psychopathie était associée négativement de façon significative aux pratiques éducatives positives et à l’engagement. Un lien significatif positif a été soulevé entre la psychopathie et l’utilisation des punitions corporelles. Les analyses secondaires ont démontré que le facteur interpersonnel de la psychopathie expliquait une proportion significative des pratiques éducatives positives. Le facteur antisocial a prédit, quant à lui, une petite partie significative de l’engagement au-delà de l’explication fournie par la désirabilité sociale. Le style de vie du psychopathe a contribué à une proportion significative de l’explication de la variance des punitions corporelles. Il semblerait pertinent d’intervenir le plus tôt possible auprès du parent et de l’enfant afin d’éviter que les mauvaises pratiques et les traits psychopathes ne se répètent dans les générations futures. Des méthodes d’intervention ont été suggérées. Les forces et les faiblesses de l’étude ont été discutées.

Association entre la dépression et les comportements reliés aux habitudes de vie et aux soins du diabète dans la population diabétique du Québec

Les personnes atteintes de diabète sont plus à risque de développer la dépression, un fardeau additionnel dans leurs activités quotidiennes. Notre étude auprès d’adultes diabétiques résidant au Québec vise à en déterminer les caractéristiques lorsque la dépression fait partie du tableau clinique. Hypothèse 1: Les adultes québécois atteints de diabète et de dépression (dépression majeure et mineure) seront plus prédisposés à avoir des indicateurs reliés aux habitudes de vie, aux soins du diabète et à l’efficacité personnelle vis-à-vis du contrôle du poids et de la quantité d’aliments consommés, moins favorables que les sujets diabétiques sans dépression. Hypothèse 2: Chez les Québécois atteints de diabète de type 2, l’association entre la dépression et l’obésité sera affectée par les indicateurs de la Variation Cyclique du Poids (VCP) et de l’efficacité personnelle. Hypothèse 3: Chez les Québécois atteints de diabète de type 2, ceux qui auront développé ou maintenu une dépression au cours de 12 mois, seront plus susceptibles de détériorer les indicateurs reliés à leurs habitudes de vie et à leur efficacité personnelle. Des personnes diabétiques au Québec ont été recrutées à l’aide d’un sondage téléphonique. Des adultes, hommes et femmes, âgés de 18 à 80 ans étaient éligibles à participer. La dépression était déterminée par le questionnaire PHQ-9 « Patient Health Questionnaire-9 ». Au total, 3 221 individus ont été contactés au départ de l’étude; 2 003 ont participé à l’étude (93% type 2)et 1 234 ont participé au suivi de 12 mois. La prévalence de dépression mineure et majeure était de 10,9% et 8,7%, respectivement. Cinquante-trois pourcent des sujets avec dépression majeure avaient deux ou trois indicateurs malsains (tabagisme, inactivité ou obésité), 33% des sujets avaient une dépression mineure et 21% des sujets étaient non déprimés. Les résultats des analyses de régression logistique ont révélé que les sujets dépressifs étaient plus susceptibles d’être de sexe féminin, moins instruits, non mariés,sédentaires, fumeurs, percevaient plus souvent avoir une faible maîtrise du contrôle de la quantité d’aliments ingérés et tendaient davantage à mesurer leur glycémie au moins une fois par jour (p<0,05). Chez les patients avec le diabète de type 2, l’association entre la dépression et l’obésité a été affectée par les variables de la VCP et d’efficacité personnelle. Une année après le début de l’étude, 11,5% des sujets ont développé une dépression et 10% ont maintenu leur état dépressif. Les sujets ayant développé une dépression ou persisté dans leur état de dépression étaient plus susceptibles d’avoir été inactifs au début de l’étude ou d’être restés inactifs au suivi de 12 mois, et d’avoir maintenu une perception d’un faible contrôle de leur poids corporel et de la quantité d’aliments ingérés. Cependant, les changements de statut de dépression n’étaient pas associés à des changements de l’indice de masse corporelle. En conclusion, l’inactivité physique et une faible efficacité personnelle sont des facteurs importants dans le développement et la persistance de la dépression chez les patients diabétiques et méritent d’être considérés dans le traitement.

Optimisation de l’administration des médicaments chez les enfants transplantés grâce à la pharmacocinétique de population

Ce travail de thèse porte sur l’application de la pharmacocinétique de population dans le but d’optimiser l’utilisation de certains médicaments chez les enfants immunosupprimés et subissant une greffe. Parmi les différents médicaments utilisés chez les enfants immunosupprimés, l’utilisation du busulfan, du tacrolimus et du voriconazole reste problématique, notamment à cause d’une très grande variabilité interindividuelle de leur pharmacocinétique rendant nécessaire l’individualisation des doses par le suivi thérapeutique pharmacologique. De plus, ces médicaments n’ont pas fait l’objet d’études chez les enfants et les doses sont adaptées à partir des adultes. Cette dernière pratique ne prend pas en compte les particularités pharmacologiques qui caractérisent l’enfant tout au long de son développement et rend illusoire l’extrapolation aux enfants des données acquises chez les adultes. Les travaux effectués dans le cadre de cette thèse ont étudié successivement la pharmacocinétique du busulfan, du voriconazole et du tacrolimus par une approche de population en une étape (modèles non-linéaires à effets mixtes). Ces modèles ont permis d’identifier les principales sources de variabilités interindividuelles sur les paramètres pharmacocinétiques. Les covariables identifiées sont la surface corporelle et le poids. Ces résultats confirment l’importance de tenir en compte l’effet de la croissance en pédiatrie. Ces paramètres ont été inclus de façon allométrique dans les modèles. Cette approche permet de séparer l’effet de la mesure anthropométrique d’autres covariables et permet la comparaison des paramètres pharmacocinétiques en pédiatrie avec ceux des adultes. La prise en compte de ces covariables explicatives devrait permettre d’améliorer la prise en charge a priori des patients. Ces modèles développés ont été évalués pour confirmer leur stabilité, leur performance de simulation et leur capacité à répondre aux objectifs initiaux de la modélisation. Dans le cas du busulfan, le modèle validé a été utilisé pour proposer par simulation une posologie qui améliorerait l’atteinte de l’exposition cible, diminuerait l’échec thérapeutique et les risques de toxicité. Le modèle développé pour le voriconazole, a permis de confirmer la grande variabilité interindividuelle dans sa pharmacocinétique chez les enfants immunosupprimés. Le nombre limité de patients n’a pas permis d’identifier des covariables expliquant cette variabilité. Sur la base du modèle de pharmacocinétique de population du tacrolimus, un estimateur Bayesien a été mis au point, qui est le premier dans cette population de transplantés hépatiques pédiatriques. Cet estimateur permet de prédire les paramètres pharmacocinétiques et l’exposition individuelle au tacrolimus sur la base d’un nombre limité de prélèvements. En conclusion, les travaux de cette thèse ont permis d’appliquer la pharmacocinétique de population en pédiatrie pour explorer les caractéristiques propres à cette population, de décrire la variabilité pharmacocinétique des médicaments utilisés chez les enfants immunosupprimés, en vue de l’individualisation du traitement. Les outils pharmacocinétiques développés s’inscrivent dans une démarche visant à diminuer le taux d'échec thérapeutique et l’incidence des effets indésirables ou toxiques chez les enfants immunosupprimés suite à une transplantation.

Hypertension artérielle dans la population adulte du Burkina Faso : prévalence, détection, traitement et contrôle

Contexte : L’hypertension artérielle (HTA) est reconnue comme un important facteur de risque des maladies cardiovasculaires et de la mortalité prématurée. Les données montrent qu’un adulte sur 4 dans le monde souffrait d’hypertension en 2000 et ce chiffre serait en augmentation. Dans les pays africains, les estimations prévoient une progression plus rapide de la prévalence de l’HTA engendrant ainsi un problème additionnel à gérer pour le système de santé qui est toujours aux prises avec les maladies transmissibles. Les progrès économiques et l’urbanisation semblent entraîner des modifications des habitudes de vie dans ces pays qui seraient associés à une émergence des maladies non transmissibles, dont l’HTA. Le Burkina Faso, pays de l’Afrique de l’Ouest classé comme un pays à faibles revenus, aurait amorcé sa transition épidémiologique et il importe de faire un état sur les maladies non transmissibles en émergence. Afin de contribuer à la connaissance des aspects épidémiologiques de l’HTA au Burkina Faso, trois objectifs spécifiques ont été retenus pour la présente recherche : 1) Estimer la prévalence de l’HTA et identifier les facteurs associés dans la population rurale et la population semi-urbaine du Système de Surveillance démographique et de Santé de Kaya (Kaya HDSS) ; 2) Déterminer la différence de prévalence de l’HTA entre la zone lotie et la zone non lotie de la ville de Ouagadougou et identifier les facteurs associés ; 3) Déterminer la détection, le traitement, le contrôle de l’HTA et estimer la fréquentation des centres de santé par les personnes hypertendues nouvellement dépistées dans la population adulte du Centre Nord du Burkina Faso. Méthodologie : Le cadre de notre recherche est le Burkina Faso. Deux sites ont fait l’objet de nos investigations. Kaya HDSS, situé dans la région du Centre Nord du Burkina Faso a servi de site pour les enquêtes ayant permis l’atteinte du premier et du troisième objectif général. Une étude transversale a été menée en fin 2012 sur un échantillon aléatoire de 1645 adultes résidents du site. Un entretien suivi de mesures anthropométriques et de la pression artérielle (PA) ont été réalisés au domicile des participants. Toutes les personnes qui avaient une PA élevée (PA systolique ≥ 140 mm Hg et/ou PA diastolique ≥ 90 mm Hg) et qui n’avaient pas été diagnostiquées auparavant ont été référées à une formation sanitaire. Un second entretien a été réalisé avec ces personnes environ un mois après. Pour le second objectif général, c’est le système de surveillance démographique et de santé de Ouagadougou (Ouaga HDSS) qui a été retenu comme site. Ouaga HDSS couvre 5 quartiers de la zone nord de Ouagadougou. Une étude transversale a été réalisée en 2010 sur un échantillon aléatoire représentatif de la population adulte résidante du site (N = 2041). Des entretiens suivis de mesures anthropométriques et de la PA ont été réalisés durant l’enquête. Résultats : Notre premier article examine la prévalence de l’HTA et les facteurs associés en milieu rural et en milieu semi-urbain. Au total 1481 participants ont été dépistés et la prévalence totale pondérée était de 9,4 % (95 % IC : 7,3 % - 11,4 %) avec une grande différence entre le milieu semi-urbain et le milieu rural : un adulte sur 10 était hypertendu en milieu semi-urbain contre un adulte sur 20 en milieu rural. L’analyse multivariée nous a permis d’identifier l’âge avancé, le milieu semi-urbain et l’histoire familiale de l’HTA comme des facteurs de risque. Dans le deuxième article, nous avons déterminé la différence entre la zone lotie et la zone non lotie du milieu urbain en ce qui concerne l’HTA. Sur 2 041 adultes enquêtés, la prévalence totale est estimée à 18,6 % (95 % IC : 16,9 % - 20,3 %). Après ajustement avec l’âge, il n’y avait pas de différence de prévalence entre la zone lotie et la zone non lotie de la ville de Ouagadougou. Dans ce milieu urbain, l’obésité et l’inactivité physique sont confirmées comme des facteurs à risque. En plus des personnes âgées qui constituent un groupe à risque, les migrants venant du milieu rural et les veuves ont été identifiés comme des personnes à risque. Notre troisième article examine la détection, le traitement, le contrôle de l’HTA ainsi que la fréquentation des structures de santé par les personnes nouvellement dépistées hypertendues dans le milieu non urbain. Sur les 1481 participants à l’étude, 41 % n’avaient jamais mesuré leur PA. Sur les 123 participants (9,4 %) dépistés comme hypertendus, 26,8 % avaient déjà bénéficié d’un diagnostic et 75,8 % de ces derniers étaient sous traitement anti hypertensif. Parmi les participants sous traitement, 60 % (15 sur 25) avaient leur PA sous contrôle. Le suivi de 2 mois a permis de retrouver 72 des 90 personnes nouvellement dépistées. Seulement 50 % ont été en consultation et parmi ces derniers 76 % (28 personnes sur les 37) ont reçu une confirmation de leur hypertension. Conclusion : Notre recherche montre l’évolution de l’HTA en fonction du niveau d’urbanisation de la population. Même si les maladies infectieuses restent la priorité du système de santé, la lutte contre l’HTA doit s’inscrire dans un cadre général de lutte contre les maladies cardiovasculaires. Cette lutte doit être amorcée maintenant avant que des proportions inquiétantes ne soient atteintes. Des actions de prévention telles que la promotion de saines habitudes de vie, le dépistage de masse et un renforcement des capacités du système de soins sont à mettre en œuvre.

Ecology And Seasonal Variation Of Microalgal Community In An Oil Refinery Effluent Holding Pond: Monitoring And Assessment

The microalgal community as primary producers has to play a significant role in the biotic and abitoic interactions of any aquatic ecosystem. Whenever a community is exposed to a pollutant, responses can occur because individuals acclimate to pollutant caused changes and selection can occur favouring resistant genotypes within a population and selection among species can result in changes in community structure. The microalgal community of industrial effluent treatment systems are continuously exposed to pollutants and there is little data available on the structure and seasonal variation of microalgal community of industrial effluent holding ponds, especially of a complex effluent like that of refinery. The aim of the present study was to investigate the annual variation in the ecology, biomass, productivity and community structure of the algal community of a refinery effluent holding pond. The results of the study showed the pond to be a eutrophic system with a resistant microalgal community with distinct seasonal variation in species composition