Morbidity characteristics related to cardiovascular outcomes in French Canadian Families of the Saguenay-Lac-Saint-Jean region of Quebec

PROBLÉMATIQUE: L’Organisation Mondiale de la Santé (OMS) considère les maladies cardiovasculaires (MCVs) comme l'hypertension, la maladie coronarienne (par exemple, infarctus du myocarde), l'insuffisance cardiaque ainsi que les accidents cérébrovasculaires, parmi les principales causes de mortalité dans le monde. Les MCVs sont des maladies multifactorielles caractérisées par des interactions complexes entre le génome et l'environnement et dont la prévalence augmente rapidement dans toutes les populations du globe, ce qui vient compliquer d'autant l'étude de leurs bases héréditaires. Nos études précédentes sur la population fondatrice des familles Canadiennes-françaises de la région du Saguenay-Lac-Saint-Jean (SLSJ) au Québec ont permis d’obtenir une carte des loci significativement liés à des déterminants qualitatifs et quantitatifs de l’hypertension et ses déterminants métaboliques [1, 2]. HYPOTHÈSE ET OBJECTIF: Puisque nos données préliminaires nous suggèrent que la mort prématurée consécutive aux MCVs possède des composantes génétique et environnementale, notre hypothèse de départ est que les maladies avec occurrences fatales et non fatales (OF et ONF, respectivement) ont des caractéristiques distinctes, surtout lorsqu’en lien avec le système CV. Pour réaliser ce projet, nos objectifs sont d’analyser les causes de morbidité/mortalité d’hypertendus avec ou sans obésité chez des familles de la région du SLSJ. Nous accomplirons ceci en interrogeant les registres des hôpitaux et de l'état civil de même que les données généalogiques de 1950 jusqu'à maintenant. Nous voulons décrire et étudier les OF pour les comparer aux NFO. RÉSULTATS: Nous avons identifié un total de 3,654 diagnostiques appartenant aux OF et ONF chez les 343 sujets étudiés. Pour les OF, nous avons trouvé que: (1) un grand total de 1,103 diagnostiques du système circulatoire ont affecté 299 sujets avec 555 occurrences et 247 premières occurrences; (2) 333 des sujets participants ont reçu 1,536 diagnostiques non-CV avec 195 occurrences et 107 premières occurrences; (3) 62 diagnostiques de toutes autres causes chez 62 des sujets participants avec 81 occurrences et 11 premières occurrences. Pour les ONF: (1) 156 diagnostiques du système circulatoire ont affecté 105 sujets; (2) 60 diagnostiques de causes non-CV chez 53 des sujets; (3) et 718 diagnostiques de toutes autres causes chez 252 des sujets. Pour les OF, 109 des 333 sujets affectés par les maladies non-CV et 58 des 62 par toutes autres maladies étaient atteints simultanément par des MCV. Nous avons décrit les caractéristiques des maladies avec occurrences fatales et non fatales. Les MCVs prédominaient dans les résultats des premières occurrences et occurrences totales tandis que les maladies non-CV étaient les plus élevées pour les diagnostiques. De plus, les OF CV ont affecté 67.1% de notre échantillon de population, incluant les sujets co-affectés par les maladies non-CV ou de toutes autres causes. En fait, nos sujets ont un risque trois fois plus élevé de développer des MCVs (p<0.0001; χ2=1,575.348), tandis qu’il diminue de moitié pour les maladies non-CV comparativement au reste de la population du SLSJ (p=0.0006; χ2=11.834). Enfin, le risque de développer des tumeurs malignes est diminué de moitié dans notre échantillon comparativement à l’incidence régionale. CONCLUSION: Cette étude a apporté une nouvelle perspective sur les OF et ONF chez nos sujets de la région SLSJ du Québec après 11 ans. Quand on observe ces résultats en conjonction avec les MCVs, ce risque double.

A natureza na lineal dos funcionamentos inferenciais: um estudo empírico com base no humor gráfico

Analisa-se se os funcionamentos inferenciais têm uma estrutura própria dos sistemas dinâmicos não lineais, estudados a partir de quatro gráficas humorísticas. Os primeiros resultados com o tratamento estadístico lineal de K-medias projetam a presencia de perfis de diferentes funcionamentos inferenciais em função das diferentes piadas. Os resultados com a técnica da wavelet, proveniente dos sistemas dinâmicos não lineais, mostram patrões dos funcionamentos inferenciais que dão conta de sua natureza multifractal, sem uma sequencialidade fixa e sem uma organização aparente. Isto implica que é necessário revisar a concepção de estádios sequenciais fixos como os que dominam os estudos de desenvolvimento cognitivo.

Improving Transition Outcomes: Prototype First Year Highlights

Highlights from the community demonstration prototypes first year.

Clinical Development Strategies and Outcomes in First-in-Human Trials of Monoclonal Antibodies.

PURPOSE: We conducted a comprehensive review of the design, implementation, and outcome of first-in-human (FIH) trials of monoclonal antibodies (mAbs) to clearly determine early clinical development strategies for this class of compounds. METHODS: We performed a PubMed search using appropriate terms to identify reports of FIH trials of mAbs published in peer-reviewed journals between January 2000 and April 2013. RESULTS: A total of 82 publications describing FIH trials were selected for analysis. Only 27 articles (33%) reported the criteria used for selecting the starting dose (SD). Dose escalation was performed using rule-based methods in 66 trials (80%). The median number of planned dose levels was five (range, two to 13). The median of the ratio between the highest planned dose and the SD was 27 (range, two to 3,333). Although in 56 studies (68%) at least one grade 3 or 4 toxicity event was reported, no dose-limiting toxicity was observed in 47 trials (57%). The highest planned dose was reached in all trials, but the maximum-tolerated dose (MTD) was defined in only 13 studies (16%). The median of the ratio between MTD and SD was eight (range, four to 1,000). The recommended phase II dose was indicated in 34 studies (41%), but in 25 (73%) of these trials, this dose was chosen without considering toxicity as the main selection criterion. CONCLUSION: This literature review highlights the broad design heterogeneity of FIH trials testing mAbs. Because of the limited observed toxicity, the MTD was infrequently reached, and therefore, the recommended phase II dose for subsequent clinical trials was only tentatively defined.

Community remoteness and birth outcomes among First Nations in Quebec

OBJECTIF: Chez les Autochtones, la relation entre le degré d'éloignement et les issues de naissance est inconnue. L’objectif de cette étude est d’évaluer cet impact parmi les Premières Nations du Québec. MÉTHODE : Nous avons utilisé les données vitales de Statistique Canada pour la province du Québec pour la période 1991-2000. L’ensemble des naissances géocodées parmi les communautés des Premières Nations groupées en quatre zones en se basant sur le degré d'éloignement a été analysé. Nous avons utilisé la régression logistique multi-niveaux pour obtenir des rapports de cotes ajustés pour les caractéristiques maternelles. RESULTATS : Le taux de naissances prématurées varie en fonction de l’éloignement de la zone d’habitation (8,2% dans la zone la moins éloignée et 5,2% dans la Zone la plus éloignée, P<0,01). En revanche, plus la zone est éloignée, plus le taux de mortalité infantile est élevé (6,9 pour 1000 pour la Zone 1 et 16,8 pour 1000 pour la Zone 4, P<0,01). Le taux élevé de mortalité infantile dans la zone la plus éloignée pourrait être partiellement expliqué par le fort taux de mortalité post-natale. Le taux de mort subite du nourrisson est 3 fois plus élevé dans la zone 4 par rapport à la zone 1. Cependant la mortalité prénatale ne présente pas de différences significatives en fonction de la zone malgré une fréquence élevée dans la zone 4. La morbidité périnatale était semblable en fonction de la zone après avoir ajusté pour l’âge, l’éducation, la parité et le statut civil. CONCLUSIONS : Malgré de plus faibles taux d’enfants à haut risque (accouchements prématurés), les Premières Nations vivant dans les communautés les plus éloignées ont un risque plus élevé de mortalité infantile et plus spécialement de mortalité post-néonatale par rapport aux Premières Nations vivant dans des communautés moins éloignées. Il y existe un grand besoin d’investissement en services de santé et en promotion de la santé dans les communautés les plus éloignées afin de réduire le taux de mortalité infantile et surtout post-néonatale.

Maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia in Brazilian women

Objective. To evaluate maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia (GTN) in Brazilian patients.Methods. This study included 252 subsequent pregnancies after chemotherapy for GTN treated between 1960-2005. Correlations of maternal and perinatal outcomes with chemotherapy regimen (single or multiagent) and the time interval between chemotherapy completion and first subsequent pregnancy were investigated.Results. There was a significant increase in adverse maternal outcomes in women who conceived <6 months than 6-12 months (76.2% and 19.6%; p<0.0001; OR=13.12; CI 95%=3.87-44.40) and >12 months (76.2% and 21.7%; P<0.0001; OR=11.56; CI 95%=3.98-33.55) after chemotherapy. Spontaneous abortion frequency was higher <6 months (71.4%) than 6-12 months (17.6%; p<0.0001: OR=11.66; CI 95%=3.55-38.22) and >12 months (9.4%; p<0.0001: OR=23.97: CI 95%=8.21-69.91) after chemotherapy. There was no difference in adverse perinatal outcomes (stillbirth, fetal malformation, and preterm birth) related to the interval after chemotherapy and Subsequent pregnancy. The overall occurrence of adverse maternal and perinatal outcomes did not significantly differ between patients on single or multiagent regimens.Conclusion. Adverse maternal outcomes and spontaneous abortion were more frequent among patients who conceived within 6 months of chemotherapy completion. In these cases, careful prenatal monitoring and hCG level measurement 6 weeks after the completion of any new pregnancy are recommended. (C) 2008 Elsevier B.V. All rights reserved.

Fertility-associated antigen on Nelore bull sperm and reproductive outcomes following first-service fixed-time AT of Nelore cows and heifers

The objective was to determine whether the presence of fertility-associated antigen (FAA) on sperm collected from Nelore (Bos indicus) bulls can be used to assess potential fertility of sperm for use at first-service fixed-time AI (TAI). Six Nelore bulls were selected based on FAA status (FAA-negative: N = 3; FAA-positive: N = 3) and the ability to produce neat semen with >= 70% morphologically normal sperm and 60% estimated progressive motility before cryopmservation. In Experiment 1, suckled multiparous Nelore cows (N = 835) were evaluated for body condition score (BCS) and received an intravaginal progesterone device (CIDR) and 2.0 mg of estradiol benzoate (Day 0). on Day 9 the CIDR was removed, 12.5 mg of PGF(2 alpha) and 0.5 mg of estradiol cypionate were administered, and calves were removed for 48 h. All cows received TAI on Day II (48 h after CIDR removal). Pregnancy per TAI (P/TAI) was not different between FAA-positive and FAA-negative bulls (41.5% vs. 39.3%, respectively). There was an effect of AI technician on P/TAI (36.0% vs. 43.9%; P < 0.05) and BCS tended to affect P/TAI (P = 0.09), as cows with BCS >= 2.75 were 1.4 times more likely to become pregnant compared with cows with BCS < 2.75. In Experiment 2, nulliparous Nelore heifers (N = 617) were evaluated for BCS and received a CIDR and estradiol benzoate (2.0 mg) on Day 0. on Day 7, all heifers received PGF(2 alpha) (12.5 mg). on Day 9, CIDR inserts were removed and all heifers received estradiol cypionate (0.6 mg) and 200 IU eCG. All heifers received TAI on Day 11 (48 h after CIDR removal). Pregnancy/TAI was different (P = 0.04) between FAA-positive and FAA-negative bulls (33.7% vs. 40.7%, respectively). Presence of FAA on sperm was unsuccessful in assessing the potential fertility of sperm for use in TAI. (C) 2012 Elsevier B.V. All rights reserved.

Nonpoint Pollution Control: Inducing First-best Outcomes through the Use of Threats

In this paper we develop a simple economic model to analyze the use of a policy that combines a voluntary approach to controlling nonpoint-source pollution with a background threat of an ambient tax if the voluntary approach is unsuccessful in meeting a pre-specified environmental goal. We first consider the case where the policy is applied to a single farmer, and then extend the analysis to the case where the policy is applied to a group of farmers. We show that in either case such a policy can induce cost-minimizing abatement without the need for farm-specific information. In this sense, the combined policy approach is not only more effective in protecting environmental quality than a pure voluntary approach (which does not ensure that water quality goals are met) but also less costly than a pure ambient tax approach (since it entails lower information costs). However, when the policy is applied to a group of farmers, we show that there is a potential tradeoff in the design of the policy. In this context, lowering the cutoff level of pollution used for determining total tax payments increases the likely effectiveness of the combined approach but also increases the potential for free riding. By setting the cutoff level equal to the target level of pollution, the regulator can eliminate free riding and ensure that cost-minimizing abatement is the unique Nash equilibrium under which the target is met voluntarily. However, this cutoff level also ensures that zero voluntary abatement is a Nash equilibrium. In addition, with this cutoff level the equilibrium under which the target is met voluntarily will not strictly dominate the equilibrium under which it is not. We show that all results still hold if the background threat instead takes the form of reducing government subsidies if a pre-specified environmental goal is not met.

Vitamin D status in the first-trimester: effects of Vitamin D deficiency on pregnancy outcomes.

Objective: To assess serum levels of 25-hydroxyvitamin D [25(OH)D] in the first trimester and to determine the factors affecting deficiency levels and its association with pregnancy outcomes. Methods: Serum 25(OH)D concentrations were measured at 11-14 weeks’ gestation in 229 singleton pregnancies using liquid chromatography-tandem mass spectrometry. Results: The median serum 25(OH)D concentration was 10.8 ng/mL and 45.9% of women had severe vitamin D deficiency with concentrations of <10 ng/mL. Logistic regression analysis revealed that covered dressing style, lack of multivitamin intake, season of blood sampling (November-April) were factors associated with 25(OH)D deficiency. There was a negative correlation between 25(OH)D levels and gestational age at sampling. Low 25(OH)D levels were not associated with adverse pregnancy outcomes. Higher rate of cesarean section (CS) was noted in women with 25(OH)D ≥10 ng/mL compared to those with 25(OH)D < 10mg/ml ( p= 0.01). Conclusion: A high prevalence of vitamin D deficiency was observed in early pregnancy which was related to dress code, use of multi-vitamins and season at sampling. Low 25(OH)D levels were not related with adverse pregnancy outcomes. Women with severe vitamin D deficiency were more likely to deliver vaginally.

Predicting Outcomes Of Balloon Laryngoplasty In Children With Subglottic Stenosis.

The treatment of subglottic stenosis in children remains a challenge for the otolaryngologist and may involve procedures such as endoscopy, open surgery, and often both. In the recent past, high-pressure balloons have been used in endoscopic treatment due to their relative facility and high success rates. To report success rates in the treatment of acquired subglottic stenosis with balloon laryngoplasty in children and identify predictive factors for the success of the technique and its complications. Descriptive, prospective study of children who were diagnosed with acquired subglottic stenosis and underwent balloon laryngoplasty as the primary treatment. Balloon laryngoplasty was performed in 48 children with an average age of 20.7 months: 31 presented with chronic subglottic stenosis and 17 with acute stenosis. Success rate was 100% for acute and 39% for chronic subglottic stenosis. Success was significantly associated with several factors, including recently acquired stenosis, initial grade of stenosis, younger patient age, and the absence of tracheotomy. Complications were transitory dysphagia observed in three children and a submucosal cyst in one of the patients. Balloon laryngoplasty may be considered as a first line of treatment for acquired subglottic stenosis. In acute cases, the success rate was 100%, and even though results are less promising in chronic cases, complications were not significant and the patients can undergo open surgery without contraindications. Predictive factors of success were acute stenosis, less severe grades of stenosis, younger patient age, and the absence of tracheotomy.

The International Collaboration on Air Pollution and Pregnancy Outcomes: Initial Results

BACKGROUND: The findings of prior studies of air pollution effects on adverse birth outcomes are difficult to synthesize because of differences in study design. OBJECTIVES: The International Collaboration on Air Pollution and Pregnancy Outcomes was formed to understand how differences in research methods contribute to variations in findings. We initiated a feasibility study to a) assess the ability of geographically diverse research groups to analyze their data sets using a common protocol and b) perform location-specific analyses of air pollution effects on birth weight using a standardized statistical approach. METHODS: Fourteen research groups from nine countries participated. We developed a protocol to estimate odds ratios (ORs) for the association between particulate matter <= 10 mu m in aerodynamic diameter (PM(10)) and low birth weight (LBW) among term births, adjusted first for socioeconomic status (SES) and second for additional location-specific variables. RESULTS: Among locations with data for the PM(10) analysis, ORs estimating the relative risk of term LBW associated with a 10-mu g/m(3) increase in average PM(10) concentration during pregnancy, adjusted for SES, ranged from 0.63 [95% confidence interval (CI), 0.30-1.35] for the Netherlands to 1.15 (95% CI, 0.61-2.18) for Vancouver, with six research groups reporting statistically significant adverse associations. We found evidence of statistically significant heterogeneity in estimated effects among locations. CONCLUSIONS: Variability in PM(10)-LBW relationships among study locations remained despite use of a common statistical approach. A more detailed meta-analysis and use of more complex protocols for future analysis may uncover reasons for heterogeneity across locations. However, our findings confirm the potential for a diverse group of researchers to analyze their data in a standardized way to improve understanding of air pollution effects on birth outcomes.

Project to investigate improving literacy and numeracy outcomes of distance education students in the early years of schooling

The project was commissioned to investigate and analyse the issue of effective support for distance education students in the early years of school to maximise literacy and numeracy outcomes. The scope of this project was limited to students living in rural and remote areas who are undertaking education at home and who are in their early years of schooling. For the purpose of this project, the early years are conceptualised as the first three years of formal compulsory schooling in each of the States and Territories. There were a number of key tasks for the project which included: 1. Examining of the role of home tutors/supervisors This included interviewing personnel from the State and Territory distance education providers as well as the principals, teachers, home tutors and children. 2. Describing literacy and numeracy teaching and learning, and the use of information and communication technologies (ICT) in distance education This aspect of the project involved a critical review and analysis of relevant literature and reports in the last five years, and a consideration of the new initiatives that had been implemented in the States and Territories in the last two years. 3. The development of resources Through examination of the role of home tutors/supervisors, and an examination of literacy and numeracy and the use of technology in distance education, three resources were developed: ● A guide for home tutors/supervisors and schools of distance education about effective intervention and assessment strategies to support students’ learning and to assist the home tutors/supervisors in implementing ICT to support the development of literacy and numeracy in the early years. ● A calendar of activities for literacy and numeracy that would act as a stimulus for integrated and authentic activity for young children. ● An embryonic website of resources for the stakeholders in rural and distance education that might act as a catalyst for future resource building and sharing. In this way the final key task of the project, which was to create a context for a strategic dissemination plan, was realised when a strategy to address effective dissemination of the findings of the project so as to maximise their usefulness for the relevant groups was achieved.

Long-term disability after first-ever stroke and related prognostic factors in the Perth Community Stroke Study, 1989-1990

Background and Purpose-Few reliable estimates of the long-term functional outcome after stroke are available. This population-based study aimed to describe disability, dependency, and related independent prognostic factors at 5 years after,a first-ever stroke in patients in Perth, Western Australia. Methods-All individuals with a suspected acute stroke who were resident in a geographically defined region (population, 138 708) of Perth, Western Australia, were registered prospectively and assessed according to standardized diagnostic criteria over a period of 18 months in 1989 to 1990. Patients were followed up prospectively at 4 and 12 months and 5 years after the index event. Results-There were 370 cases of first-ever stroke, and 277 patients survived to 30 days. Of these early survivors, 152 (55%) were alive at 5 years, and among those who were neither institutionalized (n=146) nor disabled (n=129) at the time of their stroke, 21 (14%) were institutionalized in a nursing home, and 47 (36%) were disabled. The most important predictors of death or disability at 5 years were increasing age, baseline disability defined by a Barthel Index score of <20/20 (odds ratio [OR], 6.3; 95% confidence interval [CI], 2.7 to 14), moderate hemiparesis (OR, 2.7. 95% CI, 1.1 to 6.2), severe hemiparesis (OR, 4.5; 95% CI, 1.1 to 19), and recurrent stroke (OR, 9.4; 95% CI, 3.0 to 30). A low level of activity before the stroke was a significant predictor of institutionalization, and subsequent recurrent stroke was a consistent, independent predictor of institutionalization, disability, and death or institutionalization, increasing the odds of each of these 3 adverse outcomes by 5- to 15-fold. Conclusions-Among 30-day survivors of first-ever stroke, about half survive 5 years; of survivors, one third remain disabled, and I in 7 are in permanent institutional care. The major modifiable predictors of poor long-term outcome are a low level of activity before the stroke and subsequent recurrent stroke. Efforts to increase physical activity among the elderly and to prevent recurrent stroke in survivors of a first stroke are likely to reduce the long-term burden of cerebrovascular disease.