Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study.

OBJECTIVE: The objective was to compare, in a real-world setting, the risk of mental and physical health events associated with different antipsychotic drugs (clozapine, olanzapine, risperidone, quetiapine and first-generation antipsychotics) in patients with SZ. METHODS: This is a retrospective cohort study using administrative data. Outcome measures included any mental health event (suicide, hospitalization or emergency visit for mental disorders) and physical health event (death other than suicide, hospitalization or emergency visit for physical disorders). Cox proportional hazard models were used to estimate the hazard ratios of the events associated with the use of the different antipsychotic drugs. RESULTS: The cohort included 18 869 adult patients living in the province of Quebec (Canada) with SZ and starting antipsychotic drugs between January 1998 and December 2005. Results show that quetiapine and not using any antipsychotics were associated with an increased risk of mental and physical health events as compared to other drugs. The second finding is the confirmation of better performance of clozapine. The results were robust across sensitivity analyses. CONCLUSION: Both findings call for an international public health and drug agencies surveillance of 'real-world' antipsychotic medication to ensure the optimal choices in treatment guidelines for SZ.

Secular trends of hip fractures in Québec, Canada.

UNLABELLED: This study examined the secular trends of hip fracture incidence among individuals 50 years and older in Québec between 1993 and 2004. Age-standardized rates decreased at both the provincial and regional levels. The largest relative decrease was observed among younger females, and rates declined more slowly in the elderly. INTRODUCTION: The population of the province of Québec is among the oldest in North America. Before the trend rupture reported in the late 1990s in several countries, hip fracture (HF) incidence rates did not show a secular trend (between 1981 and 1992). This study examined the secular trends of HF incidence at the provincial level and in two of the most important urban areas of the province, Montréal and Québec City, between 1993 and 2004. METHODS: All hospitalisations of individuals 50 years and older living in the province of Québec between 1993 and 2004 with a main diagnosis of HF were included. Standardized rates of HF incidence were calculated for females and males, 50-74 years and 75 years and older. RESULTS: The Québec City area showed a strong decreasing trend in HF rates for younger females, but the other groups did not show an obvious trend. Although our models did not support the existence of significant differences in trends between both areas, the rates of HF of younger males and, to a lesser extent, of older women in the Montréal area were significantly higher than in the Québec City area. CONCLUSIONS: Differences observed in hip fracture rates as well as in secular trends between age groups and gender emphasise the need for decision makers to rely on results based on age-specific and sex-specific analyses.

Inclusion probability with dropout: an operational formula.

In forensic genetics, a mixture of two or more contributors to a DNA profile is often interpreted using the inclusion probabilities theory. In this paper, we present a general formula for estimating the probability of inclusion (PI, also known as the RMNE probability) from a subset of visible alleles when dropouts are possible. This one-locus formula can easily be extended to multiple loci using the cumulative probability of inclusion. We show that an exact formulation requires fixing the number of contributors, hence to slightly modify the classic interpretation of the PI. We discuss the implications of our results for the enduring debate over the use of PI vs likelihood ratio approaches within the context of low template amplifications.

Thiols can either enhance or suppress DNA damage induction by catecholestrogens.

The estrogen metabolites catecholestrogens (or hydroxyestrogens) are involved in carcinogenesis and the development of resistance to methotrexate. This induction of drug resistance correlates with the relative efficiency of catecholestrogens in the generation of reactive oxygen species (ROS) and the induction of DNA strand breaks. Although antioxidants can neutralize ROS, the generation of these reactive species by catecholestrogens can be enhanced by electron donors like NADH. Therefore, this study was undertaken to determine the ability of different thiol agents (GSH, NAC, DTT, DHLA) to either inhibit or enhance the level of DNA damage induced by the H(2)O(2) generating system 4-hydroxyestradiol/Cu(II). Our results show that GSH, DTT, and DHLA inhibited the induction of the 4-hydroxyestradiol/Cu(II)-mediated DNA damage, with GSH showing the best potential. In contrast, the GSH precursor NAC at low concentrations was able to enhance the level of oxidative damage, as observed with NADH. NAC can reduce Cu(II) to Cu(I) producing the radical NAC&z.rad;, which can generate the superoxide anion. However, the importance of this pathway appears to be relatively minor since the addition of NAC to the 4-hydroxyestradiol/Cu(II) system generates about 15 times more DNA strand breaks than NAC and Cu(II) alone. We suggest that NAC can perpetuate the redox cycle between the quinone and the semiquinone forms of the catecholestrogens, thereby enhancing the production of ROS. In conclusion, this study demonstrates the crucial importance of the choice of antioxidant as potential therapy against the negative biological effects of estrogens.

Dyslipidemias and the primary prevention of cardiovascular disease: analysis of the FAMUS primary care register.

BACKGROUND: Primary prevention of cardiovascular disease with a pharmacological approach to dyslipidemias is controversial. Little is known about the clinical management by general practitioners in this area. OBJECTIVES: To evaluate the patterns of treatment of patients in primary prevention who were entered in the FAmily Medicine, Université de Sherbrooke (FAMUS) register and to calculate the probability of their receiving a hypolipidemic agent according to the presence of various risk profiles. PATIENTS AND METHODS: Descriptive study based on the FAMUS prospective primary care register. Data from patients in primary prevention (those who had not sustained a cardiovascular event) were extracted and analyzed. MAIN RESULTS: Of the 52,505 patients in the register, 48, 190 were identified as being in primary prevention. Of these, 22,250 (46.2%) had a complete lipid profile on record, and 2300 had received a prescription for a hypolipidemic agent (4.8%). Patients under pharmacological treatment had significantly higher lipid values. The adjusted relative risk of being treated with a hypolipidemic agent was 1.3 for smokers, 1.3 for diabetic patients, 2.0 for those with a positive family history of premature cardiovascular disease, 2.2 for hypertensives and 3.3 for men over 45 years of age or women over 55 years, compared with patients who were not taking lipid-lowering medications. The number of risk factors was even more strongly associated with the probability of being treated. CONCLUSION: Overall, few patients in primary prevention in the register were treated with a pharmacological agent. The presence of associated risk factors in this study was an important predictor for treatment, suggesting that patients in primary prevention are being evaluated globally as a function of all of their risk factors, not just their lipid and lipoprotein levels. Further attention, nonetheless, needs to be directed to the segment of the population with multiple risk factors whose lipoprotein profile is unknown or who are not being treated to guideline target levels.

Improving the selection of true incident cases of low back pain by screening retrospective administrative data.

BACKGROUND: The difficulty in identifying the onset of low back pain (LBP) limits the capacity to determine the incidence of LBP at the population level and, further, to identify risk factors. In the literature, incidence cohorts have been built with patients initially considered LBP-free for 6-12 months prior to their selection. This 'clearance period' might not be sufficient to exclude recurrent patients having experienced previous LBP episodes and might result in a misclassification bias. METHODS: Using the Canadian province of Quebec's medical administrative physicians' claims database, a cohort of prevalent claims-based recurrent LBP patients was built for 2007. The medical history of 81,329 patients was screened for a period of 11 years. Positive predictive values (PPVs), kappa statistics and a survival function were calculated to determine the optimal clearance period for capturing first-time events. RESULTS: The 2007 annual incidence of adult claims-based recurrent LBP was estimated at 242 per 100,000 persons. Men between 18 and 34 years of age were found to be 1.18 times more at risk than their counterparts. Altogether, the elderly (over 80 years) had 52% more new cases than the 18-34 age group. A very good convergence for PPV and kappa was found for a 7-year clearance period. This allowed determining the annual incidence from 2000 to 2007, showing a decrease of 26%. CONCLUSION: Screening the medical history of LBP patients can provide more accurate incidence estimates by limiting the over-ascertainment of first-time LBP patients. A 4- to 7-year clearance period should be considered.

Health inequalities associated with neighbourhood deprivation in the Quebec population with hypertension in primary prevention of cardiovascular disease.

INTRODUCTION: Although a number of studies look at prevalence, incidence, treatment, mortality and morbidity in relation to hypertension, few have taken into account the effect of residential neighbourhood on these health indicators in the population diagnosed with hypertension. OBJECTIVES: The objective of this study was to measure and compare prevalence, mortality, morbidity, use of medical resources and treatments in relation to the level of material and social deprivation of the area of residence, in a population with a diagnosis of hypertension in primary prevention for cardiovascular disease (CVD) in Quebec in 2006-2007. METHODS: This study is based on a secondary analysis of the medical administrative data of the Quebec health insurance board, the Régie de l'assurance maladie du Québec, for a cohort of 276 793 patients aged 30 years or older who had been diagnosed with hypertension in 2006 or 2007, but who did not have a known diagnosis of CVD. The health indicators adjusted for age and sex are prevalence, death, a cardiovascular event, physician visits, emergency department visits and use of antihypertensives. Twenty-five types of areas of residence were obtained by crossing the material and social deprivation quintiles. RESULTS: Compared with patients living in materially and socially advantaged areas, those living in deprived areas were at 46% higher risk of a cardiovascular event, 47% higher risk of being frequent emergency department visitors and 31% higher risk of being frequent users of a general practitioner's services, but 25% lower risk of being frequent users of medical specialists' services. Little or no variation was observed in the use of antihypertensives. CONCLUSION: This study reveals the existence, in a CVD primary prevention context, of large variations in a number of health indicators among hypertensive patients owing to the material and social deprivation of residential neighbourhood. It is therefore important to take the socioeconomic context into account when planning interventions to prevent CVDs and their consequences.

TITRE: Inégalités de santé associées à la défavorisation du secteur de résidence au sein de la population du Québec ayant reçu un diagnostic d'hypertension artérielle en prévention primaire des maladies cardiovasculaires. INTRODUCTION: Bien que plusieurs études traitent de la prévalence, de l'incidence, du traitement, de la mortalité et de la morbidité en lien avec l'hypertension artérielle (HTA), peu d'entre elles tiennent compte de l'influence des secteurs de résidence sur ces indicateurs de santé au sein de la population ayant reçu un diagnostic d'HTA. OBJECTIFS: L'objectif de cette étude était de mesurer et comparer la prévalence, la mortalité, la morbidité, l'utilisation des ressources médicales et les traitements selon le niveau de défavorisation matérielle et sociale du secteur de résidence au sein de la population ayant reçu un diagnostic d'HTA en prévention primaire des maladies cardiovasculaires (MCV) au Québec en 2006-2007. MÉTHODOLOGIE: Cette étude repose sur une analyse secondaire des données médico- administratives de la Régie de l'assurance maladie du Québec pour une cohorte de 276 793 patients de 30 ans et plus ayant reçu un diagnostic d'HTA en 2006 ou en 2007 mais sans diagnostic connu de MCV. Les indicateurs de santé ajustés pour l'âge et le sexe sont la prévalence, le décès, un événement cardiovasculaire, les consultations médicales, les consultations à l'urgence ainsi que l'utilisation d'antihypertenseurs. Vingt-cinq types de secteurs de résidence ont été obtenus par croisement des quintiles de défavorisation matérielle et sociale. RÉSULTATS: Par rapport aux patients vivant dans des secteurs favorisés matériellement et socialement, ceux vivant dans des secteurs défavorisés avaient 46 % plus de risque d'événement cardiovasculaire, 47 % plus de risque d'être de grands utilisateurs de l'urgence, 31 % plus de risque d'être de grands utilisateurs des services d'un omnipraticien, mais 25 % moins de risque d'être de grands utilisateurs des services de médecins spécialistes. Peu ou pas de variation n'a été observée quant à l'utilisation d'antihypertenseurs. CONCLUSION: Cette étude révèle l'existence, dans le cadre de la prévention primaire des MCV, d'importantes variations pour plusieurs indicateurs de santé chez des patients hypertendus en raison de la défavorisation matérielle et sociale de leur secteur de résidence. Il est donc important de tenir compte du contexte socioéconomique lors de la planification d'interventions visant à prévenir les maladies cardiovasculaires et leurs conséquences.

[The ambulatory care of the acute myocardial infarction in Quebec: description, classification and typology]. / Les soins ambulatoires de l'infarctus aigu du myocarde au Québec : description, classification et typologie.

OBJECTIVE: Description of ambulatory care of AMI, in Quebec population. DESIGN: A retrospective cohort study was designed to classify and propose a typology of ambulatory care. METHODS: The studied population was included in all 25 years and older inpatients residing in Quebec, whose admission were from January to December 2000. The principal variables were: the number of medical visits, the type of consulted physicians and the place of consultation. The secondary variables were: age, sex and the presence of a revascularization. RESULTS: A typology of ambulatory care was created from principal variables. Men, younger patients and receiving a revascularization in the index hospitalization were cared for by a specialist.

Obesity in Canada: where and how many?

CONTEXT: Obesity rates are rising sharply among all industrialized countries; the situation seems to be worse in English speaking countries. Taking into account genetic predisposition, excess of caloric intake combined with low energy expenditure will usually result in obesity. OBJECTIVES: To describe and compare regional obesity rates across Canada and assess the ecological relationship between regional rates of obesity, low level of leisure-time physical activity, and low fruit and vegetable consumption. DESIGN: Cross-sectional population-based analysis from the 2003 Canadian Community Health Survey. MEASURES AND DATA ANALYSES: Canadian population distributions of body mass index (BMI), leisure-time physical activity and daily fruit and vegetable consumption were obtained from Statistics Canada. All these measures were based on the respondent's self-reported answers to a computer-assisted personal or telephone interview. Obesity rates (BMI> or =30), rates of low level of leisure-time physical activity (less than 1.5 kcal of energy expenditure per day), and rates of low fruit and vegetable consumption (less than five times a day) for the 106 Canadian Health regions were mapped to illustrate their geographical distribution. Cartograms were used in addition to traditional mapping to take into account the differences in population density between these small areas. RESULTS: In 2003, 15.2% of Canadian individuals aged 20 years and older were considered obese. The rates of obesity varied substantially between the 106 Canadian health regions: from 6.2% in Vancouver to 47.5% in aboriginal population area. At the health region level, low leisure-time physical activity and low fruit and vegetable consumption are both good predictors of obesity (odds ratio of 9.2 and positive predictive value of 93% when considered simultaneously). CONCLUSION: There is a strong gradient in obesity prevalence between Canadian health regions. At the regional level, high rates of low level of physical activity, and high rates of low fruit and vegetable consumption were both found good predictors of high rates of obesity.

Optimal sex ratios in structured populations.

In this paper, we develop a general method to determine evolutionary equilibrium sex ratios and to check evolutionary stability, continuous stability and invadability in exact genetic models with or without dominance. This method is then applied to three kinds of models for structured populations: the first one concerns Hamilton's LMC model, except that only a fraction beta of female offspring mate with male offspring born in the same colonies, while a fraction 1-beta mate with male offspring chosen at random within the whole population; in the second model, it is assumed that partial dispersal of inseminated females occurs after mating; in the third model, partial dispersal of male and female offspring occurs before mating. In the first model, the effect of population regulation is studied while, in the other models, two kinds of dispersal are considered: proportional and uniform.

[Evaluation of sphygmomanometers used by family physicians practicing outside the hospital environment in Bas-Saint-Laurent]. / Evaluation des sphygmomanomètres utilisés par les médecins de famille en milieu extra-hospitalier du Bas-Saint-Laurent.

OBJECTIVE: To assess the precision and integrity of all aneroid and mercury sphygmomanometers regularly used by family physicians practising outside hospitals. DESIGN: Cross-sectional study. SETTING: Private medical clinics and local community health centres in Bas-Saint-Laurent, Qué. PARTICIPANTS: A total of 151 of the 166 physicians in this administrative region. MAIN OUTCOME MEASURES: Precision of the mercury sphygmomanometers was measured using the difference between a reading in the absence of pressure and level 0. Precision of the aneroid sphygmomanometers was measured using variations at pressures of 140 mm Hg and 90 mm Hg compared with those on a calibrated mercury sphygmomanometer. Integrity of sphygmomanometers, arm cuffs, and inflating bulbs was also assessed. RESULTS: In all, 258 sphygmomanometers met the inclusion criteria (111 mercury sphygmomanometers and 147 aneroid sphygmomanometers). Discrepancies of > or = 4 mm Hg were found in 15.5% of these instruments (12.6% and 17.7% of the mercury and aneroid sphygmomanometers, respectively). In 31.0% of the instruments (52.3% and 15.0% of the mercury and aneroid sphygmomanometers, respectively), one component was malfunctioning. CONCLUSION: Sphygmomanometers that measure patients' blood pressure inaccurately could result in an incorrect diagnosis of hypertension or in a normal blood pressure reading in a hypertensive patient.

Stochastic effects in LMC models.

LMC (local mate competition) was first introduced by W. D. Hamilton to explain extraordinary female-biased sex ratios observed in a variety of insects and mites. In the original model, the population is subdivided into an infinite number of colonies founded by a fixed number of inseminated females producing the same very large number of offspring. The male offspring compete within the colonies to inseminate the female offspring and then these disperse at random to found new colonies. An unbeatable sex ratio strategy is found to be female-biased. In this paper, the effects of having colonies of random size and foundresses producing a random finite number of offspring are considered. The exact evolutionarily stable strategy (ESS) sex ratio is deduced and comparisons with previous approximate or numerical results are made. As the mean or the variance of brood size increases, the ESS sex ratio becomes more female-biased. An increase in the variance of colony size increases the ESS proportion of males when the mean brood size and colony size are both small, but decreases this proportion when the mean brood size or the mean colony size is large.

Family history and the risk of coronary heart disease: comparing predictive models.

Family history is commonly used when evaluating coronary heart disease (CHD) risk yet it is usually treated as a simple binary variable according to the occurrence or non-occurrence of disease. This definition however fails to consider the potential components of a family history which may in fact exert different degrees of influence on the overall risk profile. The purpose of this paper is to compare different predictive models for CHD which incorporate family history as either a binary variable or different types of family risk indices in terms of their predictive ability. Models for estimating CHD risk were constructed based on usual risk factors and different family history variables. This construction was accomplished using logistic regression and RECursive Partition and AMalgamation (RECPAM) trees. Our analyses demonstrate the importance of using more sophisticated definitions of family history variables compared to a simple binary approach since this leads to a significant improvement in the predictive ability of CHD risk models.

Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: I. Exposure and symptomatology.

OBJECTIVE: The admission to hospital of three construction workers with acute respiratory distress caused by inhalation of chlorine gas prompted the inspection of a building site located in a kraft pulpmill. The accidental emissions had taken place in the bleach plant and the construction workers assigned there were surveyed to uncover possible large scale health effects. DESIGN AND PARTICIPANTS: A questionnaire was presented to 281 workers (participation rate = 97%); 257 workers reported an average of 24 exposure episodes to chlorine and derivatives over a three to six month period. The air monitoring data available from the pulpmill's industrial hygienist were not useful in linking specific events reported by the workers to environmental conditions in the bleach plant. RESULTS: Over 60% of the workers described a characteristic flu like syndrome that lasted for an average of 11 days and was exacerbated by new bouts of exposure. Irritation of the throat (78%) and eyes (77%), cough (67%), and headache (63%) were the most often reported symptoms. Shortness of breath was reported by 54% of the participants and was not associated with age, smoking state, or history of asthma or chronic bronchitis. First aid self referral was associated with significantly greater reporting of most symptoms, including dyspnoea and cough. A significantly greater proportion of workers in the dyspnoea group had gone at least once for first aid care after a gassing incident (64% as opposed to 48%, p = 0.008). Throat irritation and cough persisted for mean intervals of eight and 11 days respectively. A flu like syndrome lasted for an average of 20 days. Seventy one subjects were considered to be a moderate to high risk of having persisting respiratory symptoms. CONCLUSION: Throat and eye irritation as well as cough and flu like symptoms are frequent occurrences after repeated accidental inhalation of chlorine. Subjects who consulted first aid care stations after a gassing incident are more likely to have persisting dyspnoea.

Prevalence of occupational asthma among workers exposed to eastern white cedar.

We assessed the prevalence of occupational asthma among current (n = 29/31, 94%) and former (n = 13/49, 27%) employees of a sawmill in which eastern white cedar has been made into shingles during the past 3 yr. All participants answered a respiratory questionnaire, and all except one underwent spirometry and methacholine inhalation tests. All those with bronchial hyperresponsiveness (PC20 methacholine < or = 19 mg/ml) were invited to undergo specific inhalation challenges. Mean duration of exposure was 13 mo (19 workers > 12 mo). Twenty-eight workers (65%) reported a history compatible with asthma, and 25 (58%) had symptoms that were suggestive of occupational asthma. Only two subjects had significant airway obstruction (FEV1 < 80% pred) (mean value = 98% pred). Eighteen subjects (42%) had a PC20 < or = 16 mg/ml. Specific inhalation tests with plicatic acid and/or western red cedar (which contains twice as much plicatic acid as eastern white cedar), were done on 12 subjects who had a PC20 < or = 16 mg/ml when they were assessed. Three subjects were considered to have positive tests (one had an isolated immediate reaction, one had a late reaction, and one had significant changes in PC20 each time he was exposed but no changes in FEV1). Environmental monitoring showed concentrations of total dusts above 2 mg/m3 in half of the samples. The prevalence of occupational asthma in this workplace was three of 42 participants (7%) or at least three of 80 (3.8%) of all current or ex-workers. This is comparable to the prevalence of occupational asthma in subjects exposed to western red cedar.

Bronchial hyperresponsiveness can improve while spirometry plateaus two to three years after repeated exposure to chlorine causing respiratory symptoms.

Repeated exposure to chlorine in pulp mills and paper can induce persistent asthma-like symptoms such as bronchial hyperresponsiveness and variable changes in airway caliber. The long-term time course of bronchial hyperresponsiveness has not been examined. We studied 20 of 29 subjects (69% participation rate) who demonstrated bronchial hyperresponsiveness to methacholine when they were first assessed, 18 to 24 mo after repeatedly inhaling "puffs" of high concentrations of chlorine in a paper mill over a 3-mo period. Each subject answered a respiratory questionnaire and underwent spirometry and a methacholine inhalation test 12 mo after the initial survey, 30 to 36 mo after the chlorine inhalations. Three subjects required inhaled steroids at the time of the initial survey and three at the time of the second, including two who carried on using these preparations. Only one subject changed smoking habits. There were no significant overall changes in FEV1 on the two occasions, nine subjects having a FEV1 < 80% on the first occasion and eight on the second. Six of the 18 subjects (33%) who underwent a methacholine inhalation test on both occasions had significantly improved PC20 results, including five for whom the PC20 value was within the normal range. All six subjects had normal FEV1 values on both assessments. Although changes in spirometry induced by repeated exposure to chlorine seem to persist, bronchial hyperresponsiveness can improve significantly in those with normal airway caliber. This suggests that less pronounced bronchial alterations induced by repeated exposures to chlorine may be reversible.

Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: II. Follow up of affected workers by questionnaire, spirometry, and assessment of bronchial responsiveness 18 to 24 months after exposure ended.

OBJECTIVE: The aim was to determine the prevalence of persistent respiratory symptoms and bronchial hyper-responsiveness due to reactive airways dysfunction syndrome in a population of construction workers at moderate to high risk of developing the syndrome, at an interval of 18 to 24 months after multiple exposures to chlorine gas during renovations to a pulp and paper mill. DESIGN AND PARTICIPANTS: 71 of 289 exposed workers (25%) were identified on the basis of an exposure and the onset of respiratory symptoms shortly after this event (moderate to high risk). A standardised respiratory questionnaire was first presented, followed by spirometry and a methacholine inhalation test on those whose questionnaire suggested the persistence of respiratory symptoms. RESULTS: 64 of 71 (90%) subjects completed the respiratory questionnaire at the time of the follow up. The questionnaire suggested a persistence of respiratory symptoms in 58 of the 64 workers (91%). Of the 58 subjects, 51 underwent spirometry and assessment of bronchial responsiveness. All of them used bronchodilators as required (not regularly) and four required inhaled anti-inflammatory preparations. Sixteen had bronchial obstruction (forced expiratory volume in one second) (FEV1 < 80% predicted) and 29 showed significant bronchial hyper-responsiveness. CONCLUSION: Of the subjects (n = 71) who were at moderate to high risk of developing reactive airways dysfunction syndrome after being exposed to chlorine and were seen 18 to 24 months after exposure ended, 58 (82%) still had respiratory symptoms, 16 (23%) had evidence of bronchial obstruction, and 29 (41%) had bronchial hyper-responsiveness.