Nonvitamin-k-antagonist oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin. METHODS: We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies. RESULTS: Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074-0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8-2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075-0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032-0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139). CONCLUSIONS: In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.

Stability and change in party preferences.

This article analyses stability and volatility of party preferences using data from the Swiss Household-Panel (SHP), which, for the first time, allow studying transitions and stability of voters over several years in Switzerland. Analyses cover the years 1999- 2007 and systematically distinguish changes between party blocks and changes within party blocks. The first part looks at different patterns of change, which show relatively high volatility. The second part tests several theories on causes of such changes applying a multinomial random-effects model. Results show that party preferences stabilise with their duration and with age and that the electoral cycle, political sophistication, socio-structural predispositions, the household-context as well as party size and the number of parties each explain part of electoral volatility. Different results for withinand between party-block changes underlie the importance of that differentiation.

Risk factors for positive tuberculin skin tests among migrant and resident children in Lausanne, Switzerland.

SETTING: Ambulatory paediatric clinic in Lausanne, Switzerland, a country with a significant proportion of tuberculosis (TB) among immigrants. AIM: To assess the factors associated with positive tuberculin skin tests (TST) among children examined during a health check-up or during TB contact tracing, notably the influence of BCG vaccination (Bacille Calmette Guérin) and history of TB contact. METHOD: A descriptive study of children who had a TST (2 Units RT23) between November 2002 and April 2004. Age, sex, history of TB contact, BCG vaccination status, country of origin and birth outside Switzerland were recorded. RESULTS: Of 234 children, 176 (75%) had a reaction equal to zero and 31 (13%) tested positive (>10 mm). In a linear regression model, the size of the TST varied significantly according to the history of TB contact, age, TB incidence in the country of origin and BCG vaccination status but not according to sex or birth in or outside Switzerland. In a logistic regression model including all the recorded variables, age (Odds Ratio = 1.21, 95% CI 1.08; 1.35), a history of TB contact (OR = 7.31, 95% CI 2.23; 24) and the incidence of TB in the country of origin (OR = 1.01, 95% CI 1.00; 1.02) were significantly associated with a positive TST but sex (OR = 1.18, 95% CI 0.50; 2.78) and BCG vaccination status (OR = 2.97, 95% CI 0.91; 9.72) were not associated. CONCLUSIONS: TB incidence in the country of origin, BCG vaccination and age influence the TSTreaction (size or proportion of TST > or = 10 mm). However the most obvious risk factor for a positive TST is a history of contact with TB.

Treatment of severe infectious purpura in children with human plasma from donors immunized with Escherichia coli J5: a prospective double-blind study. J5 study Group.

To evaluate the efficacy of anti-J5 serum in the treatment of severe infectious purpura, 73 children were randomized to receive either anti-J5 (40) or control (33) plasma. Age, blood pressure, and biologic risk factors were similar in both groups. At admission, however, tumor necrosis factor serum concentrations were 974 +/- 173 pg/ml compared with 473 +/- 85 pg/ml (P = .023) and interleukin-6 serum concentrations were 129 +/- 45 compared with 19 +/- 5 ng/ml (P = .005) in the control and treated groups, respectively. The duration of shock and the occurrence of complications were similar in both groups. The mortality rate was 36% in the control group and 25% in the treated group (P = .317; odds ratio, 0.76; 95% confidence interval, 0.46-1.26). This trend disappeared after correction for unbalances in risk factors at randomization using a logistic regression model. These results suggest that anti-j5 plasma did not affect the course or mortality of severe infectious purpura in children.

Ruling out coronary heart disease in primary care patients with chest pain : a clinical prediction score

ABSTRACT: BACKGROUND: Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care. METHODS: Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group. RESULTS: The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%. CONCLUSIONS: This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.

Approaches to identifying and quantifying polycyclic aromatic hydrocarbons of molecular weight 302 in diesel particulates

Among the PAH class of compounds, high molecular weight PAH are now considered as relevant cancer inducers, but not all of them have the same biological activity. However, their analysis is difficult, mainly due to the presence of numerous isomers and due to their low volatility. Retention indices (Ri) for 13 dibenzopyrenes and homologues were determined by high-resolution capillary gas chromatography (GC) with four different stationary phases: a 5% phenyl-substituted methylpolysiloxane column (DB-5 ms), a 35% phenyl-substituted methylpolysiloxane column (BPX-35), a 50% phenyl-substituted methylpolysiloxane column (BPX-50), and a 35% trifluoropropylmethyl polysiloxane stationary phase (Rtx-200). Correlations for retention on each phase were investigated by using 8 independent molecular descriptors. Ri has been shown to be linearly correlated to PAH volume, polarisability alpha, Hückel-pi energy on the four examined columns. Ionisation potential Ip is a fourth variable which improves the regression model for DB-5ms, BPX-35, and BPX-50 column. Correlation coefficients ranging from r2 = 0.935 to r2 = 0.952 are then observed. Application of these indices to the identification and quantification of PAH with MW 302 in certified diesel particulate matter SRM 1650a is presented and discussed. [Authors]

Lumbar spine texture enhances 10-year fracture probability assessment.

We found that lumbar spine texture analysis using trabecular bone score (TBS) is a risk factor for MOF and a risk factor for death in a retrospective cohort study from a large clinical registry for the province of Manitoba, Canada. INTRODUCTION: FRAX® estimates the 10-year probability of major osteoporotic fracture (MOF) using clinical risk factors and femoral neck bone mineral density (BMD). Trabecular bone score (TBS), derived from texture in the spine dual X-ray absorptiometry (DXA) image, is related to bone microarchitecture and fracture risk independently of BMD. Our objective was to determine whether TBS provides information on MOF probability beyond that provided by the FRAX variables. METHODS: We included 33,352 women aged 40-100 years (mean 63 years) with baseline DXA measurements of lumbar spine TBS and femoral neck BMD. The association between TBS, the FRAX variables, and the risk of MOF or death was examined using an extension of the Poisson regression model. RESULTS: During the mean of 4.7 years, 1,754 women died and 1,872 sustained one or more MOF. For each standard deviation reduction in TBS, there was a 36 % increase in MOF risk (HR 1.36, 95 % CI 1.30-1.42, p < 0.001) and a 32 % increase in death (HR 1.32, 95 % CI 1.26-1.39, p < 0.001). When adjusted for significant clinical risk factors and femoral neck BMD, lumbar spine TBS was still a significant predictor of MOF (HR 1.18, 95 % CI 1.12-1.23) and death (HR 1.20, 95 % CI 1.14-1.26). Models for estimating MOF probability, accounting for competing mortality, showed that low TBS (10th percentile) increased risk by 1.5-1.6-fold compared with high TBS (90th percentile) across a broad range of ages and femoral neck T-scores. CONCLUSIONS: Lumbar spine TBS is able to predict incident MOF independent of FRAX clinical risk factors and femoral neck BMD even after accounting for the increased death hazard.

Association between social relationships and survival of Swiss octogenarians. A five-year prospective, population-based study.

BACKGROUND AND AIMS: Data from the literature reveal the contrasting influences of family members and friends on the survival of old adults. On one hand, numerous studies have reported a positive association between social relationships and survival. On the other, ties with children may be associated with an increased risk of disability, whereas ties with friends or other relatives tend to improve survival. A five-year prospective, population-based study of 295 Swiss octogenarians tested the hypothesis that having a spouse, siblings or close friends, and regular contacts with relatives or friends are associated with longer survival, even at a very old age. METHODS: Data were collected through individual interviews, and a Cox regression model was applied to assess the effects of kinship and friendship networks on survival, after adjusting for socio-demographic and health-related variables. RESULTS: Our analyses indicate that the presence of a spouse in the household is not significantly related to survival, whereas the presence of siblings at baseline improves the oldest old's chances of surviving five years later. Moreover, the existence of close friends is a central component in the patterns of social relationships of oldest adults, and one which is significantly associated with survival. Overall, the protective effect of social relationships on survival is more related to the quality of those relationships (close friends) than to the frequency of relationships (regular contacts). CONCLUSIONS: We hypothesize that the existence of siblings or close friends may beneficially affect survival, due to the potential influence on the attitudes of octogenarians regarding health practices and adaptive strategies.

Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study.

ABSTRACT: BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission. METHODS: We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay >=48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS: Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring [greater than or equal to]48 hours is considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission.

Publication trends of shared decision making in 15 high impact medical journals: a full-text review with bibliometric analysis.

BACKGROUND: Shared Decision Making (SDM) is increasingly advocated as a model for medical decision making. However, there is still low use of SDM in clinical practice. High impact factor journals might represent an efficient way for its dissemination. We aimed to identify and characterize publication trends of SDM in 15 high impact medical journals. METHODS: We selected the 15 general and internal medicine journals with the highest impact factor publishing original articles, letters and editorials. We retrieved publications from 1996 to 2011 through the full-text search function on each journal website and abstracted bibliometric data. We included publications of any type containing the phrase "shared decision making" or five other variants in their abstract or full text. These were referred to as SDM publications. A polynomial Poisson regression model with logarithmic link function was used to assess the evolution across the period of the number of SDM publications according to publication characteristics. RESULTS: We identified 1285 SDM publications out of 229,179 publications in 15 journals from 1996 to 2011. The absolute number of SDM publications by journal ranged from 2 to 273 over 16 years. SDM publications increased both in absolute and relative numbers per year, from 46 (0.32% relative to all publications from the 15 journals) in 1996 to 165 (1.17%) in 2011. This growth was exponential (P < 0.01). We found fewer research publications (465, 36.2% of all SDM publications) than non-research publications, which included non-systematic reviews, letters, and editorials. The increase of research publications across time was linear. Full-text search retrieved ten times more SDM publications than a similar PubMed search (1285 vs. 119 respectively). CONCLUSION: This review in full-text showed that SDM publications increased exponentially in major medical journals from 1996 to 2011. This growth might reflect an increased dissemination of the SDM concept to the medical community.

Effect of a general school-based physical activity intervention on bone mineral content and density: A cluster-randomized controlled trial.

Background: Specific physical loading leads to enhanced bone development during childhood. A general physical activity program mimicking a real-life situation was successful at increasing general physical health in children. Yet, it is not clear whether it can equally increase bone mineral mass. We performed a cluster-randomized controlled trial in children of both gender and different pubertal stages to determine whether a school-based physical activity (PA) program during one school-year influences bone mineral content (BMC) and density (BMD), irrespective of gender.Methods: Twenty-eight 1st and 5th grade (6-7 and 11-12 year-old) classes were cluster randomized to an intervention (INT, 16 classes, n = 297) and control (CON; 12 classes, n = 205) group. The intervention consisted of a multi-component PA intervention including daily physical education with at least 10 min of jumping or strength training exercises of various intensities. Measurements included anthropometry, and BMC and BMD of total body, femoral neck, total hip and lumbar spine using dual-energy X-ray absorptiometry (DXA). PA was assessed by accelerometers and Tanner stages by questionnaires. Analyses were performed by a regression model adjusted for gender, baseline height and weight, baseline PA, post-intervention pubertal stage, baseline BMC, and cluster.Results: 275 (72%) of 380 children who initially agreed to have DXA measurements had also post-intervention DXA and PA data. Mean age of prepubertal and pubertal children at baseline was 8.7 +/- 2.1 and 11.1 +/- 0.6 years, respectively. Compared to CON, children in INT showed statistically significant increases in BMC of total body, femoral neck, and lumbar spine by 5.5%, 5.4% and 4.7% (all p < 0.05), respectively, and BMD of total body and lumbar spine by 8.4% and 7.3% (both p < 0.01), respectively. There was no gender*group, but a pubertal stage*group interaction consistently favoring prepubertal children.Conclusion: A general school-based PA intervention can increase bone health in elementary school children of both genders, particularly before puberty. (C) 2010 Elsevier Inc. All rights reserved.

European cancer mortality predictions for the year 2014.

BACKGROUND: From most recent available data, we projected cancer mortality statistics for 2014, for the European Union (EU) and its six more populous countries. Specific attention was given to pancreatic cancer, the only major neoplasm showing unfavorable trends in both sexes. PATIENTS AND METHODS: Population and death certification data from stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukemias and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected 2014 numbers of deaths by age group were obtained by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: In the EU in 2014, 1,323,600 deaths from cancer are predicted (742,500 men and 581,100 women), corresponding to standardized death rates of 138.1/100,000 men and 84.7/100,000 women, falling by 7% and 5%, respectively, since 2009. In men, predicted rates for the three major cancers (lung, colorectum and prostate cancer) are lower than in 2009, falling by 8%, 4% and 10%, respectively. In women, breast and colorectal cancers had favorable trends (-9% and -7%), but female lung cancer rates are predicted to rise 8%. Pancreatic cancer is the only neoplasm with a negative outlook in both sexes. Only in the young (25-49 years), EU trends become more favorable in men, while women keep registering slight predicted rises. CONCLUSIONS: Cancer mortality predictions for 2014 confirm the overall favorable cancer mortality trend in the EU, translating to an overall 26% fall in men since its peak in 1988, and 20% in women, and the avoidance of over 250,000 deaths in 2014 compared with the peak rate. Notable exceptions are female lung cancer and pancreatic cancer in both sexes.

Mirror image atrial dilatation in adult patients with atrial fibrillation and congenital heart disease.

BACKGROUND: Atrial fibrillation (AF) is largely regarded to be initiated from left atrial (LA) dilatation, with subsequent dilatation of the right atrium (RA) in those who progress to chronic AF. We hypothesized that in adult patients with right-sided congenital heart disease (CHD) and AF, RA dilatation will predominate with subsequent dilatation of the left atrium, as a mirror image. METHODS: Adult patients with diagnosis of right-sided, ASD or left-sided CHD who had undergone an echocardiographic study and electrocardiographic recording in 2007 were included. RA and LA area were measured from the apical view. AF was diagnosed from a 12-lead electrocardiogram or Holter recording. A multivariate logistic regression model was used to identify predictors of AF and linear regression models were performed to measure relationship between RA and LA area and AF. RESULTS: A total of 291 patients were included in the study. Multivariate analysis showed that age (p=0.0001), RA (p=0.025) and LA area (p=0.0016) were significantly related to AF. In patients with pure left-sided pathologies, there was progressive and predominant LA dilatation that paralleled the development of AF from none to paroxysmal to chronic AF. In patients with pure right-sided pathologies, there was a mirror image of progressive and predominant RA dilatation with the development of AF. CONCLUSION: We observed a mirror image atrial dilatation in patients with right sided disease and AF. This may provide novel mechanistic insight as to the origin of AF in these patients and deserves further studying in the form of targeted electrophysiological studies.

Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain.

PURPOSE: Experimental evidence suggests that lactate is neuroprotective after acute brain injury; however, data in humans are lacking. We examined whether exogenous lactate supplementation improves cerebral energy metabolism in humans with traumatic brain injury (TBI). METHODS: We prospectively studied 15 consecutive patients with severe TBI monitored with cerebral microdialysis (CMD), brain tissue PO2 (PbtO2), and intracranial pressure (ICP). Intervention consisted of a 3-h intravenous infusion of hypertonic sodium lactate (aiming to increase systemic lactate to ca. 5 mmol/L), administered in the early phase following TBI. We examined the effect of sodium lactate on neurochemistry (CMD lactate, pyruvate, glucose, and glutamate), PbtO2, and ICP. RESULTS: Treatment was started on average 33 ± 16 h after TBI. A mixed-effects multilevel regression model revealed that sodium lactate therapy was associated with a significant increase in CMD concentrations of lactate [coefficient 0.47 mmol/L, 95% confidence interval (CI) 0.31-0.63 mmol/L], pyruvate [13.1 (8.78-17.4) μmol/L], and glucose [0.1 (0.04-0.16) mmol/L; all p < 0.01]. A concomitant reduction of CMD glutamate [-0.95 (-1.94 to 0.06) mmol/L, p = 0.06] and ICP [-0.86 (-1.47 to -0.24) mmHg, p < 0.01] was also observed. CONCLUSIONS: Exogenous supplemental lactate can be utilized aerobically as a preferential energy substrate by the injured human brain, with sparing of cerebral glucose. Increased availability of cerebral extracellular pyruvate and glucose, coupled with a reduction of brain glutamate and ICP, suggests that hypertonic lactate therapy has beneficial cerebral metabolic and hemodynamic effects after TBI.

Physical activity is inversely associated with high blood pressure independently of overweight in Brazilian adolescents.

The purpose of this study was to assess the relationship between blood pressure (BP) levels and physical activity (PA) domains accounting for overweight/obesity. Adolescents aged 10 to 17 years old were recruited (n = 1021). International Obesity Task Force (IOTF) criteria were used to define overweight and obesity. High BP was defined using the Center of Disease Control and Prevention criteria. Different domains of PA (school activities, sport out of school, and leisure time PA) were assessed using a validated questionnaire. The prevalence of overweight/obesity was 21.9% for boys and 14.8% for girls. Some 13.4% of boys and 10.2% of girls, respectively, had high blood pressure (HBP). A strong and positive association was found between overweight and HBP. After adjustment for body mass index (BMI), total PA was inversely associated with BP. When all PA domains were entered simultaneously in a regression model, and after adjustment for BMI, only sport out of school was significantly and inversely associated with systolic BP [β: -0.82 (-1.50; -0.13)]. These findings open avenue for the early prevention of HBP by the prevention of obesity and promotion of PA.