The relative importance of vascular structure and function in predicting cardiovascular events

OBJECTIVES We sought to assess the prognostic utility of brachial artery reactivity (BAR) in patients at risk of cardiovascular events. BACKGROUND Impaired flow-mediated vasodilation measured by BAR is a marker of endothelial dysfunction. Brachial artery reactivity is influenced by risk factors and is responsive to various pharmacological and other treatments. However, its prognostic importance is uncertain, especially relative to other predictors of outcome. METHODS A total of 444 patients were prospectively enrolled to undergo BAR and follow-up. These patients were at risk of cardiovascular events, based on the presence of risk factors or known or suspected cardiovascular disease. We took a full clinical history, performed BAR, and obtained carotid intima-media thickness (IMT) and left ventricular mass and ejection fraction. Patients were followed up for cardiovascular events and all-cause mortality. Multivariate Cox regression analysis was performed to assess the independent association of investigation variables on outcomes. RESULTS The patients exhibited abnormal BAR (5.2 +/- 6.1% [mean +/- SD]) but showed normal nitrate-mediated dilation (9.9 +/- 7.2%) and normal mean IMT (0.67 +/- 0.12 mm [average]). Forty-nine deaths occurred over the median follow-up period of 24 months (interquartile range 10 to 34). Patients in the lowest tertile group of BAR (<2%) had significantly more events than those in the combined group of highest and mid-tertiles (p = 0.029, log-rank test). However, mean IMT (rather than flow-mediated dilation) was the vascular factor independently associated with mortality, even in the subgroup (n = 271) with no coronary artery disease and low risk. CONCLUSIONS Brachial artery reactivity is lower in patients with events, but is not an independent predictor of cardiovascular outcomes in this cohort of patients. (C) 2004 by the American College of Cardiology Foundation.

Long-term oral sensitivity and feeding skills of low-risk pre-term infants

This study examined the oral sensitivity and feeding skills of low-risk pre-term infants at 11-17 months corrected age. Twenty pre-term infants (PT) born between 32 and 37 weeks at birth without any medical comorbidities were assessed. All of this PT group received supplemental nasogastric (NG) tube feeds during their birth-stay in hospital. A matched control group of 10 healthy full-term infants (FT) was also assessed. Oral sensitivity and feeding skills were assessed during a typical mealtime using the Royal Children's Hospital Oral Sensitivity Checklist (OSC) and the Pre-Speech Assessment Scale (PSAS). Results demonstrated that, at 11-17 months corrected age, the PT group displayed significantly more behaviours suggestive of altered oral sensitivity and facial defensiveness, and a trend of more delayed feeding development than the FT group. Further, results demonstrated that, relative to the FT group, pre-term infants who received greater than 3 weeks of NG feeding (PT>3NG) displayed significantly more facial defensive behaviour, and displayed significant delays across more aspects of their feeding development than pre-term infants who received less than 2 weeks of NG feeding (PT

Precautionary principles: a jurisdiction-free framework for decision-making under risk

Fundamental principles of precaution are legal maxims that ask for preventive actions, perhaps as contingent interim measures while relevant information about causality and harm remains unavailable, to minimize the societal impact of potentially severe or irreversible outcomes. Such principles do not explain how to make choices or how to identify what is protective when incomplete and inconsistent scientific evidence of causation characterizes the potential hazards. Rather, they entrust lower jurisdictions, such as agencies or authorities, to make current decisions while recognizing that future information can contradict the scientific basis that supported the initial decision. After reviewing and synthesizing national and international legal aspects of precautionary principles, this paper addresses the key question: How can society manage potentially severe, irreversible or serious environmental outcomes when variability, uncertainty, and limited causal knowledge characterize their decision-making? A decision-analytic solution is outlined that focuses on risky decisions and accounts for prior states of information and scientific beliefs that can be updated as subsequent information becomes available. As a practical and established approach to causal reasoning and decision-making under risk, inherent to precautionary decision-making, these (Bayesian) methods help decision-makers and stakeholders because they formally account for probabilistic outcomes, new information, and are consistent and replicable. Rational choice of an action from among various alternatives-defined as a choice that makes preferred consequences more likely-requires accounting for costs, benefits and the change in risks associated with each candidate action. Decisions under any form of the precautionary principle reviewed must account for the contingent nature of scientific information, creating a link to the decision-analytic principle of expected value of information (VOI), to show the relevance of new information, relative to the initial ( and smaller) set of data on which the decision was based. We exemplify this seemingly simple situation using risk management of BSE. As an integral aspect of causal analysis under risk, the methods developed in this paper permit the addition of non-linear, hormetic dose-response models to the current set of regulatory defaults such as the linear, non-threshold models. This increase in the number of defaults is an important improvement because most of the variants of the precautionary principle require cost-benefit balancing. Specifically, increasing the set of causal defaults accounts for beneficial effects at very low doses. We also show and conclude that quantitative risk assessment dominates qualitative risk assessment, supporting the extension of the set of default causal models.

Sleepiness, sleep-disordered breathing, and accident risk factors in commercial vehicle drivers

Sleep-disordered breathing and excessive sleepiness may be more common in commercial vehicle drivers than in the general population. The relative importance of factors causing excessive sleepiness and accidents in this population remains unclear. We measured the prevalence of excessive sleepiness and sleep-disordered breathing and assessed accident risk factors in 2,342 respondents to a questionnaire distributed to a random sample of 3,268 Australian commercial vehicle drivers and another 161 drivers among 244 invited to undergo polysomnography. More than half (59.6%) of drivers had sleep-disordered breathing and 15.8% had obstructive sleep apnea syndrome. Twenty-four percent of drivers had excessive sleepiness. Increasing sleepiness was related to an increased accident risk. The sleepiest 5% of drivers on the Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire had an in-creased risk of an accident (odds ratio [OR] 1.91, p = 0.02 and OR 2.23, p < 0.01, respectively) and multiple accidents (OR 2.67, p < 0.01 and OR 2.39, p = 0.01), adjusted for established risk factors. There was an increased accident risk with narcotic analgesic use (OR 2.40, p < 0.01) and antihistamine use (OR 3.44, p = 0.04). Chronic excessive sleepiness and sleep-disordered breathing are common in Australian commercial vehicle drivers. Accident risk was related to increasing chronic sleepiness and antihistamine and narcotic analgesic use.

Carotid artery intimal medial thickness, brachial artery flow-mediated vasodilation and cardiovascular risk factors in diabetic and non-diabetic indigenous Australians

Background: Indigenous Australians are at high risk for cardiovascular disease and type 2 diabetes. Carotid artery intimal medial thickness (CIMT) and brachial artery flow-mediated vasodilation (FMD) are ultrasound imaging based surrogate markers of cardiovascular risk. This study examines the relative contributions of traditional cardiovascular risk factors on CIMT and FMD in adult Indigenous Australians with and without type 2 diabetes mellitus. Method: One hundred and nineteen Indigenous Australians were recruited. Physical and biochemical markers of cardiovascular risk, together with CIMT and FMD were meausred for all subjects. Results: Fifty-three Indigenous Australians subjects (45%) had type 2 diabetes mellitus. There was a significantly greater mean CIMT in diabetic versus non-diabetic subjects (p = 0.049). In the non-diabetic group with non-parametric analyses, there were significant correlations between CIMT and: age (r = 0.64, p < 0.001), systolic blood pressure (r = 0.47, p < 0.001) and non-smokers (r = -0.30, p = 0.018). In the diabetic group, non-parametric analysis showed correlations between CIMT, age (r = 0.36, p = 0.009) and duration of diabetes (r = 0.30, p = 0.035) only. Adjusting forage, sex, smoking and history of cardiovascular disease, Hb(A1c) became the sole significant correlate of CIMT (r = 0.35,p = 0.01) in the diabetic group. In non-parametric analysis, age was the sole significant correlate of FMD (r = -0.31,p = 0.013), and only in non-diabetic subjects. Linear regression analysis showed significant associations between CIMT and age (t = 4.6,p < 0.001), systolic blood pressure (t = 2.6, p = 0.010) and Hb(A1c) (t = 2.6, p = 0.012), smoking (t = 2.1, p = 0.04) and fasting LDL-cholesterol (t = 2.1, p = 0.04). There were no significant associations between FMD and examined cardiovascular risk factors with linear regression analysis Conclusions: CIMT appears to be a useful surrogate marker of cardiovascular risk in this sample of Indigenous Australian subjects, correlating better than FMD with established cardiovascular risk factors. A lifestyle intervention programme may alleviate the burden of cardiovascular disease in Indigenous Australians by reducing central obesity, lowering blood pressure, correcting dyslipidaemia and improving glycaemic control. CIMT may prove to be a useful tool to assess efficacy of such an intervention programme. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was 28 pound 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to 11 pound 731 (CE MRI vs mammography) and 15 pound 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

“Doing” Gender in Context: Household Bargaining and Risk of Divorce in Germany and the United States

Gender relations remain embedded in their sociopolitical context. Compared here using event-history analysis is how household divisions of paid and unpaid labor affect marital stability in the former West Germany, where policy reinforced male breadwinner families, and the United States, where policy remains silent regarding the private sphere. In Germany, any moves away from separate gendered spheres in terms of either wives' relative earnings or husbands' relative participation in housework increase the risk of divorce. In the United States, however, the more stable couples are those that adapt by displaying greater gender equity. These results highlight that policy shapes how gender gets done in the intimate sphere, and that reinforcement of a gendered division of labor may be detrimental to marital stability.

Whose socioeconomic status influences a woman's obesity risk: her mother's, her father's, or her own?

Background Evidence on the relative influence of childhood vs adulthood socioeconomic conditions on obesity risk is limited and equivocal. The objective of this study was to investigate associations of several indicators of mothers', fathers', and own socioeconomic status, and intergenerational social mobility, with body mass index (BMI) and weight change in young women. Methods This population-based cohort study used survey data provided by 8756 women in the young cohort (aged 18-23 years at baseline) of the Australian Longitudinal Study on Women's Health. In 1996 and 2000, women completed mailed surveys in which they reported their height and weight, and their own, mother's, and father's education and occupation. Results Multiple linear regression models showed that both childhood and adulthood socioeconomic status were associated with women's BMI and weight change, generally in the hypothesized (inverse) direction, but the associations varied according to socioeconomic status and weight indicator. Social mobility was associated with BMI (based on father's socioeconomic status) and weight change (based on mother's socioeconomic status), but results were slightly less consistent. Conclusions Results suggest lasting effects of childhood socioeconomic status on young women's weight status, independent of adult socioeconomic status, although the effect may be attenuated among those who are upwardly socially mobile. While the mechanisms underlying these associations require further investigation, public health strategies aimed at preventing obesity may need to target families of low socioeconomic status early in children's lives.

Type 2 diabetes:assessing the relative risks and benefits of glucose-lowering medications

The selection of appropriate pharmacologic therapy for any disease requires a careful assessment of benefit and risk. In the case of type 2 diabetes, this decision typically balances the benefits accrued from improved glycemic control with the risks inherent in glucose-lowering medications. This review is intended to assist therapeutic decision-making by carefully assessing the potential benefit from improved metabolic control relative to the potential risks of a wide array of currently prescribed glucose-lowering agents. Wherever possible, risks and benefits have been expressed in terms of absolute rates (events per 1000 patient-years) to facilitate cross-study comparisons. The review incorporates data from new studies (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, Action to Control Cardiovascular Risk in Diabetes, and the Veterans Affairs Diabetes Trial), as well as safety issues associated with newer glucose-lowering medications. © 2010 Elsevier Inc. All rights reserved.

Calendar effects and the pricing of risk:the UK evidence

For some time there has been a puzzle surrounding the seasonal behaviour of stock returns. This paper demonstrates that there is an asymmetric relationship between risk and return across the different months of the year. The paper finds that systematic risk is only priced during the months of January, April and July. Variance risk and firm size are priced during several months of the year including January. An analysis of the relative behaviour of size based securities reveals that firm capitalization makes a valuable contribution to the magnitude of risk premiums.

Valószínűség, esély, relatív súlyok. Opciók és reálopciók (Probability, chance, relative weights)

There is a long debate (going back to Keynes) how to interpret the concept of probability in economics, in business decisions, in finance. Iván Bélyácz suggested that the Black–Scholes– Merton analysis of fi nancial derivatives has a contribution to this risk vs. uncertainty debate. This article tries to interpret this suggestion, from the viewpoint of traded options, real options, Arrow–Debreu model, Heath–Jarrow–Morton model, insurance business. The article suggests making clear distinction and using different naming ● when the frequents approach and the statistics is relevant, ● when we just use consequent relative weights during the no-arbitrage pricing, and these weight are just interpreted as probabilities, ● when we just lack the necessary information, and there is a basic uncertainty in the business decision making process. The paper suggests making a sharp distinction between fi nancial derivatives used for market risk management and credit risk type derivatives (CDO, CDS, etc) in the reregulation process of the fi nancial markets.

Effects of adolescent depressive symptoms, pubertal development, and interpersonal relationship satisfaction on sexual risk behaviors in adolescent romantic couples

This study examined links between adolescent depressive symptoms, actual pubertal development, perceived pubertal timing relative to one’s peers, adolescent-maternal relationship satisfaction, and couple sexual behavior. Assessments of these variables were made on each couple member separately and then these variables were used to predict the sexual activity of the couple. Participants were drawn from the National Longitudinal Study of Adolescent Health (Add Health; Bearman et al., 1997; Udry, 1997) data set (N = 20,088; aged 12–18 years). Dimensions of adolescent romantic experiences using the total sample were described and then a subsample of romantically paired adolescents ( n = 1,252) were used to test a risk and protective model for predicting couple sexual behavior using the factors noted above. Relevant measures from the Wave 1 Add Health measures were used. Most of the items used in Add Health to assess romantic relationship experiences, adolescent depressive symptoms, pubertal development (actual and perceived), adolescent-maternal relationship satisfaction, and couple sexual behavior were drawn from other national surveys or from scales with well documented psychometric properties. Results demonstrated that romantic relationships are part of most adolescents’ lives and that adolescents’ experiences with these relationships differ markedly by age, sex, and race/ethnicity. Further, each respective couple member’s pubertal development, perceived pubertal timing, and maternal relationship satisfaction were useful in predicting sexual risk-promoting and risk-reducing behaviors in adolescent romantic couples. Findings in this dissertation represent an initial step toward evaluating explanatory models of adolescent couple sexual behavior.

Exploring therapy process and outcome in interventions that target at risk adolescents

The purpose of this study was to conduct a larger scale replication and extension study on the use of a Session Impact Measure the Session Evaluation Form. Ninety-one public high school students in Miami Florida were obtained through self or counselor referrals and placed in one or two of five counseling groups for one or two school semesters. To investigate differences in therapy processes across counseling groups, participants were administered a Session Evaluation Form at the end of each therapy session. This assessed group members' perception of four therapy process domains, Group, Facilitator, Skills and Exploration Impacts. The pattern significant results for the MANOVAs provided strong evidence for the greater impact of the group on therapy process relative to the impact of facilitator. Further research is needed to identify more specifically, ways, group process differences interact with other treatment variables.

Effects of Adolescent Depressive Symptoms, Pubertal Development, and Interpersonal Relationship Satisfaction on Sexual Risk Behaviors in Adolescent Romantic Couples

This study examined links between adolescent depressive symptoms, actual pubertal development, perceived pubertal timing relative to one’s peers, adolescent-maternal relationship satisfaction, and couple sexual behavior. Assessments of these variables were made on each couple member separately and then these variables were used to predict the sexual activity of the couple. Participants were drawn from the National Longitudinal Study of Adolescent Health (Add Health; Bearman et al., 1997; Udry, 1997) data set (N = 20,088; aged 12-18 years). Dimensions of adolescent romantic experiences using the total sample were described and then a subsample of romantically paired adolescents (n = 1,252) were used to test a risk and protective model for predicting couple sexual behavior using the factors noted above. Relevant measures from the Wave 1 Add Health measures were used. Most of the items used in Add Health to assess romantic relationship experiences, adolescent depressive symptoms, pubertal development (actual and perceived), adolescent-maternal relationship satisfaction, and couple sexual behavior were drawn from other national surveys or from scales with well documented psychometric properties. Results demonstrated that romantic relationships are part of most adolescents’ lives and that adolescents’ experiences with these relationships differ markedly by age, sex, and race/ethnicity. Further, each respective couple member’s pubertal development, perceived pubertal timing, and maternal relationship satisfaction were useful in predicting sexual risk-promoting and risk-reducing behaviors in adolescent romantic couples. Findings in this dissertation represent an initial step toward evaluating explanatory models of adolescent couple sexual behavior.

Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials

Objective: To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. Design: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. Data sources: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. Review methods: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. Results: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9/%year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. Conclusions: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess.