The ADVANCE trial: clarifying the role of perindopril/indapamide fixed-dose combination in the reduction of cardiovascular and renal events in patients with diabetes mellitus.

Patients with type 2 diabetes mellitus exhibit a marked increase in cardiovascular and renal risk. A number of interventional trials have shown that these patients benefit greatly from aggressive BP lowering, especially when the drug regimen comprises an inhibitor of the renin-angiotensin system. The results of the placebo-controlled ADVANCE (Action in Diabetes and Vascular disease: PreterAx and DiamicroN MR Controlled Evaluation) trial, conducted in patients with type 2 diabetes, are exemplary in this respect. The systematic use of a fixed-dose combination containing the ACE inhibitor perindopril and the diuretic indapamide afforded substantial protection against cardiovascular mortality and myocardial infarction, while providing important renoprotection, reducing the development of micro- and macroalbuminuria, and allowing regression of nephropathy. The beneficial effects were obtained regardless of baseline BP and whether or not the patients were receiving antihypertensive therapy.

Amlodipine and valsartan as components of a rational and effective fixed-dose combination.

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists and blockers of the renin-angiotensin system are widely used today to initiate antihypertensive therapy but, when given as monotherapy, do not suffice in most patients to normalize blood pressure. Combining the two types of agents considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. This is exemplified by the experience accumulated with the recently developed fixed dose combination containing the AT(1)-receptor blocker valsartan (160 mg) and the dihydropyridine amlodipine (5 or 10 mg). In a randomized trial, an 8-week treatment normalized blood pressure (<140/90 mmHg) within 8 weeks in a large fraction of hypertensive patients (78.4% and 85.2% using the 5/160 [n = 371] and 10/160 mg [n = 377] dosage, respectively). Like all AT(1)-receptor blockers valsartan has a placebo-like tolerability. Valsartan prevents to a large extent the occurrence amlodipine-induced peripheral edema. Both amlodipine and valsartan have beneficial effects on cardiovascular morbidity and mortality, as well as protective effects on renal function. The co-administration of these two agents is therefore very attractive, as it enables a rapid and sustained blood pressure control in hypertensive patients. The availability of a fixed-dose combination based on amlodipine and valsartan is expected therefore to facilitate the management of hypertension, to improve long-term adherence with antihypertensive therapy and, ultimately, to have a positive impact on cardiovascular and renal outcomes.

Women in leadership: Three essays

GENDER EMPOWERMENT: EFFECTS OF GODS, GEOGRAPHY, AND GDP¦Fenley, M., & Antonakis, J.¦ABSTRACT¦We examined the determinants of women's empowerment in the economy and political leadership in 178 countries. Given the androcentric nature of most religions, we hypothesized that high degrees of country-level theistic belief create social conditions that impede the progression of women to power. The dependent variable was the Gender Empowerment index of the United Nations Development Program, which captures the participation of women in political leadership, management, and their share of national income. Controlling for GDP per capita as well as the fixed-effects of the dominant type of religion and legal origin and instrumenting all endogenous variables with geographic or historical variables, our results show that atheism has a significant positive effect on gender empowerment. These results are driven by the rule of law, which in addition to being a catalyst for economic development, appears to crowd-out the informal regulation of behavior due to religious norms.¦DEVELOPING WOMEN LEADERS: COMPARING A TRANSFORMATIONAL AND A CHARISMATIC LEADERSHIP INTERVENTION¦Fenley, M., Jacquart, P., & Antonakis, J.¦ABSTRACT¦Along with a gender imbalance in leadership role occupancy, most leadership interventions have been conducted with samples of men. We conducted an experiment wherein we assigned female participants (n = 38, mean age = 35 years) to one of two conditions: Transformational (i.e., "standard") leadership training or charismatic leadership training. The two interventions were essentially equivalent, except that we also focused on developing the "charismatic leadership tactics" (e.g., rhetorical skills) of participants in the charismatic condition. After the interventions, we randomly assigned participants into problem-solving teams that required extensive interaction. Each team had an equal number of participants having received transformational training or charismatic training. At the end of the team exercises, participants rated each of their team members on a leadership prototypicality measure. Results indicated that those who received charismatic training scored higher (a) on prototypicality (standardized  = .42) and (b) on a test of declarative knowledge of charismatic rhetorical strategies (i.e., a manipulation check, standardized  = .76). Furthermore, the score on the test fully mediated the effect of the treatment on prototypicality (standardized indirect  = .32). We discuss the importance and practical implications of these results.¦CHANGING ATTITUDES TOWARDS WOMEN IN A MALE SEX-TYPE WORK ENVIRONMENT: EVIDENCE FROM A FIELD EXPERIMENT IN EUROPEAN ATHLETICS¦Fenley, M.¦ABSTRACT¦Most sports organizations have a similar gender gap in leadership as do the majority of non-sport organizations. Women's careers sputter somewhere at coaching level positions and few women obtain top leadership positions. Greater awareness of gender inequalities in general, and in leadership in particular, could decrease gender discrimination and increase women's presence at upper levels. The goal of this study was to evaluate the impact of an intervention using an online gender awareness exercise. Participants (n = 1,001 participants, n = 32 countries) were randomly assigned to one of eight conditions in a 2 (a discriminating perspective-taking story or a non-discriminating perspective-taking story) by 2 (gender quiz or no gender quiz) by 2 (diversity quiz or no diversity quiz) factorial design. The results show that the online perspective taking exercise changed initial sexist attitudes. Participants having taken a diversity quiz had less sexist attitudes (as measured by the Modern- and Old-fashioned sexism scale) than did participants who did not take the diversity quiz (irrespective of perspective-taking story). The combination of having taken a diversity quiz with a gender quiz had the biggest impact on attitudes for the non-discriminating story.

Survival of zirconia- and metal-supported fixed dental prostheses: a systematic review

Purpose: The aim of this review was to systematically evaluate and compare the frequency of veneer chipping and core fracture of zirconia fixed dental prostheses (FOPS) and porcelain-fused-to-metal (PFM) FDPs and determine possible influencing factors. Materials and Methods: The SCOPUS database and International Association of Dental Research abstracts were searched for clinical studies involving zirconia and PFM FDPs. Furthermore, studies that were integrated into systematic reviews on PFM FDPs were also evaluated. The principle investigators of any clinical studies on zirconia FDPs were contacted to provide additional information. Based on the available information for each FOP, a data file was constructed. Veneer chipping was divided into three grades (grade 1 = polishing, grade 2 = repair, grade 3 = replacement). To assess the frequency of veneer chipping and possible influencing factors, a piecewise exponential model was used to adjust for a study effect. Results: None of the studies on PFM FDPs (reviews and additional searching) sufficiently satisfied the criteria of this review to be included. Thirteen clinical studies on zirconia FDPs and two studies that investigated both zirconia and PFM FDPs were identified. These studies involved 664 zirconia and 134 PFM FDPs at baseline. Follow-up data were available for 595 zirconia and 127 PFM FDPs. The mean observation period was approximately 3 years for both groups. The frequency of core fracture was less than 1% in the zirconia group and 0% in the PFM group. When all studies were included, 142 veneer chippings were recorded for zirconia FDPs (24%) and 43 for PFM FDPs (34%). However, the studies differed extensively with regard to veneer chipping of zirconia: 85% of all chippings occurred in 4 studies, and 43% of all chippings included zirconia FDPs. If only studies that evaluated both types of core materials were included, the frequency of chipping was 54% for the zirconia-supported FDPs and 34% for PFM FDPs. When adjusting the survival rate for the study effect, the difference between zirconia and PFM FDPs was statistically significant for all grades of chippings (P = .001), as well as for chipping grade 3 (P = .02). If all grades of veneer chippings were taken into account, the survival of PFM FDPs was 97%, while the survival rate of the zirconia FDPs was 90% after 3 years for a typical study. For both PFM and zirconia FDPs, the frequency of grades 1 and 2 veneer chippings was considerably higher than grade 3. Veneer chipping was significantly less frequent in pressed materials than in hand-layered materials, both for zirconia and PFM FDPs (P = .04). Conclusions: Since the frequency of veneer chipping was significantly higher in the zirconia FDPs than PFM FDPs, and as refined processing procedures have started to yield better results in the laboratory, new clinical studies with these new procedures must confirm whether the frequency of veneer chipping can be reduced to the level of PFM. Int J Prosthodont 2010;23:493-502

Cardiovascular disease and the changing face of global public health : a focus on low and middle income countries

Eighty percent of the global 17 million deaths due to cardiovascular disease (CVD) occur in low and middle income countries (LMICs). The burden of CVD and other noncommunicable diseases (NCDs) is expected to markedly increase because of the global aging of the population and increasing exposure to detrimental lifestyle-related risk in LMICs. Interventions to reduce four main risks related to modifiable behaviors (tobacco use, unhealthy diet, low physical activity and excess alcohol consumption) are key elements for effective primary prevention of the four main NCDs (CVD, cancer, diabetes and chronic pulmonary disease). These behaviors are best improved through structural interventions (e.g., clean air policy, taxes on cigarettes, new recipes for processed foods with reduced salt and fat, urban shaping to improve mobility, etc.). In addition, health systems in LMICs should be reoriented to deliver integrated cost-effective treatment to persons at high risk at the primary health care level. The full implementation of a small number of highly cost effective, affordable and scalable interventions ("best buys") is likely to be the necessary and sufficient ingredient for curbing NCDs in LMICs. NCDs are both a cause and a consequence of poverty. It is therefore important to frame NCD prevention and control within the broader context of social determinants and development agenda. The recent emphasis on NCDs at a number of health and economic forums (including the September 2011 High Level Meeting on NCDs at the United Nations) provides a new opportunity to move the NCD agenda forward in LMICs.

Availability, Cost or Culture ? : Obstacles to Childcare Services for Low-Income Families

Recent research has highlighted the existence of a social bias in the extent to which children have access to childcare. In general, children living in higher income households are more likely to be cared for in childcare centres. While the existence of a social bias in access to childcare services has been clearly demonstrated, we currently lack a clear explanation as to why this is the case. This paper uses a unique dataset based on survey data collected specifically to study patterns of childcare use in the Swiss canton of Vaud (N = 875). The paper exploits the variation in the way childcare is organised within the canton. Childcare is a municipal policy, as a result of which there are twenty-nine different systems in operation. Fees are progressive everywhere, but variation is substantial. Availability is also very different. This peculiar institutional setup provides an ideal situation to examine the determinants of childcare use by different income groups. Our findings suggest that differences in the fees charged to low-income households, as well as the degree of progressivity of the fee structure, are significant predictors of use, while availability seems to matter less.

Screening for cardiovascular disease risk and subsequent management in low and middle income countries : challenges and opportunities

Background: Cardiovascular disease (CVD), mainly heart attack and stroke, is the leading cause of premature mortality in low and middle income countries (LMICs). Identifying and managing individuals at high risk of CVD is an important strategy to prevent and control CVD, in addition to multisectoral population-based interventions to reduce CVD risk factors in the entire population. Methods: We describe key public health considerations in identifying and managing individuals at high risk of CVD in LMICs. Results: A main objective of any strategy to identify individuals at high CVD risk is to maximize the number of CVD events averted while minimizing the numbers of individuals needing treatment. Scores estimating the total risk of CVD (e.g. ten-year risk of fatal and non-fatal CVD) are available for LMICs, and are based on the main CVD risk factors (history of CVD, age, sex, tobacco use, blood pressure, blood cholesterol and diabetes status). Opportunistic screening of CVD risk factors enables identification of persons with high CVD risk, but this strategy can be widely applied in low resource settings only if cost effective interventions are used (e.g. the WHO Package of Essential NCD interventions for primary health care in low resource settings package) and if treatment (generally for years) can be sustained, including continued availability of affordable medications and funding mechanisms that allow people to purchase medications without impoverishing them (e.g. universal access to health care). This also emphasises the need to re-orient health systems in LMICs towards chronic diseases management.

Social insurances system's shortcomings : the example of the low-income young retirees' access to healthcare [Imperfections du système d'assurances sociales : l'exemple de l'accès aux soins des jeunes retraité(e)s à revenu modeste]

This article presents the results of a study involving 2445 recently retired persons from the Canton of Vaud in Switzerland who choose to forego health care. These persons of modest means barely qualify for government assistance programs and do not benefit from the social safety net that is provided to the truly destitute. 17.9% of the respondents to the questionnaire said that they forego health care for financial reasons. Interviews reveal the complex reasons that lie behind such a choice, as well as the compensation strategies that are sometimes used to get medical treatment. These strategies show that the people are able to act when the circumstances require them to do so. Despite that, their situation remains insecure. Cet article analyse les résultats d'une étude sur le renoncement aux soins menée auprès de 2445 Vaudois∙e∙s récemment retraité∙e∙s. Ces personnes de situation modeste sont proches des limites d'accès aux aides étatiques et ne bénéficient pas du même filet de protection sociale que d'autres plus démunies. 17.9% des répondant∙e∙s au questionnaire déclarent renoncer à des soins pour raisons financières. Des entretiens mettent en évidence la complexité du renoncement, ainsi que les stratégies compensatoires que les personnes adoptent pour accéder à certains soins. Ces dernières démontrent une capacité d'agir en situation qui reste toutefois précaire.

Cost-effectiveness of Tenofovir / Emtricitabine / Efavirenz versus Zidovudine / Lamivudine / Efavirenz as fist-line regimens for the treatment of HIV-infected patients in low-income settings

The Highly Active Antiretroviral Therapy (HAART) is the combination of at least three antiretroviral compounds. The combination purpose is to reduce the likelihood of drug resistance. However in the long-term the resistance to the first-line combination occurs and leads to treatment failure. Thus, a second-line and even a third-line regimen are recommended in the long run. [...] [P. 5] The two treatment alternatives under comparison: Tenofovir (300 mg) CO-formulated with Emtricitabine (200 mg) and Efavirenz (600 mg) currently known under the brand name Atripla (R) was introduced in July 2006 in the United States market. The excellent safety profile and ease of use make this combination a perfect first-line regimen in low-income settings. Therefore, this treatment option was recommended in WHO 2006 reviewed guidelines. Unfortunately, Tenofovir and Emtricitabine compounds are still costly and not yet widely available. For a matter of simplification this regimen is referred in this report as "the recent" therapy. Initially, we had in mind to consider the most frequently used first-line regimen in low-income countries (Stavudine / Larnivudme / Nevirapine) as a comparator for this economic evaluation. Unfortunately, according to the literature review results (see Annex 3); there was no data available comparing head to head the effectiveness of this regimen with the recent one. Instead, we selected a less frequently but commonly used first-line regimen in low-income countries as a comparator: Zidovudine, Lamivudine, Efavirenz. This combination has extensive experience in durability, safety and toxicity and seems to be an optimal choice for a first-line regimen according to the clinical trial group 384 team. Furthermore, Zidovudine, one of the compounds of this combination is now recommended as one of the preferred NNRTI [Non Nucleoside Reverse Transcriptase Inhibitors] options to be considered by countries instead of Stavudine (the most used NNRTI in limited-income countries). As this combination has been included in the WHO guidelines as a first-line therapy since 2003 when WHO launched the "3 by 5" scaling-up initiative, this combination of drugs is referred in this report as the "old" therapy. Objectives: The primary objective of this economic evaluation is to compare the two first-line HAARTs introduced above, in a low-income setting context. Both of these combinations are recommended by the 2006 WHO guidelines as potential first-line regimens. The secondary objective is to provide a simplified and comprehensible cost-effectiveness modeling tool in order to help policy makers, in resource-limited settings, make decisions about which first-line HAART to fund using the scarce resources available. [P. 6-7]

Ideal Body Size as a Mediator for the Gender-Specific Association Between Socioeconomic Status and Body Mass Index: Evidence From an Upper-Middle-Income Country in the African Region.

While obesity continues to rise globally, the associations between body size, gender, and socioeconomic status (SES) seem to vary in different populations, and little is known on the contribution of perceived ideal body size in the social disparity of obesity in African countries. We examined the gender and socioeconomic patterns of body mass index (BMI) and perceived ideal body size in the Seychelles, a middle-income small island state in the African region. We also assessed the potential role of perceived ideal body size as a mediator for the gender-specific association between SES and BMI. A population-based survey of 1,240 adults aged 25 to 64 years conducted in December 2013. Participants' BMI was calculated based on measured weight and height; ideal body size was assessed using a nine-silhouette instrument. Three SES indicators were considered: income, education, and occupation. BMI and perceived ideal body size were both higher among men of higher versus lower SES (p< .001) but lower among women of higher versus lower SES (p< .001), irrespective of the SES indicator used. Multivariate analysis showed a strong and direct association between perceived ideal body size and BMI in both men and women (p< .001) and was consistent with a potential mediating role of perceived ideal body size in the gender-specific associations between SES and BMI. Our study emphasizes the importance of gender and socioeconomic differences in BMI and ideal body size and suggests that public health interventions that promote perception of healthy weight could help mitigate SES-related disparities in BMI.