Physicians' estimates of the 10 year cardiovascular risk in hypertensive patients: an evaluation in primary care physicians in training.

To evaluate how young physicians in training perceive their patients' cardiovascular risk based on the medical charts and their clinical judgment. Cross sectional observational study. University outpatient clinic, Lausanne, Switzerland. Two hundred hypertensive patients and 50 non-hypertensive patients with at least one cardiovascular risk factor. Comparison of the absolute 10-year cardiovascular risk calculated by a computer program based on the Framingham score and adapted for physicians by the WHO/ISH with the perceived risk as assessed clinically by the physicians. Physicians underestimated the 10-year cardiovascular risk of their patients compared to that calculated with the Framingham score. Concordance between methods was 39% for hypertensive patients and 30% for non-hypertensive patients. Underestimation of cardiovascular risks for hypertensive patients was related to the fact they had a stabilized systolic blood pressure under 140 mm Hg (OR = 2.1 [1.1; 4.1]). These data show that young physicians in training often have an incorrect perception of the cardiovascular risk of their patients with a tendency to underestimate the risk. However, the calculated risk could also be slightly overestimated when applying the Framingham Heart Study model to a Swiss population. To implement a systematic evaluation of risk factors in primary care a greater emphasis should be placed on the teaching of cardiovascular risk evaluation and on the implementation of quality improvement programs.

Large-scale gene-centric analysis identifies novel variants for coronary artery disease.

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.

Long-Lasting Protection of Activity of Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors (PIs) by Boosted PI Containing Regimens.

BACKGROUND: The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments. METHODS: We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3-6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression. RESULTS: Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3-6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3-6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1-42.8), p<0.001). CONCLUSIONS: The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring.

Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

A case-control study on chronic Chagas heart disease (CCHD) was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD). Fourty-six patients (51.1%) with Chagas heart disease (anomalous ECG) were assigned to the case group and 44 (48.9%) were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin), epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking), and clinical (systemic hypertension) variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age - presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%: 1.09-7.61) - and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11-7.23). Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.

Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments.

BACKGROUND: Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS. METHODS: We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (nR1=168, nR2=188) and in several large population-based samples (n1=5338; n2=123 865; n3>100 000). RESULTS: HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (Pcorrected<0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (Pcorrected<0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (Pcorrected=0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, Pcorrected=0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. CONCLUSIONS: Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population.

Polymorphism in the promoter region of the mannose-binding lectin gene among human T-cell lymphotropic virus infected subjects

The present study investigated the frequency of the mutations at positions -550 and -221 of the mannose-binding lectin (MBL) gene in a sample of 75 human T-cell lymphotropic virus (HTLV) infected patients and 96 HTLV seronegative controls, in order to evaluate the occurrence of a possible association between the polymorphism and HTLV infection. A sequence specific primer-polymerase chain reaction was used for discrimination of the polymorphism. The analysis of allele frequencies at position -550 did not show any significant differences between HTLV infected group and controls, but there was a significant difference at position -221. The comparative analysis of haplotypes frequencies were not significant, but the genotype frequencies between the two groups, revealed a higher prevalence of genotype LYLX (25.3%), associated with medium and low MBL serum levels among HTLV infected subjects. The odds ratio estimation demonstrated that the presence of genotype LYLX was associated with an increased risk of HTLV infection (p = 0.0096; 1.38 < IC95% < 7.7605). There was no association between proviral load and the promoter polymorphism, but when promoter and exon 1 mutations were matched, it was possible to identify a significant higher proviral load among HTLV infected individuals carrying haplotypes correlated to low serum levels of MBL. The present study shows that the polymorphism in the promoter region of the MBL gene may be a genetic marker associated with HTLV infection, and emphasizes the need for further studies to determinate if the present polymorphism have any impact on diseases linked to HTLV infection.

Trabecular bone score improves fracture risk prediction in non-osteoporotic women: the OFELY study.

The use of areal bone mineral density (aBMD) for fracture prediction may be enhanced by considering bone microarchitectural deterioration. Trabecular bone score (TBS) helped in redefining a significant subset of non-osteoporotic women as a higher risk group. INTRODUCTION: TBS is an index of bone microarchitecture. Our goal was to assess the ability of TBS to predict incident fracture. METHODS: TBS was assessed in 560 postmenopausal women from the Os des Femmes de Lyon cohort, who had a lumbar spine (LS) DXA scan (QDR 4500A, Hologic) between years 2000 and 2001. During a mean follow-up of 7.8 ± 1.3 years, 94 women sustained 112 fragility fractures. RESULTS: At the time of baseline DXA scan, women with incident fracture were significantly older (70 ± 9 vs. 65 ± 8 years) and had a lower LS_aBMD and LS_TBS (both -0.4SD, p < 0.001) than women without fracture. The magnitude of fracture prediction was similar for LS_aBMD and LS_TBS (odds ratio [95 % confidence interval] = 1.4 [1.2;1.7] and 1.6 [1.2;2.0]). After adjustment for age and prevalent fracture, LS_TBS remained predictive of an increased risk of fracture. Yet, its addition to age, prevalent fracture, and LS_aBMD did not reach the level of significance to improve the fracture prediction. When using the WHO classification, 39 % of fractures occurred in osteoporotic women, 46 % in osteopenic women, and 15 % in women with T-score > -1. Thirty-seven percent of fractures occurred in the lowest quartile of LS_TBS, regardless of BMD. Moreover, 35 % of fractures that occurred in osteopenic women were classified below this LS_TBS threshold. CONCLUSION: In conclusion, LS_aBMD and LS_TBS predicted fractures equally well. In our cohort, the addition of LS_TBS to age and LS_aBMD added only limited information on fracture risk prediction. However, using the lowest quartile of LS_TBS helped in redefining a significant subset of non-osteoporotic women as a higher risk group which is important for patient management.

Watching television: a previously unrecognized powerful trigger of λ waves.

OBJECTIVE: To assess whether lambda waves are elicited by watching television (TV) and their association with demographical and EEG features. METHODS: We retrospectively compared lambda wave occurrence in prolonged EEG monitorings of outpatients who were allowed to watch TV and in standard EEGs recorded in TV-free rooms. All EEGs were interpreted by the same two electroencephalographers. RESULTS: Of 2,072 standard EEG reports, 36 (1.7 %) mentioned lambda waves versus 46 (32.2%) of 143 prolonged EEG monitoring reports (P < 0.001). Multivariable comparison of prolonged EEG monitorings and standard EEGs disclosed that recordings performed in rooms with a TV (odds ratio, 20.6; 95% confidence interval, 4.8-88.0) and normal EEGs (odds ratio, 3.03; 95% confidence interval, 1.5-6.25) were independently associated with lambda waves. In the prolonged EEG monitoring group, all recordings with lambda waves also had positive occipital sharp transients of sleep. CONCLUSIONS: Watching TV likely represents a powerful and previously unrecognized stimulus for lambda waves. Furthermore, this study confirms the benign nature of this EEG variant and its strong association with positive occipital sharp transients of sleep.

Urban transmission of Chagas disease in Cochabamba, Bolivia

Chagas disease is a major public health problem in Bolivia. In the city of Cochabamba, 58% of the population lives in peripheral urban districts ("popular zones") where the infection prevalence is extremely high. From 1995 to 1999, we studied the demographics of Chagas infections in children from five to 13 years old (n = 2218) from the South zone (SZ) and North zone (NZ) districts, which differ in social, environmental, and agricultural conditions. Information gathered from these districts demonstrates qualitative and quantitative evidence for the active transmission of Trypanosoma cruzi in urban Cochabamba. Seropositivity was high in both zones (25% in SZ and 19% in NZ). We observed a high risk of infection in children from five to nine years old in SZ, but in NZ, a higher risk occurred in children aged 10-13, with odds ratio for infection three times higher in NZ than in SZ. This difference was not due to triatomine density, since more than 1,000 Triatoma infestans were captured in both zones, but was possibly secondary to the vector infection rate (79% in SZ and 37% in NZ). Electrocardiogram abnormalities were found to be prevalent in children and pre-adolescents (SZ = 40%, NZ = 17%), indicating that under continuous exposure to infection and re-infection, a severe form of the disease may develop early in life. This work demonstrates that T. cruzi infection should also be considered an urban health problem and is not restricted to the rural areas and small villages of Bolivia.

Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women.

BACKGROUND: Frailty, as defined by the index derived from the Cardiovascular Health Study (CHS index), predicts risk of adverse outcomes in older adults. Use of this index, however, is impractical in clinical practice. METHODS: We conducted a prospective cohort study in 6701 women 69 years or older to compare the predictive validity of a simple frailty index with the components of weight loss, inability to rise from a chair 5 times without using arms, and reduced energy level (Study of Osteoporotic Fractures [SOF index]) with that of the CHS index with the components of unintentional weight loss, poor grip strength, reduced energy level, slow walking speed, and low level of physical activity. Women were classified as robust, of intermediate status, or frail using each index. Falls were reported every 4 months for 1 year. Disability (> or =1 new impairment in performing instrumental activities of daily living) was ascertained at 4(1/2) years, and fractures and deaths were ascertained during 9 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis and -2 log likelihood statistics were compared for models containing the CHS index vs the SOF index. RESULTS: Increasing evidence of frailty as defined by either the CHS index or the SOF index was similarly associated with an increased risk of adverse outcomes. Frail women had a higher age-adjusted risk of recurrent falls (odds ratio, 2.4), disability (odds ratio, 2.2-2.8), nonspine fracture (hazard ratio, 1.4-1.5), hip fracture (hazard ratio, 1.7-1.8), and death (hazard ratio, 2.4-2.7) (P < .001 for all models). The AUC comparisons revealed no differences between models with the CHS index vs the SOF index in discriminating falls (AUC = 0.61 for both models; P = .66), disability (AUC = 0.64; P = .23), nonspine fracture (AUC = 0.55; P = .80), hip fracture (AUC = 0.63; P = .64), or death (AUC = 0.72; P = .10). Results were similar when -2 log likelihood statistics were compared. CONCLUSION: The simple SOF index predicts risk of falls, disability, fracture, and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice.

Primary percutaneous coronary intervention for unprotected left main disease in patients with acute ST-segment elevation myocardial infarction the AMIS (Acute Myocardial Infarction in Switzerland) plus registry experience.

OBJECTIVES: This study sought to assess outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) for unprotected left main (LM) disease. BACKGROUND: Limited data are available on outcomes in patients with ST-segment elevation myocardial infarction undergoing LM PCI. METHODS: Of 9,075 patients with ST-segment elevation myocardial infarction enrolled in the AMIS (Acute Myocardial Infarction in Switzerland) Plus registry between 2005 and June 30, 2010, 6,666 underwent primary PCI. Of them, 348 (5.2%; mean age: 63.5 ± 12.6 years) underwent LM PCI, either isolated (n = 208) or concomitant to PCI for other vessel segments (n = 140). They were compared with 6,318 patients (94.8%; mean age: 61.9 ± 12.5 years) undergoing PCI of non-LM vessel segments only. RESULTS: The LM patients had higher rates of cardiogenic shock (12.2% vs. 3.5%; p < 0.001), cardiac arrest (10.6% vs. 6.3%; p < 0.01), in-hospital mortality (10.9% vs. 3.8%; p < 0.001), and major adverse cardiac and cerebrovascular events (12.4% vs. 5.0%; p < 0.001) than non-LM PCI. Rates of mortality and major adverse cardiac and cerebrovascular events were highest for concurrent LM and non-LM PCI (17.9% and 18.6%, respectively), intermediate for isolated LM PCI (6.3% and 8.3%, respectively), and lowest for non-LM PCI (3.8% and 5.0%, respectively). Rates of mortality and major adverse cardiac and cerebrovascular events for LM PCI were higher than for non-LM multivessel PCI (10.9% vs. 4.9%, p < 0.001, and 12.4% vs. 6.4%, p < 0.001, respectively). LM disease independently predicted in-hospital death (odds ratio: 2.36; 95% confidence interval: 1.34 to 4.17; p = 0.003). CONCLUSIONS: Emergent LM PCI in the context of acute myocardial infarction, even including 12% cardiogenic shock, appears to have a remarkably high (89%) in-hospital survival. Concurrent LM and non-LM PCI has worse outcomes than isolated LM PCI.

Sociodemographic and occupational risk factors associated with the development of different burnout types: the cross-sectional University of Zaragoza study

BACKGROUND: Three different burnout types have been described: The "frenetic" type describes involved and ambitious subjects who sacrifice their health and personal lives for their jobs; the "underchallenged" type describes indifferent and bored workers who fail to find personal development in their jobs, and the "worn-out" in type describes neglectful subjects who feel they have little control over results and whose efforts go unacknowledged. The study aimed to describe the possible associations between burnout types and general sociodemographic and occupational characteristics. METHODS: A cross-sectional study was carried out on a multi-occupational sample of randomly selected university employees (n = 409). The presence of burnout types was assessed by means of the "Burnout Clinical Subtype Questionnaire (BCSQ-36)", and the degree of association between variables was assessed using an adjusted odds ratio (OR) obtained from multivariate logistic regression models. RESULTS: Individuals working more than 40 hours per week presented with the greatest risk for "frenetic" burnout compared to those working fewer than 35 hours (adjusted OR = 5.69; 95% CI = 2.52-12.82; p < 0.001). Administration and service personnel presented the greatest risk of "underchallenged" burnout compared to teaching and research staff (adjusted OR = 2.85; 95% CI = 1.16-7.01; p = 0.023). Employees with more than sixteen years of service in the organisation presented the greatest risk of "worn-out" burnout compared to those with less than four years of service (adjusted OR = 4.56; 95% CI = 1.47-14.16; p = 0.009). CONCLUSIONS: This study is the first to our knowledge that suggests the existence of associations between the different burnout subtypes (classified according to the degree of dedication to work) and the different sociodemographic and occupational characteristics that are congruent with the definition of each of the subtypes. These results are consistent with the clinical profile definitions of burnout syndrome. In addition, they assist the recognition of distinct profiles and reinforce the idea of differential characterisation of the syndrome for more effective treatment.

A comparative study of dyslipidaemia in men and woman with androgenic alopecia

Several studies have analyzed the relationship between androgenetic alopecia and cardiovascular disease (mainly heart disease). However few studies have analyzed lipid values in men and women separately. This case-control study included 300 patients consecutively admitted to an outpatient clinic, 150 with early onset androgenetic alopecia (80 males and 70 females) and 150 controls (80 males and 70 females) with other skin diseases. Female patients with androgenic alopecia showed significant higher triglycerides values (123.8 vs 89.43 mg/dl, p = 0.006), total cholesterol values (196.1 vs 182.3 mg/dl, p = 0.014), LDL-C values (114.1 vs 98.8 mg/dl, p = 0.0006) and lower HDL-C values (56.8 vs 67.7 mg/dl, p <0.0001) versus controls respectively. Men with androgenic alopecia showed significant higher triglycerides values (159.7 vs 128.7 mg/dl, p = 0.04) total cholesterol values (198.3 vs 181.4 mg/dl, p = 0.006) and LDL-C values (124.3 vs 106.2, p = 0.0013) versus non-alopecic men. A higher prevalence of dyslipidemia in women and men with androgenic alopecia has been found. The elevated lipid values in these patients may contribute, alongside other mechanisms, to the development of cardiovascular disease in patient with androgenic alopecia.

Parental occupational exposure to organic solvents and anencephaly in Mexico

Objective: To assess the relationship between parental occupational exposure to organic solvents, and the risk of anencephaly in Mexico. Methods: A case-control study was conducted based on the registers of the Epidemiological Surveillance System for Neural Tube Defects in Mexico; 151 cases of anencephaly of ≥20 weeks’ gestation were included. A control, born alive and without any apparent congenital malformations at birth, was selected for each case in the same maternity service in which the case was born. Information on occupational exposures, lifestyle habits, reproductive history, use of medicines, supplementation with multivitamins and folic acid, was obtained by a general questionnaire; a food frequency questionnaire was also applied to obtain information of daily intake of folate and other B vitamins. Occupational exposure to organic solvents was based on job title as a proxy for exposure and analysed considering two critical periods around conception. Results: In logistic regression analysis, the odds of having a child with anencephaly was higher if the mother or the father was occupationally exposed to organic solvents during the periconceptional period, or when both parents or at least one of them were occupationally exposed during this period with an adjusted odds ratio of 2.97 (95% CI 1.36 to 6.52). Conclusions: The results support the hypothesis that both maternal and paternal occupational exposure to organic solvents can increase the probability of having a child with anencephaly.

Influencia de las características individuales y de las condiciones laborales en la gravedad de las lesiones por accidente de trabajo registradas en Andalucía en 2003

Background. The study of the severity of occupational injuries is very important for the establishment of prevention plans. The aim of this paper is to analyze the distribution of occupational injuries by a) individual factors b) work place characteristics and c) working conditions and to analyze the severity of occupational injuries by this characteristics in men and women in Andalusia. Methods. Injury data came from the accident registry of the Ministry of Labor and Social Issues in 2003. Dependent variable: the severity of the injury: slight, serious, very serious and fatal; the independent variables: the characteristics of the worker, company data, and the accident itself. Bivariate and multivariate analysis were done to estimate the probability of serious, very serious and fatal injury, related to other variables, through odds ratio (OR), and using a 95% confidence interval (CI 95%). Results. The 82,4% of the records were men and 17,6% were women, of whom the 78,1% are unskilled manual workers, compared to 44,9% of men. The men belonging to class I have a higher probability of more severe lesions (OR = 1,67, 95% CI = 1,17 – 2,38). Conclusions. The severity of the injury is associated with sex, age and type of injury. In men it is also related with the professional situation, the place where the accident happened, an unusual job, the size and the characteristics of the company and the social class, and in women with the sector