Lipid profile of patients with increased risk for cardiovascular events in daily clinical practice

Although there are specific guidelines regarding the treatment of dyslipidemia in highly risk patients, these recommendations are usually inadequately followed. The aim of this study is to investigate risk factors in patients with increased cardiovascular risk currently treated in Brazil and Venezuela. Medical charts of 412 patients were selected in 4 institutions. Patients were divided into groups according to the use of lipid-lowering drugs (LLD), particularly statins. Patients who did not use LLD showed higher levels of total cholesterol (p< 0.001), LDL cholesterol (p< 0,001) and HDL cholesterol (p< 0.001), besides lower levels of triglycerides (p< 0.001). The use of statins was associated with a decrease in levels of total cholesterol (from 251.0 +/- 40.0 to 196.0 +/- 46.0), LDL cholesterol (from 168.0 +/- 36.0 to 116.0 +/- 39.0), HDL cholesterol (from 51.0 +/- 46.0 to 46.0 +/- 12.0) and triglycerides (from 181.0 +/- 120.0 to 160.0 +/-79.0). Finally, only a small percentage of patients, even those under treatment with LLD, showed cholesterol levels according to currently available guidelines. Therefore, although the guidelines for the treatment of dyslipidemia are widely known, only a small percentage of patients achieve adequate levels of cholesterol. It is necessary to decrease lipid levels of these patients by increasing the dose of the statins or using a second drug.     

Genetic variation in myosin IXB is associated with ulcerative colitis

BACKGROUND & AIMS: Common germline genetic variation in the 3' region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. METHODS: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3' region of MYO9B. These included the strongest celiac disease-associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. RESULTS: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P = 1.9 x 10(-6); odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. CONCLUSIONS: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases.     

Mechanism of the Frank-Starling law--a simulation study with a novel cardiac muscle contraction model that includes titin and troponin I

A stretch-induced increase of active tension is one of the most important properties of the heart, known as the Frank-Starling law. Although a variation of myofilament Ca(2+) sensitivity with sarcomere length (SL) change was found to be involved, the underlying molecular mechanisms are not fully clarified. Some recent experimental studies indicate that a reduction of the lattice spacing between thin and thick filaments, through the increase of passive tension caused by the sarcomeric protein titin with an increase in SL within the physiological range, promotes formation of force-generating crossbridges (Xbs). However, the mechanism by which the Xb concentration determines the degree of cooperativity for a given SL has so far evaded experimental elucidation. In this simulation study, a novel, rather simple molecular-based cardiac contraction model, appropriate for integration into a ventricular cell model, was designed, being the first model to introduce experimental data on titin-based radial tension to account for the SL-dependent modulation of the interfilament lattice spacing and to include a conformational change of troponin I (TnI). Simulation results for the isometric twitch contraction time course, the length-tension and the force-[Ca(2+)] relationships are comparable to experimental data. A complete potential Frank-Starling mechanism was analyzed by this simulation study. The SL-dependent modulation of the myosin binding rate through titin's passive tension determines the Xb concentration which then alters the degree of positive cooperativity affecting the rate of the TnI conformation change and causing the Hill coefficient to be SL-dependent.     

Performance of drug-drug interaction software for personal digital assistants

BACKGROUND: Personal digital assistants (PDAs) allow healthcare professionals to check for potential drug-drug interactions (DDIs) at the point of care, reducing the need to consult traditional references. However, PDAs can only be as effective as the software programs they use. OBJECTIVE: To examine the ability of DDI software programs manufactured for Palm OS-compatible PDAs in detecting clinically important DDIs. METHODS: Eight PDA software programs were assessed for sensitivity, specificity, and positive and negative predictive values for 16 well-documented DDIs contained within 6 simulated patient profiles. RESULTS: Sensitivity of the software programs ranged from 0.81 to 1.0, specificity ranged from 0.52 to 1.0, positive predictive values ranged from 0.62 to 1.0, and negative predictive values ranged from 0.88 to 1.0. Five programs scored perfect sensitivity scores: DrugIx, ePocrates Rx, ePocrates Rx Pro, Lexi-Interact, and the Tarascon pocket Pharmacopoeia. Of these, the ePocrates programs scored the highest in specificity (0.9), while Lexi-Interact and the Tarascon pocket Pharmacopoeia scored considerably lower (0.52). MosbyIx was the only program to score a 1.0 in specificity; however, its sensitivity was just 0.81. CONCLUSIONS: ePocrates Rx and ePocrates Rx Pro scored greater than or equal to 90% in regard to both sensitivity and specificity, making them the most reliable in detecting the clinically relevant interactions studied without the distraction of detecting those of no clinical significance. In addition, ePocrates Rx is updated regularly and is easily accessible on the Internet at no cost.     

The relationship between patella position and length of the iliotibial band as assessed using Ober's test

The purpose of the study was to investigate the relationship between length of the iliotibial band (ITB) and the medio-lateral position patella. Eighty subjects (37 male, 43 female) were examined for patella position and ITB length. All subjects were physically active, asymptomatic and aged between 18 and 34 years (mean 21.5 years). ITB length was assessed using the Ober's test and modified Ober's test, with hip adduction angle being measured using a fluid goniometer. Patella position was assessed using the method first described by McConnell [The management of chondromalacia patellae: a long term solution. Australian Journal of Physiotherapy 1986;32:215-22]. Patella position had a weak correlation (r=0.28) with modified Ober's (extended knee) test and a poor correlation with Ober's (knee flexed) test (r=0.1). In the group of 47 subjects with laterally displaced patellae, patella position had a moderate statistically significant correlation to ITB length measured by modified Ober's test (r=0.34, P=0.012). Only a poor relationship existed between Ober's test and patella position in the laterally displaced group. The results of this study only partially support the hypothesis that there is a relationship between ITB length and lateral patella displacement. The relationship was not strong enough to confirm ITB length as the only cause of lateral patella displacement.     

A critical discourse analysis of provision of end-of-life care in key UK critical care documents

This article highlights certain practical and professional difficulties in providing end-of-life (EOL) care for patients in critical care units and explores discourses arising from guidelines for critical care services. BACKGROUND: A significant number of patients die in critical care after decisions to withdraw or withhold treatment. Guidelines for provision of critical care suggest, wherever possible, moving patients out of critical care at the EOL. This may not necessarily be conducive to a 'good death' for patients or their loved ones. There is a moral responsibility for both nurses and doctors to ensure that decision-making around EOL issues is sensitively implemented, that decisions about care includes families, patients when able, nurses and doctors, and that good EOL care is provided. METHODS: A critical discourse analysis (CDA) of four key UK critical care documents published since 1996. FINDINGS AND RECOMMENDATIONS: The key documents give little clear guidance about how to provide EOL care in critical care. Discourses include the power dynamic in critical care between professions, families and patients, and how this impacts on provision of EOL care. Difficulties encountered include dilemmas at discharge and paternalism in decision-making. The technological environment can act as a barrier to good EOL care, and critical care nurses are at risk of assuming the dominant medical model of care. Nurses, however, are in a prime position to ensure that decision-making is an inclusive process, patient needs are paramount, the practical aspects of withdrawal lead to a smooth transition in goals of care and that comfort measures are implemented.     

Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities

Neural crest cells are a migratory cell population that give rise to the majority of the cartilage, bone, connective tissue, and sensory ganglia in the head. Abnormalities in the formation, proliferation, migration, and differentiation phases of the neural crest cell life cycle can lead to craniofacial malformations, which constitute one-third of all congenital birth defects. Treacher Collins syndrome (TCS) is characterized by hypoplasia of the facial bones, cleft palate, and middle and external ear defects. Although TCS results from autosomal dominant mutations of the gene TCOF1, the mechanistic origins of the abnormalities observed in this condition are unknown, and the function of Treacle, the protein encoded by TCOF1, remains poorly understood. To investigate the developmental basis of TCS we generated a mouse model through germ-line mutation of Tcof1. Haploinsufficiency of Tcof1 leads to a deficiency in migrating neural crest cells, which results in severe craniofacial malformations. We demonstrate that Tcof1/Treacle is required cell-autonomously for the formation and proliferation of neural crest cells. Tcof1/Treacle regulates proliferation by controlling the production of mature ribosomes. Therefore, Tcof1/Treacle is a unique spatiotemporal regulator of ribosome biogenesis, a deficiency that disrupts neural crest cell formation and proliferation, causing the hypoplasia characteristic of TCS craniofacial anomalies.     

Disseminating contingency management to increase attendance in two community substance abuse treatment centers: Lessons learned

Although contingency management (CM) has been shown to be effective in substance use treatments, community adoption has been slow. To increase dissemination of CM into community practice, two community treatment programs collaborated with university faculty investigators to design, implement, and evaluate low-cost, prize-based CM interventions delivered by treatment staff using Petry's (2000) fishbowl technique. A pre–post study design was used to evaluate the impact of CM on outpatient group attendance. All clients attending the targeted outpatient groups at both treatment programs were eligible to participate. Group attendance was significantly positively impacted after intervention implementation. This is one of the first studies demonstrating successful implementation of CM by community treatment program counselors within their existing treatment groups. The discussion focuses on practical lessons learned during the planning and implementation of the interventions.     

Social desirability biases in self-reported alcohol consumption and harms

Aims

Self-reports remain the most common means of assessing alcohol consumption despite concern for their validity. The objective of this research is to assess the extent to which social desirability biases relate to self-reported consumption, hazardous use, and harms.

Methods

In each of two studies presented, undergraduate students (N = 391 and N = 177) who reported that they had consumed alcohol in the past year completed online confidential surveys.

Results

Both studies show consistent associations between impression management bias and self-reported consumption such that high impression managers report 20 to 33% less consumption and are about 50% less likely to report risky drinking. No significant correlations involving consumption were found for self-deception bias. Study 2 also indicated that high impression managers report 30–50% fewer acute harms following a drinking episode, and that these effects are maintained after controlling statistically for trait impulsivity/constraint.

Conclusions

Impression management bias represents a significant threat to the validity of self-reported alcohol use and harms. Such bias may lead to misspecification of models and under-estimates of harmful or hazardous use.