Modeling the hot flash experience in breast cancer survivors

OBJECTIVE: To evaluate relationships among different measures of hot flashes, perceived hot flash interference, and associated outcomes (positive affect, negative affect) while controlling potential covariates. DESIGN: Breast cancer survivors (N=236) provided demographic data, objective hot flash frequency data via sternal skin conductance monitoring, prospective diary-based hot flash frequency and severity data, and questionnaire data via the Hot Flash Related Daily Interference Scale and the Positive and Negative Affect Scale. RESULTS: Objective hot flash frequency and subjective hot flash severity emerged as separate factors in the structural equation model. Subjective hot flash frequency was associated with a high degree of unexplained variance (error) and seemed to be a potentially less accurate measure of either frequency or severity. Objective frequency was directly related to greater positive affect. In contrast, greater hot flash severity was (1) directly related to greater perceived hot flash interference and (2) indirectly related to more negative affect and lower positive affect through interference. CONCLUSIONS: Findings provide a theoretical basis for selecting among symptom measures and anticipating how interventions aimed at different hot flash measures might affect perceived hot flash interference or associated outcomes. Because objective hot flash frequency and subjective hot flash severity seemed to measure different dimensions, measuring both may provide a more comprehensive picture of women's symptom experiences.     

Clinical significance of HLA DRB103-DRB104 in type 1 autoimmune hepatitis.

BACKGROUND: HLA DRB1*03-DRB1*04 combines both susceptibility factors for type-1 autoimmune hepatitis. AIMS: Determine whether this phenotype is a risk factor for autoimmune hepatitis in white North American patients, assess its associations with clinical features and treatment outcome, and determine whether alleles within this phenotype affect prognosis. METHODS: One hundred and ninety-eight patients with type 1 autoimmune hepatitis and 102 normal adults were evaluated. HLA typing was performed by DNA-based techniques. RESULTS: Twenty-eight patients had HLA DRB1*03-DRB1*04, and the frequency was higher than in normal subjects (14% vs 4%, OR 4.0%, 95% CI 1.4-11.8, P = 0.01). Patients with DRB1*03-DRB1*04 relapsed less frequently than patients with DRB1*03 (1.3 +/- 0.3 vs 2.1 +/- 0.2, P = 0.04), but they otherwise had outcomes similar to patients with other phenotypes. Patients with DRB1*03-DRB1*04 who had 3-4 alleles encoding lysine at position DRbeta71 within the class II molecule of the major histocompatibility complex developed cirrhosis more commonly (75% vs 9%, P = 0.05) and had a higher frequency of hepatic-related death or liver transplantation (40% vs 0%, P = 0.04) than patients with fewer alleles. CONCLUSIONS: HLA DRB1*03-DRB1*04 is a risk factor for type-1 autoimmune hepatitis, and its impact on outcome relates to the diversity of DRB1*04 alleles that encode a critical motif.     

The therapeutic potential in targeting CCR5 and CXCR4 receptors in infectious and allergic pulmonary disease

Targeting chemokines and chemokine receptors in various acute and chronic pulmonary diseases remains a vibrant area of basic and clinical research despite major hurdles including cross-species barriers, toxicity, and redundancy. In this review, we draw upon our basic research with a murine model in which innate and acquired immunity are linked in the development and maintenance of chronic asthma due to Aspergillus fumigatus. Using intact and genetically altered mice, studies have also been undertaken to elucidate safe and effective therapeutic strategies that interrupt the initiation and amplification of inflammatory and immune events that follow the intrapulmonary introduction of Aspergillus into A. fumigatus-sensitized mice. These events include resident immune cell activation, immune and inflammatory cell recruitment to the airways, changes in lung physiology, and profound changes in the architecture of the airway due to the activation of lung resident cells. The expression of 2 major chemokine receptors, namely, CC chemokine receptor (CCR) 5 and CXC chemokine receptor (CXCR) 4, has been identified and their roles in innate and acquired immune events during fungal asthma have been explored. CCR5 and CXCR4 are best known for their roles in human immunodeficiency virus-1 (HIV-1) infection, but both are attractive targets in the context of overt inflammatory and remodeling responses in the lung. This avenue of research is markedly enhanced by the existence of numerous small molecule antagonists that are available to selectively target these receptors.     

Prognostic value of cardiovascular magnetic resonance in patients with suspected arrhythmogenic right ventricular cardiomyopathy

Background

Early recognition and accurate risk stratification are important in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Identification of predictors of outcome by cardiovascular magnetic resonance (CMR) in patients undergoing evaluation for ARVC is limited. We investigated the predictive value of morphological abnormalities detected by CMR for major clinical events in patients with suspected ARVC.

Methods

We performed a longitudinal study on 369 consecutive patients with at least one criterion for ARVC. Abnormal CMR was defined by the presence of one of the following: increased right ventricular (RV) volumes, reduced RV ejection fraction, RV regional wall motion abnormalities, myocardial fatty infiltration, and myocardial fibrosis. The end-point was a composite of cardiac death, sustained ventricular tachycardia, ventricular fibrillation, and appropriate ICD discharge.

Results

Twenty patients met the composite end-point over a mean follow-up of 4.3 ± 1.5 years. An abnormal CMR was an independent predictor of outcomes (p < 0.001). The presence of multiple abnormalities heralded a particular high risk of events (HR 23.0, 95% CI 5.7–93.2, p < 0.001 for 2 abnormalities; HR 35.8, 95% CI 9.7–132.6, p < 0.001 for 3 or more abnormalities). The positive predictive value of an abnormal CMR study was 21.0% for an adverse event, whilst the negative predictive value of a normal CMR study was 98.8% over the follow-up period.

Conclusions

CMR provides important prognostic information in patients under evaluation for ARVC. A normal study portends a good prognosis. Conversely, the presence of multiple abnormalities identifies a high risk group of patients who may benefit from ICD implantation.     

Photochemistry of aqueous pyruvic acid

The study of organic chemistry in atmospheric aerosols and cloud formation is of interest in predictions of air quality and climate change. It is now known that aqueous phase chemistry is important in the formation of secondary organic aerosols. Here, the photoreactivity of pyruvic acid (PA; CH₃COCOOH) is investigated in aqueous environments characteristic of atmospheric aerosols. PA is currently used as a proxy for α-dicarbonyls in atmospheric models and is abundant in both the gas phase and the aqueous phase (atmospheric aerosols, fog, and clouds) in the atmosphere. The photoreactivity of PA in these phases, however, is very different, thus prompting the need for a mechanistic understanding of its reactivity in different environments. Although the decarboxylation of aqueous phase PA through UV excitation has been studied for many years, its mechanism and products remain controversial. In this work, photolysis of aqueous PA is shown to produce acetoin (CH₃CHOHCOCH₃), lactic acid (CH₃CHOHCOOH), acetic acid (CH₃COOH), and oligomers, illustrating the progression from a three-carbon molecule to four-carbon and even six-carbon molecules through direct photolysis. These products are detected using vibrational and electronic spectroscopy, NMR, and MS, and a reaction mechanism is presented accounting for all products detected. The relevance of sunlight-initiated PA chemistry in aqueous environments is then discussed in the context of processes occurring on atmospheric aerosols.     

Duplex criteria for determination of 50% or greater carotid stenosis.

Recently the North American Symptomatic Carotid Endarterectomy Trial investigators reported a benefit of carotid endarterectomy compared with medical therapy for symptomatic patients with 50% or greater carotid stenosis. This has necessitated the development of screening parameters for diagnosis of 50% or greater carotid stenosis on the basis of the reference standards used in the study by the North American Symptomatic Carotid Endarterectomy Trial. The duplex scans and arteriograms of 110 patients (210 carotid arteries) were reviewed by blinded readers. Duplex measurements of peak systolic velocity and end diastolic velocity were recorded, and the ratio of these velocities in the internal and common carotid arteries was calculated. The criteria determined for detection of 50% or greater stenosis were as follows: peak systolic velocity of the internal carotid artery greater than 170 cm/s (sensitivity, 92%; specificity, 90%; positive predictive value, 92%; negative predictive value, 90%; and accuracy, 91 %); end diastolic velocity of the internal carotid artery greater than 60 cm/s (sensitivity, 92%; specificity, 86%; positive predictive value, 95%; negative predictive value, 79%; and accuracy, 91 %); ratio of peak systolic velocity of the internal carotid artery to peak systolic velocity of the common carotid artery greater than 2 (sensitivity, 93%; specificity, 75%; positive predictive value, 83%; negative predictive value, 89%; and accuracy, 85%); and ratio of end diastolic velocity of the internal carotid artery to end diastolic velocity of the common carotid artery greater than 2.4 (sensitivity, 96%; specificity, 79%; positive predictive value, 88%; negative predictive value, 92%; and accuracy, 89%). It is concluded that 50% or greater carotid artery stenosis can be reliably determined by duplex criteria. The use of receiver operating characteristic curves allows the individualization of duplex criteria to the clinical situation.     

18 Graduate Medical Education and Knowledge Translation: One Problem-Specific Approach in Residency

Traditional graduate medical education approaches to improving clinical performance based upon the latest research have included Journal Club and didactic lectures. Unfortunately, these educational interventions have rarely been demonstrated to change practice behavior or improve patient-important outcomes. Using a structured approach to identifying a gap between best-evidence knowledge and clinical practice, an illustrative one-year residency-wide translational research project was developed in a four year emergency medicine training program. Step one (assigned to the second year residents): identify and quantitatively justify a Knowledge Translation (KT) deficit within our institution. They identified steroids in adult bacterial meningitis as an unequivocal therapeutic option. Based upon a structured one-year chart review, they next demonstrated that only 7% of meningitis patients received pre-antimicrobial steroids. The next step (assigned to the first year residents): identify and quantify the physician "leaks" within the pipeline of information from publication to bedside utilization via an online survey. The third year residents hypothesized plugs for these information leaks, including examples of other specialties or institutions which have successfully navigated this specific clinical scenario. Finally, at an end-of-year Journal Club, the fourth year residents formulated a protocol for the appropriate use of steroids in suspected adult meningitis and brought together individuals from within the institution contributing to the best-practice leak. Knowledge Translation involves multiple stages beyond simple evidence awareness and usually involves continuation beyond the emergency department. The Washington University KT project offers a structured, multidisciplinary example of moving beyond contemplation to implementation of an unequivocal therapy.