Interpreting High-Sensitive Troponins in Patients with Hypertension.

PURPOSE OF REVIEW: As the high-sensitivity cardiac troponin (hs-cTn) becomes more broadly used, physicians must understand the strengths and limitations of using the hs-cTn in the hypertensive population. RECENT FINDINGS: The most common cause of hs-cTn elevation is cardiac myocyte injury and death; alternate mechanisms for hs-cTn elevation in the absence of cardiac myocyte death are not clearly understood. Hs-cTn elevation has been found in significant proportions of patients with asymptomatic hypertension, in patients with acute hypertensive crisis, and has even been used to predict patients who will go on to develop hypertension. While the mechanisms remain undefined, there is evidence that elevations in hs-cTn are associated with both short- and long-term morbidity and mortality. While ongoing research further defines the relationship between hypertension and hs-cTn, the emergency medicine physician must make clinical decisions today regarding the utility of this increasingly used biomarker. Given the current evidence, clinical context must be utilized including a complete clinical picture, EKGs findings, and importantly serial hs-cTn when needed to establish whether myocardial injury or myocardial infarction is occurring.

Improving handover competency in preclinical medical and health professions students: establishing the reliability and construct validity of an assessment instrument.

BACKGROUND: As part of the worldwide call to enhance the safety of patient handovers of care, the Association of American Medical Colleges (AAMC) requires that all graduating students "give or receive a patient handover to transition care responsibly" as one of its Core Entrustable Professional Activities (EPAs) for Entering Residency. Students therefore require educational activities that build the necessary teamwork skills to perform structured handovers. To date, a reliable instrument designed to assess teamwork competencies, like structured communication, throughout their preclinical and clinical years does not exist. METHOD: Our team developed an assessment instrument that evaluates both the use of structured communication and two additional teamwork competencies necessary to perform safe patient handovers. This instrument was utilized to assess 192 handovers that were recorded from a sample of 229 preclinical medical students and 25 health professions students who participated in a virtual course on safe patient handovers. Five raters were trained on utilization of the assessment instrument, and consensus was established. Each handover was reviewed independently by two separate raters. RESULTS: The raters achieved 72.22 % agreement across items in the reviewed handovers. Krippendorff's alpha coefficient to assess inter-rater reliability was 0.6245, indicating substantial agreement among the raters. A confirmatory factor analysis (CFA) demonstrated the orthogonal characteristics of items in this instrument with rotated item loadings onto three distinct factors providing preliminary evidence of construct validity. CONCLUSIONS: We present an assessment instrument with substantial reliability and preliminary evidence of construct validity designed to evaluate both use of structured handover format as well as two team competencies necessary for safe patient handovers. Our assessment instrument can be used by educators to evaluate learners' handoff performance as early as their preclinical years and is broadly applicable in the clinical context in which it is utilized. In the journey to optimize safe patient care through improved teamwork during handovers, our instrument achieves a critical step in the process of developing a validated assessment instrument to evaluate learners as they seek to accomplish this goal.

Acute pulmonary hemorrhage associated with metastatic testicular choriocarcinoma in a 46-year-old incarcerated male.

Pure testicular choriocarcinoma is a rare histological subtype of germ cell tumor (GCT) and typically presents with distant metastases and aggressive features leading to a generally poor prognosis. Unique to choriocarcinoma among GCT histological subtypes is the propensity of spontaneous hemorrhage into metastatic lesions. We report a case of pure testicular choriocarcinoma in a 46-year-old male with postoperative acute pulmonary hemorrhage secondary to tumor invasion of the lungs, and the subsequent management of his disease with a discussion of relevant literature.

Simulation-Based Mastery Learning Improves Medical Student Performance and Retention of Core Clinical Skills.

INTRODUCTION: Simulation-based mastery learning (SBML) improves procedural skills among medical trainees. We employed an SBML method that includes an asynchronous knowledge acquisition portion and a hands-on skill acquisition portion with simulation to assess senior medical student performance and retention of the following 6 core clinical skills: (a) ultrasound-guided peripheral intravenous placement, (b) basic skin laceration repair, (c) chest compressions, (d) bag-valve mask ventilation, (e) defibrillator management, and (f) code leadership. METHODS: Seven emergency medicine (EM) faculty members developed curricula, created checklists, and set minimum passing standards (MPSs) to test mastery of the 6 skills. One hundred thirty-five students on an EM clerkship were pretested on all 6 skills, viewed online videos asynchronously followed by a multiple choice computer-based skill-related quiz, received one-on-one hands-on skill training using deliberate practice with feedback, and were posttested until MPS was met. We compared pretest and posttest performance. We also retested, unannounced, a convenience sample (36%) of students from 1 to 9 months postintervention to assess skill retention. RESULTS: All students passed each quiz. The percentage of students who reached each MPS increased significantly (P < 0.001) from pretest to posttest for all 6 clinical skills. Ninety-eight percent of the students scored at or above the MPS when retested 1 to 9 months later. There was no significant decrease in mean score for any of the 6 skills between posttest and retention testing. CONCLUSIONS: Simulation-based mastery learning using a substantial asynchronous component is an effective way for senior medical students to learn and retain EM clinical skills. This method can be adapted to other skill training necessary for residency readiness.

The chi-square test of independence.

The Chi-square statistic is a non-parametric (distribution free) tool designed to analyze group differences when the dependent variable is measured at a nominal level. Like all non-parametric statistics, the Chi-square is robust with respect to the distribution of the data. Specifically, it does not require equality of variances among the study groups or homoscedasticity in the data. It permits evaluation of both dichotomous independent variables, and of multiple group studies. Unlike many other non-parametric and some parametric statistics, the calculations needed to compute the Chi-square provide considerable information about how each of the groups performed in the study. This richness of detail allows the researcher to understand the results and thus to derive more detailed information from this statistic than from many others. The Chi-square is a significance statistic, and should be followed with a strength statistic. The Cramer's V is the most common strength test used to test the data when a significant Chi-square result has been obtained. Advantages of the Chi-square include its robustness with respect to distribution of the data, its ease of computation, the detailed information that can be derived from the test, its use in studies for which parametric assumptions cannot be met, and its flexibility in handling data from both two group and multiple group studies. Limitations include its sample size requirements, difficulty of interpretation when there are large numbers of categories (20 or more) in the independent or dependent variables, and tendency of the Cramer's V to produce relative low correlation measures, even for highly significant results.

The role of consultation calls for clinic supervisors in supporting large-scale dissemination of evidence-based treatments for children.

This study explores the content of consultation provided to clinic supervisors within the context of a statewide training program in an evidence-based practice. Minute-to-minute live coding of consultation calls with clinic supervisors was conducted in order to identify the content and distribution of call topics. Results indicated that approximately half of the total speaking time was spent on a range of clinically relevant topics (e.g., cognitive-behavioral therapy techniques, fidelity to the treatment protocols). The remaining time was spent on program administration and CBT-related supervisory issues. This pilot study has broad implications for structuring the content of consultation process in large-scale dissemination efforts involving multiple portions of the clinical workforce.

Interrater reliability: the kappa statistic.

The kappa statistic is frequently used to test interrater reliability. The importance of rater reliability lies in the fact that it represents the extent to which the data collected in the study are correct representations of the variables measured. Measurement of the extent to which data collectors (raters) assign the same score to the same variable is called interrater reliability. While there have been a variety of methods to measure interrater reliability, traditionally it was measured as percent agreement, calculated as the number of agreement scores divided by the total number of scores. In 1960, Jacob Cohen critiqued use of percent agreement due to its inability to account for chance agreement. He introduced the Cohen's kappa, developed to account for the possibility that raters actually guess on at least some variables due to uncertainty. Like most correlation statistics, the kappa can range from -1 to +1. While the kappa is one of the most commonly used statistics to test interrater reliability, it has limitations. Judgments about what level of kappa should be acceptable for health research are questioned. Cohen's suggested interpretation may be too lenient for health related studies because it implies that a score as low as 0.41 might be acceptable. Kappa and percent agreement are compared, and levels for both kappa and percent agreement that should be demanded in healthcare studies are suggested.

Gastric heterotopia with extensive involvement of the small intestine associated with congenital short bowel syndrome and intestinal malrotation.

We present a case of extensive gastric heterotopia involving the small intestine associated with congenital short bowel syndrome and malrotation. The infant showed a normal mesenteric artery, without signs of "apple peel" deformity. Gastric heterotopia extended from the duodenum to the mid-ileum involving the short bowel. Gastric mucosa heterotopia may involve any segment of the gastrointestinal tract. It can be associated with pancreatic heterotopia and Meckel diverticulum. However, our case showed involvement of two-thirds of the small intestine without pancreatic heterotopia. To our knowledge, this is the first report of gastric heterotopia with congenital short gut syndrome and malrotation.

Anastrozole and letrozole: an investigation and comparison of quality of life and tolerability.

Previous studies have demonstrated that both anastrozole and letrozole are well tolerated. Letrozole suppresses estrogen to a greater degree than anastrozole in the serum and breast tumor. Concerns have been raised that greater potency may adversely affect patients' quality of life (QOL). One hundred eighty-one postmenopausal women with invasive estrogen receptor-positive breast cancers were randomized to receive either 12 weeks of letrozole followed by 12 weeks of anastrozole or the reverse sequence. One hundred and six received immediate adjuvant aromatase inhibitors (AIs) following surgery, and 75 received extended adjuvant therapy. The Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-B-ES) QOL questionnaires were completed to assess QOL on each drug. Additional side-effect profiles were collected. Each patient completed a patient preference form. Twenty-one patients withdrew before study end, 10/179 (5.6%) while taking letrozole and 4/173 (2.3%) while taking anastrozole (P = 0.12). Tamoxifen-naïve patients had a higher mean ES (endocrine symptoms subscale) score at entry versus those having extended therapy (66.0 vs. 61.9; P = 0.001). There was no significant change in FACT-B-ES (overall) scores or ES scores while patients were taking anastrozole or letrozole and no significant differences between drugs. Nearly 80% of patients reported one or more side effects with either agent. No differences in frequency, grade, or range of side effects were seen between drugs. Of 160 patients, 49 (30.6%) preferred letrozole, 57 (35.6%) preferred anastrozole, and 54 (33.8%) had no preference (P = 0.26, Pearson's Chi-squared test). In conclusion, both AIs are equally well tolerated. There were no significant differences in QOL scores between the two drugs.

Multiple comparison analysis testing in ANOVA.

The Analysis of Variance (ANOVA) test has long been an important tool for researchers conducting studies on multiple experimental groups and one or more control groups. However, ANOVA cannot provide detailed information on differences among the various study groups, or on complex combinations of study groups. To fully understand group differences in an ANOVA, researchers must conduct tests of the differences between particular pairs of experimental and control groups. Tests conducted on subsets of data tested previously in another analysis are called post hoc tests. A class of post hoc tests that provide this type of detailed information for ANOVA results are called "multiple comparison analysis" tests. The most commonly used multiple comparison analysis statistics include the following tests: Tukey, Newman-Keuls, Scheffee, Bonferroni and Dunnett. These statistical tools each have specific uses, advantages and disadvantages. Some are best used for testing theory while others are useful in generating new theory. Selection of the appropriate post hoc test will provide researchers with the most detailed information while limiting Type 1 errors due to alpha inflation.

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer.

ALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; n = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; n = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen (n = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption.

An extraction-free method by which a single slot blot can be used to quantify intracellular DNA damage (crosslinks or strand breaks) and changes in DNA damage response proteins or replication.

We report an extraction-free assay in which the same slot blot membrane can be used to assess total genomic DNA damage (i.e., crosslinks or strand breaks) and DNA replication (i.e., bromodeoxyuridine incorporation) or protein levels (i.e., gamma-H2AX). 14C-thymidine radiolabeling of HCT116 cells loaded directly on a Hybond N+ membrane slot blot enables the quantitation of DNA interstrand crosslinks and DNA breaks, while bromodeoxyuridine incorporation or levels of gamma-H2AX can be assessed by incubating blots with primary monoclonal antibodies followed by detection with horseradish peroxidase (HRP) secondary antibodies. Uniform Ponceau staining of all samples on the membrane indicates that protein binding to the membrane is independent of DNA damage or elution. The use of a single membrane to assay levels of DNA damage and concomitant changes in damage response proteins or replication allows the direct quantitation of diverse parameters under identical conditions.

C-1027, a radiomimetic enediyne anticancer drug, preferentially targets hypoxic cells.

The hypoxic nature of cells within solid tumors limits the efficacy of anticancer therapies such as ionizing radiation and conventional radiomimetics because their mechanisms require oxygen to induce lethal DNA breaks. For example, the conventional radiomimetic enediyne neocarzinostatin is 4-fold less cytotoxic to cells maintained in low oxygen (hypoxic) compared with normoxic conditions. By contrast, the enediyne C-1027 was nearly 3-fold more cytotoxic to hypoxic than to normoxic cells. Like other radiomimetics, C-1027 induced DNA breaks to a lesser extent in cell-free, or cellular hypoxic, compared with normoxic environments. However, the unique DNA interstrand cross-linking ability of C-1027 was markedly enhanced under the same hypoxic conditions that reduced its DNA break induction. Although the unique chemistry of C-1027 allows it to concurrently generate both DNA breaks and cross-links in normoxic cells, a low oxygen environment represses the former and promotes the latter. Thus, treatment with C-1027 offers a facile approach for overcoming the radioresistance associated with poorly oxygenated cells.

Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer.

PURPOSE: To compare the effects of anastrozole and letrozole on plasma estradiol (E2) and estrone sulfate (E1S) levels. PATIENTS AND METHODS: Fifty-four postmenopausal women with estrogen receptor-positive breast cancer receiving aromatase inhibitors (AIs) as part of their adjuvant therapy were randomly assigned to receive either 3 months of anastrozole (1 mg) followed by 3 months of letrozole (2.5 mg), both given orally once daily, or 3 months of the opposite sequence. Blood was taken at the same time and the same day of the week from each patient, before and after 3 months of each drug, and plasma levels of E2 and E1S were determined using highly sensitive radioimmunoassays. RESULTS: There were 27 patients in each group. The mean age of the patients was 63 years (range, 49 to 83 years). Baseline E2 levels ranged from 3 pmol/L to 91 pmol/L with a mean of 25.7 pmol/L. Only one of 54 (2%) patients had an E2 value >or= 3 pmol/L after receiving letrozole, versus 20 of 54 (37%) patients after receiving anastrozole (P < .001). Extrapolation revealed a mean E2 level after anastrozole treatment of 2.71 pmol/L (range, 2.38 to 3.08 pmol/L). Following letrozole, it was 1.56 pmol/L (range, 1.37 to 1.78 pmol/L). Mean residual E2 was 10.1% for anastrozole and 5.9% for letrozole. Residual E1S levels were 4.6% for anastrozole and 2.0% for letrozole (P = .001). CONCLUSION: Letrozole reduces plasma E2 and E1S levels to a significantly greater extent than anastrozole in postmenopausal women taking AIs as part of their adjuvant therapy for hormone receptor-positive breast cancer.

A novel non-synonymous polymorphism (p.Arg240His) in C4b-binding protein is associated with atypical hemolytic uremic syndrome and leads to impaired alternative pathway cofactor activity.

Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) alpha-chain (c.719G>A; p.Arg240His), which is associated with aHUS. This heterozygous change was found in 6/166 aHUS patients compared with 5/542 normal (chi2 = 6.021; p = 0.014), which was replicated in a second cohort of aHUS patients in which we found 5/170 carriers. The polymorphism does not decrease expression efficiency of C4BP. p.Arg240His is equally efficient as the wild type in binding and supporting degradation of C4BP but its ability to bind C3b and act as cofactor to its degradation both in fluid phase and on surfaces is impaired. This observation supports the hypothesis that dysregulation of the alternative pathway of complement is pivotal for aHUS. Three of the patients carry also mutations in membrane cofactor protein and factor H strengthening the hypothesis that individuals may carry multiple susceptibility factors with an additive effect on the risk of developing aHUS.

Psychometric tests of Expectations of Filial Piety Scale in a Mexican-American population.

AIMS AND OBJECTIVES: This paper reports the development of the Expectations of Filial Piety Scale for use with Mexican-American parents regarding expectations they have of their adult children for care and support. BACKGROUND: Earlier work by the authors demonstrated that filial piety is a cross-cultural construct that can be used with Hispanic/Latino populations. More refined development of the construct required testing with more homogeneous subsets (i.e. Mexican-Americans) within the broad designation of Hispanic/Latino adults. DESIGN: Non-experimental methodological design for field testing of the instrument's psychometric properties. METHODS: A convenient sample of 80 Mexican-American adults in California and Texas completed a brief biographical survey and field tested the Expectations of Filial Piety Scale. RESULTS: Common factor analysis with orthogonal rotation was used to extract three factors, which accounted for 58% of the variance in scale scores. These factors included: I: respect for parents (24.05%); II: honouring parents (12.5%); and III: family unity (16.56%). Overall scale reliability was 0.87 with individual factor reliability coefficients ranging from 0.74 to 0.87 and test-retest correlation was 0.73. CONCLUSIONS: The results show that the Expectations of Filial Piety Scale is an internally consistent and reliable tool for use in studies of the Mexican-American population. Mexican elders historically underuse formal services; a large portion of this population will most likely depend on support from their family members when they reach advanced ages. There is a lack of culturally sensitive instruments to measure family values in caring for older adults in Mexican-Americans. RELEVANCE TO CLINICAL PRACTICE: This scale can enable case workers and nurses in long-term care settings to assess the elder's expectations for family support accurately and compare these expectations with available family support, children's intentions to care for a dependent parent or other family member and the need for supplemental care in Mexican-American families.