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Maya R Chilbert,1,2 Dylan VanDuyn,3 Sara Salah,1 Collin M Clark,1,2 Qing Ma1 1Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA; 2Department of Pharmacy, Buffalo General Medical Center, Buffalo, NY, USA; 3Department of Pharmacy, Buffalo Veterans Affairs Medical Center, Buffalo, NY, USACorrespondence: Maya R Chilbert, Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 202 Pharmacy Building, Buffalo, NY, USA, Tel +1 716 829-5172, Fax +1 716-829-6093, Email mayahols@buffalo.eduAbstract: Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient’s elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease.Keywords: hypercholesterolemia, hyperlipidemia, cardiac events, lipid biomarkers, atherosclerosis

Background: Florbetapir F 18 (F-AV-45) is a positron emission tomography imaging ligand for the detection of amyloid aggregation associated with Alzheimer disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid (Aβ) plaques in human brain homogenates (Kd=3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. This study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and Aβ density measured by established neuropathologic methods.Methods: The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 patients with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of Aβ identified by silver staining, thioflavin S staining, and immunohistochemistry.Results: There were strong quantitative correlations between florbetapir F 18 tissue binding and both Aβ plaques identified by light microscopy (Silver staining and thioflavin S fluorescence) and by immunohistochemical measurements of Aβ using 3 antibodies recognizing different epitopes of the Aβ peptide. Florbetapir F 18 did not bind to neurofibrillary tangles.Conclusions: Florbetapir F 18 selectively binds Aβ in human brain tissue. The binding intensity was quantitatively correlated with the density of Aβ plaques identified by standard neuropathologic techniques and correlated with the density of Aβ measured by immunohistochemistry. As Aβ plaques are a defining neuropathologic feature for Alzheimer disease, these results support the use of florbetapir F 18 as an amyloid positron emission tomography ligand to identify the presence of Alzheimer disease pathology in patients with signs and symptoms of progressive late-life cognitive impairment. [ABSTRACT FROM AUTHOR]

The best-studied biomarkers of Alzheimer's disease (AD) are the pathologically-linked cerebrospinal fluid (CSF) proteins amyloid-β 42 (Aβ(1-42)), total tau (t-tau), and tau phosphorylated on amino acid 181 (p-tau(181)). Many laboratories measure these proteins using enzyme-linked immunosorbent assay (ELISA). Multiplex xMAP Luminex is a semi-automated assay platform with reduced intra-sample variance, which could facilitate its use in CLIA-approved clinical laboratories. CSF concentrations of these three biomarkers reported using xMAP technology differ from those measured by the most commonly used ELISA, confounding attempts to compare results. To develop a model for converting between xMAP and ELISA levels of the three biomarkers, we analyzed CSF samples from 140 subjects (59 AD, 30 controls, 34 with mild cognitive impairment, and 17 with Parkinson's disease, including 1 with dementia). Log-transformation of ELISA and xMAP levels made the variance constant in all three biomarkers and improved the linear regression: t-tau concentrations were highly correlated (r = 0.94); p-tau(181) concentrations by ELISA can be better predicted using both the t-tau and p-tau(181) xMAP values (r = 0.96) as compared to p-tau(181) concentrations alone (r = 0.82); correlation of Aβ(1-42) concentrations was relatively weaker but still high (r = 0.77). Among all six protein/assay combinations, xMAP Aβ(1-42) had the best accuracy for diagnostic classification (88%) between AD and control subjects. In conclusion, our study demonstrates that multiplex xMAP is an appropriate assay platform providing results that can be correlated with research-based ELISA values, facilitating the incorporation of this diagnostic biomarker into routine clinical practice. [ABSTRACT FROM AUTHOR]

Context: The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease.Objective: To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of β-amyloid in the brain at autopsy.Design, Setting, and Participants: Prospective clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice, long-term care, and community health care facilities near the end of their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures of brain β-amyloid after their death used as the reference standard. PET images were also obtained in 74 young individuals (18-50 years) presumed free of brain amyloid to better understand the frequency of a false-positive interpretation of a florbetapir-PET image.Main Outcome Measures: Correlation of florbetapir-PET image interpretation (based on the median of 3 nuclear medicine physicians' ratings) and semiautomated quantification of cortical retention with postmortem β-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis of Alzheimer disease in the first 35 participants autopsied (out of 152 individuals enrolled in the PET pathological correlation study).Results: Florbetapir-PET imaging was performed a mean of 99 days (range, 1-377 days) before death for the 29 individuals in the primary analysis cohort. Fifteen of the 29 individuals (51.7%) met pathological criteria for Alzheimer disease. Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of β-amyloid pathology at autopsy as measured by immunohistochemistry (Bonferroni ρ, 0.78 [95% confidence interval, 0.58-0.89]; P <.001]) and silver stain neuritic plaque score (Bonferroni ρ, 0.71 [95% confidence interval, 0.47-0.86]; P <.001). Florbetapir-PET images and postmortem results rated as positive or negative for β-amyloid agreed in 96% of the 29 individuals in the primary analysis cohort. The florbetapir-PET image was rated as amyloid negative in the 74 younger individuals in the nonautopsy cohort.Conclusions: Florbetapir-PET imaging was correlated with the presence and density of β-amyloid. These data provide evidence that a molecular imaging procedure can identify β-amyloid pathology in the brains of individuals during life. Additional studies are required to understand the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia. [ABSTRACT FROM AUTHOR]

Disruptive student behavior is an emerging concern in institutions of higher education in the People's Republic of China (PRC). Faculty from a nursing college in the PRC expressed a desire to study the type and frequency of student incivility. Nursing faculty from the United States of America and the PRC collaborated on a study to measure faculty and student perceptions of student incivility in a Chinese nursing college. Student incivility in nursing education is a relatively new field of investigation; however, this preliminary study in the PRC shows it to be a substantial problem that needs to be addressed [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the T1rho (T(1rho)) MRI relaxation time in hippocampus in the brain of Alzheimer's disease (AD), mild cognitive impairment (MCI), and control, and to determine whether the T(1rho) shows any significant difference between these cohorts.Materials and Methods: With informed consent, AD (n = 49), MCI (n = 48), and age-matched control (n = 31) underwent T(1rho) MRI on a Siemens 1.5T Scanner. T(1rho) values were automatically calculated from the left and right hippocampus region using in-house developed software. Bonferroni post-hoc multiple comparisons was performed to compare the T(1rho) value among the different cohorts.Results: Significantly higher T(1rho) values were observed both in AD (P = 0.000) and MCI (P = 0.037) cohorts compared to control; also, the T(1rho) in AD was significantly high over (P = 0.032) MCI. Hippocampus T(1rho) was 13% greater in the AD patients than control, while in MCI it was 7% greater than control. Hippocampus T(1rho) in AD patients was 6% greater than MCI.Conclusion: Higher hippocampus T(1rho) values in the AD patients might be associated with the increased plaques burden. A follow-up study would help to determine the efficacy of T(1rho) values as a predictor of developing AD in the control and MCI individuals. [ABSTRACT FROM AUTHOR]

Incivility in nursing education is a challenging problem and difficult to measure. This paper describes both the development and description of the Incivility in Nursing Education (INE) survey. The INE includes eight demographic items, six quantitative items, and four open-ended questions. It measures nursing students' and faculty's perceptions of and experience with academic incivility. The INE was initially tested in a 2004 pilot study using a convenience sample of 356 nursing students and faculty and re-tested in a 2006 study with another convenience sample of 504 nursing faculty and students. Revisions were made to the INE based on findings fom these two studies and from findings derived from a 2006 qualitative study. The INE is easily administered to nursing students and faculty and measures both groups' perceptions of uncivil student and faculty behaviors and their perceived frequency. The INE also provides suggestions for prevention and intervention. Preliminary testing of the INE survey supports its continued use in nursing education and research. [ABSTRACT FROM AUTHOR]

Colaizzi's phenomenological method for qualitative study was used to describe nursing students' lived experiences with uncivil encounters with nursing faculty. Seven current and former nursing students from various levels of nursing education were interviewed to investigate their perceptions of faculty incivility in nursing education and to examine the emotional and behavioral impact the perceived incivility had on them. Three major themes emerged regarding faculty incivility: 1) behaving in demeaning and belittling ways, 2) treating students unfairly and subjectively, and 3) pressuring students to conform to unreasonable faculty demands. Three major themes emerged from students' emotional responses to faculty incivility: 1) feeling traumatized, 2) feeling powerless and helpless, and 3) feeling angry and upset. Behavioral responses are also reported. A conceptual model is presented to illustrate the findings. Recommendations for further research are included. [ABSTRACT FROM AUTHOR]

The concept of civility in nursing education is analyzed using a modification of Wilson's classic concept analysis procedure described by Walker and Avant. This analysis provides a common understanding of the concept of the civility in nursing education and is an attempt to more precisely clarify its meaning. Civility is integral to establishing meaningful relationships among students, faculty, and administrators and is a growing area of research in nursing education. Because the concept of civility lacks consistent definition, this article provides an operational definition of civility using relevant sources from a variety of disciplines. [ABSTRACT FROM AUTHOR]

The epsilon4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer's disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21-87 years of age (n=134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE epsilon4 and correlation between SNPs (linkage disequilibrium). APOE epsilon4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis. [ABSTRACT FROM AUTHOR]

Faculty members complain about the rise of uncivil behavior in their students, and students voice similar complaints about faculty. Using an interpretive qualitative method for research, this study examined student and faculty perceptions of incivility in nursing education, possible causes of incivility, and potential remedies. Narrative analysis yielded the following categories: in-class disruption by students, out-of-class disruption by students, uncivil faculty behaviors, and possible causes of incivility in nursing education. The authors argue that further research is needed to increase awareness and understanding about academic incivility, its impact, and its psychological and social consequences. [ABSTRACT FROM AUTHOR]

Based on 88 non-demented controls and 140 AD patients enrolled at the University of Southern California, and 102 Spanish-speaking dementia patients at the University of Pennsylvania, we developed norms, stratified by disease severity, for the Spanish-language CERAD Neuropsychological Battery, and examined the impact of demographic characteristics. Adequacy of information and level of performance differed between sites, indicating hazards that occur in the absence of crosssite planning, including characteristics of 'retrofitted' data (e.g., missing information), small samples, additional countries of origin, and multiple dementing disorders. Nevertheless, controls generally performed better than even very mild AD patients, and performance decreased with increase in severity of disease. In the absence of larger, more representative samples, norms for Spanish-speaking patients and control subjects may be site-specific, and should be treated with caution. [ABSTRACT FROM AUTHOR]

Context: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined.Objective: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia.Design, Setting, and Patients: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000.Main Outcome Measures: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses.Results: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001).Conclusion: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur. [ABSTRACT FROM AUTHOR]

The survival of health care institutions depends upon a delivery system focusing on appropriate use of resources and controlling length of stay while monitoring clinical progress toward identified outcomes. Using a clinical path as a tool for managing resources, research activities, continuous quality improvement, and increased collaborative practice can enhance the professional practice environment and benefit patient care. [ABSTRACT FROM AUTHOR]

Background: The need of an early and noninvasive diagnosis of AD requires the development of imaging-based techniques. As an alternative, the magnetic resonance image (MRI) relaxation time constant (T1ρ) was measured in brains of Alzheimer's disease (AD), mild-cognitive impairment (MCI), and age-matched controls in order to determine whether T1ρ values correlated with the neurological diagnosis.Methods: MRI was performed on AD (n=48), MCI (n=45), and age-matched control (n=41), on a 1.5 Tesla Siemens clinical MRI scanner. T1ρ maps were generated by fitting each pixel's intensity as a function of the duration of the spin-lock pulse. T1ρ values were calculated from the gray matter (GM) and white matter (WM) of medial temporal lobe (MTL).Results: GM and WM T1ρ values were 87.5±1.2 ms and 80.5±1.4 ms, respectively, in controls, 90.9±1.3 ms and 84.1±1.7 ms in MCI, and 91.9±.8 ms and 88.3±1.3 ms in AD cohorts. Compared to control, AD patients showed 9% increased WM T1ρ and 5% increased GM T1ρ. Compared to control, MCI individuals showed 4% increased T1ρ both in WM and GM. A 5% increased T1ρ was found in WM of AD over MCI.Conclusion: The increased T1ρ in WM and GM of MTL in AD may be associated with the pathological changes that are not evident on conventional MRI. [ABSTRACT FROM AUTHOR]