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1.
Am J Pharm Educ ; 88(3): 100674, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38360186

RESUMEN

OBJECTIVE: To assess the impact of student pharmacist state anxiety on vasopressor calculation accuracy in advanced cardiac life support (ACLS) simulations. METHODS: Third-year professional students participated in 2 ACLS-related simulation laboratory sessions. In week 1, students completed 3 calculations at their workstation with no stressors. Students were then randomized into teams for a bedside simulation where they independently completed 3 additional calculations either with or without stressors. Team assignments were maintained for week 2 where all participants completed a high-fidelity ACLS simulation that included a team vasopressor calculation. At both encounters, calculation accuracy was assessed as well as pre- and post-state anxiety using the Spielberger State-Trait Anxiety Inventory (STAI) survey tool. RESULTS: Students' (N = 145) trait anxiety aligned with normative data for similarly aged professional students. Post-simulation state anxiety in week 1 was found to be higher for those completing the activity with stressors than without (STAI score 44.7 vs 36.9) paired with lower bedside calculation accuracy, despite similar initial workstation calculation accuracy. In week 2, pre-simulation state anxiety score and calculation accuracy were not significantly different between the 2 groups. However, the state anxiety score significantly increased post-simulation for those exposed to stress in the previous week. CONCLUSION: Stress negatively impacted student pharmacist vasopressor calculation accuracy. However, the repeated exposure to a stressed simulation did not result in a significant difference in pre- or post-simulation state anxiety score or calculation accuracy when compared to a non-stressed control. Consideration should be made whether to include more "real-life" simulations in student pharmacist education.


Asunto(s)
Apoyo Vital Cardíaco Avanzado , Educación en Farmacia , Humanos , Anciano , Apoyo Vital Cardíaco Avanzado/educación , Farmacéuticos , Evaluación Educacional , Competencia Clínica , Ansiedad , Estudiantes
3.
Am J Pharm Educ ; 88(1): 100623, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37951575

RESUMEN

OBJECTIVE: To determine the prevalence of board certification among pharmacy practice faculty in the United States, motivators and barriers to certification, and association between board certification and professional achievements and accomplishments that may support career advancement. METHODS: In phase I, the prevalence of board-certified pharmacy practice faculty in the United States was determined by cross-referencing lists of faculty and board-certified pharmacists. In phase II, faculty were stratified by rank and invited to participate in a survey regarding professional characteristics, motivators and barriers to board certification, and professional achievements and accomplishments that may support career advancement for pharmacy practice faculty. RESULTS: The prevalence of board certification among the 3276 pharmacy practice faculty was 56%. The prevalence was the highest among assistant professors (61%). A total of 746 faculty completed the survey (33% response rate). Of those respondents, 73% reported being currently certified, 23% never certified, and 4% previously certified. Overall, to be recognized as an expert in the field was identified as the most commonly perceived reason faculty obtain board certification (44%). Currently and previously certified faculty ranked the desire to be recognized as an expert in the field as the most common reason they obtained board certification (61%). There was a positive correlation between board certification and certain professional accomplishments. CONCLUSION: The prevalence of board-certified pharmacy practice faculty has increased since 2011, but motivators and barriers for board certification remain similar. Board certification may support career advancement for pharmacy practice faculty.


Asunto(s)
Educación en Farmacia , Farmacia , Estados Unidos , Humanos , Prevalencia , Certificación , Docentes
4.
Nutr Clin Pract ; 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37735988

RESUMEN

BACKGROUND: Literature on optimal energy provision via parenteral nutrition (PN) is limited and the evidence quality is low. The purpose of this study is to determine if there is a difference in outcomes in adult critically ill patients when receiving lower vs higher calorie provision via PN early in intensive care unit (ICU) stay. METHODS: Adult patients initiated on PN within the first 10 days of ICU stay from May 2014 to June 2021 were included in this retrospective study. The primary outcome was to determine the impact of lower (<20 kcal/kg/day) vs higher (>25 kcal/kg/day) calorie provision on all-cause, in-hospital mortality. Secondary outcomes were to determine the impact of calorie provision on hospital or ICU length of stay and incidence of complications. RESULTS: This study included 133 patients: a lower calorie provision group (n = 77) and a higher calorie provision group (n = 56). There was a significant difference in all-cause, in-hospital mortality between the lower and the higher calorie provision groups (36.36% and 17.86%, respectively; P = 0.02). However, upon a multivariate analysis of death at discharge, the specific calorie provision group did not affect the probability of death at hospital discharge. The secondary outcomes were not significantly different between groups. CONCLUSION: When comparing lower calorie provision with higher calorie provision in adult critically ill patients receiving PN early within their ICU stay, there were no differences in outcomes after controlling for significant confounders. Future larger prospective studies should further evaluate optimal caloric provision via PN in this population.

5.
Curr Pharm Teach Learn ; 14(10): 1283-1291, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36167725

RESUMEN

INTRODUCTION: Transitions of care (TOC) continue to evolve as a problem within our health care system and is a direct driver to worsened patient outcomes. Currently information of in-depth instruction and application of TOC content within health care education, especially pharmacy, is limited. In 2012, a small team of faculty members created a specialized TOC pharmacy elective for third year doctor of pharmacy students. The purpose of this paper is to describe the impact of this TOC course on students' perceptions on their TOC knowledge, skills, and attitudes over the four years course span. METHODS: A pre-/post-paper anonymous survey was distributed to the students. Descriptive statistics captured the analyzed survey questions into four main themes. Within each respective theme, quantitative data were provided for pre- and post-survey responses to illustrate the difference in the scores with corresponding P values to showcase if significance was present. RESULTS: The response rate of the survey was 100%. Within all of the respective themes, all of the survey questions, pre- to post-responses, had a significant shift toward a higher degree of agreement. CONCLUSIONS: This study illustrates the impact a course dedicated to TOC has on student's learning.


Asunto(s)
Educación en Farmacia , Estudiantes de Farmacia , Humanos , Evaluación Educacional , Curriculum , Actitud
6.
BMJ Open ; 12(8): e061756, 2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-36008066

RESUMEN

INTRODUCTION: Glycaemic variability and other metrics are not well characterised in subjects without diabetes. More comprehensive sampling as obtained with continuous glucose monitoring (CGM) may improve diagnostic accuracy of the transition from health to pre-diabetes. Our goal is to investigate the glycaemic system as it shifts from health to pre-disease in adult patients without diabetes using CGM metrics. New insights may offer therapeutic promise for reversing dysglycaemia more successfully with dietary, nutritional and lifestyle change before progression occurs to pre-diabetes and diabetes. METHODS AND ANALYSIS: This systematic review will include comprehensive searches of the PubMed, Scopus, Cochrane Library and ClinicalTrials.gov databases, with restrictions set to studies published in the last 10 years in English and planned search date 10 March 2022. Reference lists of studies that meet eligibility criteria in the screening process will subsequently be screened for the potential inclusion of additional studies. We will include studies that examine CGM use and report diagnostic criteria such as fasting glucose and/or haemoglobin A1c such that we can assess correlation between CGM metrics and established diagnostic criteria and describe how CGM metrics are altered in the transition from health to pre-diabetes. The screening and data extraction will be conducted by two independent reviewers using Covidence. All included papers will also be evaluated for quality and publication bias using Cochrane Collaboration risk of bias tools. If there are two or more studies with quantitative estimates that can be combined, we will conduct a meta-analysis after assessing heterogeneity. ETHICS AND DISSEMINATION: The systematic review methodology does not require formal ethical review due to the nature of the study design. Study findings will be publicly available and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022308222.


Asunto(s)
Diabetes Mellitus , Estado Prediabético , Adulto , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus/diagnóstico , Humanos , Metaanálisis como Asunto , Estado Prediabético/diagnóstico , Revisiones Sistemáticas como Asunto
7.
Nutrients ; 14(2)2022 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-35057538

RESUMEN

Individuals living with cancer often experience multiple nutrition-related side effects from cancer treatment, including changes in taste and smell, nausea, diarrhea, loss of appetite, and pain during eating. These side effects can profoundly impact nutritional status and quality of life. The purpose of this study was to explore experiences with nutrition-related cancer treatment side effects among cancer patients and their family caregivers, the way they manage such side effects, and the resulting changes in food preferences and behaviors. Structured surveys and in-depth interviews were conducted. Interviews focused on the presence and management of treatment side effects, how those changes influenced food preferences, and the extent to which they interfered with quality of life. Most patients (72%) reported treatment side effects; 61% reported that these side effects impacted their eating and drinking. Common side effects included fatigue (58%), dry mouth (30%), nausea (24%), constipation (20%) and diarrhea (20%). Six overarching qualitative themes were identified: Spiral of side effects; Pain of eating; Burden of eating; Loss of taste/change in taste; Symptom management; and Solutions. The authors conclude with implications for food and nutrition practice-moving beyond traditional recommendations of what to eat or avoid-to consider the overall patient and caregiver experience.


Asunto(s)
Cuidadores/psicología , Conducta Alimentaria/psicología , Neoplasias/psicología , Trastornos Nutricionales/psicología , Calidad de Vida/psicología , Adolescente , Adulto , Femenino , Humanos , Enfermedad Iatrogénica , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Trastornos Nutricionales/etiología , Investigación Cualitativa , Adulto Joven
8.
J Infect Public Health ; 14(11): 1642-1649, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34627059

RESUMEN

BACKGROUND: Diarrhea and pseudomembranous colitis associated with Clostridioides difficile - a spore-forming anaerobic Gram-positive bacillus - is a major infection in hospitalized patients with a profound impact on clinical and economic outcomes. Recurrence (rCDI) is common and predisposes to further episodes with poor outcomes. METHOD: We aimed to identify a wide range of risk factors for recurrence to guide stewardship initiatives. After ethical approval, we commenced collecting demographic and clinical data of patients older than 18 years with clinically and microbiologically confirmed C. difficile infection. Data were statistically analyzed using R software. RESULTS: Of 204 patients included in the analysis, 36 (18%) suffered 90-day recurrence, rCDI was higher among females (23%) compared to males (13%), overall age median (IQR) was 66 (51-77), and for rCDI cases 81 (69-86) years. Among 26 variables analyzed to evaluate their association with rCDI, prior clindamycin exposure, concurrent use of aztreonam, patients >76 years, total hospital length of stay, and LOS before diagnosis ≤7 days, WBC ≤ 9.85 × 103 at discharge were more likely to experience rCDI. CONCLUSION: As identified in this analysis, patients with risk factors for rCDI could be candidates for close monitoring, a high index of suspicion, and risk mitigation interventions to avoid rCDI and improve clinical outcomes.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Antibacterianos/uso terapéutico , Clostridioides , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo
9.
J Chemother ; 33(3): 165-173, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32715951

RESUMEN

C. difficile infections (CDI) are increasingly recognized as a leading cause of infectious diarrhea, with increasing morbidity and mortality. Treatment primarily centers around oral vancomycin treatment. A wide range of dosing regimens exist in clinical practice, with little evidence to help distinguish the therapeutic benefit between them. This is a retrospective cohort study conducted at an academic medical center that enrolled adult patients admitted with CDI. The primary outcome was a composite of complete or partial cure at the end of treatment and was assessed using a test of equivalency with a 20% equivalency limit. Subjects were divided into low dose (125 mg) or high dose (250 mg or 500 mg) of oral vancomycin dosed every 6 hours. Overall, 78 patients were included who received low dose vancomycin and 33 who received high dose. Generally, the two groups were similar, except the low dose group had significantly more leukocytosis and less ICU admission or hypotension compared to the high dose group. Equivalency between the two treatment groups was demonstrated (Absolute Risk Difference -0.022, 90% confidence interval: -0.13 to 0.18, p = 0.03). A stepwise logistic regression identified gender, baseline albumin, and ICU admission as significant predictors of the chance for complete or partial cure. No differences between groups for the secondary outcomes of 90-day readmission/recurrence, 30-day all-cause mortality, or time to resolution of diarrhea were demonstrated. Low dose oral vancomycin was demonstrated to result in equivalent outcomes compared to high dose vancomycin for the treatment of CDI.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Infecciones por Clostridium/tratamiento farmacológico , Vancomicina/administración & dosificación , Factores de Edad , Anciano , Anciano de 80 o más Años , Clostridioides difficile , Infecciones por Clostridium/mortalidad , Relación Dosis-Respuesta a Droga , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Recurrencia , Estudios Retrospectivos , Albúmina Sérica/análisis , Índice de Severidad de la Enfermedad , Factores Sexuales , Vancomicina/uso terapéutico
10.
J Eval Clin Pract ; 27(2): 414-420, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32820591

RESUMEN

RATIONALE, AIMS AND OBJECTIVES: Transitions of care between healthcare facilities are associated with increased risk of adverse events and hospital readmissions. Previous studies employing pharmacists in transitions of care showed reduced 30-day readmissions, however, many were without an active comparator. There is no standardized approach to pharmacist involvement in transitions of care services, making it difficult to ascertain where pharmacist expertise is most meaningful. This paper aims to compare the 30-day hospital readmissions between an interprofessional hospital discharge visit (iHDV) with physician and pharmacist involvement to a non-interprofessional HDV (PHDV) without pharmacist involvement. METHOD: This was a retrospective quality improvement initiative examining patients of two outpatient clinical practices within a large, academic medical centre. The primary analysis compared 30-day hospital readmission rates for patients with a scheduled PHDV or iHDV within 30-days of index hospital discharge date, regardless of attendance at the HDV. The secondary outcome compared 30-day hospital readmission rates for patients who completed a PHDV or iHDV. Primary and secondary outcomes were evaluated using bivariate analysis and multivariate analysis by stepwise logistic regression, for both intention-to-treat (ITT) and per protocol (PP). RESULTS: This study found significantly lower 30-day hospital readmissions for patients scheduled for a PHDV compared to an iHDV (16.7% vs 21.5%, P = .0230) in an unadjusted analysis, but no significant difference in adjusted analyses (P = .4856). Per-protocol analysis found no significant difference in 30-day hospital readmission rates between groups in unadjusted and adjusted analyses. Visit completion rates were significantly different between groups, with approximately twice as many PHDV group patients completing visits as compared to the iHDV group (74.1% vs 61.5%, P < .0001). CONCLUSION: This study demonstrates an interprofessional clinic visit employing a clinical pharmacist in the post-hospital discharge visit did not significantly reduce 30-day hospital readmission rates compared to a post-hospital discharge visit without pharmacist involvement.


Asunto(s)
Pacientes Ambulatorios , Readmisión del Paciente , Humanos , Alta del Paciente , Farmacéuticos , Estudios Retrospectivos
11.
AIDS Care ; 33(11): 1507-1513, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33103919

RESUMEN

This prospective cohort study enrolled people living with HIV initiating antiretroviral therapy (ART) containing the integrase inhibitors, dolutegravir (DTG) or elvitegravir (EVG) and administered the Montreal Cognitive Assessment (MoCA) at baseline and again after approximately six months to compare changes in MoCA scores. The proportion of patients found to have cognitive impairment, as indicated by a MoCA score <26/30, on each agent were also compared and comparisons were made between changes in each domain assessed by the MoCA (visuospatial/executive, naming, attention, language, abstraction, delayed recall, and orientation). Thirty-five evaluable participants were enrolled, 18 on DTG and 17 on EVG. The median [interquartile range(IQR)] age was 44 (32 to 54) years, 63% were male, 57% were African American. The median (IQR) MoCA score at baseline was 25 (23 to 27) with no difference between groups (p=0.249). The median (IQR) change in MoCA score was 0 (-1 to 2) for DTG and 1 (0 to 3) for EVG (p = 0.183). Of those on DTG, 8 (44%) had MoCA scores <26 on follow-up compared to 11 (65%) on EVG (p = 0.229). There were no significant differences in changes in any of the individual MoCA domains.


Asunto(s)
Infecciones por VIH , Inhibidores de Integrasa VIH , VIH-1 , Adulto , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Estudios Prospectivos , Piridonas , Quinolonas
12.
Aging (Albany NY) ; 12(14): 15104-15120, 2020 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-32633727

RESUMEN

Ductal carcinoma in situ (DCIS) is one of the earliest stages of breast cancer (BCa). The mechanisms by which DCIS lesions progress to an invasive state while others remain indolent are yet to be fully characterized and both diagnosis and treatment of this pre-invasive disease could benefit from better understanding the pathways involved. While a decreased expression of Caveolin-1 (Cav-1) in the tumor microenvironment of patients with DCIS breast cancer was linked to progression to invasive breast cancer (IBC), the downstream effector(s) contributing to this process remain elusive. The current report shows elevated expression of Signal Transducer and Activator of Transcription 5a (STAT5a) within the DCIS-like lesions in Cav-1 KO mice following estrogen treatment and inhibition of STAT5a expression prevented the formation of these mammary lesions. In addition, STAT5a overexpression in a human DCIS cell line (MCF10DCIS.com) promoted their invasion, a process accelerated by estrogen treatment and associated with increased levels of the matrix metalloproteinase-9 (MMP-9) precursor. In sum, our results demonstrate a novel regulatory axis (Cav-1♦STAT5a♦MMP-9) in DCIS that is fully activated by the presence of estrogen. Our sudies suggest to further study phosphorylated STAT5a (Y694) as a potential biomarker to guide and predict outcome of DCIS patient population.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Caveolina 1/metabolismo , Estrógenos , Invasividad Neoplásica , Factor de Transcripción STAT5/metabolismo , Animales , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Estrógenos/metabolismo , Estrógenos/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/prevención & control , Fosforilación , Microambiente Tumoral
13.
Nutr Clin Pract ; 35(4): 627-633, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32579257

RESUMEN

BACKGROUND: The European Society for Clinical Nutrition and Metabolism Guidelines for Parenteral Nutrition in Geriatric Patients state metabolic complications are more frequent in elderly patients. However, literature provides limited information about metabolic complications in older patients receiving parenteral nutrition (PN). Consequently, the purpose of this study was to compare the development of metabolic complications in older vs younger patients receiving PN. METHODS: Patients receiving PN from May 1, 2014, to February 7, 2017, at Cooper University Hospital were included. Metabolic complications assessed included acid-base disturbances, hepatic complications, hypercapnia, hyperchloremia, hyperglycemia, hypernatremia, hypertriglyceridemia, hypochloremia, hypoglycemia, hypokalemia, hypophosphatemia, and refeeding syndrome. RESULTS: 595 patients were included (older group [≥65 years]: n = 245, median age: 76 years; younger group [<65 years]: n = 350, median age: 53 years]. Certain characteristics were similar between groups (female, 51%; mean body mass index of 28; critically ill, 34%; central PN, 97%; median duration of PN, 7 days; mean energy provision PN, 25.4 kcal/kg/d; mean dextrose infusion rate, 2.31 mg/kg/min). Overall, metabolic complications developed in 58% of patients and occurred more frequently in older vs younger patients (65.7% vs 53.4%; P = .003). Multivariate logistic analysis demonstrated increased odds of metabolic complications in the older group (odds ratio, 1.55; 95% CI, 1.014-2.375). CONCLUSIONS: Older hospitalized patients are more likely to develop a metabolic complication during their PN course than younger patients. This study heightens awareness that patients of advanced age are subject to metabolic complications; practitioners should anticipate and resolve complications in a timely manner.


Asunto(s)
Factores de Edad , Enfermedad Crítica/terapia , Enfermedades Metabólicas/epidemiología , Nutrición Parenteral/efectos adversos , Anciano , Resultados de Cuidados Críticos , Femenino , Humanos , Hipercapnia/epidemiología , Hipercapnia/etiología , Hepatopatías/epidemiología , Hepatopatías/etiología , Modelos Logísticos , Masculino , Enfermedades Metabólicas/etiología , Persona de Mediana Edad , Oportunidad Relativa , Nutrición Parenteral/métodos , Síndrome de Realimentación/epidemiología , Síndrome de Realimentación/etiología , Estudios Retrospectivos , Resultado del Tratamiento
14.
Cancer Biol Ther ; 21(6): 506-521, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32164483

RESUMEN

Triple-negative breast cancer (TNBC) displays an aggressive clinical course, heightened metastatic potential, and is linked to poor survival rates. Through its lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), this subtype remains unresponsive to traditional targeted therapies. Undesirable and sometimes life-threatening side effects associated with current chemotherapeutic agents warrant the development of more targeted treatment options. Targeting signal transducer and activator of transcription 3 (STAT3), a transcription factor implicated in breast cancer (BCa) progression, has proven to be an efficient approach to halt cancer growth in vitro and in vivo. Currently, there are no FDA-approved STAT3 inhibitors for TNBC. Although pimozide, a FDA-approved antipsychotic drug, has been attributed a role as a STAT3 inhibitor in several cancers, its role on this pathway remains unexplored in TNBC. As a "one size fits all" approach cannot be applied to TNBC therapies due to the heterogeneous nature of this aggressive cancer, we hypothesized that STAT3 could be a novel biomarker of response to guide pimozide therapy. Using human cell lines representative of four TNBC subtypes (basal-like 1, basal-like 2, mesenchymal-like, mesenchymal stem-like), our current report demonstrates that pimozide significantly reduced their invasion and migration, an effect that was predicted by STAT3 phosphorylation on tyrosine residue 705 (Tyr705). Mechanistically, phosphorylated STAT3 (Tyr705) inhibition resulting from pimozide treatment caused a downregulation of downstream transcriptional targets such as matrix metalloproteinase-9 (MMP-9) and vimentin, both implicated in invasion and migration. The identification of biomarkers of response to TNBC treatments is an active area of research in the field of precision medicine and our results propose phosphorylated STAT3 (Tyr705) as a novel biomarker to guide pimozide treatment as an inhibitor of invasion and migration.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Antagonistas de Dopamina/farmacología , Pimozida/farmacología , Factor de Transcripción STAT3/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Apoptosis , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Fosforilación , Factor de Transcripción STAT3/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Células Tumorales Cultivadas
15.
Cell Cycle ; 19(4): 432-447, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31931653

RESUMEN

Triple negative breast cancer (TNBC) is a heterogeneous disease, which lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor 2 receptor (HER2). This subtype of breast cancer has the poorest prognosis with limited therapies currently available, and hence additional options are needed. CAPER is a coactivator of the activator protein-1 (AP-1) (interacting specifically with the c-Jun component) and the ER and is known to be involved in human breast cancer pathogenesis. Recent published data have demonstrated a role for CAPER in TNBC and, as such, disrupting the function of CAPER with c-Jun could be a novel approach to treat TNBC patients. The data presented here shows the development and in vitro testing of CAPER-derived peptides that inhibit the coactivator activity of CAPER with c-Jun. These CAPER peptides result in a decrease in cell number and an increase in apoptosis in two TNBC cell lines, MDA-MB-231 and BT-549, while having no effect on the non-tumorigenic cell line MCF 10A. Additionally, two modes of action were demonstrated which appear to be cell line dependent: 1) a modulation of phosphorylated c-Jun leading to a decrease in Bcl-2 in MDA-MB-231 cells and a decrease in p21 in BT-549 cells and 2) a decrease in DNA repair proteins, leading to impaired DNA repair function in MDA-MB-231 cells. The data presented here supports further development of CAPER-derived peptides for the treatment of TNBC.


Asunto(s)
Péptidos/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Secuencia de Aminoácidos , Apoptosis/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Carcinogénesis/patología , Recuento de Células , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Ciclina D1/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Histonas/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Péptidos/química , Péptidos/farmacología , Fosforilación/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Recombinantes/metabolismo , Neoplasias de la Mama Triple Negativas/patología
16.
ACR Open Rheumatol ; 1(5): 279-286, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31777804

RESUMEN

OBJECTIVE: To develop and establish the reliability, validity, measurement error, and minimum detectable change of a novel 30-second fast-paced walk test (30SFW) in persons with knee osteoarthritis (OA) that is easy to administer and can quantify walking performance in persons of all abilities. METHODS: Twenty females with symptomatic knee OA (mean age [SD] 58.30 [8.05] years) and 20 age- and sex-matched asymptomatic controls (57.25 [8.71] years) participated in the study. Participants completed questionnaires of demographic and clinical data, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 36-item Short Form Health Survey (SF-36) followed by 30SFW performance. Participants returned 2-7 days later and performed the 30SFW again. RESULTS: The knee OA group reported function that was worse than controls (all KOOS subscales; P < 0.0001). The 30SFW intrarater and interrater reliability were excellent [ICC (2,1) = 0.95-0.99]. Knee OA participants walked a shorter distance in the 30SFW than controls (mean [SD]: OA 44.4 m [9.5 m]; control 58.1 m [7.8 m]; P < 0.0001). Positive strong correlations were found between the 30SFW and the KOOS-Activity of Daily Living, SF-36-Physical Functioning, and SF-36-Physical Health Composite scores (P < 0.0001). A nonsignificant, weak correlation between 30SFW and SF-36-Mental Health scores was present (r = 0.32, P = 0.05). CONCLUSION: The 30SFW has excellent intrarater and interrater reliability. The 30SFW demonstrated excellent known groups, convergent, and discriminant validity as a measure of short-distance walking ability in persons with knee OA. Clinicians and researchers should consider using the 30SFW to quantify walking ability in persons with knee OA and assess walking ability change.

17.
Hosp Pharm ; 54(5): 294-299, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31555004

RESUMEN

Background: Treatment of severe Clostridium difficile infection (CDI) with oral vancomycin (VAN) is known to be superior to treatment with metronidazole (MDZ). However, previous studies have not evaluated the impact on patients when oral VAN therapy is delayed after diagnosis of severe CDI. Materials and Methods: This was a single-center, retrospective study of adult patients who were diagnosed with severe CDI. The objective was to compare clinical outcomes for patients treated initially with oral VAN versus patients receiving delayed oral VAN after at least 48 hours of initial treatment with MDZ. The primary outcome was all-cause in-hospital mortality. Results: There were 101 patients who comprised the initial oral VAN group, while 20 patients comprised the delayed oral VAN group. There was no significant difference in all-cause in-hospital mortality for patients in the initial oral VAN treatment group compared to those who had delayed oral VAN therapy (4.95% vs 15.00%, P = 0.13). Patients who were initially treated with oral VAN experienced a significantly higher rate of clinical cure (49.50% vs 20.00%, P = 0.02), shorter median postinfection length of hospitalization (7.0 days vs 13.0 days, P < 0.001), shorter median time to resolution of leukocytosis (3.9 days vs 10.4 days, P = 0.01), and were less likely to have an end of treatment serum creatinine greater than 1.5 times their baseline (8.7% vs 29.4%, P = 0.03). Conclusion: Patients who receive oral VAN as their initial treatment for severe CDI experience improved clinical outcomes compared to patients receiving delayed oral VAN after being initially treated with MDZ.

18.
Nutr Metab Insights ; 12: 1178638819859315, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31320803

RESUMEN

BACKGROUND: The optimal time to initiate parenteral nutrition (PN) in critically ill adults in whom enteral nutrition is not feasible is controversial. OBJECTIVE: The objectives were to compare in-hospital mortality and hospital length of stay in patients initiated on PN within 7 days or after 7 days of poor nutrient intake. METHODS: This single-center, retrospective study included critically ill adult patients who received at least 2 consecutive days of PN during hospitalization from May 2014 to July 2016. RESULTS: The median duration of PN (interquartile range) was 8 (5-13) days. In total, 110 patients received PN within 7 days of poor nutrient intake while 49 patients received PN after 7 days of poor nutrient intake. There was no statistically significant difference in in-hospital mortality between groups (29.09% vs 18.37%, P = .1535). Patients initiated within 7 days had a significantly shorter median hospital length of stay than patients initiated after 7 days (20 days vs 27 days, P = .0013). There were 69 patients who were classified as obese. Obese patients initiated within 7 days had a significantly shorter median hospital length of stay than obese patients initiated after 7 days (17 days vs 33 days, P = .0007). CONCLUSIONS: Time to initiation of PN did not impact in-hospital mortality. However, there was an association between early initiation of PN and a shorter hospital length of stay that was most pronounced among obese patients.

19.
Curr Pharm Teach Learn ; 11(6): 603-608, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31213316

RESUMEN

BACKGROUND AND PURPOSE: To evaluate the impact of two standardized patient (SP) approaches on student communication skills and self-perceived confidence. EDUCATIONAL ACTIVITY AND SETTING: Second professional year pharmacy students were assessed on overall and area of improvement (AOI) communication skills and self-perceived confidence. Students were invited to participate in a SP intervention activity, following a fall and before a spring class assessment, where they were randomized to an individualized or non-specific SP group. Communication skills were assessed using a four component 64-point rubric; confidence was assessed using an 11-question Likert-type survey. FINDINGS: Nineteen students participated in the SP intervention activity; 11 students comprised the individualized group and eight students comprised the non-specific group. Students in the individualized group demonstrated a significantly higher median change in AOI communication scores compared to the non-specific group [five points vs. three points, respectively (p = 0.033)]. There was a significantly higher median change in overall communication skills in the individualized compared to the non-specific group of 12 points and 6.5 points, respectively (p = 0.017). Student self-perceived confidence in the individualized and non-specific group showed similar improvements overall from pre- to post assessment [seven points vs. eight points, respectively (p = 0.62)]. SUMMARY: The use of SPs in pharmacy curricula can improve student communication skills. However, tailoring the activity to students' needs significantly improves their communication AOI and overall communication skill scores more than a non-specific activity. Student self-perceived confidence improved similarly in both groups, although no statistically significant differences were found between groups.


Asunto(s)
Comunicación , Estándares de Referencia , Estudiantes de Farmacia/psicología , Humanos , Relaciones Interprofesionales , Estudiantes de Farmacia/estadística & datos numéricos
20.
Can J Physiol Pharmacol ; 97(10): 952-962, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31238009

RESUMEN

Protein restriction throughout pregnancy and lactation reduces liver triglyceride (TG) content in adult male rat offspring. The study determined the contribution of hepatic lipogenesis to the reduction in liver TG content. Rats received either control or protein-restricted diets throughout pregnancy and lactation. Offspring were sacrificed on day 65. Hepatic fatty acid uptake and de novo fatty acid and TG biosynthesis were similar between control and low-protein (LP) offspring. These results indicate that hepatic lipogenesis cannot mediate the decrease in liver TG content in LP offspring. We then determined whether increased lipid utilization in adipose tissue and muscle was responsible for the decrease in liver TG content. There was suggestive evidence of increased sympathetic nervous system tone in epididymal adipose tissue of LP offspring that increased fatty acid uptake, TG lipolysis, and utilization of fatty acids in mitochondrial thermogenesis. Measurement of similar parameters demonstrated that such alterations do not occur in gastrocnemius muscle, another major lipid-utilizing tissue. Our results suggest that the decrease in liver TG content in LP offspring is likely due to increased diversion of fatty acids to white and brown adipose tissue depots and their enhanced utilization to fuel mitochondrial thermogenesis.


Asunto(s)
Dieta con Restricción de Proteínas , Lactancia/metabolismo , Lipogénesis , Hígado/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Tejido Adiposo/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Femenino , Masculino , Modelos Animales , Músculo Esquelético/metabolismo , Embarazo , Ratas , Factores Sexuales , Triglicéridos/metabolismo
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