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1.
Public Health ; 224: 82-89, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37741156

RESUMEN

OBJECTIVE: In Australia, first and second compared to third dose of a COVID-19 vaccine were implemented under different policies and contexts, resulting in greater discretion in decisions to receive a third compared to first and second dose. We quantified socio-economic inequalities in first and third dose to understand how discretion is associated with differences in uptake. STUDY DESIGN: Whole-of-population cohort study. METHODS: Linked immunisation, census, death and migration data were used to estimate weekly proportions who received first and third doses of a COVID-19 vaccine until 31 August 2022 for those with low (no formal qualification) compared to high (university degree) education, stratified by 10-year age group (from 30 to 89 years). We estimated relative rates using Cox regression, including adjustment for sociodemographic factors. RESULTS: Among 13.1 million people in our study population, 94% had received a first and 80% a third dose by 31 August 2022. Rates of uptake of first and third dose were around 50% lower for people with low compared to high education. Gaps were small in absolute terms for first dose, and at the end of the study period ranged from 1 to 11 percentage points across age groups. However, gaps were substantial for third dose, particularly at younger ages where the socio-economic gap was as wide as 32 percentage-points. CONCLUSION: Education-related inequalities in uptake were larger where discretion in decisions was larger. Policies that limited discretion in decisions to receive vaccines may have contributed to achieving the dual aims of maximising uptake and minimising inequalities.

2.
Contemp Clin Trials ; 129: 107170, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37019180

RESUMEN

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading liver disorder among U.S. children and is most prevalent among Hispanic children with obesity. Previous research has shown that reducing the consumption of free sugars (added sugars + naturally occurring sugars in fruit juice) can reverse liver steatosis in adolescents with NAFLD. This study aims to determine if a low-free sugar diet (LFSD) can prevent liver fat accumulation and NAFLD in high-risk children. METHODS: In this randomized controlled trial, we will enroll 140 Hispanic children aged 6 to 9 years who are ≥50th percentile BMI and without a previous diagnosis of NAFLD. Participants will be randomly assigned to either an experimental (LFSD) or a control (usual diet + educational materials) group. The one-year intervention includes removal of foods high in free sugars from the home at baseline, provision of LFSD household groceries for the entire family (weeks 1-4, 12, 24, and 36), dietitian-guided family grocery shopping sessions (weeks 12, 24, and 36), and ongoing education and motivational interviewing to promote LFSD. Both groups complete assessment measures at baseline, 6, 12, 18, and 24 months. Primary study outcomes are percent hepatic fat at 12 months and incidence of clinically significant hepatic steatosis (>5%) + elevated liver enzymes at 24 months. Secondary outcomes include metabolic markers potentially mediating or moderating NAFLD pathogenesis. DISCUSSION: This protocol describes the rationale, eligibility criteria, recruitment strategies, analysis plan as well as a novel dietary intervention design. Study results will inform future dietary guidelines for pediatric NAFLD prevention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05292352.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Niño , Humanos , Dieta , Hispánicos o Latinos , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Azúcares
3.
Int J Equity Health ; 20(1): 178, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34344367

RESUMEN

BACKGROUND: Life expectancy in Australia is amongst the highest globally, but national estimates mask within-country inequalities. To monitor socioeconomic inequalities in health, many high-income countries routinely report life expectancy by education level. However in Australia, education-related gaps in life expectancy are not routinely reported because, until recently, the data required to produce these estimates have not been available. Using newly linked, whole-of-population data, we estimated education-related inequalities in adult life expectancy in Australia. METHODS: Using data from 2016 Australian Census linked to 2016-17 Death Registrations, we estimated age-sex-education-specific mortality rates and used standard life table methodology to calculate life expectancy. For men and women separately, we estimated absolute (in years) and relative (ratios) differences in life expectancy at ages 25, 45, 65 and 85 years according to education level (measured in five categories, from university qualification [highest] to no formal qualifications [lowest]). RESULTS: Data came from 14,565,910 Australian residents aged 25 years and older. At each age, those with lower levels of education had lower life expectancies. For men, the gap (highest vs. lowest level of education) was 9.1 (95 %CI: 8.8, 9.4) years at age 25, 7.3 (7.1, 7.5) years at age 45, 4.9 (4.7, 5.1) years at age 65 and 1.9 (1.8, 2.1) years at age 85. For women, the gap was 5.5 (5.1, 5.9) years at age 25, 4.7 (4.4, 5.0) years at age 45, 3.3 (3.1, 3.5) years at 65 and 1.6 (1.4, 1.8) years at age 85. Relative differences (comparing highest education level with each of the other levels) were larger for men than women and increased with age, but overall, revealed a 10-25 % reduction in life expectancy for those with the lowest compared to the highest education level. CONCLUSIONS: Education-related inequalities in life expectancy from age 25 years in Australia are substantial, particularly for men. Those with the lowest education level have a life expectancy equivalent to the national average 15-20 years ago. These vast gaps indicate large potential for further gains in life expectancy at the national level and continuing opportunities to improve health equity.


Asunto(s)
Escolaridad , Disparidades en el Estado de Salud , Esperanza de Vida , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Femenino , Humanos , Esperanza de Vida/tendencias , Masculino , Registro Médico Coordinado , Persona de Mediana Edad
4.
Nurse Educ Today ; 100: 104864, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33744816

RESUMEN

There is limited research regarding the impact of self-care practices on psychological distress, specifically on nursing students during a pandemic, such as COVID-19 (Corona Virus Disease- 2019). A 10-minute electronic survey was sent to nursing students at a large academic-medical center, and data from 285 student respondents were analyzed to assess psychological status, attitudes and behaviors in regards to the COVID-19 pandemic. Significant differences were found when comparing self-care practice scores by school grade for total scores (F = 4.48 [df = 4,250], p = .002), emotional subscale (F = 4.78 [df = 4,250], p = .001), and relationship subscale (F = 3.44 [df = 4,250], p = .009). While there were no significant differences in psychological distress by school grade, graduate students had the lowest self-care practice score compared to all the other grades. Finally, the subscale and total self-care practice scores were significantly and negatively associated with psychological distress. These findings suggest that utilization of self-care practices is associated with lower psychological distress, and should therefore be promoted among nursing student populations and integrated into curricula. Future studies should assess specific needs geared towards populations that may have poor self-care practices, such as graduate students, and understand ways to improve sleep quality to mitigate rates of psychological distress during a pandemic.


Asunto(s)
COVID-19/psicología , Distrés Psicológico , Autocuidado , Estudiantes de Enfermería/psicología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Pandemias , Adulto Joven
5.
J Biomed Phys Eng ; 11(1): 103-108, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33564645

RESUMEN

There is a growing interest in examining alterations in telomere length as a reliable biomarker of general health, as well as a marker for predicting later morbidity and mortality. Substantial evidence shows that telomere length is associated with aging; telomere shortening acts as a "counting mechanism" that drives replicative senescence by limiting the mitotic potential of normal (but not malignant) cells. In this Correspondence, we attempt to answer the question of why recently published papers about telomere length alterations increase our uncertainty rather than reduce it. This discussion includes three major research areas regarding telomere length: environmental stressors, aging, and life span. Our review suggests that activation of telomerase activity due to stressors in space might be a double-edged sword with both favorable and unfavorable consequences. The selection of an effect's consequence must clearly elucidate the experimental conditions as well as associated stressors. In this Correspondence, we attempt to answer the question of why recently published papers about telomere length alterations increase our uncertainty rather than reduce it. The selection of an effect's consequence must clearly elucidate the experimental conditions as well as associated stressors. Both positive and negative consequences must be clearly addressed in order to bolster the conclusions, as well as identify future research directions.

6.
J Steroid Biochem Mol Biol ; 201: 105688, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32360595

RESUMEN

The vitamin D receptor (VDR) and its ligand 1,25(OH)2D3 (1,25D) exert anti-tumor effects, but considerable heterogeneity has been reported in different model systems. In general, cell lines derived from aggressive tumor subtypes such as Triple Negative Breast Cancer (TNBC) express low levels of VDR and are less sensitive to 1,25D than those derived from more differentiated tumor types. We have previously reported that 1,25D inhibits hyaluronic acid synthase 2 (HAS2) expression and hyaluronic acid (HA) synthesis in murine TNBC cells. Here we confirmed the inhibitory effect of 1,25D on HA synthesis in human Hs578T cells representative of the mesenchymal/stem-like (MSL) subtype of TNBC. Because HA synthesis requires the production of hexoses for incorporation into HA, we predicted that the high HA production characteristic of Hs578T cells would require sustained metabolic changes through the hexosamine biosynthetic pathway (HBP). We thus examined metabolic gene expression in Hs578T cell variants sorted for High (HAHigh) and Low (HALow) HA production, and the ability of 1,25D to reverse these adaptive changes. HAHigh populations exhibited elevated HA production, smaller size, increased proliferation and higher motility than HALow populations. Despite their more aggressive phenotype, HAHigh populations retained expression of VDR protein at levels comparable to that of parental Hs578T cells and HALow subclones. Treatment with 1,25D decreased production of HA in both HAHigh and HALow populations. We also found that multiple metabolic enzymes were aberrantly expressed in HAHigh cells, especially those involved in glutamine and glucose metabolism. Notably, Glutaminase (GLS), a known oncogene for breast cancer, was strongly upregulated in HAHigh vs. HALow cells and its expression was significantly reduced by 1,25D (100 nM, 24 h). Consistent with this finding, Seahorse extracellular flux analysis indicated that respiration in HAHigh cells was significantly more dependent on exogenous glutamine than HALow cells, however, acute 1,25D exposure did not alter metabolic flux. In contrast to GLS, the glutamate transporter SLC1A7 was significantly reduced in HAHigh cells compared to HALow cells and its expression was enhanced by 1,25D. These findings support the concept that 1,25D can reverse the metabolic gene expression changes associated with HA production in cancer cells with aggressive phenotypes.


Asunto(s)
Calcitriol/farmacología , Hialuronano Sintasas/metabolismo , Ácido Hialurónico/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Línea Celular Tumoral , Expresión Génica/efectos de los fármacos , Humanos , Hialuronano Sintasas/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Receptores de Calcitriol/metabolismo , Neoplasias de la Mama Triple Negativas/genética
7.
BMC Med Res Methodol ; 20(1): 55, 2020 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-32138694

RESUMEN

BACKGROUND: Single time-point assessments of psychological distress are often used to indicate chronic mental health problems, but the validity of this approach is unclear. The aims of this study were to investigate how a single assessment of distress relates to longer-term assessment and quantify misclassification from using single measures to indicate chronic distress. METHODS: Data came from the Household, Income and Labour Dynamics in Australia Survey, a nationally representative study of Australian adults. Psychological distress, measured with the Kessler10 and categorised into low (scores:10- < 12), mild (12- < 16), moderate (16- < 22) and high (22-50), has been assessed in the Survey biennially since wave 7. Among respondents who were aged ≥25 years and participated in all waves in which distress was measured, we describe agreement in distress categories, and using a mixed linear model adjusting for age and sex we estimate change in scores, over a two-, four-, six- and eight-year follow-up period. We applied weights, benchmarked to the Australian population, to all analyses. RESULTS: Two-years following initial assessment, proportions within identical categories of distress were 66.0% for low, 54.5% for mild, 44.0% for moderate and 50.3% for high, while 94.1% of those with low distress initially had low/mild distress and 81.4% with high distress initially had moderate/high distress. These patterns did not change materially as follow-up time increased. Over the full eight-year period, 77.3% of individuals with high distress initially reported high distress on ≥1 follow-up occasion. Age-and sex- adjusted change in K10 scores over a two-year period was 1.1, 0.5, - 0.7 and - 4.9 for low, mild, moderate and high distress, respectively, and also did not change materially as follow-up time increased. CONCLUSION: In the absence of repeated measures, single assessments are useful proxies for chronic distress. Our estimates could be used in bias analyses to quantify the magnitude of the bias resulting from use of single assessments to indicate chronic distress.


Asunto(s)
Encuestas Epidemiológicas/métodos , Encuestas Epidemiológicas/estadística & datos numéricos , Salud Mental/estadística & datos numéricos , Distrés Psicológico , Estrés Psicológico/diagnóstico , Adulto , Anciano , Ansiedad/diagnóstico , Ansiedad/psicología , Australia , Depresión/diagnóstico , Depresión/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Clase Social , Estrés Psicológico/psicología
9.
J Chromatogr A ; 1611: 460601, 2020 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-31648785

RESUMEN

X-ray computed tomography has been demonstrated to be capable of imaging 1 mL (5 mm diameter, 50 mm height) chromatography packed beds under compression, visualising the 3D structure and measuring changes to geometry of the packing. 1 mL pre-packed columns did not exhibit any structural changes at vendor specified flow rate limits, however cellulose beds did compress at higher flow rates that were imaged before, during and after flow. This was used to visualise and quantitate changes to porosity, tortuosity and permeability based on simulation of flow through the packed bed structure using the imaging data. When using a high flow rate it was found that a decrease in porosity could be measured during compression before reverting after flow had ceased, with corresponding changes to tortuosity and permeability also occurring. X-ray CT imaging of packed beds and individual beads exposed to foulant-rich process streams resulted in considerable image quality loss, associated with residual biological material. In order to address this, digital processing using an erosion-dilation method was applied at bead and bed scales to computationally alter the porosity by adding or removing material from the existing surface to calculate the impact upon tortuosity factor. The eroded and dilated bead volumes of agarose, cellulose and ceramic materials were used to simulate diffusivity whilst mimicking internal bead pore constriction and blocking mechanisms.


Asunto(s)
Simulación por Computador , Reología/métodos , Celulosa/química , Porosidad , Presión
10.
Diabet Med ; 36(12): 1637-1642, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31267573

RESUMEN

AIMS: To identify clinically useful associations between HbA1c levels and various continuous glucose monitoring-derived metrics. METHODS: We retrospectively analysed end-of-study HbA1c levels and >2 weeks of continuous glucose monitoring data collected from 530 adults with Type 1 diabetes or insulin-requiring Type 2 diabetes during four randomized trials. Each trial lasted ≥24 weeks and provided central laboratory end-of-study HbA1c levels and continuous glucose monitoring data from the preceding 3 months. Participants were assigned to groups based on either HbA1c levels or continuous glucose monitoring-derived glucose values. RESULTS: HbA1c was strongly correlated with mean glucose value (r=0.80), time spent with glucose values in the 3.9-10.0 mmol/l range (time in range; r=-0.75) and percentage of glucose values >13.9 mmol/l (r=0.72), but was weakly correlated with the percentage of glucose values <3.9 mmol/l (r=-0.39) or <3.0 mmol/l (r=-0.21). The median percentage of glucose values <3.0 mmol/l was <1.2% (<20 min/day) for all HbA1c -based groups, but the median percentage of values >13.9 mmol/l varied from 2.5% (0.6 h/day) to 27.8% (6.7 h/day) in the lowest and highest HbA1c groups, respectively. More than 90% of participants with either <2% of glucose values >13.9 mmol/l, mean glucose <7.8 mmol/l, or time in range >80% had HbA1c levels ≤53 mmol/mol (≤7.0%). For participants with HbA1c ≥64 mmol/mol (≥8.0%), the median time in range was 44%, with 90% of participants having a time in range of <59%. CONCLUSIONS: The associations shown in the present study suggest that continuous glucose monitoring-derived metrics may help guide diabetes therapy intensification efforts in an HbA1c -independent manner.


Asunto(s)
Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/análisis , Adulto , Humanos , Hipoglucemia/diagnóstico , Hipoglucemia/epidemiología , Hipoglucemia/prevención & control , Persona de Mediana Edad , Estudios Retrospectivos
12.
J Chromatogr A ; 1566: 79-88, 2018 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-29970222

RESUMEN

X-ray computed tomography (CT) and focused ion beam (FIB) microscopy were used to generate three dimensional representations of chromatography beads for quantitative analysis of important physical characteristics including tortuosity factor. Critical-point dried agarose, cellulose and ceramic beads were examined using both methods before digital reconstruction and geometry based analysis for comparison between techniques and materials examined. X-ray 'nano' CT attained a pixel size of 63 nm and 32 nm for respective large field of view and high resolution modes. FIB improved upon this to a 15 nm pixel size for the more rigid ceramic beads but required compromises for the softer agarose and cellulose materials, especially during physical sectioning that was not required for X-ray CT. Digital processing of raw slices was performed using software to produce 3D representations of bead geometry. Porosity, tortuosity factor, surface area to volume ratio and pore diameter were evaluated for each technique and material, with overall averaged simulated tortuosity factors of 1.36, 1.37 and 1.51 for agarose, cellulose and ceramic volumes respectively. Results were compared to existing literature values acquired using established imaging and non-imaging techniques to demonstrate the capability of tomographic approaches used here.


Asunto(s)
Microscopía , Tomografía Computarizada por Rayos X , Cromatografía/instrumentación , Imagenología Tridimensional , Porosidad , Programas Informáticos
13.
Obes Rev ; 19(9): 1205-1235, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29761610

RESUMEN

Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis.


Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Dieta , Enfermedades Metabólicas/complicaciones , Enfermedades Cardiovasculares/metabolismo , Ingestión de Energía/fisiología , Humanos , Enfermedades Metabólicas/metabolismo , Valor Nutritivo , Aumento de Peso/fisiología
14.
Transfus Med ; 28(5): 335-345, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29675833

RESUMEN

AIM: To evaluate the risks of restrictive red blood cell transfusion strategies (haemoglobin 7-8 g dL-1 ) in patients with and without known cardiovascular disease (CVD). BACKGROUND: Recent guidelines recommend restrictive strategies for CVD patients hospitalised for non-CVD indications, patients without known CVD and patients hospitalised for CVD corrective procedures. METHODS/MATERIALS: Database searches were conducted through December 2017 for randomised clinical trials that enrolled patients with and without known CVD, hospitalised either for CVD-corrective procedures or non-cardiac indications, comparing effects of liberal with restrictive strategies on major adverse coronary events (MACE) and death. RESULTS: In CVD patients not undergoing cardiac interventions, a liberal strategy decreased (P = 0·01) the relative risk (95% CI) (RR) of MACE [0·50 (0·29-0·86)] (I2  = 0%). Among patients without known CVD, the incidence of MACE was lower (1·7 vs 3·9%), and the effect of a liberal strategy on MACE [0·79, (0·39-1·58)] was smaller and non-significant but not different from CVD patients (P = 0·30). Combining all CVD and non-CVD patients, a liberal strategy decreased MACE [0·59, (0·39-0·91); P = 0·02]. Conversely, among studies reporting mortality, a liberal strategy decreased mortality in CVD patients (11·7% vs·13·3%) but increased mortality (19·2% vs 18·0%) in patients without known CVD [interaction P = 0·05; ratio of RR 0·73, (0·53-1·00)]. A liberal strategy also did not benefit patients undergoing cardiac surgery; data were insufficient for percutaneous cardiac procedures. CONCLUSIONS: In patients hospitalised for non-cardiac indications, liberal transfusion strategies are associated with a decreased risk of MACE in both those with and without known CVD. However, this only provides a survival benefit to CVD patients not admitted for CVD-corrective procedures.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Transfusión de Eritrocitos , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Factores de Riesgo , Tasa de Supervivencia
15.
Br J Anaesth ; 120(4): 874-876, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29576129
16.
Pediatr Obes ; 13(4): 213-221, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29318755

RESUMEN

BACKGROUND: Sugars and their primary dietary sources (milk, fruits, sweetened foods and beverages) are associated, in different ways, with a range of health outcomes, including obesity. The contribution made to total sugar intake and how the different types and forms of sugar associate with body weight is unclear. OBJECTIVE: To describe sugar consumption and examine its association with weight status among U.S. children by sugar type [added {AS} vs. naturally occurring {NOS}] and form (solid vs. liquid). DESIGN: Cross-sectional dietary data (2 24-h recalls) from children 2-19 years in the National Health and Nutrition Examination Survey, 2009-2014 (n = 8136) were used to estimate the amount of each type and form of sugar by age and weight status. Linear regression models tested trends and the multivariate adjusted association between the different sugars and weight status. RESULTS: Mean total sugar, AS, and NOS was 118.1 g [25.3% total energy {TE}], 71.5 g (14.8% TE), 46.7 g (10.5% TE), respectively. AS in sugar-sweetened (non-dairy) beverages and NOS in juices contributed 6.9% and 2.4% of TE, respectively. Only %TE from AS (controlled for potential demographic, lifestyle confounders) was associated with change in body mass index z-score (BMIz) [AS in beverages: BMIz ß + 0.01 {95% CI: 0.002, 0.03}; AS in foods: BMIz ß - 0.03 {95% CI: -0.04, -0.02}]. CONCLUSION: Dietary sugars, most of which are AS, are a major contributor of calories in the diets of U.S. children. Only AS in non-dairy sources were associated with weight although the direction differed by the form consumed. AS in beverages were associated positively and those in foods were associated inversely with children's weight status.


Asunto(s)
Peso Corporal , Azúcares de la Dieta/administración & dosificación , Encuestas Nutricionales , Edulcorantes/administración & dosificación , Adolescente , Animales , Bebidas/análisis , Índice de Masa Corporal , Niño , Preescolar , Estudios Transversales , Dieta , Ingestión de Energía , Femenino , Alimentos , Jugos de Frutas y Vegetales/análisis , Humanos , Masculino , Obesidad/epidemiología , Obesidad/etiología , Estados Unidos/epidemiología
17.
J Thromb Haemost ; 15(3): 526-537, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27992950

RESUMEN

Essentials Methods were developed to image the hemostatic response in mouse femoral arteries in real time. Penetrating injuries produced thrombi consisting primarily of platelets. Similar to arterioles, a core-shell architecture of platelet activation occurs in the femoral artery. Differences from arterioles included slower platelet activation and reduced thrombin dependence. SUMMARY: Background Intravital studies performed in the mouse microcirculation show that hemostatic thrombi formed after penetrating injuries develop a characteristic architecture in which a core of fully activated, densely packed platelets is overlaid with a shell of less activated platelets. Objective Large differences in hemodynamics and vessel wall biology distinguish arteries from arterioles. Here we asked whether these differences affect the hemostatic response and alter the impact of anticoagulants and antiplatelet agents. Methods Approaches previously developed for intravital imaging in the mouse microcirculation were adapted to the femoral artery, enabling real-time fluorescence imaging despite the markedly thicker vessel wall. Results Arterial thrombi initiated by penetrating injuries developed the core-and-shell architecture previously observed in the microcirculation. However, although platelet accumulation was greater in arterial thrombi, the kinetics of platelet activation were slower. Inhibiting platelet ADP P2Y12 receptors destabilized the shell and reduced thrombus size without affecting the core. Inhibiting thrombin with hirudin suppressed fibrin accumulation, but had little impact on thrombus size. Removing the platelet collagen receptor, glycoprotein VI, had no effect. Conclusions These results (i) demonstrate the feasibility of performing high-speed fluorescence imaging in larger vessels and (ii) highlight differences as well as similarities in the hemostatic response in the macro- and microcirculation. Similarities include the overall core-and-shell architecture. Differences include the slower kinetics of platelet activation and a smaller contribution from thrombin, which may be due in part to the greater thickness of the arterial wall and the correspondingly greater separation of tissue factor from the vessel lumen.


Asunto(s)
Arteria Femoral/diagnóstico por imagen , Hemostasis , Microcirculación , Heridas Penetrantes/terapia , Adenosina Difosfato/metabolismo , Animales , Anticoagulantes/farmacología , Arteriolas/metabolismo , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/metabolismo , Arteria Femoral/lesiones , Fibrina/metabolismo , Hemodinámica , Microscopía Intravital , Ratones , Ratones Endogámicos C57BL , Activación Plaquetaria , Inhibidores de Agregación Plaquetaria/farmacología , Transducción de Señal , Trombina/antagonistas & inhibidores , Trombina/metabolismo , Tromboplastina/metabolismo , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico
18.
Am J Crit Care ; 26(1): 62-69, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27965231

RESUMEN

BACKGROUND: Factors that precipitate hospitalization for exacerbation of heart failure provide targets for intervention to prevent hospitalizations. OBJECTIVES: To describe demographic, clinical, behavioral, and psychosocial factors that precipitate admission for exacerbation of heart failure and assess the relationships between precipitating factors and delay before hospitalization, and between delay time and length of hospital stay. METHODS: All admissions in 12 full months to a tertiary medical center were reviewed if the patient had a discharge code related to heart failure. Data on confirmed admissions for exacerbation of heart failure were included in the study. Electronic and paper medical records were reviewed to identify how long it took patients to seek care after they became aware of signs and symptoms, factors that precipitated exacerbation, and discharge details. RESULTS: Exacerbation of heart failure was confirmed in 482 patients. Dyspnea was the most common symptom (92.5% of patients), and 20.3% of patients waited until they were severely dyspneic before seeking treatment. The most common precipitating factor was poor medication adherence. Delay times from symptom awareness to seeking treatment were shorter in patients who had a recent change in medicine for heart failure, renal failure, or poor medication adherence and longer in patients with depressive symptoms and hypertension. CONCLUSIONS: Depressive symptoms, recent change in heart failure medicine, renal failure, poor medication adherence, and hypertension are risk factors for hospitalizations for exacerbation of heart failure.


Asunto(s)
Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Hospitalización/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Depresión/epidemiología , Disnea/epidemiología , Femenino , Conductas Relacionadas con la Salud , Humanos , Hipertensión/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Insuficiencia Renal/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos
19.
Vet Pathol ; 53(6): 1264-1265, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27733703
20.
Vox Sang ; 111(1): 43-54, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26848822

RESUMEN

BACKGROUND AND OBJECTIVES: Preclinical studies generated the hypothesis that older stored red blood cells (RBCs) can increase transfusion risks. To examine the most updated and complete clinical evidence and compare results between two trial designs, we assessed both observational studies and randomized controlled trials (RCTs) studying the effect of RBC storage age on mortality. MATERIALS AND METHODS: Five databases were searched through December 2014 for studies comparing mortality using transfused RBCs having longer and shorter storage times. RESULTS: Analysis of six RCTs found no significant differences in survival comparing current practice (average storage age of 2 to 3 weeks) to transfusion of 1- to 10-day-old RBCs (OR 0·91, 95% CI 0·77-1·07). RBC storage age was lower in RCTs vs. observational studies (P = 0·01). The 31 observational studies found an increased risk of death (OR 1·13, 95% CI 1·03-1·24) (P = 0·01) with increasing age of RBCs, a different mortality effect than RCTs (P = 0·02). CONCLUSION: RCTs established that transfusion of 1- to 10-day-old stored RBCs is not superior to current practice. The apparent discrepancy in mortality between analyses of RCTs and observational studies may in part relate to differences in hypotheses tested and ages of stored RBCs studied. Further trials investigating 1- to 10-day-old stored RBC benefits would seem of lower priority than studies to determine whether 4- to 6-week stored units have safety and efficacy equivalent to the 2- to 3-week-old stored RBCs commonly transfused today.


Asunto(s)
Conservación de la Sangre/métodos , Seguridad de la Sangre , Eritrocitos/citología , Ensayos Clínicos como Asunto , Bases de Datos Factuales , Transfusión de Eritrocitos/efectos adversos , Humanos , Oportunidad Relativa , Factores de Tiempo
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