36 monocyte subpopulations counts and associations with global longitudinal strain in st-elevation myocardial infarction patients with normal ejection fraction

Introduction - Monocytes, with 3 different subsets, are implicated in the initiation and progression of the atherosclerotic plaque contributing to plaque instability and rupture. Mon1 are the “classical” monocytes with inflammatory action, whilst Mon3 are considered reparative with fibroblast deposition ability. The function of the newly described Mon2 subset is yet to be fully described. In PCI era, fewer patients have globally reduced left ventricular ejection fraction post infarction, hence the importance of studying regional wall motion abnormalities and deformation at segmental levels using longitudinal strain. Little is known of the role for the 3 monocyte subpopulations in determining global strain in ST elevation myocardial infarction patients (STEMI). Conclusion In patients with normal or mildly impaired EF post infarction, higher counts of Mon1 and Mon2 are correlated with GLS within 7 days and at 6 months of remodelling post infarction. Adverse clinical outcomes in patients with reduced convalescent GLS were predicted with Mon1 and Mon2 suggestive of an inflammatory role for the newly identified Mon2 subpopulation. These results imply an important role for monocytes in myocardial healing when assessed by subclinical ventricular function indices. Methodology - STEMI patients (n = 101, mean age 64 ± 13 years; 69% male) treated with percutaneous revascularisation were recruited within 24 h post-infarction. Peripheral blood monocyte subpopulations were enumerated and characterised using flow cytometry after staining for CD14, CD16 and CCR2. Phenotypically, monocyte subpopulations are defined as: CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3). Phagocytic activity of monocytes was measured using flow cytometry and Ecoli commercial kit. Transthoracic 2D echocardiography was performed within 7 days and at 6 months post infarct to assess global longitudinal strain (GLS) via speckle tracking. MACE was defined as recurrent acute coronary syndrome and death. Results - STEMI patients with EF ≥50% by Simpson’s biplane (n = 52) had GLS assessed. Using multivariate regression analysis higher counts of Mon1 and Mon 2 and phagocytic activity of Mon2 were significantly associated with GLS (after adjusting for age, time to hospital presentation, and peak troponin levels) (Table 1). At 6 months, the convalescent GLS remained associated with higher counts of Mon1, Mon 2. At one year follow up, using multivariate Cox regression analysis, Mon1 and Mon2 counts were an independent predictor of MACE in patients with a reduced GLS (n = 21)

Heparin elevates circulating soluble fms-like tyrosine kinase-1 immunoreactivity in pregnant women receiving anticoagulation therapy

Background—Alterations in circulating levels of pro- and antiangiogenic factors have been associated with adverse pregnancy outcomes. Heparin is routinely administered to pregnant women, but without clear knowledge of its impact on these factors. Methods and Results—We conducted a longitudinal study of 42 pregnant women. Twenty-one women received prophylactic heparin anticoagulation, and 21 healthy pregnant women served as controls. Compared with gestational age-matched controls, heparin treatment was associated with increased circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) in the third trimester (P<0.05), in the absence of preeclampsia, placental abruption, or fetal growth restriction. Heparin had no effect on circulating levels of vascular endothelial growth factor, placenta growth factor, or soluble endoglin as assessed by ELISA. In vitro, low-molecular weight and unfractionated heparins stimulated sFlt-1 release from placental villous explants, in a dose- and time-dependent manner. This effect was not due to placental apoptosis, necrosis, alteration in protein secretion, or increased transcription. Western blot analysis demonstrated that heparin induced shedding of the N-terminus of Flt-1 both in vivo and in vitro as indicated by a predominant band of 100–112 kDa. By using an in vitro angiogenesis assay, we demonstrated that serum of heparin-treated cases inhibited both basal and vascular endothelial growth factor-induced capillary-like tube formation. Conclusions—Heparin likely increases the maternal sFlt-1 through shedding of the extracellular domain of Flt-1 receptor. Our results imply that upregulation of circulating sFlt-1 immunoreactivity in pregnancy is not always associated with adverse outcomes, and that heparin's protective effects, if any, cannot be explained by promotion of angiogenesis.

Sedative load and frailty among community-dwelling population aged ≥65 years

OBJECTIVE: To explore the association between use of sedative drugs and frailty. DESIGN: Cross-sectional study. SETTING: First wave of The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort of the community-dwelling population aged 50 years or older in Ireland. PARTICIPANTS: Participants were 1642 men and 1804 women aged 65 years or older. MEASUREMENTS: Regular use of sedative drugs determined according to the sedative load (SL) model, frailty phenotype status, and frailty deficit index (FI) score assessed using validated, established protocols. RESULTS: Overall, 19% of the participants took sedative drugs, most frequently hypnotics and antidepressants. Sedative drug use was at 46% for frail, 23% for prefrail, and 9% for nonfrail participants. After adjustment for covariates, SL was positively associated with being prefrail (odds ratio [OR] 1.27; 95% confidence interval [CI] 1.11-1.46) and frail (OR 1.30; 95% CI 1.02-1.64). Advancing age but not sex remained significant (P < .001). After adjustment for covariates, the association between SL and the FI was also significant at P ≤ .001 (β = 1.77; 95% CI 1.13-2.42). CONCLUSION: Higher SL was positively associated with phenotype frailty and the FI. This suggests that careful consideration must be given when prescribing sedatives to frail older adults, who are most vulnerable to adverse drug reactions and adverse health outcomes.

Safety of antidiabetes medications:an update

Adverse iatrogenic effects of especial relevance for antidiabetes medications include hypoglycemic episodes, major adverse cardiovascular (CV) events, cancer, bone fractures, pancreatic effects, genital/urinary tract infections, and weight gain. Here, recent clinical studies addressing safety profiles of antidiabetes medications are reviewed. On balance, new prospective and population-based studies continue to indicate that the benefits of improved glucose control outweigh the risks associated with antidiabetes medications in most patients with type 2 diabetes.

Hypertension, poor glycemic control, and microalbuminuria in Cuban Americans with type 2 diabetes

Purpose: To investigate to what degree the presence of hypertension (HTN) and poor glycemic control (GC) influences the likelihood of having microalbuminuria (MAU) among Cuban Americans with type 2 diabetes (T2D).Methods: A cross-sectional study conducted in Cuban Americans (n = 179) with T2D. Participants were recruited from a randomly generated mailing list purchased from KnowledgeBase Marketing, Inc. Blood pressure (BP) was measured twice and averaged using an adult size cuff. Glycosylated hemoglobin (A1c) levels were measured from whole blood samples with the Roche Tina-quant method. First morning urine samples were collected from each participant to determine MAU by a semiquantitative assay (ImmunoDip).Results: MAU was present in 26% of Cuban Americans with T2D. A significantly higher percentage of subjects with MA had HTN (P = 0.038) and elevated A1C (P = 0.002) than those with normoalbuminuria. Logistic regression analysis showed that after controlling for covariates, subjects with poor GC were 6.76 times more likely to have MAU if they had hypertension compared with those without hypertension (P = 0.004; 95% confidence interval [CI]: 1.83, 23.05). Conclusion: The clinical significance of these findings emphasizes the early detection of MAU in this Hispanic subgroup combined with BP and good GC, which are fundamentals in preventing and treating diabetes complications and improving individuals’ renal and cardiovascular outcomes.

Relação entre desempenho funcional e indicadores de doença arterial obstrutiva periférica em idosas

The presence of peripheral arterial disease (PAD) increases the risk and vulnerability to adverse clinical outcomes in the elderly. Like this, we investigated the relationship between functional performance and indicators of PAD in elderly women. METHODS: Cross-sectional study in which 54 elderly were assessed by questionnaire mini mental state examination, Short Phisical Performance Battery (SPPB), ankle-brachial index (ABI), human activity profile (HAP) and Edinburgh questionnaire. Statistical analysis was performed using ANOVA, t test and Pearson correlation. We considered p <0.05 as significance level. RESULTS: The mean age SPPB and ABI were 69.2 (± 6.9) years, SPPB 9.42 (± 2.55) and ABI 1.04 (± 0.14). The prevalence of PAD was 16.3%. There was a significant correlation between ABI and gait speed (r = 0.75, p = 0.001) and between PAH with SPPB (p = 0.001). CONCLUSIONS: It is suggested that the decline in functional performance in older, expressed in gait velocity component of the SPPB, is related to the presence of PAD

Hyperemesis gravidarum: current perspectives.

Hyperemesis gravidarum is a complex condition with a multifactorial etiology characterized by severe intractable nausea and vomiting. Despite a high prevalence, studies exploring underlying etiology and treatments are limited. We performed a literature review, focusing on articles published over the last 10 years, to examine current perspectives and recent developments in hyperemesis gravidarum.

Estrategias resilientes ante la situación adversa de los desahucios

Los desahucios en España se han convertido en los últimos años en un fenómeno social emergente, de interés tanto para la investigación como para la intervención de los profesionales de la acción social. Aun así, no existen estudios suficientes relacionados con esta situación adversa, y menos aún centrados en las respuestas resilientes que las personas son capaces de ofrecer ante ella. Con el objetivo de identificar los factores internos y externos que se presentan en la experiencia de las familias que viven procesos de desahucios y que les están permitiendo desarrollar estrategias resilientes ante dicha adversidad, se lleva a cabo la presente investigación en la que participan 20 sujetos, pertenecientes a familias que acuden a la Plataforma de Afectados por las Hipotecas (PAH) de Málaga. A los participantes se les realiza una entrevista semi-estructurada y a través de ellas se han podido definir las características socio-familiares de las personas afectadas, las diferentes estrategias de afrontamiento desarrolladas, las principales fuentes de apoyo con las que han contado, así como las preocupaciones que les han acompañado. Los resultados muestran los principales factores internos y externos que están presenten en las estrategias resilientes que han desarrollado las familias afectadas por los desahucios durante el proceso vivido y destacan como fuente de apoyo informacional a la PAH. Se concluye con la necesidad de continuar con esta línea de investigación para tratar de diseñar intervenciones que refuercen y fomenten las estrategias de afrontamiento ante la situación adversa del desahucio.

Importance of risk factor management in diabetic patients and reduction in Stage B heart failure

BACKGROUND: A number of studies have demonstrated the presence of a diabetic cardiomyopathy, increasing the risk of heart failure development in this population. Improvements in present-day risk factor control may have modified the risk of diabetes-associated cardiomyopathy.

AIM: We sought to determine the contemporary impact of diabetes mellitus (DM) on the prevalence of cardiomyopathy in at-risk patients with and without adjustment for risk factor control.

DESIGN: A cross-sectional study in a population at risk for heart failure.

METHODS: Those with diabetes were compared to those with other cardiovascular risk factors, unmatched, matched for age and gender and then matched for age, gender, body mass index, systolic blood pressure and low density lipoprotein cholesterol.

RESULTS: In total, 1399 patients enrolled in the St Vincent's Screening to Prevent Heart Failure (STOP-HF) cohort were included. About 543 participants had an established history of DM. In the whole sample, Stage B heart failure (asymptomatic cardiomyopathy) was not found more frequently among the diabetic cohort compared to those without diabetes [113 (20.8%) vs. 154 (18.0%), P = 0.22], even when matched for age and gender. When controlling for these risk factors and risk factor control Stage B was found to be more prevalent in those with diabetes [88 (22.2%)] compared to those without diabetes [65 (16.4%), P = 0.048].

CONCLUSION: In this cohort of patients with established risk factors for Stage B heart failure superior risk factor management among the diabetic population appears to dilute the independent diabetic insult to left ventricular structure and function, underlining the importance and benefit of effective risk factor control in this population on cardiovascular outcomes.

Methods for Confounding Adjustment and High-Dimensional Environmental Exposures

Thesis (Ph.D.)--University of Washington, 2016-08

Responsiveness of the frontal EMG for monitoring the sedation state of critically ill patients.

Background. Excessive sedation is associated with adverse patient outcomes during critical illness, and a validated monitoring technology could improve care. We developed a novel method, the responsiveness index (RI) of the frontal EMG. We compared RI data with Ramsay clinical sedation assessments in general and cardiac intensive care unit (ICU) patients. Methods. We developed the algorithm by iterative analysis of detailed observational data in 30 medical–surgical ICU patients and described its performance in this cohort and 15 patients recovering from scheduled cardiac surgery. Continuous EMG data were collected via frontal electrodes and RI data compared with modified Ramsay sedation state assessments recorded regularly by a blinded trained observer. RI performance was compared with EntropyTM across Ramsay categories to assess validity. Results. RI correlated well with the Ramsay category, especially for the cardiac surgery cohort (general ICU patients r¼0.55; cardiac surgery patients r¼0.85, both P,0.0001). Discrimination across all Ramsay categories was reasonable in the general ICU patient cohort [PK¼0.74 (SEM 0.02)] and excellent in the cardiac surgery cohort [PK¼0.92 (0.02)]. Discrimination between ‘lighter’ vs ‘deeper’ (Ramsay 1–3 vs 4–6) was good for general ICU patients [PK¼0.80 (0.02)] and excellent for cardiac surgery patients [PK¼0.96 (0.02)]. Performance was significantly better than EntropyTM. Examination of individual cases suggested good face validity. Conclusions. RI of the frontal EMG has promise as a continuous sedation state monitor in critically ill patients. Further investigation to determine its utility in ICU decision-making is warranted.

Oxidative stress and its haemodynamic consequences in chronic kidney disease

Chronic kidney disease (CKD) is associated with increased cardiovascular risk in comparison with the general population. This can be observed even in the early stages of CKD, and rises in proportion to the degree of renal impairment. Not only is cardiovascular disease (CVD) more prevalent in CKD, but its nature differs too, with an excess of morbidity and mortality associated with congestive cardiac failure, arrhythmia and sudden death, as well as the accelerated atherosclerosis which is also observed. Conventional cardiovascular risk factors such as hypertension, dyslipidaemia, obesity, glycaemia and smoking, are highly prevalent amongst patients with CKD, although in many of these examples the interaction between risk factor and disease differs from that which exists in normal renal function. Nevertheless, the extent of CVD cannot be fully explained by these conventional risk factors, and non-conventional factors specific to CKD are now recognised to contribute to the burden of CVD. Oxidative stress is a state characterised by excessive production of reactive oxygen species (ROS) and other radical species, a reduction in the capacity of antioxidant systems, and disturbance in normal redox homeostasis with depletion of protective vascular signalling molecules such as nitric oxide (NO). This results in oxidative damage to macromolecules such as lipids, proteins and DNA which can alter their functionality. Moreover, many enzymes are sensitive to redox regulation such that oxidative modification to cysteine thiol groups results in activation of signalling cascades which result in adverse cardiovascular effects such as vascular and endothelial dysfunction. Endothelial dysfunction and oxidative stress are present in association with many conventional cardiovascular risk factors, and can be observed even prior to the development of overt, clinical, vascular pathology, suggesting that these phenomena represent the earliest stages of CVD. In the presence of CKD, there is increased ROS production due to upregulated NADPH oxidase (NOX), increase in a circulating asymmetric dimethylarginine (ADMA), uncoupling of endothelial nitric oxide synthase (eNOS) as well as other mechanisms. There is also depletion in exogenous antioxidants such as ascorbic acid and tocopherol, and a reduction in activity of endogenous antioxidant systems regulated by the master gene regulator Nrf-2. In previous studies, circulating markers of oxidative stress have been shown to be increased in CKD, together with a reduction in endothelial function in a stepwise fashion relating to the severity of renal impairment. Not only is CVD linked to oxidative stress, but the progression of CKD itself is also in part dependent on redox sensitive mechanisms. For example, administration of the ROS scavenger tempol attenuates renal injury and reduces renal fibrosis seen on biopsy in a mouse model of CKD, whilst conversely, supplementation with the NOS inhibitor L-NAME causes proteinuria and renal impairment. Previous human studies examining the effect of antioxidant administration on vascular and renal function have been conflicting however. The work contained in this thesis therefore examines the effect of antioxidant administration on vascular and endothelial function in CKD. Firstly, 30 patients with CKD stages 3 – 5, and 20 matched hypertensive controls were recruited. Participants with CKD had lower ascorbic acid, higher TAP and ADMA, together with higher augmentation index and pulse wave velocity. There was no difference in baseline flow mediated dilatation (FMD) between groups. Intravenous ascorbic acid increased TAP and O2-, and reduced central BP and augmentation index in both groups, and lowered ADMA in the CKD group only. No effect on FMD was observed. The effects of ascorbic acid on kidney function was then investigated, however this was hindered by the inherent drawbacks of existing methods of non-invasively measuring kidney function. Arterial spin labelling MRI is an emerging imaging technique which allows measurement of renal perfusion without administration of an exogenous contrast agent. The technique relies upon application of an inversion pulse to blood within the vasculature proximal to the kidneys, which magnetically labels protons allowing measurement upon transit to the kidney. At the outset of this project local experience using ASL MRI was limited and there ensued a prolonged pre-clinical phase of testing with the aim of optimising imaging strategy. A study was then designed to investigate the repeatability of ASL MRI in a group of 12 healthy volunteers with normal renal function. The measured T1 longitudinal relaxation times and ASL MRI perfusion values were in keeping with those found in the literature; T1 time was 1376 ms in the cortex and 1491 ms in the whole kidney ROI, whilst perfusion was 321 mL/min/100g in the cortex, and 228 mL/min/100g in the whole kidney ROI. There was good reproducibility demonstrated on Bland Altman analysis, with a CVws was 9.2% for cortical perfusion and 7.1% for whole kidney perfusion. Subsequently, in a study of 17 patients with CKD and 24 healthy volunteers, the effects of ascorbic acid on renal perfusion was investigated. Although no change in renal perfusion was found following ascorbic acid, it was found that ASL MRI demonstrated significant differences between those with normal renal function and participants with CKD stages 3 – 5, with increased cortical and whole kidney T1, and reduced cortical and whole kidney perfusion. Interestingly, absolute perfusion showed a weak but significant correlation with progression of kidney disease over the preceding year. Ascorbic acid was therefore shown to have a significant effect on vascular biology both in CKD and in those with normal renal function, and to reduce ADMA only in patients with CKD. ASL MRI has shown promise as a non-invasive investigation of renal function and as a biomarker to identify individuals at high risk of progressive renal impairment.

Conceptualisation, design and development of a primary school based child healthy weight intervention

INTRODUCTION: In common with much of the developed world, Scotland has a severe and well established problem with overweight and obesity in childhood with recent figures demonstrating that 31% of Scottish children aged 2-15 years old were overweight including obese in 2014. This problem is more pronounced in socioeconomically disadvantaged groups and in older children across all economic groups (Scottish Health Survey, 2014). Children who are overweight or obese are at increased risk of a number of adverse health outcomes in the short term and throughout their life course (Lobstein and Jackson-Leach, 2006). The Scottish Government tasked all Scottish Health Boards with developing and delivering child healthy weight interventions to clinically overweight or obese children in an attempt to address this health problem. It is therefore imperative to deliver high quality, affordable, appropriately targeted interventions which can make a sustained impact on children’s lifestyles, setting them up for life as healthy weight adults. This research aimed to inform the design, readiness for application and Health Board suitability of an effective primary school-based curricular child healthy weight intervention. METHODS: the process involved in conceptualising a child healthy weight intervention, developing the intervention, planning for implementation and subsequent evaluation was guided by the PRECEDE-PROCEED Model (Green and Kreuter, 2005) and the Intervention Mapping protocol (Lloyd et al. 2011). RESULTS: The outputs from each stage of the development process were used to formulate a child healthy weight intervention conceptual model then develop plans for delivery and evaluation. DISCUSSION: The Fit for School conceptual model developed through this process has the potential to theoretically modify energy balance related behaviours associated with unhealthy weight gain in childhood. It also has the potential to be delivered at a Health Board scale within current organisational restrictions.

Rail passenger crowding, stress, health and safety in Britain

There has long been a question as to whether crowding in rail passenger transport poses a threat to passenger health related to the experience of stress. A review of the scientific literature was conducted. Little rail-specific empirical research was identified. The more general research that does exist suggests that high-density environments are not necessarily perceived as crowded and that stress-related physiological, psychological and behavioural reactions do not necessarily follow from exposure to such environments. Several factors are identified that may moderate the impact of a high-density environment on perceptions of crowding and the subsequent experience and effects of stress. These include, inter alia, perceptions of control and predictability of events. However, if caused, the experience and effects of stress may be made worse by inadequate coach design that gives rise to discomfort. The model that emerges from these findings offers a suitable framework for the development of research questions that should help translate emerging knowledge into practical interventions, for the reduction of any adverse health outcomes associated with crowding.

The effects of vitamin D supplementation on maternal and neonatal outcome: A randomized clinical trial

Background: Vitamin D supplementation during pregnancy has been supposed to defend against adverse gestational outcomes. Objective: This randomized clinical trial study was conducted to assess the effects of 50,000 IU of vitamin D every two weeks supplementation on the incidence of gestational diabetes (GDM), gestational hypertension, preeclampsia and preterm labor, vitamin D status at term and neonatal outcomes contrasted with pregnant women that received 400 IU vitamin D daily. Materials and Methods: 500 women with gestational age 12-16 weeks and serum 25 hydroxy vitamin D (25 (OH) D ) less than 30 ng/ml randomly categorized in two groups. Group A received 400 IU vitamin D daily and group B 50,000 IU vitamin D every 2 weeks orally until delivery. Maternal and Neonatal outcomes were assessed in two groups. Results: The incidence of GDM in group B was significantly lower than group A (6.7% versus 13.4%) and odds ratio (95% Confidence interval) was 0.46 (0.24-0.87) (P=0.01). The mean ± SD level of 25 (OH) D at the time of delivery in mothers in group B was significantly higher than A (37.9 ± 19.8 versus 27.2 ± 18.8 ng/ml, respectively) (P=0.001). There were no differences in the incidence of preeclampsia, gestational hypertension, preterm labor, and low birth weight between two groups. The mean level of 25 (OH) D in cord blood of group B was significantly higher than group A (37.9 ± 18 versus 29.7 ± 19ng/ml, respectively). Anthropometric measures between neonates were not significantly different. Conclusion: Our study showed 50,000 IU vitamin D every 2 weeks decreased the incidence of GDM.