No description available.

No description available.

Vascular calcification (VC) is accelerated in patients with chronic kidney disease (CKD), resulting in increased risk of cardiovascular disease and mortality. Although the consequences of VC are associated with elevated pulse wave velocity (PWV) and left ventricular hypertrophy (LVH), the temporal impact on blood pressure changes is unknown. Mineral imbalance in CKD greatly contributes to the development of VC, and elevated serum phosphate is a major risk factor. Magnesium, which plays an important role in bone regulation, has been recently shown to be a modifier of VC, but whether magnesium inhibits calcification in CKD is unknown. A modified adenine model of CKD was developed in rats, characterized by mineral imbalance and progressive VC. During the development of VC, pulse pressure increased, which was driven by a drop in diastolic blood pressure, rather than systolic hypertension. Continuous pressure recordings in conscious rats using radiotelemetry revealed a significant increase in systolic variability associated with development of VC. Regional VC was associated with regional changes in the hemodynamic profile of the CKD rats. For example, only thoracic aortic calcification was associated with elevated PWV and pulse pressure. In contrast, the presence of abdominal and thoracic calcification differentially affected proximal and distal arterial pressure wave forms. CKD animals exhibited LVH, which was further increased by the presence of VC. In addition, fibroblast growth factor 23, which regulates renal excretion of phosphate, was elevated in CKD animals at every time point and was associated with LVH independently from VC. Development of VC was characterized in an in vitro organ model. Phosphate elevation in vitro caused VC in aortas. In vitro, magnesium supplementation inhibited initiation and progression of VC. CKD animals given a magnesium diet also demonstrated attenuated development of VC. In patients with stage 3-5 CKD (excluding dialysis), dietary phosphate was associated with the progression of coronary artery calcification even after adjusting for use of phosphate binders, total dietary energy and total dietary protein. Given the serious negative outcomes associated with development of VC, these findings fill key gaps in knowledge regarding the detection, management, prevention and treatment of VC in CKD. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2013-12-01 15:12:54.388

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There is biochemical evidence that the acute phase protein, a1-antichymotrypsin (ACT), is involved in Alzheimer's disease (AD), the most common form of dementia. Inflammation increases the level of ACT in the plasma, and it has been suggested that AD provokes chronic neuroinflammation. One of the key proteins in AD is beta-amyloid which associates with ACT in the senile plaques characteristic of AD. Studies to demonstrate a genetic association between polymorphisms in the ACT gene and AD have, to date, been inconclusive and contradictory. The discovery, in our laboratory, of a single nucleotide polymorphism in the promoter region of ACT suggested a new marker to test for a genetic association between ACT and AD. To determine if the ACT promoter polymorphism had a functional effect which could modify the risk of AD, the promoter region was cloned into reporter constructs and transfected into mammalian cells in culture. These included hepatocytes, astrocytes, neuronal cells and mixed population neural cells, and these were stimulated with oncostatin M. In astrocytes, the T allele of the promoter allele demonstrates 208% and 146% higher activity than the G allele under basal and stimulated conditions, respectively. In neuronal cells these values are 37% and 46%. Electrophoretic mobility shift assays demonstrated differences in binding affinity of a DNA-binding protein, probably TFIIB, and the two alleles of the ACT promoter polymorphism. However, an analysis of ACT promoter genotypes in AD cases (n= 389) and controls (n= 335) revealed no significant difference in the distribution of genotypes between cases and controls (p= 0.250), nor did any ACT promoter genotype appear to modify the age of onset of AD (p= 0.997). The association between the ACT -51bp polymorphism and early onset AD was not investigated, due to the small number of EOAD cases in the population studied.

UK care home residents are frail, dependent and multimorbid. General practitioners (GPs) provide their healthcare but there is evidence that existing provision fails to meet their needs. Comprehensive Geriatric Assessment (CGA) comprises comprehensive multidisciplinary assessment, goal setting and frequent review. This thesis considers a possible role for CGA in UK care homes through three research projects. The Care Home Literature Review (CHoLiR) was a systematic mapping review of randomized controlled trials (RCTs) in care homes. It found no evidence supporting CGA as a whole but described some CGA components supported by RCTs: advanced care planning; interventions to reduce prescribing; staff education around dementia and end-of-life; calcium/vitamin D and alendronate in preventing fractures and osteoporosis; vaccination/neuraminidase inhibitors in preventing influenza; functional incidental and bladder training for incontinence; and risperidone/olanzapine for agitation. The Care Home Outcome Study (CHOS) was a longitudinal cohort study recording dependency, cognition, behaviour, diagnoses, prescribing, nutrition and healthcare resource use in 227 residents across 11 care homes over six months. It reported high levels of dependency, cognitive impairment, malnutrition, multimorbidity and frequent behavioural disturbance. Polypharmacy and prescribing errors were common. Variability between homes and individuals was significant for most baseline and outcome measures. Staff Interviews in Care Homes (STICH) was a qualitative interview study of 32 staff working with care homes including: GPs; care home managers and nurses; NHS community nurses and specialist practitioners. It described care defined by discontinuity and lack-of-anticipation; driven by communication failure, inadequate training and expertise in frail older patients, and arbitrary boundaries between care homes and the NHS which interfered with care. Using the findings of these studies, the author proposes a model of care which is multidisciplinary, guided by comprehensive assessment, reinforced by frequent review and delivered by experts in the care of frail older patients: CGA has a role in UK care homes.

Systematic Review: Chronic pain and insomnia are highly comorbid, and evidence suggests a reciprocal relationship between these. CBT-I has been shown to improve sleep in those with chronic pain, therefore the potential of improved sleep leading to improvements in pain symptoms is a possibility. This led to the question: Does CBT-I improve pain symptoms in those with chronic pain and insomnia? A systematic review of the literature was conducted resulting in eight papers regarding six studies. Evidence was moderate that CBT-I improved sleep and pain related disability, but did not improve self reported pain levels. This discrepancy between improvements in pain related disability and no changes in self-reported pain levels led to the research question for the empirical element of the current thesis. Empirical Element of Thesis Objective: Chronic low back pain (CLBP) is a common form of chronic pain that affects a large population each year. Chronic pain and insomnia are highly comorbid conditions, yet knowledge about how patients perceive their interaction is limited. This qualitative study aims to inform our understanding of the patient experience with particular reference to beliefs and attributions surrounding pain, poor sleep and their interaction. Methods: 11 outpatients from a chronic pain clinic were recruited who suffered CLBP as their main symptom, and who had subsequently developed insomnia as a result. Data were analysed using Interpretative Phenomenological Analysis (IPA). Results: Qualitative analysis produced five super-ordinate themes: 1) the privacy of pain and solitude of sleep; 2) sleep/pain interaction; 3) night-time thinking; 4) adjustment and acceptance; and 5) self-management. Discussion: The first three themes combine to create the individual experience of CLBP: the visceral, emotional experience; the pre-existing and shifting beliefs; and the thought content. Once this is in place, the individual can reflect on what this means to them, and through acceptance, move through to adjustment. The individual accepts elements of their current experience, but where they see the opportunity to take control, these adjustments are translated into actions relating to self-management. These themes suggest CBT-I should be adapted to include pain specific beliefs to form a CBT for Insomnia and Chronic Pain (‘CBT-CPI’).

No description available.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The aim of this study is to conduct a systematic review of the existing evidence on marijuana use and its association, or the absence of an association, with an increased risk of developing chronic obstructive pulmonary disease (COPD), lung cancer, and/or chronic respiratory symptoms. We hypothesize that a systematic review will not demonstrate sufficient evidence to determine that marijuana use increases the risk of developing COPD, lung cancer, and/or chronic respiratory symptoms. The term “chronic respiratory symptoms” encompasses the following: cough, sputum production, wheeze, shortness of breath, acute bronchitis, and chest tightness. The following databases were searched for the topics of marijuana smoking, COPD, lung cancer, and chronic respiratory symptoms: MEDLINE (PubMed/OvidSP), the Cochrane Controlled Trials Register, the Cochrane Database of Systematic Reviews, PsycINFO, the Database of Abstracts of Reviews of Effects, and Google Scholar. The search ended September 7th, 2016. Studies were initially limited only by the requirement that they were based upon human research and published in English. Studies were included if they were systematic reviews, randomized controlled trials (RCTs), prospective or retrospective cohort studies, case control studies, or cross‐sectional studies. A total of 739 articles were screened for eligibility, 17 unique studies met the inclusion criteria and underwent qualitative analysis1‐17. The quality of systematic reviews was evaluated using the AMSTAR criteria18; cohort, case‐control, and cross sectional studies were evaluated based upon the Newcastle‐Ottawa Quality Assessment Scale (NOS) 19. No RCTs were identified. The overall quality of the evidence for each outcome was determined by utilizing the GRADE methodology20‐21. Studies were primarily assessed by a single reviewer, with random validation of assessments on a limited number of studies by a second reviewer. Overall, there is very low quality evidence that assesses for an association between marijuana smoking and an increased risk of developing lung cancer, COPD, and/or chronic respiratory symptoms. There was no conclusive finding for lung cancer and COPD. However, seven of eight studies concluded that there was an association between marijuana use and chronic respiratory symptoms. The totality of evidence describing any associations between marijuana smoking and the risk of developing lung cancer, COPD, and/or chronic respiratory symptoms is not strong enough to confidently state that marijuana use is associated with any of these chronic pulmonary conditions. Of all the evidence examined in this systematic review, the most convincing appears to be that relating to a potential positive association between marijuana smoking and the risk of developing chronic respiratory symptoms. Unfortunately, the overall quality of evidence was very low due to significant methodological weaknesses within the studies. Thus, there is insufficient evidence in the current literature to make a definitive statement regarding this possible association.

Cartas al editor