54 research outputs found
Prior events predict cerebrovascular and coronary outcomes in the PROGRESS trial
No full text<p><b>Background and Purpose:</b> The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)–lowering.</p>
<p><b>Methods:</b> Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP–lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s).</p>
<p><b>Results:</b> Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64; P=0.1 for large artery infarction, P<0.0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25%; P<0.0001 for ischemic stroke; 42%, P=0.0006 for hemorrhagic stroke; 17%, P=0.3 for coronary events; P homogeneity=0.4).</p>
<p><b>Conclusions:</b> Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP–lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.</p>
C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study
No full textSummaryBackgroundIt has been suggested that inflammation status, as assessed by C-reactive protein (CRP) concentration, modifies the vascular protective effects of statin therapy. In particular, there have been claims that statins might be more beneficial in people with raised CRP concentrations, and might even be ineffective in people with low concentrations of both CRP and LDL cholesterol. This study aimed to test this hypothesis.MethodsIn 69 UK hospitals, 20 536 men and women aged 40–80 years at high risk of vascular events were randomly assigned to simvastatin 40 mg daily versus matching placebo for a mean of 5·0 years. Patients were categorised into six baseline CRP groups (<1·25, 1·25–1·99, 2·00–2·99, 3·00–4·99, 5·00–7·99, and ≥8·00 mg/L). The primary endpoint for subgroup analyses was major vascular events, defined as the composite of coronary death, myocardial infarction, stroke, or revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN48489393.FindingsOverall, allocation to simvastatin resulted in a significant 24% (95% CI 19–28) proportional reduction in the incidence of first major vascular event after randomisation (2033 [19·8%] allocated simvastatin vs 2585 [25·2%] allocated placebo). There was no evidence that the proportional reduction in this endpoint, or its components, varied with baseline CRP concentration (trend p=0·41). Even in participants with baseline CRP concentration less than 1·25 mg/L, major vascular events were significantly reduced by 29% (99% CI 12–43, p<0·0001; 239 [14·1%] vs 329 [19·4%]). No significant heterogeneity in the relative risk reduction was recorded between the four subgroups defined by the combination of low or high baseline concentrations of LDL cholesterol and CRP (p=0·72). In particular, there was clear evidence of benefit in those with both low LDL cholesterol and low CRP (27% reduction, 99% CI 11–40, p<0·0001; 295 [15·6%] vs 400 [20·9%]).InterpretationEvidence from this large-scale randomised trial does not lend support to the hypothesis that baseline CRP concentration modifies the vascular benefits of statin therapy materially.FundingUK Medical Research Council, British Heart Foundation, Merck, Roche Vitamins, and GlaxoSmithKline
Clinical assessment of Renal Ischaemic Injury and the Role of Cryopreservation; Peritoneal Cooling an Non-Heart-Beating Donation and Topical Cooling for Laparoscopic Surgery
No full textAbstract
The project aims focussed on three main areas of study; ischaemic injury assessment, laparoscopic renal cryopreservation and peritoneal cooling for non-heart-beating organ donation. The effects of renal ischaemia represent significant challenges for transplantation and urological surgery in that with sufficient unchecked ischaemic duration, permanent loss of function is inevitable. Prior to consideration of novel approaches to ischaemic protection, aimed at producing improved graft quality for transplantation and an increased safe operating times for partial renal resections, deficiencies in the literature regarding the efficacy of viability testing were targeted. Techniques of ischaemic injury assessment are intended to allow identification of retrieved kidneys which are likely to have lost the potential for adequate function if transplanted. Such organs can then be discarded, thus improving outcomes and decreasing rates of primary non-function.
Results pertaining to ischaemic injury assessment provided support for protocols of viability assessment based on hypothermic machine perfusion. The effect of warm ischaemia on renal viability criteria has been successfully demonstrated in a large animal model, and novel approaches to the use of such assessments have been explored in order to maximise organ resource opportunities and utilisation.
The project has made an important contribution in the technical approach to laparoscopic partial nephrectomy and laparoscopic renal hypothermia. The studies involving the ‘Newcastle Laparoscopic Renal Cooling Device’ succeeded in achieving ‘proof of concept’ with demonstration of effective renal cooling and preservation..
Studies relating to preservation interventions in the porcine model of the uncontrolled NHBD have produced striking results. These results strongly suggest that uncontrolled NHBD centres employing cold in-situ perfusion approaches to preservation would be wise to consider supplementary techniques of organ cooling
Study of Heart and Renal Protection (SHARP): Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease
No full textGenome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
No full textNumerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans1, 2, 3. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10−8 to P = 2.3 × 10−13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP
Assessment of a novel biomarker panel for the earlier prediction of acute kidney injury in patients with diabetes mellitus undergoing coronary angiography and intervention
No full textPhDDiabetes mellitus triples the risk of developing coronary heart disease (CHD).
The manifestations of CHD are more severe in patients with diabetes with both
more extensive and more diffuse disease. Outcomes in patients with diabetes
are significantly worse both in terms of Major Adverse Cardiovascular Events
(MACE) overall and specifically following revascularisation procedures such as
percutaneous coronary intervention (PCI). Furthermore patients with chronic
kidney disease (CKD) are excluded from the vast majority of cardiology trials and
therefore there is a lack of data for these patients. Contrast induced acute kidney
injury (AKI) is an important complication following procedures in the cardiac
catheterisation laboratory and patients with diabetes are at particular risk.
Patients with diabetes and CKD are a particular challenge. They have an
extremely high incidence of co-morbidities such as CHD and peripheral vascular
disease (PVD). When renal function is already impaired by other pathological
processes, the kidney is much less capable of tolerating the stress of excreting a
contrast load. If AKI develops, there is a risk of further loss of nephron units and
irreversible reduction in residual renal function. Earlier identification of patients
as risk of developing AKI will allow earlier therapeutic intervention which might
translate into improved clinical outcomes for these patients.
The study aimed to evaluate the incidence of contrast induced AKI in a high risk
population (diabetes and CKD) undergoing coronary angiography and PCI.
From a literature review Neutrophil Gelatinase Associated Lipocalin (NGAL) and
Interleukin-18 (IL-18) were identified as promising candidates for inclusion in a
‘renal injury’ biomarker panel for development of AKI early post coronary
angiography or PCI. It was then determined if concentrations of these markers
changed significantly at various time intervals post procedure. The aim was to
establish a panel of markers with the best predictive ability for identifying
development of AKI.
208 patients with a known diagnosis of diabetes mellitus and CKD (eGFR < 60
ml/min) were recruited over a one year period at The London Chest Hospital. 39
patients (18.8%) developed contrast induced AKI. There were no significant
differences between patients who did/did not develop AKI with respect to
baseline demographics, cardiac risk factors and co-morbidities. There was a
significant trend towards patients in the AKI group having a higher NYHA Class
(p=0.048) and this was further supported by echocardiogram and other imaging
data. Additional reinforcement came from the higher rate of loop diuretic
prescription (59% vs 26.9%) in the AKI group, p=0.012.
59 patients underwent renal angiography at the time of their coronary procedure.
There was no association between presence of structural renal disease and
development of AKI. 7 patients (12.5%) had moderate or severe renal artery
stenosis with 1 patient requiring further renal angioplasty due to the presence of
a critical lesion
The performance of landscape concepts in spatial planning : branding, bonding and bringing about
No full textSpatial planners are expressive people. They often use landscape concepts, being metaphors that refer to landscape ideas and planning principles. Examples are Green Heart, Nature Pearls and the Camelisation of landscapes. Such landscape concepts seem ‘innocent’ but are ‘guilty’ of powerful effects. The power of a landscape concept is rooted in its colourful, rhetorical and multiple nature, in combination with the drives and political practice of its users. Accordingly, the first part of this study provides a theoretical or philosophical reflection on the use of landscape concepts in spatial planning, including views of Foucault, Deleuze and Latour. The effect of a landscape concept can be subtle and unexpected. For example, media indirectly couple assumptions about 'good planning' to the concept of National Landscape, i.e. the limited ideal of open landscapes. Using a concept also provides opportunities: it can be used for bonding people and promoting landscapes. For example, the concept Waterpark in a vision for the Dutch IJmeer region was a flexible and informal concept. This allowed the organisations involved to identify with the concept and bundle interests, although it was a temporarily success. The second part of this study provides more insight into Dutch regional planning practice and the use of landscape concepts. Finally, this study discusses the benefit of a 'will to connect' by planners in contrast to a 'will to control'
Does taking vitamin, mineral and fatty acid supplements prevent cognitive decline? A systematic review of randomized controlled trials
No full textBackground Observational studies have shown associations between nutritional status and cognition in later life but evidence from intervention studies is unclear. The present study systematically reviewed the evidence on the effect of nutrient supplementation on cognitive function in people aged ≥65 years.
Methods Databases including MEDLINE and EMBASE were searched up to 1 September 2006. Randomized controlled trials using at least one kind of vitamin, mineral or omega-3 fatty acid, evaluating standardized neuropsychological test(s), were included. There were no restrictions on participants' baseline nutritional status or cognitive function. Quality assessment and data abstraction were conducted by one author and checked by another.
Results Of 4229 articles retrieved, 22 trials (3442 participants) were identified. Many were small, short duration and of poor methodology. Only 16 out of 122 cognitive tests were significantly different between groups. A meta-analysis showed no significant effect of taking B vitamins or antioxidant vitamins on global cognitive function. There was insufficient evidence to evaluate the effect of omega-3 fatty acids on any cognitive domains.
Conclusion There was little evidence of a beneficial effect from taking B vitamins or antioxidant supplements on global cognitive function in later life. Larger-scale randomized controlled trials of longer duration in selected age groups are needed.Institute of Applied Health Science, University of Aberdeen;
Chief Scientist Office of the Scottish Government Health Directorates;
Chief Scientist of the Scottish Government Health Directorate
Investigation of overprotection in pediatric cardiology
No full textHumanity grows from making mistakes. However, there is a group of people, and their cost of mistakes might be higher than the average. They are therefore protected by others, and their opportunity to explore the world is deprived. This protective behavior could be unnecessary or excessive, which is defined as overprotection. To detect the overprotection issue in the field of pediatric cardiology, the researcher, together with Erasmus MC- Sophia Children's Hospital, set up a collaborative program. The ultimate goal of the program was to design a smart product-service system which can prevent overprotective behavior in children with congenital heart disease. The present thesis is the initial step of the collaborative program— investigation of overprotection in pediatric cardiology. It addresses the concept of overprotection (OP) and vulnerable child syndrome (VCS), studies on the health-related life of children with congenital heart disease (CCHD), and their parents (PCCHD), then proposes a reformulated design goal and three tangible design missions as the final result. In the literature review, theoretical knowledge of overprotection and vulnerable child syndrome is elaborated. Three factors are especially highlighted, respectively risk factor, challenge, and indicator. The risk factor indicates the event that may trigger overprotection development; challenge means the parental barrier of performing proper protection; indicator expresses the theoretical assessment of overprotection. These factors are further brought to the empirical study to see how they influence life of CCHD and PCCHD. Empirical insights are captured during the empirical study. A total number of eight interviews were conducted, and the researcher also attended a sharing event in which five CCHD gave speeches on their grown-up experience. Collecting the medical history, interaction with people around, and narratives or opinions about overprotection was the main purpose of the empirical study. Factors derived from the literature were continuously reflected and compared with the empirical data. Theoretical knowledge and empirical insights were further integrated and synthesized. Based on the empirical narratives, the applicability of the theoretical overprotection indicators in pediatric cardiology is evaluated. Two indicators are found to have the highest significance and thus are suggested as the prioritized behavior that needs to be prevented. In addition, extreme quotes and narratives are selected and formulated in a positive case and a negative case. The positive case indicates good patient-parent relation without overprotection reported, while the negative case means tension in patient-parent relation with overprotection reported. Each case contains a patient persona, a parent persona, a health journey map, and an interactive map. Besides discerning the existing factors, four beneficial triggers are generated and highlighted as the main determinants which contribute to the difference between the positive case and the negative case. The insights provide a hint for potential design directions— prevent risk factors, support users to overcome the challenges, and guide users toward the beneficial trigger. Based on the design directions, a reformulated design goal and three corresponding design briefs were proposed as the final result of the thesis. The design goal was framed as “Design a product-service system which facilitates rational discussions within children with congenital heart disease, their parents and medical experts, in order to achieve a consensus upon diagnosis-specific and personalized boundaries between proper-protection and overprotection.” The three design briefs are further written as three dependent design assignments that provide guidelines and suggestions to the following designers.Strategic Product Desig
Investigations into the stability of growth factor induced-vasculature and the effects of synthetic biomaterials on heart remodelling after myocardial infarction
No full textThis work was based on the hypothesis that optimization of growth factor delivery rate and duration, combined with a biomaterial scaffold, could lead to an improved strategy for therapeutic neovascularization. To test this hypothesis, a novel in vivo model system that allows for characterization of stability and mural cell investment of newly created vessels was designed
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