Comparison of estimates and calculations of risk of coronary heart disease by doctors and nurses using different calculation tools in general practice: cross sectional study

OBJECTIVE: To assess the effect of using different risk calculation tools on how general practitioners and practice nurses evaluate the risk of coronary heart disease with clinical data routinely available in patients' records. DESIGN: Subjective estimates of the risk of coronary heart disease and results of four different methods of calculation of risk were compared with each other and a reference standard that had been calculated with the Framingham equation; calculations were based on a sample of patients' records, randomly selected from groups at risk of coronary heart disease. SETTING: General practices in central England. PARTICIPANTS: 18 general practitioners and 18 practice nurses. MAIN OUTCOME MEASURES: Agreement of results of risk estimation and risk calculation with reference calculation; agreement of general practitioners with practice nurses; sensitivity and specificity of the different methods of risk calculation to detect patients at high or low risk of coronary heart disease. RESULTS: Only a minority of patients' records contained all of the risk factors required for the formal calculation of the risk of coronary heart disease (concentrations of high density lipoprotein (HDL) cholesterol were present in only 21%). Agreement of risk calculations with the reference standard was moderate (kappa=0.33-0.65 for practice nurses and 0.33 to 0.65 for general practitioners, depending on calculation tool), showing a trend for underestimation of risk. Moderate agreement was seen between the risks calculated by general practitioners and practice nurses for the same patients (kappa=0.47 to 0.58). The British charts gave the most sensitive results for risk of coronary heart disease (practice nurses 79%, general practitioners 80%), and it also gave the most specific results for practice nurses (100%), whereas the Sheffield table was the most specific method for general practitioners (89%). CONCLUSIONS: Routine calculation of the risk of coronary heart disease in primary care is hampered by poor availability of data on risk factors. General practitioners and practice nurses are able to evaluate the risk of coronary heart disease with only moderate accuracy. Data about risk factors need to be collected systematically, to allow the use of the most appropriate calculation tools.

Bayesian neural network approach for determining the risk of re-intervention after endovascular aortic aneurysm repair

This article proposes a Bayesian neural network approach to determine the risk of re-intervention after endovascular aortic aneurysm repair surgery. The target of proposed technique is to determine which patients have high chance to re-intervention (high-risk patients) and which are not (low-risk patients) after 5 years of the surgery. Two censored datasets relating to the clinical conditions of aortic aneurysms have been collected from two different vascular centers in the United Kingdom. A Bayesian network was first employed to solve the censoring issue in the datasets. Then, a back propagation neural network model was built using the uncensored data of the first center to predict re-intervention on the second center and classify the patients into high-risk and low-risk groups. Kaplan-Meier curves were plotted for each group of patients separately to show whether there is a significant difference between the two risk groups. Finally, the logrank test was applied to determine whether the neural network model was capable of predicting and distinguishing between the two risk groups. The results show that the Bayesian network used for uncensoring the data has improved the performance of the neural networks that were built for the two centers separately. More importantly, the neural network that was trained with uncensored data of the first center was able to predict and discriminate between groups of low risk and high risk of re-intervention after 5 years of endovascular aortic aneurysm surgery at center 2 (p = 0.0037 in the logrank test).

Retinal vascular function and cardiovascular risk factors

The current platform of conventional cardiovascular risk assessments tends to forsake the importance of endothelial function - a key biological mechanism by which cardiovascular risk factors exert their propensity for adverse vascular events. Moreover, the presence and severity of endothelial dysfunction in ‘low-risk’ individuals suggests considerable variability in pre-clinical risk that could potentially be detected well before the onset of disease. The aim of the present thesis was to investigate the presence and impact of retinal vascular dysfunction, as a barometer of endothelial function, in otherwise healthy individuals with one or more cardiovascular risk factors, but low to moderate cardiovascular risk. Systemic circulatory influences on retinal vascular function were also evaluated. The principle sections and findings of this work are: 1. Ageing effect on retinal vascular function • In low-risk individuals, there are age differences in retinal vascular function throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the dilatory phase and are only present in young individuals. 2. Retinal vascular function in healthy individuals with a family history of cardiovascular disease • In low-risk individuals with a family history of cardiovascular disease, impairments in microvascular function at the retinal level correlate with established plasma markers for cardiovascular risk. 3. Ethnic differences in retinal vascular function • When compared to age-matched White Europeans, in low-risk middle-aged South Asians, there are impairments in retinal vascular function that correlate with established cardiovascular risk indicators. 4. Systemic circulatory influences on retinalµvascular function • Systemic antioxidant capacity (redox index) and plasma markers for cardiovascular risk (lipids) influence retinal microvascular function at both arterial and venous levels. 5. Retinal vascular function in individuals with obstructive sleep apnoea: a preliminarystudy • Patients with moderate to severe sleep apnoea exhibit attenuated retinal vascular function.

Renal glucose reabsorption inhibitors to treat diabetes

Current therapies to reduce hyperglycaemia in type 2 diabetes mellitus (T2DM) mostly involve insulin-dependent mechanisms and lose their effectiveness as pancreatic ß-cell function declines. In the kidney, filtered glucose is reabsorbed mainly via the high-capacity, low-affinity sodium glucose cotransporter-2 (SGLT2) at the luminal surface of cells lining the first segment of the proximal tubules. Selective inhibitors of SGLT2 reduce glucose reabsorption, causing excess glucose to be eliminated in the urine; this decreases plasma glucose. In T2DM, the glucosuria produced by SGLT2 inhibitors is associated with weight loss, and mild osmotic diuresis might assist a reduction in blood pressure. The mechanism is independent of insulin and carries a low risk of hypoglycaemia. This review examines the potential of SGLT2 inhibitors as a novel approach to the treatment of hyperglycaemia in T2DM.

The impact of the language barrier on the management of multinational companies : a case study and survey, based exploration of the impact of the language barrier on the strategies, policies and systems by which multinational companies manage their subsidaries

The thesis begins with a conceptual model of the way that language diversity affects the strategies, organisation and subsidiary control policies of multinational companies. The model is based solely on the researcher'’ personal experience of working in a variety of international management roles, but in Chapter 2 a wide-ranging review of related academic literature finds evidence to support the key ideas. The model is developed as a series of propositions which are tested in a comparative case study, refined and then re-tested in a global survey of multinational subsidiaries. The principal findings of the empirical phases of the thesis endorse the main tenets of the model: - That language difference between parent and subsidiary will impair communication, create mistrust and impede relationship development. - That subsequently the feelings of uncertainty, suspicion and mistrust will influence the decisions taken by the parent company. - They will have heightened sensitivity to language issues and will implement policies to manage language differences. - They will adopt low-risk strategies in host countries where they are concerned about language difference. - They will use organisational and manpower strategies to minimise the consequences and risks of the communications problems with the subsidiary. - As a consequence the level of integration and knowledge flow between parent and subsidiary will be curtailed. - They will adopt styles of control that depend least on their ability to communicate with their subsidiary. Although there is adequate support for all of the above conclusions, on some key points the evidence of the Case Studies and Survey is contradictory. The thesis, therefore, closes with an agenda for further research that would address these inconsistencies.

An evaluation of task analysis techniques for industrial process control

The concept of a task is fundamental to the discipline of ergonomics. Approaches to the analysis of tasks began in the early 1900's. These approaches have evolved and developed to the present day, when there is a vast array of methods available. Some of these methods are specific to particular contexts or applications, others more general. However, whilst many of these analyses allow tasks to be examined in detail, they do not act as tools to aid the design process or the designer. The present thesis examines the use of task analysis in a process control context, and in particular the use of task analysis to specify operator information and display requirements in such systems. The first part of the thesis examines the theoretical aspect of task analysis and presents a review of the methods, issues and concepts relating to task analysis. A review of over 80 methods of task analysis was carried out to form a basis for the development of a task analysis method to specify operator information requirements in industrial process control contexts. Of the methods reviewed Hierarchical Task Analysis was selected to provide such a basis and developed to meet the criteria outlined for such a method of task analysis. The second section outlines the practical application and evolution of the developed task analysis method. Four case studies were used to examine the method in an empirical context. The case studies represent a range of plant contexts and types, both complex and more simple, batch and continuous and high risk and low risk processes. The theoretical and empirical issues are drawn together and a method developed to provide a task analysis technique to specify operator information requirements and to provide the first stages of a tool to aid the design of VDU displays for process control.

Pharmacist monitoring of patient health in the community

The Government has established essential principles in order to make significant improvements in the health of the people and has placed an emphasis on shifting care to the primary sening. This research has explored the potential role of the community pharmacist in health promotion in the pharmacy, and at general medical practices. The feasibility of monitoring patients' health status in the community was evaluated by intervention to assess and alter cardiovascular risk factors.68, hypertensive patients, monitored at one surgery, had a change in mean systolic blood pressure from 158.28 to 146.55 mmHg, a reduction of 7.4%, and a change in mean diastolic bood pressure from 90.91 to 84.85 mmHg, a reduction of 6.7%.120 patients, from a cohort of 449 at the major practice, with an initial serum total cholesterol of 6.0+mmol/L, experienced a change in mean value from 6.79 to 6.05 mmol/L, equivalent to a reduction of 10.9%. 86% of this patient cohort showed a decrease in cholesterol concentration. Patients, placed in a high risk category according to their coronary rank score, assessed at the first health screening, showed a consistent and significant improvement in coronary score throughout the study period of two years. High risk and intermediate risk patients showed improvements in coronary score of 52% and 14% respectively. Patients in the low risk group maintained their good coronary score. In some cases, a patient's improvement was effected in liaison with the GP, after a change or addition of medication and/or dosage.Pharmacist intervention consisted of advice on diet and lifestyle and adherence to medication regimes. It was concluded that a pharmacist can facilitate a health screening programme in the primary care setting, and provide enhanced continuity of care for the patient.

Evaluating digital diabetic retinopathy screening in people aged 90 years and over

Introduction: The English National Screening Programme determines that all people with diabetes aged 12 and over should be screened annually for diabetic retinopathy (DR) until they die. Purpose: This study aimed to evaluate digital DR screening in patients aged 90 and over to establish whether it is appropriate to cease screening at age 90. Methods: A retrospective analysis of 200 randomly selected patients with diabetes aged 90 and over within the Birmingham and Black Country Screening Programme. Results: 179 (90%) patients attended screening at least once after turning 90 years of age. To date, the mean number of screens per person 90+ was two (range 1–6) and the mean age of the first of these screens was 91 years (range 90–98 years). 133 (74%) were put on annual recall after their first screen in their 90’s, of which 58% had no visible DR bilaterally. 38 (21%) were referred to ophthalmology - 35 (92%) for non-DR reasons and three for maculopathy. Of the 133 patients put on annual recall, 75 (56%) were screened at least once more. Seven improved, 36 remained stable, three became unsuitable and 29 deteriorated. Of the latter, 18 patients were referred to ophthalmology; one of these for DR. Conclusion: Patients with diabetes aged 90 and over are at low risk of sight threatening DR and annual screening in this age group may be unnecessary. However, annual screening does provide opportunistic identification.

An initial evaluation of gellan gum as a material for tissue engineering applications

Alpha-modified minimum essential medium (αMEM) has been found to cross-link a 1% gellan gum solution, resulting in the formation of a self-supporting hydrogel in 1:1 and 5:1 ratios of polysaccharide: αMEM. Rheological data from temperature sweeps confirm that in addition to orders of magnitude differences in G' between 1% gellan and 1% gellan with αMEM, there is also a 20°C increase in the temperature at which the onset of gelation takes place when αMEM is present. Frequency sweeps confirm the formation of a true gel; mechanical spectra for mixtures of gellan and αMEM clearly demonstrate G' to be independent of frequency. It is possible to immobilize cells within a three-dimensional (3D) gellan matrix that remain viable for up to 21 days in culture by adding a suspension of rat bone marrow cells (rBMC) in αMEM to 1% gellan solution. This extremely simple approach to cell immobilization within 3D constructs, made possible by the fact that gellan solutions cross-link in the presence of millimolar concentrations of cations, poses a very low risk to a cell population immobilized within a gellan matrix and thus indicates the potential of gellan for use as a tissue engineering scaffold. © 2007 Sage Publications.

SGLT inhibitors in management of diabetes

The two main sodium-glucose cotransporters (SGLTs), SGLT1 and SGLT2, provide new therapeutic targets to reduce hyperglycaemia in patients with diabetes. SGLT1 enables the small intestine to absorb glucose and contributes to the reabsorption of glucose filtered by the kidney. SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors with varying specificities for these transporters (eg, dapagliflozin, canagliflozin, and empagliflozin) can slow the rate of intestinal glucose absorption and increase the renal elimination of glucose into the urine. Results of randomised clinical trials have shown the blood glucose-lowering efficacy of SGLT inhibitors in type 2 diabetes when administered as monotherapy or in addition to other glucose-lowering therapies including insulin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Effective SGLT2 inhibition needs adequate glomerular filtration and might increase risk of urinary tract and genital infection, and excessive inhibition of SGLT1 can cause gastro-intestinal symptoms. However, the insulin-independent mechanism of action of SGLT inhibitors seems to offer durable glucose-lowering efficacy with low risk of clinically significant hypoglycaemia at any stage in the natural history of type 2 diabetes. SGLT inhibition might also be considered in conjunction with insulin therapy in type 1 diabetes. © 2013 Elsevier Ltd.

New drugs for type 2 diabetes mellitus:what is their place in therapy?

Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulforylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women. Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagonlike peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on P cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety. In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.

An artificial neural network stratifies the risks of reintervention and mortality after endovascular aneurysm repair:a retrospective observational study

Background Lifelong surveillance after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is considered mandatory to detect potentially life-threatening endograft complications. A minority of patients require reintervention but cannot be predictively identified by existing methods. This study aimed to improve the prediction of endograft complications and mortality, through the application of machine-learning techniques. Methods Patients undergoing EVAR at 2 centres were studied from 2004-2010. Pre-operative aneurysm morphology was quantified and endograft complications were recorded up to 5 years following surgery. An artificial neural networks (ANN) approach was used to predict whether patients would be at low- or high-risk of endograft complications (aortic/limb) or mortality. Centre 1 data were used for training and centre 2 data for validation. ANN performance was assessed by Kaplan-Meier analysis to compare the incidence of aortic complications, limb complications, and mortality; in patients predicted to be low-risk, versus those predicted to be high-risk. Results 761 patients aged 75 +/- 7 years underwent EVAR. Mean follow-up was 36+/- 20 months. An ANN was created from morphological features including angulation/length/areas/diameters/ volume/tortuosity of the aneurysm neck/sac/iliac segments. ANN models predicted endograft complications and mortality with excellent discrimination between a low-risk and high-risk group. In external validation, the 5-year rates of freedom from aortic complications, limb complications and mortality were 95.9% vs 67.9%; 99.3% vs 92.0%; and 87.9% vs 79.3% respectively (p0.001) Conclusion This study presents ANN models that stratify the 5-year risk of endograft complications or mortality using routinely available pre-operative data.

Is it safe to increase diabetic retinopathy screening intervals in patients with no background diabetic retinopathy?

Introduction. A 4 year retrospective follow up of 996 patients who pre-sented with no DR and 500 with background DR at baseline digital DR screening in 2006. Purpose. To evaluate the safety of increasing screening intervals in patients with no diabetic retinopathy (DR) or with background DR.Methods. A 4 year retrospective follow up of 996 patients who presented with no DR and 500 with background DR at baseline digital DR screening in 2006.results. Background DR Group: Of the 500 subjects that had back-ground DR in 2006, 231 were referred for DR, with an average DR routine referral rate of 12% (46 subjects) per year. nodrgrouP. Of the 996 patients who had no DR at baseline, 51 were referred over the 4 years for sight threatening DR (STDR), of these 45 patients have definite STDR confirmed by ophthalmological examination. 78% of these had type 2 diabetes and mean age at referral was 60 years (25-87). Mean diabetes duration was 10.7 years (3-32), with a mean HbA1c of 7.8% (5.7-11.3%). Eight patients (0.9%) were referred in the first year, 9 (0.9%) in the second year, 19 (1.9%) in the third year and 15 (1.5%) in the fourth year. 86% of referrals were for maculopathy, and all had observable retinopathy and none required ophthalmology clinic assessment or laser treatment.If biannual screening was adopted for patients with no DR at baseline, allowing for patients who subsequently develop background DR and would then revert to annual screening, a total of 7 (0.7%) patients would not have been appropriately referred for STDR and would have waited a further year for identification. None of the 51 referrals across the 4 years required laser treatment apart from just one patient who developed PDR in year 4 (2010) and had background since 2007.conclusIons. It could be recommended that it is safe to screen pa-tients with no DR biannually due to the low risk of developing STDR. However, patients who present with background DR should continue to be screened annually as there is a significant proportion developing STDR and would not be identified at an appropriate screening interval.

Take up of property-level flood protection:an exploratory study in Worcester

Significant numbers of homes within the UK are at risk of flooding. Although community level flood protection schemes are the first line of defence for mitigating flood risk, not all properties are protectable. Property-Level Flood Protection (PLFP) provides those unprotected homeowners with an approach for protecting their homes from flooding. This study sought to establish why property-level flood protection is needed and secondly assess the extent of take up using Worcester as the study area. An exploratory questionnaire survey was conducted to achieve these objectives. After consultation of available literature it was established that the introduction of PLFP protection provided numerous benefits including limiting the health & psychological effects flooding poses, the direct financial benefits and also the possible influence on gaining flood insurance. Despite the benefits and the recognition given to PLFP by the government it was found that the overall take up of the measures was low, findings which were further backed up by data collected in the study area of Worcester with only 23% of the sample having introduced PLFP measures. Reasoning for the low take up numbers typically included; unawareness of the measures, low risk of flood event, installation costs and inability to introduce due to tenancy. Age was noted as a significant impacting factor in the study area with none of the respondents under 25 suggesting they had “a good amount of knowledge of PLFP measures” even when they claimed their properties to be at risk of flooding. Guidance and support is especially recommended to those who are unable to manage their own flood risk for e.g. social housing/rental tenants.

Vaccines

Vaccines continue to offer the key line of protection against a range of infectious diseases; however, the range of vaccines currently available is limited. One key consideration in the development of a vaccine is risk-versus-benefit, and in an environment of perceived low risk, the benefit of vaccination may not be recognised. To address this, there has been a move towards the use of subunit-based vaccines, which offer low side-effect profiles but are generally weakly immunogenic. This can be compensated for by the development of effective adjuvants. Nanotechnology offers key attributes in this field through the ability of nanoparticulates to incorporate and protect antigens from rapid degradation, combined with their potential to effectively deliver the antigens to appropriate cells within the immune system. These characteristics can be exploited in the development of new adjuvants. This chapter will outline the applications of nanosystems in vaccine formulations and consider the mechanisms of action behind a range of formulations.