Ethics in research: practice and respect.

Nursing practice is informed by research, and all nurses, midwives and care staff should be research aware even if they do not consider themselves research active. The principles of research ethics, based on respect for individuals, should not be confined to research. All nurses must be aware of these principles, and practise in accordance with them.

Are routinely collected NHS administrative records suitable for endpoint identification in clinical trials? Evidence from the West of Scotland Coronary Prevention Study.

Background: Routinely collected electronic patient records are already widely used in epidemiological research. In this work we investigated the potential for using them to identify endpoints in clinical trials.

Methods: The events recorded in the West of Scotland Coronary Prevention Study (WOSCOPS), a large clinical trial of pravastatin in middle-aged hypercholesterolaemic men in the 1990s, were compared with those in the record-linked deaths and hospitalisations records routinely collected in Scotland.

Implementing a centralised pharmacovigilance service in a non-commercial setting in the United Kingdom.

The implementation of a pharmacovigilance service compliant with the legal and regulatory responsibilities of clinical trial sponsors presents particular challenges for sponsors in a non-commercial setting.In this paper we examine these challenges in detail. We identify and discuss the key steps in the development of a pharmacovigilance service within a public health service and university setting in the United Kingdom.

Exposing unethical human research: the transatlantic correspondence of Beecher and Pappworth.

Henry K. Beecher and Maurice H. Pappworth were the 2 most prominent medical whistleblowers in research ethics of the 20th century.

Low-density lipoprotein cholesterol and high-sensitivity C-reactive protein lowering with atorvastatin in patients of South Asian compared with European origin: insights from the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study.

The aim of this study was to determine the effects of atorvastatin in patients of South Asian versus European origin who participated in the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study. ACTFAST was a 12-week prospective, open-label study in patients at high risk for atherosclerosis (European origin, n = 1978; South Asian origin, n = 64). Compared with patients of European origin, patients of South Asian origin were younger, were less likely to smoke, and had lower body mass index, systolic blood pressure, low-density lipoprotein cholesterol (LDL-C) and triglycerides.

Clinical Trials: Minimising source data queries to streamline endpoint adjudication in a large multi-national trial.

Background: The UK Clinical Trial Regulations and Good Clinical Practice guidelines specify that the study sponsor must ensure clinical trial data are accurately reported, recorded and verified to ensure patient safety and scientific integrity. The methods that are utilised to assess data quality and the results of any reviews undertaken are rarely reported in the literature. We have recently undertaken a quality review of trial data submitted to a Clinical Endpoint Committee for adjudication.

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.

Lipoprotein-associated phospholipase A(2), inflammatory biomarkers, and risk of cardiovascular disease in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

Objective: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an inflammatory biomarker that circulates mainly bound to LDL. We evaluated the association of Lp-PLA(2) with vascular events in the elderly where the importance of LDL is diminished as a risk factor for coronary disease.

Methods: Mass and activity of Lp-PLA(2) were related to risk over 3.

Accuracy of patient recall of preoperative symptom severity (angina and breathlessness) at one year following aorta-coronary artery bypass grafting.

Aim And Objective: The accuracy with which patients recall their cardiac symptoms prior to aorta-coronary artery bypass grafting is assessed approximately one year after surgery together with patient-related factors potentially influencing accuracy of recall.

Background: This is a novel investigation of patient's rating of preoperative symptom severity before and approximately one year following aorta-coronary artery bypass grafting.

Design: Patients undergoing aorta-coronary artery bypass grafting (n = 208) were recruited preoperatively and 177 of these were successfully followed up at 16.

Atorvastatin decreases elevated soluble CD40L in subjects at high cardiovascular risk. Atorvastatin on inflammatory markers study: a substudy of ACTFAST.

The CD40/CD40 ligand plays a role in the inflammatory and prothrombotic processes in atherosclerosis. We analyzed whether short-term treatment with atorvastatin affects soluble CD40 ligand (sCD40L) plasma levels in subjects at high cardiovascular risk. sCD40L plasma concentrations were measured in 852 subjects from the Atorvastatin on Inflammatory Markers (AIM) Study, a 12-week prospective multicenter, open-label trial which enrolled statin-free subjects with coronary heart disease (CHD), CHD-equivalent (diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%.

How to reach LDL targets quickly in patients with diabetes or metabolic syndrome.

Purpose: To investigate whether using an algorithm to select the starting dose of a statin according to baseline and target LDL-cholesterol (LDL-C) values would facilitate achieving lipid targets in patients with diabetes or the metabolic syndrome.

Methods: Two 12-week, prospective, open-label trials enrolled 2717 high-risk subjects, of whom 1024 had diabetes and 1251 had metabolic syndrome. Subjects with LDL-C between 100 and 220 mg/dL (2.

Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk.

Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%.

Association between apolipoprotein E4 and cognitive decline in elderly adults.

Objective: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women.

Design: Prospective study.

Setting: Scotland, Ireland, and the Netherlands.

Elevated ICAM-1 and MCP-1 plasma levels in subjects at high cardiovascular risk are diminished by atorvastatin treatment. Atorvastatin on Inflammatory Markers study: a substudy of Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration.

Background: Plasma levels of soluble intercellular adhesion molecule 1 (sICAM-1) and monocyte chemoattractant protein 1 (sMCP-1) are associated with increased risk for future coronary events. However, the effect of statins on these inflammatory markers has hardly been studied. We analyzed whether treatment with the different doses of atorvastatin affects sICAM-1 and sMCP-1 plasma levels in subjects at high cardiovascular risk.

Serial metabolic measurements and conversion to type 2 diabetes in the west of Scotland coronary prevention study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor.

To examine metabolic changes (lipids, liver enzymes, blood pressure, and weight) potentially associated with conversion to diabetes, we analyzed serial glucose and other metabolic measures obtained every 6 months within the West of Scotland Coronary Prevention Study trial. Changes in parameters for 86 men who converted to new-onset diabetes ("converters": two consecutive glucose levels > or =7 mmol/l) were compared with 860 "nonconverters" matched for age and treatment allocation. Eighteen months before the diagnosis, converters to diabetes had elevated (P < 0.

C-reactive protein and prediction of coronary heart disease and global vascular events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

Background: The role of C-reactive protein (CRP) in predicting vascular events and response to statin therapy remains uncertain. Additional large prospective studies are required.

Methods And Results: Baseline CRP was related to risk over 3.

Increased soluble Fas plasma levels in subjects at high cardiovascular risk: Atorvastatin on Inflammatory Markers (AIM) study, a substudy of ACTFAST.

Objective: Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment.

Methods And Results: ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk > 20%.