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Biomedical subjects

A S Hall

Publications and source records attributed to A S Hall.

At least 19 recordsLinked to original sources

Perindopril.

Perindopril is a third-generation ACE inhibitor that is characterised as a small, lipophilic molecule with a therapeutically active carboxyl side group. These and other features combine to make this a unique member of a very well-established class of drugs that have proven efficacy in a wide range of cardiovascular diseases. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) demonstrated benefit in the secondary prevention of patients with stroke, whereas the Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) trial supports extended routine use after myocardial infarction. The most recent evidence from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) show that perindopril is able to improve the prognosis of patients with a relatively low global cardiovascular risk, denoted either by the presence of stable coronary artery disease or of essential hypertension in conjunction with at least three other risk factors. The fact that major relative risk reductions have been reported for these two studies is matched by the significance of the findings to modern clinical practice. Both studies were conducted in the context of advance concomitant care that is typically better in clinical trials than in routine practice. In particular, the benefits observed were seen to be of a similar magnitude, and also independent of those resulting from statin therapy. Of particular interest is the likely complimentary action of these treatment strategies with regard to the stabilisation of atheromatous plaques. Perindopril is a well-established drug, the full value of which is only now becoming fully apparent.

Angiotensin-Converting Enzyme Inhibitors↗

External validation, extension and recalibration of Braunwald's simple risk index in a community-based cohort of patients with both STEMI and NSTEMI.

BACKGROUND: Using the simple risk index (SRI) that is based on age, heart rate and systolic blood pressure, we sought to evaluate the ability to predict outcome in AMI patients in a community-based population. METHODS AND RESULTS: We identified and evaluated 3684 consecutive patients with an admission diagnosis of possible AMI, who attended between 1st September and 30th November 1995. Two thousand one hundred fifty three patients had confirmed evidence of WHO definition AMI, of whom 1656 survived to hospital discharge. We evaluated the ability of the SRI to predict mortality over 30 days using the score generated by the equation (heart ratex[age/10]2)/systolic blood pressure. The SRI was a strong (c-statistic = 0.77 CI 0.74-0.79) predictor of 30-day mortality in both STEMI and all consecutive cases of WHO definition AMI. However, the model showed poor calibration when used on a community-based population with 30-day mortality being underestimated across all risk quintiles. Consequently we sought to recalibrate the quantitative aspects of the model for the total AMI population in the following way (Risk Index; 30-day mortality) (< or = 29.2; 9.2%), (29.3-37.8; 23.9%), (37.9-47.3; 34.6%), (47.4-61.5; 40.3%), (> or = 61.6; 65.5%). CONCLUSION: We have externally validated the SRI in an unselected cohort of consecutive WHO definition AMI patients. However, the original model consistently underestimated the likelihood of death at 30 days regardless of the calculated risk score. We have therefore suggested corrections to the risk estimates, to allow its application in an unselected community cohort.

Age Factors↗

The British Cardiac Society Working Group definition of myocardial infarction: implications for practice.

OBJECTIVE: To assess the impact on observed mortality of the British Cardiac Society (BCS) definition of myocardial infarction (MI) in 11 UK hospitals. DESIGN: Prospective observational registry. SETTING: 11 adjacent hospitals in the West Yorkshire region. PATIENTS: 2484 patients with the acute coronary syndrome (ACS) were identified during a six month period (28 April to 28 October 2003). Demographic, clinical, and treatment variables were collected on all patients. Deaths were monitored through the Office of National Statistics. Patients were categorised into three groups according to the BCS definition of MI: ACS with unstable angina (UA), ACS with myocyte necrosis, and ACS with clinical MI. RESULTS: 30 day mortality was 4.5%, 10.4%, and 12.9% (p < 0.001) in the ACS with UA, ACS with myocyte necrosis, and ACS with clinical MI groups, respectively. At six months the mortality for patients in the groups ACS with clinical MI and ACS with myocyte necrosis was similar (19.2% v 18.7%), being higher than for ACS with UA (8.6%). Same admission percutaneous coronary intervention was similar in groups with clinical MI and myocyte necrosis (11.1% v 10.7%, respectively) as was coronary artery bypass grafting (2.6% v 2.7%, respectively). However, these two groups differed significantly in the prescribing of secondary prevention (aspirin, 79% v 69%; statins, 80% v 68%; beta blockers, 66% v 53%; and angiotensin converting enzyme inhibitors, 65% v 53%; p < 0.001). CONCLUSIONS: At 30 days the new BCS categories for MI predict three distinct outcomes. However, within a contemporary UK population this was no longer apparent at six months, as mortality for patients with ACS with myocyte necrosis had risen to the same level as those for patients with ACS with clinical MI. One possible explanation for this is the apparent under use of drugs known to improve prognosis after traditionally defined MI.

Aged↗

An evaluation of the relationship between specialist training in cardiology and implementation of evidence-based care of patients following acute myocardial infarction.

AIMS: Large clinical trials have provided evidence of prognostically beneficial treatment strategies for patients with acute myocardial infarction. However, the implementation of this evidence into routine clinical practice is suboptimal. We hypothesised that the speciality of the attending physician (cardiologist or not) would affect the use of evidence-based strategies. METHODS: Over a 3-month period (1st September to 30th November 1995), 3684 consecutive potential cases of acute myocardial infarction (AMI) in 20 adjacent hospitals in the Yorkshire Region were identified from coronary care registers, clinical coding and biochemistry records of cardiac enzyme assay requests. There were 2153 consecutive cases of AMI identified, of which 1643 patients were alive at discharge. We compared the admission use of aspirin and thrombolysis, and the use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and statins at discharge between cardiologists and other physicians. RESULTS: AMI patients under the care of cardiologists are more likely to receive aspirin and thrombolysis on the day of their event and to be prescribed aspirin, beta-blockers and statins on discharge. After correction for contraindications to their use, the above findings were broadly confirmed. DISCUSSION: Cardiologists are more likely than general physicians to use evidence-based treatment strategies recognised to improve AMI patient outcome. It is likely that this will translate into a reduction of mortality or other hard endpoints in patient outcomes.

Adrenergic beta-Antagonists↗

The effects of corticosteroids on behavior in children with nephrotic syndrome.

The objective of this study was to measure the frequency and severity of the behavioral effects of high-dose oral steroid therapy in children with nephrotic syndrome. We conducted a prospective assessment of the behavior of 12 children using a standardized psychological questionnaire at the time of diagnosis and again after 4 weeks of steroid therapy. A group of control children was also assessed. There was a significant increase in the total behavior score ( P=0.03) and specifically in aggressive and poor attention behavior items in the group of nephrotic children compared with the control group. Four of the children with nephrotic syndrome developed abnormal behavior in the clinical range compared with none of the controls. In conclusion, children with nephrotic syndrome treated with high-dose oral steroids are at risk of developing clinically relevant behavioral changes.

Adrenal Cortex Hormones↗

Identifying acute myocardial infarction: effects on treatment and mortality, and implications for National Service Framework audit.

BACKGROUND: The National Service Framework (NSF) for Coronary Heart Disease requires annual clinical audit of the care of patients with myocardial infarction, with little guidance on how to achieve these standards and monitor practice. AIM: To assess which method of identification of acute myocardial infarction (AMI) cases is most suitable for NSF audit, and to determine the effect of the definition of AMI on the assessment of quality of care. DESIGN: Observational study. METHODS: Over a 3-month period, 2153 consecutive patients from 20 hospitals across the Yorkshire region, with confirmed AMI, were identified from coronary care registers, biochemistry records and hospital coding systems. The sensitivity and positive predictive value of AMI patient identification using clinical coding, biochemistry and coronary care registers were compared to a 'gold standard' (the combination of all three methods). RESULTS: Of 3685 possible cases of AMI singled out by one or more methods, 2153 patients were identified as having a final diagnosis of AMI. Hospital coding revealed 1668 (77.5%) cases, with a demographic profile similar to that of the total cohort. Secondary preventative measures required for inclusion in NSF were also of broadly similar distribution. The sensitivities and positive predictive values for patient identification were substantially less in the cohorts identified through biochemistry and coronary care unit register. Patients fulfilling WHO criteria (n=1391) had a 30-day mortality of 15.9%, vs. 24.2% for the total cohort. DISCUSSION: Hospital coding misses a substantial proportion (22.5%) of AMI cases, but without any apparent systematic bias, and thus provides a suitably representative and robust basis for NSF-related audit. Better still would be the routine use of multiple methods of case identification.

Aged↗

An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals at risk of coronary events. A WOSCOPS substudy.

AIMS: The Glycine389 variant of the beta-1 adrenergic receptor generates markedly less cAMP when stimulated in vitro than the more prevalent Arginine389 variant and may confer protection against coronary events similar to that observed with beta-blockers. The aim of this study was to ascertain whether this Glycine389 variant protects against coronary events. METHODS AND RESULTS: We identified the genotype at position 389 of the beta1AR in 1554 individuals taken from men enrolled in the West of Scotland Coronary Prevention Study. Men with a coronary event (event group) were each matched for age and smoking status with two control subjects from the same cohort who had not had a coronary event (control group). We compared the distribution of genotypes in the event and control groups. Conditional logistic regression was used to calculate odds ratios for each of the genotypes. The prevalence of the three genotypes in the entire cohort was ArgArg 53.5%, ArgGly 39.6%, GlyGly 6.9%. The Arg389Gly beta-1 adrenergic receptor polymorphism was not associated with coronary events. Using the ArgArg genotype as the reference, the odds ratio for the ArgGly genotype was 1.1 (95% CI, 0.88-1.38) and for the GlyGly genotype it was 1.05 (95% CI, 0.68-1.62). CONCLUSION: Our longitudinal case-control study demonstrates that the Glycine389 variant of the beta-1 adrenergic receptor does not protect against coronary events.

Adult↗

Use of cumulative mortality data in patients with acute myocardial infarction for early detection of variation in clinical practice: observational study.

OBJECTIVES: Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. DESIGN: Observational study. SETTING: 20 hospitals across the former Yorkshire region. PARTICIPANTS: All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. MAIN OUTCOME MEASURES: Variable life-adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. RESULTS: The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life-adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of -4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. CONCLUSIONS: Variable life-adjusted display has been integrated into surgical care as a graphical display of risk-adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction.

Age Factors↗

Long-term effects of 60-Hz electric vs. magnetic fields on IL-1 and IL-2 activity in sheep.

This study was designed to assess the effect of exposure to long-term extremely low-frequency electric and magnetic fields (ELF-EMF) from a 500 kV transmission line on IL-1 and IL-2 activity in sheep. The primary hypothesis was that the reduction in IL-1 activity observed in our two previous short-term studies (10 months) was due to EMF exposure from this transmission line. To repeat and expand these studies and to characterize the components of EMF responsible for the previously observed reduction in IL-1 activity, the current experiment examined not only the effect of exposure to electric and magnetic fields, but also the magnetic field component alone. In the current study, IL-2 was examined to characterize the effects of EMF exposure on an indicator of T cell responses. 45 Suffolk ewe lambs were randomized into three groups of 15 animals each. One group of animals was placed in the EMF pen, located directly beneath the transmission line. A second group was placed in the shielded MF (magnetic field only) pen, also directly beneath the transmission line. The third group of animals was placed in the control pen located several hundred meters away from the transmission line. During the 27 month exposure period, blood samples were taken from all animals monthly. When the data were analyzed collectively over time, no significant differences between the groups were found for IL-1 or IL-2 activity. In previous studies ewe lambs of 8-10 weeks of age were used as the study animals and significant differences in IL-1 activity were observed after exposure of these animals to EMF at mean magnetic fields of 3.5-3.8 microT (35-38 mG) and mean electric fields of 5.2-5.8 kV/m. At the start of the current study EMF levels were reduced as compared to previous studies. One interpretation of the current data is that magnetic field strength and age of the animals may be important variables in determining whether EMF exposure will affect IL-1 activity.

Analysis of Variance↗

Left ventricular volume reduction without ventriculectomy.

Partial left ventriculectomy (the Batista procedure) to achieve left ventricular volume reduction (LVVR) has been advocated as an alternative to cardiac transplantation in patients with end-stage dilated left ventricles. Here, we describe a new technique of LVVR that uses realignment of the papillary muscles, thus avoiding ventriculectomy, and report preliminary results. Eight patients (all male, mean age 49.3 [range 38 to 70] years) underwent LVVR between October 1998 and March 2000 as an adjunct to surgical coronary revascularization. Five were assessed with echocardiography and cardiopulmonary exercise testing before and after (mean follow-up time 267 [range 94 to 416] days) the operation. LVVR significantly improved left ventricular end-diastolic volume (254 +/- 32 to 218 +/- 36 mL, p = 0.03), left ventricular ejection fraction (20.14% +/- 1.36% to 31.28% +/- 2.32%, p = 0.007), and exercise duration (from 394 +/- 88 to 611 +/- 79 seconds, p = 0.03). A nonsignificant improvement in maximal oxygen consumption was also observed. This technique of LVVR is relatively simple to perform and is accomplished through a small apical cardiotomy. Preliminary results show an encouraging functional improvement following surgery. Future controlled studies are required to assess this novel technique further.

Adult↗

A simple benchmark for evaluating quality of care of patients following acute myocardial infarction.

OBJECTIVE: To develop a simple risk model as a basis for evaluating care of patients admitted with acute myocardial infarction. METHODS: From coronary care registers, biochemistry records and hospital management systems, 2153 consecutive patients with confirmed acute myocardial infarction were identified. With 30 day all cause mortality as the end point, a multivariable logistic regression model of risk was constructed and validated in independent patient cohorts. The areas under receiver operating characteristic curves were calculated as an assessment of sensitivity and specificity. The model was reapplied to a number of commonly studied subgroups for further assessment of robustness. RESULTS: A three variable model was developed based on age, heart rate, and systolic blood pressure on admission. This produced an individual probability of death by 30 days (P(30)) where P(30) = 1/(1 + exp(-L(30))) and L(30) = -5.624 + (0.085 x age) + (0.014 x heart rate) - (0.022 x systolic blood pressure). The areas under the receiver operating characteristic curves for the reference and test cohorts were 0.79 (95% CI 0.76 to 0.82) and 0.76 (95% CI 0.72 to 0.79), respectively. To aid application of the model to routine clinical audit, a normogram relating observed mortality and sample size to the likelihood of a significant deviation from the expected 30 day mortality rate was constructed. CONCLUSIONS: This risk model is simple, reproducible, and permits quality of care of acute myocardial infarction patients to be reliably evaluated both within and between centres.

Adult↗

Poor prognosis of patients presenting with symptomatic myocardial infarction but without chest pain.

OBJECTIVE: To describe the clinical features, prognosis, and treatment of patients presenting with atypical forms of acute myocardial infarction. DESIGN: Consecutive cases of possible acute myocardial infarction were sought from coronary care registers, biochemistry records, and hospital management systems. Case notes were reviewed and predefined epidemiological and clinical variables were abstracted. SETTING: 20 adjacent hospitals in the former Yorkshire region. PATIENTS: 3684 consecutive cases of possible acute myocardial infarction admitted in a three month period were identified, of whom 2096 had a first episode of confirmed acute myocardial infarction. RESULTS: 20.2% of all patients admitted with an eventual diagnosis of acute myocardial infarction presented with symptoms other than chest pain. Compared with the group presenting with chest pain, these patients were older (76.6 v 69.1 years, p < 0.001), were more often women (54.6% v 35.3%, p < 0.001), and were more likely to have a history of heart failure (18.6% v 6.9%, p < 0.001). They had a higher 30 and 365 day mortality (49.2% and 61.0%, respectively) compared with patients presenting with chest pain (17.9% and 26.2%). In a Cox regression analysis the hazard ratio for presentation without chest pain was 1.60 (95% confidence interval 1.30 to 1.97) (p < 0.001) adjusted for age, heart rate, blood pressure, left ventricular impairment, and infarction with ST segment elevation as covariates. Importantly, they were also less likely to receive treatments with a proven ability to improve prognosis. CONCLUSIONS: Atypical presentation of myocardial infarction without chest pain is common and associated with increased mortality. This may result in part from a failure to use beneficial treatment strategies.

Age Distribution↗

Ramipril reduces QT dispersion in patients with acute myocardial infarction and heart failure.

In a cohort of 67 patients from the Acute Infarction Ramipril Efficacy study, we showed that ramipril therapy was associated with a significant reduction in QT dispersion over a 2-month period after acute myocardial infarction. This reduction of ventricular repolarization inhomogeneity indicates an antiarrhythmic effect and may be an important additional mechanism for the reduced all-cause mortality and sudden death incidence achieved with angiotensin-converting enzyme inhibition after acute myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

Pre-polarized saline: an in vivo feasibility study of a potential contrast agent.

The potential for using pre-polarized liquids as contrast agents in vivo is investigated and the feasibility of the method demonstrated. In this study we show the enhancement obtained following intravenous delivery of pre-polarized saline into the antecubital vein of a volunteer. This form of contrast agent provides signal gain on time scales commensurate with its T(1) and allows repeated doses to be administered, thus making alternate acquisitions of data with and without enhancement practicable.

Adult↗