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Biomedical subjects

A M Skene

Publications and source records attributed to A M Skene.

At least 19 recordsLinked to original sources
PubMed2000

Graft material and results of platelet inhibitor trials in peripheral arterial reconstructions: reappraisal of results from a meta-analysis.

AIMS: To investigate the characteristics of published trials in order to establish the origin of the differing results obtained in trials of platelet inhibitors after peripheral bypass procedures. METHODS: Analysis of the information from 11 randomised, controlled trials of platelet inhibitors after peripheral bypass procedures published up until 1999 and involving 2302 patients undergoing peripheral bypass operations, 1250 of whom were treated with platelet inhibitors. RESULTS: There is a significant treatment benefit of platelet inhibitors on meta-analysis of the trials, but a significant heterogeneity amongst the individual trial results. The proportion of patients in a trial with prosthetic grafts was a significant factor in explaining the heterogeneity. Proportion of prosthetic grafts was associated with sample size and with the proportion of grafts above the knee, but these were not found to make an independent contribution to the heterogeneity observed. The platelet inhibitor regimen used, the severity of ischaemic symptoms and the proportion of smokers included were also not found to be important. CONCLUSIONS: The improvement of graft patency by aspirin and related platelet inhibitors in clinical trials in peripheral bypass procedures can be attributed to an effect on patients with prosthetic grafts. There is little evidence that these agents prevent occlusion of vein grafts. The conclusion of an earlier meta-analysis that antiplatelet agents should be used for all bypasses is not supported.

Arteries↗
PubMed2000

Comparison of the SF-36 health survey questionnaire with the Nottingham Health Profile in long-term survivors of a myocardial infarction.

BACKGROUND: Health-related quality of life, an important outcome measure in health interventions, can readily be assessed by questionnaire. Two widely evaluated examples are the Short Form 36 (SF-36) and Nottingham Health Profile (NHP) questionnaires, but as yet the discriminatory power of these tools has not been compared in a large population of patients with coronary heart disease. METHODS: All 4-year survivors of a myocardial infarction, identified from the Nottingham heart attack register, were sent the SF-36, NHP and additionally the Rose angina and dyspnoea questionnaires. Mean scores on the SF-36 and NHP were compared with age- and sex-adjusted norms in patients under and over 65 years. Sensitivity of the respective tools was assessed in distinguishing patients with differing degrees of cardiovascular symptomatology. RESULTS: In patients under 65 years the SF-36 and NHP differed to the same extent from normative data--scores were lower in the comparable domains physical functioning/mobility, bodily pain/pain and energy/vitality, but not in mental health/emotional reaction scores. In social functioning/social isolation results were disparate--SF-36 scores were lower and the NHP similar to normative data. In patients over 65 years mean scores in all five domains were not significantly different from normative data for either tool. The SF-36 was more sensitive than the NHP at detecting the impact of breathlessness, particularly in patients with mild symptoms. Similarly, the SF-36, but not the NHP, could distinguish the effect of differing degrees of angina severity and frequency on social functioning. CONCLUSION: At least in myocardial infarction survivors, the SF-36 appears a more sensitive tool and may have benefits for assessing health-related quality of life in this patient group.

Activities of Daily Living↗
PubMed1999

Quality of life four years after acute myocardial infarction: short form 36 scores compared with a normal population.

OBJECTIVES: To assess the impact of myocardial infarction on quality of life in four year survivors compared to data from "community norms", and to determine factors associated with a poor quality of life. DESIGN: Cohort study based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban/rural population. SUBJECTS: All patients admitted with acute myocardial infarction during 1992 and alive at a median of four years. MAIN OUTCOME MEASURES: Short form 36 (SF 36) domain and overall scores. RESULTS: Of 900 patients with an acute myocardial infarction in 1992, there were 476 patients alive and capable of responding to a questionnaire in 1997. The response rate was 424 (89. 1%). Compared to age and sex adjusted normative data, patients aged under 65 years exhibited impairment in all eight domains, the largest differences being in physical functioning (mean difference 20 points), role physical (mean difference 23 points), and general health (mean difference 19 points). In patients over 65 years mean domain scores were similar to community norms. Multiple regression analysis revealed that impaired quality of life was closely associated with inability to return to work through ill health, a need for coronary revascularisation, the use of anxiolytics, hypnotics or inhalers, the need for two or more angina drugs, a frequency of chest pain one or more times per week, and a Rose dyspnoea score of >/= 2. CONCLUSIONS: The SF 36 provides valuable additional information for the practising clinician. Compared to community norms the greatest impact on quality of life is seen in patients of working age. Impaired quality of life was reported by patients unfit for work, those with angina and dyspnoea, patients with coexistent lung disease, and those with anxiety and sleep disturbances. Improving quality of life after myocardial infarction remains a challenge for physicians.

Aged↗
PubMed1999

Relevance of clinical trial results in myocardial infarction to medical practice: comparison of four year outcome in participants of a thrombolytic trial, patients receiving routine thrombolysis, and those deemed ineligible for thrombolysis.

OBJECTIVE: To assess the medium to long term outcome of patients ineligible for thrombolysis compared to those enrolled in a clinical trial of thrombolysis and patients receiving non-trial thrombolysis. DESIGN: Cohort study based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban/rural population. SUBJECTS: All patients admitted with a confirmed acute myocardial infarction during 1992 categorised as either participants of a thrombolytic trial (group A, n = 140), receiving non-trial thrombolysis (group B, n = 329), or deemed ineligible for lytic treatment (group C, n = 431). MAIN OUTCOME MEASURES: Background characteristics, inhospital treatment, patterns of follow up, referrals to cardiologists, revascularisation rates, and short and long term survival. RESULTS: Clinical trial recruits were younger by almost 10 years, were less likely to have a previous history of myocardial infarction, and more likely to be in Killip class 1 on admission than those ineligible for thrombolysis. Cardiology follow up was mandatory for all surviving trial participants but 22% of patients in group B and 31% of patients in group C received no follow up, and during four years less than 50% ever saw a cardiologist. Revascularisation was performed in 17.2% of patients in group A, 13.6% of patients in group B, and 7.5% of patients in group C. Cumulative mortality at a median of four years was 24.3% in group A, 36.8% in B, and 59.6% in group C. Adjusting for age, sex, previous myocardial infarction, type of infarction, and Killip class in a logistic regression model the odds ratios (OR) of death at four years for groups B and C were 1.60 (95% confidence intervals (CI) 0.97 to 2.63, p = 0.065) and 2.64 (95% CI 1.61 to 4. 32, p < 0.001), respectively, when compared to group A (OR 1). CONCLUSIONS: Patients enrolled into thrombolytic trials are at low risk. Patients deemed ineligible for thrombolysis are high risk, receive less surveillance, are less likely to be revascularised or receive trial proven treatments, have a poor long term outcome not entirely explained by increased age or severity of infarction, and deserve further evaluation.

Aftercare↗
PubMed1997

Inpatient deaths from acute myocardial infarction, 1982-92: analysis of data in the Nottingham heart attack register.

OBJECTIVE: To assess longitudinal trends in admissions, management, and inpatient mortality from acute myocardial infarction over 10 years. DESIGN: Retrospective analysis based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban and rural population. SUBJECTS: All patients admitted with a confirmed acute myocardial infarction during 1982-4 and 1989-92 (excluding 1991, when data were not collected). MAIN OUTCOME MEASURES: Numbers of patients, background characteristics, time from onset of symptoms to admission, ward of admission, treatment, and inpatient mortality. RESULTS: Admissions with acute myocardial infarction increased from 719 cases in 1982 to 960 in 1992. The mean age increased from 62.1 years to 66.6 years (P < 0.001), the duration of stay fell from 8.7 days to 7.2 days (P < 0.001), and the proportion of patients aged 75 years and over admitted to a coronary care unit increased significantly from 29.1% to 61.2%. A higher proportion of patients were admitted to hospital within 6 hours of onset of their symptoms in 1989-92 than in 1982-4, but 15% were still admitted after the time window for thrombolysis. Use of beta blockers increased threefold between 1982 and 1992, aspirin was used in over 70% of patients after 1989, and thrombolytic use increased 1.3-fold between 1989 and 1992. Age and sex adjusted odds ratios for inpatient mortality remained unchanged over the study period. CONCLUSIONS: Despite an increasing uptake of the "proved" treatments, inpatient mortality from myocardial infarction did not change between 1982 and 1992.

Age Factors↗
PubMed1997

Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators.

BACKGROUND: Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study. METHODS: Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done. FINDINGS: After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients. INTERPRETATION: Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.

Adult↗
PubMed1996

Late assessment of thrombolytic efficacy (LATE) study: prognosis in patients with non-Q wave myocardial infarction. (LATE Study Investigators)

OBJECTIVES: We examined the impact of thrombolytic therapy and the prognosis of patients with non-Q wave myocardial infarction in a randomized placebo-controlled trial known as the Late Assessment of Thrombolytic Efficacy (LATE) study. BACKGROUND: Patients with non-Q wave as compared with Q wave myocardial infarction in the era before thrombolytic therapy were traditionally thought to have a higher rate of reinfarction and death between hospital discharge and 1 year such that the overall prognosis for outcome at 1 year was similar in the two groups. METHODS: The study patients began treatment with either recombinant tissue-type plasminogen activator (rt-PA) or matching placebo, 6 to 24 h after the onset of chest pain. Post hoc analysis of mortality and reinfarction was carried out by comparing rt-PA and placebo in various subsets of patients based on the presenting electrocardiogram (ECG) and the evolution of the ECG with respect to the development of Q waves. RESULTS: Among 5,711 participants, 4,759 had a confirmed myocardial infarction, including 1,309 classified as having a non-Q wave infarction at hospital discharge. Irrespective of treatment assignment, all patients with non-Q wave versus Q wave infarction had a lower 1-year mortality rate (13.3% vs. 17.1%, p = 0.001) and a similar 1-year reinfarction rate (8.6% vs. 7.9%, p = 0.7). Of the 4,759 patients with confirmed myocardial infarction, 2,973 presented with ST segment elevation or bundle branch block, 528 with ST depression and 1,258 with neither ST elevation nor depression. No overall benefit from rt-PA versus placebo with respect to mortality rate at 1 year was seen among patients presenting with ST elevation (21.2% vs. 22.4%, p = 0.5 [90% power to detect 20% relative difference]). Patients with ST elevation who were treated with rt-PA versus placebo <3 h after hospital admission had a lower mortality rate at 1 year (15.8% vs. 19.6%, p = 0.028) than did those treated after 3 h (17.6% vs. 13.0%, p = 0.055). Patients presenting initially with ST depression >2 mm had significant benefit from treatment with rt-PA with respect to 1 year mortality rate (20.1% vs. 31.9%, p = 0.006). CONCLUSIONS: Patients with non-Q wave myocardial infarction constitute a heterogeneous group of patients. Although the observations presented here are limited by post hoc analysis, it is apparent that patients classified as having a non-Q wave infarction after thrombolytic therapy have a better prognosis than do those given placebo. Late admission of thrombolytic therapy (after 6 h) may also be beneficial in patients presenting with ST depression >2 mm and confirmed myocardial infarction. These hypotheses require prospective testing in a larger number of patients.

Electrocardiography↗
PubMed1994

Treatment of severe heart failure: quantity or quality of life? A trial of enoximone. Enoximone Investigators.

OBJECTIVES: To determine the effects of enoximone on mortality and quality of life in patients with severe end stage heart failure. DESIGN: A randomised, double blind, placebo controlled trial of the addition of enoximone to conventional treatment. Planned minimum follow up of one year. SETTING: District general hospitals and cardiological referral centres in the United Kingdom. PATIENTS: Planned 200 patients with severe, symptomatic heart failure despite treatment with diuretics and where appropriate and tolerated angiotensin converting enzyme inhibitors and digoxin. RESULTS: The study was ended early by the ethics committee after 151 patients had been recruited because of an excess mortality in the enoximone group: 27 deaths compared with 18 in the placebo group (P < 0.05). Quality of life measured with a disease specific questionnaire showed a clinically significant improvement at week 2 with a mean increase score of 0.48 in the enoximone treated patients compared with 0.14 in those receiving placebo (P = 0.0086). With the Nottingham health profile questionnaire the physical mobility score was improved after three months in the enoximone group, median 21.3 compared with 41.8 in the placebo group (P = 0.008). CONCLUSIONS: In patients with severe heart failure who remain incapacitated despite conventional treatment enoximone reduced survival but had a beneficial effect on the quality of life. Drugs that improve symptoms in severe end stage heart failure should not be discarded lightly.

Aged↗
PubMed1993

The use of simulation in the design of two cardiovascular survival studies.

Simulation has become practical as an everyday tool given the wide availability of high performance workstations. We argue that simulation can play an important role in determining the number of patients required in a survival study, particularly if the assumption of proportional hazards does not hold, or if the study design is complex. The argument is illustrated by two examples. The first considers the design of a post myocardial infarction survival trial in which the hazard ratio is not constant. The second provides sample size estimates for a multicentre heart failure study in which both the treatment effect and the control mortality rate vary across centres.

Computer Simulation↗
PubMed1993

Impact of hospital thrombolysis policy on out-of-hospital response to suspected myocardial infarction.

The treatment of acute myocardial infarction changed when several trials reported that thrombolytic agents given within a few hours of infarction improved outcome. We present data from the Nottingham Heart Attack Register comparing 1982-84, when thrombolysis was not available, and 1989-90, when it was hospital policy to give thrombolysis to all patients who arrived within 6 hours of the onset of symptoms, in the absence of a specific contraindication. The number of patients referred with symptoms suggestive of acute myocardial infarction increased by 75% from 1982 to 1990; a diagnosis of "possible infarction" was made in about half of all patients in 1982-84 and 23% in 1989-90. Our current thrombolytic policy has had little impact on patient and general practitioner (GP) behaviour. The GP was contacted by most patients. The median time between the onset of a patient's symptoms and admission to hospital when the GP was involved was 229 min in 1982-84 and 210 min in 1989-90; when he was not involved in arranging the admission median times to admission were 89 min and 75 min, respectively. By 6 hours from symptom onset, 60% of patients had been admitted; by 12 hours, about 70% were in hospital and by 24 hours, 80%. Of 7855 patients admitted with suspected acute myocardial infarction in 1989-90, 4465 were admitted within 6 hours of symptom onset. Of these, 736 (16%) patients received a thrombolytic drug. 389 (9%) patients had a specific, documented contraindication to thrombolysis. Although we estimate that the policy has saved about 8 lives per year, it is not surprising that there has been no improvement in overall case fatality after myocardial infarction.

Emergency Medical Services↗
PubMed1992

Sample sizes for proportional hazards survival studies with arbitrary patient entry and loss to follow-up distributions.

In proportional hazards survival studies, power depends on the observed number of deaths, d*. For a given choice of survival, loss, and patient entry distributions, sample sizes can be determined by equating d* to the expected number of deaths. Approximating the survival and loss distributions with piecewise exponential distributions, and patient entry with a piecewise linear distribution, significantly reduces the computational overhead, and the expected number of deaths can be evaluated routinely. The merits of this approach are illustrated by a clinical trial of chemotherapy for large bowel cancer.

Colonic Neoplasms↗
PubMed1992

A latent class model for repeated measurements experiments.

Standard models for the analysis of repeated measurements assume a common response profile for all experimental units within a treatment group. However, in many applications this under-represents the nature of the response. There may be several distinct modes of response within a group (for example, responders versus non-responders to a given treatment), or there may be a set of distinct response profiles which are common to all the treatment groups. In these situations the effect of treatment can be characterized both by the shape of the fitted profiles and by estimating the proportion of cases who exhibit each particular response profile. This paper describes how such experiments may be analysed through the introduction of a latent variable into the standard model. Maximum likelihood estimation is straight-forward using the EM algorithm. Model choice requires some care, but good-fitting models can be identified via inspection of residuals and the use of empirical semi-variogram plots. Once the number of distinct profiles has been determined, treatment effects can be investigated using likelihood-ratio statistics. The approach is illustrated with a re-analysis of a dataset first described by Grizzle and Allen.

Animals↗
PubMed1992

Management of myocardial infarction: implications for current policy derived from the Nottingham Heart Attack Register.

OBJECTIVE: A register of patients with heart attacks in the Nottingham Health District has been maintained since 1973. Data from 1982 to 1984 inclusive, a period before trials of thrombolytic therapy started in Nottingham, were analysed to provide background information for the introduction of a policy of routine thrombolysis for appropriate patients. DESIGN: Data were collected prospectively on all patients transported to hospital in the Nottingham Health District with suspected myocardial infarction in the years 1982-84 and on patients treated at home during that time. SETTING: Two district general hospitals responsible for all emergency admissions in the health district. PATIENTS: 6712 patients admitted to hospital with suspected myocardial infarction and 1887 patients found dead on arrival at hospital. Approximately 1500 patients in whom a myocardial infarction was suspected were treated at home, but only 125 were identified who had a definite or probable infarction. RESULTS: Among the patients admitted within 24 hours of the onset of symptoms, the median delay from onset to hospital admission was 174 minutes; 25% of patients were admitted within 91 minutes. The only factor that seemed to affect the time taken was the patient's decision to call a general practitioner or an emergency ambulance. If a general practitioner referred the patient to hospital the median delay was 247 minutes, compared with 100 minutes when the patient summoned an ambulance. Ninety three per cent of all patients were transported by ambulance. The median time from the call for the ambulance to hospital arrival was 29 minutes. Once a patient was admitted to hospital, the time to admission and general practitioner involvement seemed relatively unimportant as predictors of outcome. Patients admitted more than nine hours after onset of symptoms with a diagnosis of definite or probable infarction had a poorer outcome than those admitted earlier (in-hospital mortality 22.4% v 13.1%). The fatality rates of those admitted to a coronary care unit or to an ordinary medical ward are similar. CONCLUSION: Although the introduction of thrombolytic therapy has brought with it an increased awareness of the need to minimise any delay in time to admission, it seems that in a predominantly urban area like Nottingham, patients with a suspected heart attack will continue to be admitted to hospital most quickly if an ambulance crew rather than a general practitioner is called. Because the ambulance crew was in contact with such patients for only a short time it seems unlikely that administration of a thrombolytic drug in the ambulance would be helpful.

Coronary Care Units↗
PubMed1992

Myocardial infarction in patients over 75 1982-1990.

Admissions to hospital of patients aged 75 or over with symptoms suggestive of acute myocardial infarction have increased markedly since 1982. Patients over 75 present to hospital as soon after the onset of symptoms as do younger patients; they require more treatment with diuretics and digoxin than do younger patients and their fatality rate is higher. Despite this, the chance of patients over 75, especially women, being admitted to a Coronary Care Unit, and so being treated with a thrombolytic and being monitored closely for the complications of acute infarction are much less than those for patients under 75. If we are confident that we can influence the outcome of and reduce fatality from acute myocardial infarction, we should be prepared to offer elderly patients the same opportunities for treatment that we currently afford to younger patients.

Age Factors↗
PubMed1991

Exercise capability in heart failure: is cardiac output important after all?

The exercise capability of 39 patients with severe chronic heart failure was assessed in several ways and compared with measurements of cardiac output. The relation between cardiac index and exercise tolerance measured on a treadmill was poor (r = 0.191, p = 0.245). However, exercise tolerance measured with a series of self-paced corridor walk tests showed moderate correlations with cardiac index (r = -0.404, p = 0.015 to r = -0.516, p = 0.001) and customary activity assessed by step counting correlated better with cardiac index (r = 0.537, p less than 0.001). Cardiac output therefore seems to be a factor determining patients' exercise capability when they choose their own walking speed but not when they undergo formal treadmill tests in the laboratory.

Aged↗
PubMed1991

Ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) in suspected acute myocardial infarction.

Continuous electrocardiography during the first 24 hours of a stay in a coronary care unit was used to record ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) or placebo. Recordings were made on 378 of the 436 patients admitted to a double blind trial of alteplase or placebo in one participating centre of the Anglo-Scandinavian study of early thrombosis (ASSET), patients being selected according to the availability of recorders. Of these, 309 (158 given alteplase and 151 placebo) had greater than 5 hours of analysable data. Most of the arrhythmias were recorded in patients with an in hospital diagnosis of myocardial infarction. Ventricular couplets and ventricular tachycardia were significantly more common in the patients treated with alteplase. Further, in patients with myocardial infarction who had ventricular extrasystoles, couplets, or ventricular tachycardia type a, the number of hours in which each arrhythmia was recorded was significantly higher in the alteplase group. The various ventricular arrhythmias in the alteplase group tended to cluster in the first 4-12 hours of the recordings. During the first 24 hours admission there were four episodes of ventricular fibrillation in the alteplase group and five in the placebo group of taped patients. By one month there had been 18 deaths in these 309 patients (alteplase four, placebo 14). These bore no relation to any recorded arrhythmia. Clinical records for the patients with no or minimal tape data yielded six further episodes of ventricular fibrillation during the first 24 hours (three in the alteplase group and three in the placebo group). Of the total 436 patients, 10 of the 218 patients in the alteplase group had died by one month compared with 22 of the 218 patients treated with placebo. The use of alteplase increases the incident of non-life threatening ventricular arrhythmias. These results, however suggest that arrhythmia after thrombolysis in the pre-hospital phase may be less of a problem than it is perceived to be.

Adolescent↗
PubMed1990

Effects of alteplase in acute myocardial infarction: 6-month results from the ASSET study. Anglo-Scandinavian Study of Early Thrombolysis.

In a randomised, controlled trial 2514 patients with suspected acute myocardial infarction received 100 mg intravenous alteplase (recombinant tissue plasminogen activator [rt-PA]) plus heparin within 5 h of onset of symptoms, and 2499 similar controls received placebo plus heparin. At 1 month the overall mortality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval [CI] 11-39%). At 6 months the mortality rates were 10.4% (alteplase) and 13.1% (placebo), a relative reduction of 21% (95% Cl 8%-32%, p = 0.0026). 6-month mortality rates in patients with proven myocardial infarction were 12.6% and 17.1%, respectively (relative reduction 26%; 95% Cl 14-37%); this effect was similar for anterior (15.6% vs 21.2%) and inferior (7.7% vs 12.8%) myocardial infarction. 6-month mortality rates were lower in those treated with alteplase irrespective of other recognised cardiac risk factors. However, treatment with alteplase made no difference to subsequent cardiac events after one month (readmissions, reinfarctions, death) nor to treatment for angina or heart failure. Product limit estimates of one year mortality are 13.2% with alteplase and 15.1% with placebo. The corresponding figures for patients with an index diagnosis of myocardial infarction are 15.7% and 18.9%, a relative reduction of 16.9%.

Adolescent↗