Trend analysis of socioeconomic differentials in deaths from injury in childhood in Scotland, 1981-95.
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Adolescent↗
Biomedical subjects
J Norrie
Publications and source records attributed to J Norrie.
Risk of major gastrointestinal bleeding with aspirin.
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Aged↗
Comparison of the short-term effects of candoxatril, an orally active neutral endopeptidase inhibitor, and frusemide in the treatment of patients with chronic heart failure.
BACKGROUND: Candoxatril is a novel neutral endopeptidase inhibitor that increases plasma concentrations of atrial natriuretic factor and thereby produces natriuresis, diuresis, and vasorelaxation. This profile of action offers theoretical advantages over standard diuretic therapy in the treatment of patients with heart failure. The aims of the study were to compare the effects of candoxatril with those of frusemide in the treatment of patients with mild heart failure. METHODS: Male patients with mild heart failure were randomly assigned to 9 days of therapy with 20 mg frusemide twice a day, 200 mg candoxatril twice a day, or 400 mg candoxatril twice a day (n = 10 per group) after a 14-day placebo washout phase. Systemic hemodynamic measurements, exercise tolerance, and urinary and plasma hormone concentrations were assessed during the placebo run-in and at the beginning and end of the double-blind therapy. RESULTS: Frusemide and candoxatril caused similar diuresis and natriuresis. Candoxatril caused a slight decrease in systolic blood pressure and a dose-dependent increase in plasma and urinary concentrations of atrial natriuretic factor without elevating plasma renin activity. Frusemide reduced plasma concentrations of atrial natriuretic factor and increased plasma renin activity. Treadmill exercise capacity decreased 30 +/- 26 seconds after use of frusemide, compared with increases of 12 +/- 35 seconds after use of 200 mg candoxatril twice a day and 35 +/- 31 seconds after use of 400 mg candoxatril twice a day (P =.13; frusemide versus 400 mg candoxatril twice a day). CONCLUSIONS: In the treatment of patients with mild heart failure, candoxatril has diuretic effects equivalent to those of 20 mg frusemide twice a day without the associated and potentially detrimental activation of the renin-angiotensin-aldosterone system. The trend for improved exercise capacity with candoxatril warrants further investigation.
Atrial Natriuretic Factor↗
International economic analysis of primary prevention of cardiovascular disease with pravastatin in WOSCOPS. West of Scotland Coronary Prevention Study.
AIMS: The results of the West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated the clinical benefit of using pravastatin for the primary prevention of cardiovascular disease in hypercholesterolaemic men. To inform decision makers, who must also consider costs, this study assesses the economic efficiency of such an intervention in a broad range of countries. METHODS AND RESULTS: A generalized model of cardiovascular disease prevention was used to estimate the cost-effectiveness of primary prevention with pravastatin compared to diet alone. This model follows a cohort of hypercholesterolaemic men over a given period quantifying the effect in terms of the avoidance of cardiovascular disease based on treatment-specific risks derived from WOSCOPS data and extensive record-linkage data on disease-specific survival. Country-specific costs are accounted for by expressing all such parameters in terms of the ratio of monthly treatment to that of managing a myocardial infarction. Over a broad range of inputs the cost-effectiveness ratios remain below $25,000 per life years gained, regardless of country. Subgroups with even better economic efficacy can be defined on the basis of higher baseline risk. CONCLUSIONS: In contrast to some previous reports, this analysis based on trial data demonstrates that pravastatin provides not only an effective means of primary cardiovascular disease prevention, but also an efficient one.
Aged↗
Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures.
OBJECTIVE: To determine whether permanent cardiac pacing could prevent syncope and seizures in children with frequent severe neurally mediated syncope, and if so whether dual chamber pacing was superior to single chamber ventricular pacing. METHODS: Dual chamber pacemakers were implanted into 12 children (eight male, four female) aged 2-14 years (median 2.8 years) with frequent episodes of reflex anoxic seizures and a recorded prolonged asystole during an attack. The pacemaker was programmed to sensing only (ODO), single chamber ventricular pacing with hysteresis (VVI), and dual chamber pacing with rate drop response (DDD) for four month periods, with each patient allocated to one of the six possible sequences of these modes, according to chronological order of pacemaker implantation. The parent and patient were blinded to the pacemaker mode and asked to record all episodes of syncope or presyncope ("near miss" events). The doctor analysing the results was blinded to the patient and pacemaker mode. RESULTS: One patient was withdrawn from the study after the pacemaker was removed because of infection. In the remaining children, both dual chamber and single chamber pacing significantly reduced the number of syncopal episodes compared with sensing only (p = 0.0078 for both). VVI was as effective as DDD for preventing syncope, but DDD was superior to VVI in reducing near miss events (p = 0.016). CONCLUSIONS: Permanent pacing is an effective treatment for children with severe neurally mediated syncope and reflex anoxic seizures. VVI is as effective as DDD in preventing syncope and seizures, but DDD is superior in preventing overall symptoms.
Adolescent↗
Screening for Chlamydia trachomatis. Contacts attendance rate is 70% in Hertfordshire.
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Adolescent↗
The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin.
OBJECTIVE: To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia. DESIGN: Economic benefit analysis based on data from the West of Scotland coronary prevention study. Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated. Scottish record linkage data provided disease specific survival. Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotland coronary prevention study. SUBJECTS: Men with hypercholesterolaemia similar to the subjects in the West of Scotland coronary prevention study. MAIN OUTCOME: Cost consequences, the number of transitions from health to cardiovascular disease prevented, the number needed to start treatment, and cost per life year gained. RESULTS: If 10,000 of these men started taking pravastatin, 318 of them would not make the transition from health to cardiovascular disease (number needed to treat, 31.4), at a net discounted cost of 20m Pounds over 5 years. These benefits imply an undiscounted gain of 2,460 years of life, and thus 8121 Pounds per life year gained, or 20,375 Pounds per life year gained if benefits are discounted. Restriction to the 40% of men at highest risk reduces the number needed to treat to 22.5 (5601 Pounds per life year gained (undiscounted) and 13,995 Pounds per life year gained (discounted)). CONCLUSIONS: In subjects without evidence of prior myocardial infarction but who have hypercholesterolaemia, the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups.
Anticholesteremic Agents↗
Natural variability of transient myocardial ischaemia during daily life: an obstacle when assessing efficacy of anti-ischaemic agents?
OBJECTIVE: To assess the degree of variability of transient myocardial ischaemia during daily life in patients with coronary artery disease, which could confound the interpretation of trials of the therapeutic effects of anti-ischaemic agents. DESIGN: Prospective method evaluation. SETTING: Tertiary referral centre, outpatient clinic. PATIENTS: Patients with stable angina, confirmed coronary artery disease, and a positive treadmill exercise test for ischaemia. Patients were not preselected on the basis of prior documented transient ischaemia during ambulatory ST segment monitoring. INTERVENTIONS: A simulated drug-study with 4 monitoring phases in 16 subjects. To minimise variability in ischaemic activity, patients underwent weekly 48 hour ambulatory ST segment monitoring outside hospital off all prophylactic therapy on the same weekdays for 4 weeks. MAIN OUTCOME MEASURE: Variability in the frequency and duration of transient myocardial ischaemia. RESULTS: There was marked variability in both ischaemic activity and mean duration of ischaemia in patients with confirmed ischaemia, the greatest degree of variability being between patients and from day to day within weeks within patients, with a further contribution to variability being noted between fortnights within patients. CONCLUSIONS: Despite assessment off all therapy and an adequate period of monitoring (48 hours) with small intervals between monitoring periods (5 days), marked variability in ischaemic activity was noted, and regression towards the mean was clearly shown. Ambulatory ST segment monitoring outside hospital is not a reliable method for assessing the therapeutic effects of anti-ischaemic agents.
Activities of Daily Living↗
Model inconsistency, illustrated by the Cox proportional hazards model.
We consider problems involving the comparison of two or more treatments where we have the opportunity to adjust for relevant covariates either conditionally in a regression model or implicitly in repeated measures data, for example, in crossover trials. It is seen that for data arising from non-Normal distributions there is the possibility that models adjusting for covariates and those not adjusting for covariates will be inconsistent, that is, at most one of the models can be valid. Alternatively, even if conditional and unconditional models are valid, parameters in each model may have different interpretations. We note that this presents difficulties for the specification and interpretation of the analysis. It is also clear that model validation is critical. Specific attention is paid to survival data analysed by the Cox proportional hazards model.
Analysis of Variance↗
Does the exercise protocol matter when assessing the anti-anginal effects of drug therapy?
Four exercise test protocols (Bruce, Balke, Ellestad and Steep) were compared in 16 patients with proven coronary artery disease in demonstrating the anti-anginal effects of sublingual glyceryl trinitrate in a randomization double-blind trial. Glyceryl trinitrate significantly improved the time, heart rate and rate pressure product to peak exercise, onset of angina and 1 mm ST segment depression in all four protocols (P < 0.05) (except rate pressure product to angina in the Balke protocol). The increase in exercise time was greatest for the Balke protocol at peak exercise (188.1 +/- 187.1) (mean +/- SD in s), at onset of angina (251.9 +/- 247.1) and at 1 mm ST depression (233.6 +/- 243.8), followed by the Steep and Bruce protocols, and was lowest for the Ellestad protocol 41.9 +/- 42.4, 96.5 +/- 65.8, 82.6 +/- 74.0, respectively. Increase in time to peak exercise with glyceryl trinitrate was significantly greater for the Balke protocol in comparison with the other three protocols and for the Bruce and Steep protocols when compared to the Ellestad protocol. Time to 1 mm ST depression with treatment was significantly greater on the Balke and Bruce protocols than the Ellestad protocol, and to onset of angina for the Balke compared to other three protocols. There were no significant differences between the Bruce and Steep protocols for any of the endpoints. The magnitude of treatment effect in the different protocols was accompanied by correspondingly greater inter-patient variability such that no protocol was more, or less, sensitive than another in detecting treatment effect. Changes in heart rate and rate pressure product with treatment were generally similar between the different protocols. In conclusion, a protocol with small and frequent increments (Balke), although able to show greater increase in exercise duration with glyceryl trinitrate than more aggressive protocols, is no more sensitive at detecting treatment effect.
Adult↗
Cardiorespiratory and symptomatic variables during maximal and submaximal exercise in men with stable effort angina: a comparison of atenolol and celiprolol.
Celiprolol is a novel beta 1 selective adrenoreceptor blocker with partial beta 2 agonism and direct vasodilator activity. These ancillary properties may reduce symptomatic breathlessness and fatigue and modify respiration during exercise. To test this hypothesis 20 men with stable effort angina were enrolled in a double-blind crossover study to investigate the effects of atenolol 100 mg once daily (A) and celiprolol 400 mg once daily (C) on cardiorespiratory and symptomatic variables during maximal and submaximal exercise. Total exercise time on a modified Bruce protocol was similar on both treatments: C12.5 min, A 13.1 min. During steady state submaximal exercise at 60-75% (mean 68%) of maximum work capacity, minute ventilation (C33.81 min-1, A 33.51 min-1), oxygen uptake (C14.6 ml.kg-1.min-1, A15.1 ml.kg-1.min-1), respiratory exchange ratio (C 0.89, A 0.87), ratio of VE/VCO2 (C 33.6, A 33.4), ratio of VE/VO2 (C 2.34, A 2.72), Borg perceived exertion score (C 11.2, A 10.9) and visual analogue scores for breathlessness (C 29.5, A 25.9) and muscle fatigue (C 28.9, A 26.0) were all similar on both treatments. At maximal exercise capacity on the modified Bruce protocol, minute ventilation (C 58.31 min-1, A 60.41 min-1), oxygen uptake (C 21.3 ml.kg-1.min-1, A 21.7 ml.kg-1.min-1), respiratory exchange ratio (C 1.02, A.1.05), ratio VE/VCO2 (C 34.8, A 35.9), and ratio VE/VO2 (C 2.80, A 2.83) were also similar on both drugs. Over a 10 day period anginal attacks (C 10.1 +/- 10.4, A 5.4 +/- 5.9) and sublingual GTN use (C 5.9 +/- 10.3, A 4.4 +/- 9.8) were both more frequent on celiprolol).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗