The expanding role of simulators in risk management.
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Biomedical subjects
Publications and source records attributed to M Tooley.
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There have been few longitudinal studies of bronchial responsiveness. We wanted to assess the long-term variability and associations of bronchial responsiveness in the general population. Spirometry, bronchial provocation tests, skin-prick tests for allergy, and respiratory symptom questionnaires were repeated every 4 months, for 2 years (August 1987-August 1989), in 122 volunteers recruited from a cross-sectional survey of population. Provocation dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) and dose-response slope (SL), which gives values for methacholine responsiveness, were measured in all subjects. SL correlated well with PD20FEV1 but repeatability was impaired in those subjects with unmeasurably high PD20FEV1. The 95% range for repeatability of PD20FEV1 was +/- 3.11 doubling doses and +/- 4.52 doubling slopes for SL. Bronchial responsiveness increased in those with self-reported colds and reduced FEV1 in winter 1987-1988, and in males in winter 1988-1989. Bronchial responsiveness increased during the summer (June-August) of both years, significantly in year 1. We conclude that bronchial responsiveness showed minor seasonal variability and that colds were the strongest predictors of increased bronchial responsiveness over the 2 yr period.
Metoclopramide is a dopamine receptor antagonist and, in large doses, has been shown to reverse the increase in renal blood flow, the diuresis and the natriuresis produced by a low-dose infusion of dopamine. We gave a single i.v. dose of metoclopramide 10 mg to 21 patients on an intensive care unit who were haemodynamically stable and receiving dopamine 3 micrograms kg-1 min-1. Renal vascular resistance index, measured by duplex Doppler ultrasonography, did not change after metoclopramide. Renal function, measured by creatinine and osmolar clearance, natriuresis, kaliuresis and excretion fractions of sodium and potassium did not change after metoclopramide. We conclude that normal doses of metoclopramide (< 0.2 mg kg-1) do not antagonize the renal effects of a low-dose infusion of dopamine in critically ill patients.
The prevalence and associations of bronchial hyperresponsiveness were investigated in a general practice population. The sample was obtained by using every 12th patient on the practice age-sex register, replacing non-responders with corresponding age and sex matched individuals from up to two further 1 in 12 samples. The response rate was 43%; 366 patients were studied. Doubling concentrations of methacholine were given to a maximum of 32 mg/ml or until a 20% fall in forced expiratory volume in one second (FEV1) occurred (provocation concentration, PC20FEV1). Bronchial hyperresponsiveness was defined arbitrarily as a PC20FEV1 of 2 mg/ml or less (or 11 mumol cumulative dose, PD20FEV1). The prevalence of bronchial hyperresponsiveness was 23%. Bronchial hyperresponsiveness was not associated with age but was more prevalent in women than men (31%:13%). It was also more common in those who had ever wheezed (39%) and in those who had had an attack of rhinitis in the preceding month (45%, p less than 0.1), in atopic individuals (30%), and in smokers (32%), but it was not associated with cough or dyspnoea. There was a positive correlation between PC20FEV1 and resting FEV1 (r = 0.288) and a negative correlation between PC20FEV1 and mean daily peak flow variability (r = -0.356). Stepwise binary logistic regression analysis showed significant independent effects on PC20FEV1 for mean daily peak flow variability, gender, number of positive skin test responses, resting FEV1, and mean histamine skin weal area, but no relation with smoking or mean allergen weal area. The prevalence of bronchial hyperresponsiveness was much higher than the prevalence of diagnosed asthma in the practice in 1984 (4.9%). Analysis of case notes of 169 individuals showed that those with bronchial hyperresponsiveness had not attended the practice more frequently for respiratory complaints during the previous five years.
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A series of comparative trials on nine popular and pharmacologically distinct regimens for the treatment of hay fever was undertaken in the course of normal general practice in the pollen seasons of 1981-83. One hundred and forty doctors recruited 640 patients to assess the overall usefulness of the treatments on daily diaries. ;Usefulness' was scored on a linear analogue scale weighing up the degree of hay fever symptoms during treatment, side effects and ease of use of the preparation.The regimen with the highest overall usefulness score was beclomethasone diproprionate with sodium cromoglycate eye drops (Beconase and Opticrom). Although the score was not significantly higher than those for methylprednisolone acetate (Depo-Medrone), astemizole (Hismanal) or terfenadine (Triludan), Beconase/Opticrom scored significantly better than mequitazine (Primalan), chlorpheniramine maleate (Piriton), sodium cromoglycate nasal insufflation with xylometazoline/antazoline eye drops (Rynacrom and Otrivine-Antistin) and azatadine maleate (Optimine). Beconase/Opticrom was first in rank order with respect to all the other regimens for the treatment of both mild and severe hay fever. Dimethothiazine (Banistyl), also shown to be useful, has since been withdrawn from prescription.
The efficacy and tolerability of ketanserin was compared with metoprolol in a double-blind parallel group study. After a 4-week placebo run-in on no treatment patients with a diastolic blood pressure (BP) of 95 mmHg or more received ketanserin 40 mg (n = 16) or metoprolol 100 mg (n = 17) twice daily. Blood pressure was measured in duplicate using a Hawksley random zero sphygmomanometer. Both blood pressure and heart rate were recorded after 5 min supine and 1 min standing. Patients visited after 2, 4, 8 and 12 weeks of treatment. Systolic, diastolic and mean arterial BPs, both supine and standing, were significantly reduced from week 2 by both treatments (P less than 0.05, Student's t-test). The mean (+/- s.e.m.) changes in supine BP at 3 months compared with baseline were -15.7 (3.6) mmHg systolic and -13.9 (2.7) mmHg diastolic in the ketanserin group and -26.6 (7.9) mmHg systolic and -15.2 (2.7) mmHg diastolic in the metoprolol group. There was a tendency for the fall in systolic BP to be greater in the metoprolol group, but this did not reach statistical significance except for the standing systolic BP at 1 month. Metoprolol caused a significant fall in heart rate compared with baseline values throughout the study, and the metoprolol group was significantly different from the ketanserin group at 2 months for the supine heart rate and at all time points for standing heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
One-hundred and eight women participated in a study which screened for depressive symptoms in the antenatal period. Of these women, 92 completed at least two further screenings during the postnatal year. The screening tool was the Hamilton Depression Rating Scale, adapted for self-rating, and administered by a microcomputer. It was found that mean scores and the prevalence of depressive symptoms rose throughout pregnancy, with a sharp peak in the third trimester. Following delivery there was an abrupt fall in the prevalence of depressive symptoms, followed by another rise, with a postnatal peak at six months.There were significant associations, at all levels of severity, between raised scores antenatally, and those developing postnatally in women completing the study. These were more marked in multiparae than primiparae. There was also a significant association between a past history of treated depression and the development of raised postnatal scores for depression.The routine use of a microcomputer to administer questionnaires to patients has proved feasible within general practice.
In 10 patients with intact retrograde (V-A) conduction (mean retrograde conduction time 296 +/- 45 msec), bipolar atrial electrograms were recorded simultaneously from three atrial sites (high right atrium [HRA], low right atrium [LRA], and right atrial appendage [RAA]) during sinus rhythm (anterograde electrogram) and paced ventricular rhythm (retrograde electrogram). Atrial electrograms were digitized and analyzed by a special feature detection program which uses sequential slew-rate changes to discriminate different analogue signals. In all patients, it was possible to distinguish anterograde and retrograde atrial depolarizations using the analogue or digital signal recorded from one and usually two [HRA and RAA] lead sites. Digital signal recognition was machine-based and fully automatic, and could be applied to the prevention of pacemaker-mediated tachycardia if incorporated into future microprocessor-based pulse generators.
1. Cardiac output measured by transthoracic impedance cardiography has been compared with simultaneous measurements made by the indirect Fick CO2 rebreathing method in nine adults and 14 children. All were healthy normal volunteers. Sixty-six comparisons were made at rest and during steady exercise at work loads up to 100 W. 2. Impedance measurements of cardiac output were consistently higher than indirect Fick measurements of cardiac output, but after application of a correction factor related to packed cell volume there was close correlation between the results obtained by the two methods (r = 0.94). 3. The mean coefficient of variation of impedance measurements of cardiac output was 13% at rest and 5% during steady-state exercise. 4. Changes of lung volume due to breath holding or resulting from addition of an expiratory resistance did not affect the measurement of cardiac output by impedance. 5. Transthoracic impedance cardiography is a rapid, non-invasive technique for measurement of cardiac output. It requires very little active co-operation from the subject. The method would probably give reliable results for patients with respiratory illnesses such as acute asthma or bronchiolitis, during which changes of lung volume may be expected to occur.
Two groups of eight asthmatic children carried out serial treadmill exercise tests at 2-hourly intervals, after double-blind premedication with oxatomide (2 mg/kg by mouth), sodium cromoglycate powder (20 mg by inhalation) or matched placebo preparations. The drugs were studied in one group up to 6 hr and in the other group (omitting sodium cromoglycate) from 4 to 10 hr after administration. Peak expiratory flow rate was measured before and after exercise to give an index of exercise-induced asthma. Oxatomide had a slight but significant bronchodilator effect. After a lag period of up to 4 hours, oxatomide exerted a significant protective effect against exercise-induced asthma which lasted until at least 8 hr. At 10 hr after ingestion, the effect had gone. A mean maximum diminution of exercise-induced asthma of 49% was found, in comparison with placebo. Oral oxatomide after a lag period, exerts a significant protective effect against exercise-induced asthma. The relevance of these observations for the clinical management of asthma remains to be determined.
Thirty-three asthmatics were followed up for a mean of 8 1/2 years in prospective study in order to observe the clinical course of the disease. The severity of asthma was graded according to the treatment each required to keep him in reasonable health. Regular exercise tests were performed so that a comparison could be made between the degree of exercise-induced asthma and the severity of the disease. In this group of severe perennial childhood asthmatics profound exercise-induced asthma was found to exist throughout the entire clinical spectrum of the disease with no appreciable difference until the patient became symptom-free. Exercise-induced asthma then disappeared only to return if clinical asthma recurred. This study showed that exercise-induced asthma is a sensitive indicator of clinical asthma but has no prognostic significance in the symptom-free patient.
14 children with severe asthma were studied for 2 months in a double-blind cross-over trial to compare the efficacy of beclomethasone dipropionate delivered as an aerosol and as a powder from a rotahaler. Inhalation via the aerosol was satisfactory in 13 patients, each of whom used the rotahaler correctly. Younger children preferred to use the rotahaler. Comparison of daily symptoms, twice daily peak expiratory flow rate (PEFR), and use of salbutamol during the 2 months of the trial showed that control of asthma was equally good, irrespective of the device used to deliver active beclomethasone.
To examine further the relation between type of exercise, workload, ventilation, and exercise-induced asthma, we compared treadmill walking with treadmill running and treadmill running with isocapnic hyperventilation in separate studies in children and adolescents. Inspired air conditions were identical during each pair of tests. Walking and running with similar minute ventilation and oxygen consumption were followed by similar falls in peak expiratory flow rate as were running and hyperventilation with similar minute ventilation and end-tidal carbon dioxide tension. This study supports the concept that hyperventilation is a central mechanism in exercise-induced asthma.
Fourteen children with perennial asthma previously treated with beclomethasone dipropionate were studied for four months in a crossover trial to compare the efficacy of choline theophyllinate and beclomethasone dipropionate aerosol in the control of their symptoms. Assessments were made using twice daily peak flow measurements, together with daily records of symptom scores and use of extra salbutamol. Beclomethasone and oral choline theophyllinate together improved control of asthma in comparison with beclomethasone alone. Reduction of the dose of beclomethasone from 400 microgram/day caused worsening of asthma. Oral choline theophyllinate did not prevent this deterioration and therefore cannot replace beclomethasone for the long-term treatment of such asthmatic patients.
Nineteen asthmatic children treated with the aerosol steroid, beclomethasone dipropionate, were followed 3 to 5 yr. Good control was maintained in all but one child throughout, although 73% have needed 1 or 2 wk of supplementary oral steroids per year for exacerbations. Growth has been along the percentile on which the child entered the study. No serious side effects have been encountered among 41 children treated between 1 and 5 yr with beclomethasone dipropionate. Seventeen percent needed prolonged alternate-day oral steroids, although all but one child did eventually return to good control with beclomethasone dipropionate.
A study was carried out to determine whether an episode of exercise-induced asthma (EIA) is followed by a refractory period and to assess the factors that affect it. Nine children, 9 to 14 years of age, were studied during repeated, paired exercise tests on a treadmill. Respiratory function was assessed by measuring peak expiratory flow rate before and after exercise. Changes were related to measured uptake of O2 during exercise. When paired tests were at a constant metabolic load, the severity of EIA was relatively constant in the first test of each pair, but it diminished in the second tests as the interval between tests decreased. The ability to bronchoconstrict fully was recovered within 4 hours after a test. When tests at varying metabolic loads were followed after 30 min by tests at a constant load, the severity of EIA increased in proportion to the load in the first test of each pair. In the second tests it was inversely related to that which occurred in the first tests. These results were compatible with the suggestion that the development of EIA requires the release of a stored mediator or enzyme precursor.
28 children with chronic asthma (15 in Denver and 13 in London) completed a 12 wk double-blind trial of treatment with sodium cromoglycate (cromolyn sodium), theophylline, and a combination of both. The three regimens were administered, each for 4 wk, in random sequence as part of a collaborative investigation of the relative efficacy of the two antiasthmatic agents. Cromoglycate was administered by inhalation in standard doses of 20 mg q.i.d. Theophylline dosage was individualized with the assistance of serum-theophylline measurements and averaged 6 mg/kg/dose q.i.d. (range 3-8--8-5 mg/kg/dose). Peak expiratory-flow rates measured twice daily on all patients averaged 75% of that predicted during cromoglycate administration, 79% during theophylline, and 81% during the combined-drug regimen (P less than 0.05). Patients had an average of 59% of days free of symptoms while on cromoglycate and 71% of days symptom-free when on both the theophylline and the combination regimens (P less than 0.025). None of the 13 patients whose asthmatic symptoms were previously controlled with cromoglycate was unable to complete the 4 wk trial with theophylline alone; 1 patient whose symptoms had been previously controlled with theophylline twice developed severe asthmatic symptoms while receiving cromoglycate, and he had to be withdrawn from that study period. No significant differences in adverse effects of the medication were observed during the 12 wk trial.