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Biomedical subjects

T M MacDonald

Publications and source records attributed to T M MacDonald.

At least 55 records · Page 3Linked to original sources
PubMed2001

Adverse cardiac effects of salt with fludrocortisone in hypertension.

The effect of salt on blood pressure (BP) is controversial. A more important question is whether salt can produce cardiac target-organ damage, irrespective of its effect on BP. We assessed the effect of salt with fludrocortisone on QT dispersion and echocardiographic left ventricular diastolic function in a prospective interventional study involving 29 hypertensive subjects with a raised aldosterone/renin ratio who were hospitalized for investigation of possible primary aldosteronism. Each subject over 4 days was given a total of 28.8 g (480 mmol) of sodium chloride and 1.5 mg of fludrocortisone with potassium supplementation. Baseline and posttreatment 12-lead ECGs and echocardiograms were obtained. There were no significant changes in body weight, pulse rate, or BP after treatment with salt and fludrocortisone. Plasma sodium was significantly increased from 141.4 (SD 2.1) to 142.6 (SD 2.4) mmol/L (P:=0.001). QT and QTc dispersion both significantly increased: +19.6 (SD 16.5) ms (95% CI, 13.4 to 25.9) (P:<0.001) and +19.8 (SD 20.9) ms (95% CI, 11.8 to 27.7) (P:<0.001), respectively. There were no significant changes in (n=15) left ventricular dimensions or systolic function, but all diastolic filling indexes, including the preload-independent index, flow propagation velocity (55.49 [SD 10.91] to 48.96 [SD 11.40] cm/s, P:=0.018) worsened, suggesting significant deterioration of left ventricular diastolic function with salt and fludrocortisone. In conclusion, a combination of salt with fludrocortisone increased QT dispersion and impaired left ventricular diastolic relaxation in hypertensive patients with high aldosterone/renin ratios. This raises the possibility that salt may have BP-independent adverse cardiac effects in susceptible hypertensive subjects.

Aldosterone↗
PubMed2001

Post exertional broad complex tachycardia in a normotensive patient: a rare presentation of phaeochromocytoma.

Phaeochromocytomas are rare cause of secondary hypertension with significant morbidity and mortality, if left untreated. Paroxysms with hypertension are considered as "textbook" presentations but atypical forms represent considerable diagnostic challenge. We report an unusual association between phaeochromocyotoma and post-exertional malignant arrhythmia in a normotensive subject.

Adrenal Gland Neoplasms↗
PubMed2000

Selegiline and mortality in subjects with Parkinson's disease: a longitudinal community study.

OBJECTIVE: To estimate mortality by drug use in a cohort of patients with PD relative to age- and sex-matched comparators. METHODS: two longitudinal cohorts of patients with 7 and 11 years' duration of PD were constructed with matched comparators in Tayside, Scotland. Subjects were eligible for inclusion if they received a first prescription for an anti-Parkinson's drug from July 1989 to December 1995, with no PD drug prescription in the previous 6 months. Those who had previously taken a neuroleptic drug or were younger than 40 years of age were excluded. RESULTS: Overall, subjects with PD in relation to comparators had higher mortality with a rate ratio (RR) of 1.76 (95% CI 1.11, 2.81) in the 7-year cohort. There was significantly greater mortality in patients with PD who received levodopa monotherapy (RR = 2.45, 95% CI 1.42, 4.23) relative to the comparators, adjusting for previous cardiovascular drug use and diabetes. However, there was no significant difference in mortality in those with PD receiving combination therapy of selegiline with levodopa and other drugs in relation to the comparators (RR = 0.92, 95% CI 0.37, 2.31). CONCLUSIONS: Subjects with PD had twice the rate of mortality relative to age- and sex-matched comparators. However, those subjects who received selegiline at any time in combination with co-careldopa or co-beneldopa showed no significant difference in mortality compared with the comparators. Monotherapy with levodopa was associated with the highest mortality.

Aged↗
PubMed2000

The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients.

AIMS: The aims of this study were to study the efficacy and tolerability of felodipine extended release (ER) 5 mg and metoprolol controlled release (CR/ZOC) 50 mg given as a fixed combination (Logimax) or as a free combination in elderly (age greater than 60 years) hypertensive patients, using ambulatory blood pressure (BP) monitoring. A secondary aim was to relate the efficacy of the free and fixed combinations with pharmacokinetic profiles. METHODS: This was a double-blind, placebo-controlled randomised three-way crossover multi-centre study. BP was measured for 26 h using ambulatory blood pressure monitoring (ABPM), which was performed on the last day of the three treatment phases. RESULTS: Mean sitting BPs, measured during the trough period with ABPM, were significantly lower with both the free and fixed combinations of metoprolol and felodipine than placebo (141/83 mmHg free, 140/83 mmHg fixed, 156/93 mmHg placebo). The mean BPs measured over 24 h using ABPM were 143/82 mmHg, 140/82 mmHg and 158/93 mmHg for the free, fixed and placebo treatment arms, respectively. The trough-to-peak ratios (T:P) were 75% and 79% for the systolic BP and 70% and 70% for the diastolic BP for the free and fixed combinations, respectively. Pharmacokinetic evaluation revealed identical plasma concentration-time curves for felodipine given as the free or fixed combination. Comparison of the plasma concentration-time curves for metoprolol revealed a delay in the release rate from the fixed combination formulation. No significant differences in BP control between the active treatments were noted during this period. Of 26 patients entered into the study, 3 withdrew during active phase for non-drug-related reasons. No patient withdrew from active treatment due to treatment-related adverse events. The frequency of adverse event reporting for the fixed combination of felodipine and metoprolol was similar to that for placebo (60% and 58%, respectively). CONCLUSION: The results suggest that once-daily dosing with either the free or fixed combination of felodipine 5 mg and metoprolol 50 mg produces a significant sustained reduction in systolic and diastolic BP with similar plasma concentration profiles over a 24-h period.

Aged↗
PubMed2000

The influence of physical activity on the variability of ambulatory blood pressure.

The aim of this study was to assess the contribution of physical activity levels to blood pressure (BP) variability, and to assess the effect age, gender, body mass index, and use of antihypertensive medications on this relationship. We simultaneously monitored 24-h ambulatory BP by automated recorder and activity by actigraphy in 431 patients. Mean activity scores for the 5, 10, 15, and 20 min preceding each BP measurement were calculated, and BP and heart rate were related to these variables using linear mixed model regression. Various patient characteristics were added to the mixed model as covariates. Patients were heterogeneous in age (48 +/- 13 years), sex (49% men), and average 24-h BP (132/81 +/- 15/10 mm Hg). Mean daytime activity level was 44 +/- 15 U. During the daytime, systolic BP (r = 0.33), diastolic BP (r = 0.29), and heart rate (r = 0.42) correlated best with the average activity for the 15 min preceding each measurement (P < .001). Variance was very high, with activity explaining from 0% to 62% of BP variability for different individuals. Men and the obese had a greater reactivity of systolic BP to activity; older patients and those on antihypertensive therapy had a lower reactivity of heart rate. Blood pressure level is significantly associated with physical activity, but the percentage of variance of BP explained by physical activity varies greatly between individuals. Correlation is strongest between BP and average activity integrated over the previous 15 min. Much of the variance in blood pressure remains unexplained.

Adolescent↗
PubMed2000

Does the Dundee Step Test predict outcome in treated hypertension? A sub-study protocol for the ASCOT trial. Anglo-Scandinavian Cardiac Outcome Trial.

Treated hypertensive subjects may remain five times more likely to die of cardiac and cerebrovascular diseases than normotensive subjects with equivalent resting blood pressure (BP) levels. Research evidence suggests that exercise BP is a better predictor of end-organ damage and mortality than resting BP, and data from our centre show that a significant proportion of treated hypertensives have uncontrolled BP during a 5-min Dundee Step Test. The prognostic usefulness of exercise BP has yet to be translated into clinical practice because of the lack of a suitable technique. The Dundee Step Test is being evaluated in the ASCOT (Anglo-Scandinavian Cardiac Outcome Trial) study, a 5-year follow-up multicentre, multinational trial comparing the effect of newer (amlodipine and perindopril) and older (bendroflumethiazide and atenolol) antihypertensive agents stratified according to cholesterol levels on cardiac outcome. If the value of the Dundee Step Test is proven, then it may be adopted into routine clinical practice for the assessment of exercise BP. This may result in the improved management of hypertension with a subsequent reduction in morbidity and mortality. The publication of this study protocol is meant to be a statement of on-going research which may stimulate interest among those with an interest in this area of research. Journal of Human Hypertension (2000) 14, 75-78.

Adult↗
PubMed2000

High prevalence of primary aldosteronism in the Tayside hypertension clinic population.

Primary aldosteronism (PA) was thought to be rare but recent evidence from Australia suggests that it may be more common. As this has important implications in terms of hypertension management, we undertook to screen for this treatable condition in our hypertension clinic. We obtained blood samples in sequential patients referred for assessment in our hypertension clinic in Tayside for plasma renin activity (PRA) and aldosterone. The aldosterone to PRA ratio (ARR) was used as an initial screening test to identify potential patients with PA. Those patients with an elevated ratio (> or =750) were admitted for the salt loading and fludrocortisone suppression test. These patients also underwent adrenal CT scanning, and in selected patients, adrenal scintigraphy. Between May 1995 and January 1997 (21 months), we screened a total of 495 patients. ARR was available in 465 (93.9%) patients. Out of that number, 77 (16. 6%) had an elevated ratio of > or =750, five of whom had an adrenal adenoma (one had previous adrenalectomy). Forty-five of these patients were admitted for the salt loading and fludrocortisone suppression test with 41 positive test results suggesting PA. One patient with a negative salt loading test result however had an adenoma proven on histology. A total of 43 cases of PA were identified, giving a minimum prevalence of 9.2% (43/465). Potentially the prevalence may be up to 15% assuming that the ARR has a sensitivity of 93% (42/45) in predicting PA. In conclusion, about one in 10 patients attending a hypertension clinic may have PA. This suggests that the prevalence of PA in Tayside is as high as that in the Australian hypertensive population, and this is likely to be true elsewhere, with obvious important implications for hypertension management.

Adult↗
PubMed2000

How well do office and exercise blood pressures predict sustained hypertension? A Dundee Step Test Study.

Exercise systolic blood pressure (BP) appears to be a better predictor of cardiac mortality than casual office BP. We tested whether this could be explained by exercise systolic BP being a better predictor of sustained hypertension than casual office BP. Exercise systolic BP was measured using the lightweight 3-min single stage, submaximal Dundee Step Test in 191 consecutive subjects (102 male, age 52 (s.d. 13) years) who were referred to a specialist hypertension clinic for assessment. Exercise systolic BP was compared with office BP and daytime ambulatory BP (ABP). Sustained hypertension was defined as a mean daytime systolic and/or diastolic ABP of >/=140/90 mm Hg. Receiver operating characteristic (ROC) curves of exercise systolic BP and office BP in predicting sustained hypertension were compared. The positive predictive value of office diastolic BP >/=90 mm Hg and office systolic BP >/=140 mm Hg for sustained hypertension were 64% and 67% respectively. However, exercise systolic BP >/=180 mm Hg had a positive predictive value of 76%. Twenty-two percent (42/191) of subjects had an exercise systolic BP rise to >/=210 mm Hg, and 93% of this group had sustained hypertension on ABP. Whilst exercise systolic BP was a better predictor of sustained hypertension using currently recommended office BP treatment thresholds, the ROC curves of these indices were not different. In a multiple regression analysis, exercise systolic BP was an independent predictor of sustained hypertension, accounting for 36% of the variance of daytime systolic ABP after adjusting for age, gender and antihypertensive drug treatment. In conclusion, exercise systolic BP was a marginally better predictor of sustained hypertension than office BP. This may partly explain why exercise systolic BP is a potent predictor of cardiac mortality.

Adult↗
PubMed2000

Design issues for drug epidemiology.

Despite the difficulties involved in designing drug epidemiology studies, these studies are invaluable for investigating the unexpected adverse effects of drugs. The aim of this paper is to discuss various aspects of study design, particularly those issues that are not easily found in either textbooks or review papers. We have also compared and contrasted drug epidemiology with the randomized controlled trial (RCT) wherever possible. Drug epidemiology is especially useful in the many situations where the RCT is not suitable, or even possible. The study base has to be defined before the appropriate cohort of subjects is assembled. If all of the cases are identified, then a referent sample of controls may be assembled by random sampling of the study base. If all of the cases cannot be assembled, a hypothetical secondary base may need to be created. Preferably, only new-users of the drug should be included, and the risk-ratio will be different for acute users and chronic users. Studies will usually only be possible when researching the unintended effects of drugs. It is difficult to study efficacy because of confounding by indication. In occasional circumstances it may be possible to study efficacy (examples are given). Discussion of the dangers of designing with generalisability in mind is provided. Additionally, the similarities in study design between drug epidemiology and the RCT are discussed in detail, as well as the design-characteristics that cannot be shared between the two methods.

Cohort Studies↗
PubMed2000

Practice factors that influence antibiotic prescribing in general practice in Tayside.

A cohort design was used to evaluate antibiotic prescribing in relation to patient and general practice characteristics. The study included prescribing to all subjects resident in Tayside, from January to December 1994 and found 215217 antibiotic prescriptions dispensed to 118596 people. Training status of general practitioners (GPs) was found to be the characteristic most associated with prescribing. Adjusting for other GP characteristics had little effect on these results. Training practice status was the dominant factor associated with significant differences in rates of antibiotic prescribing, in class of antibiotic prescribed and in performance indicators of antibiotic prescribing.

Anti-Bacterial Agents↗
PubMed2000

Epidemiology and pharmacoeconomic implications of non-steroidal anti-inflammatory drug-associated gastrointestinal toxicity.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and used, especially to treat patients with osteoarthritis and rheumatoid arthritis. Since their introduction as a therapeutic class, a large body of literature has accumulated on the side-effects of these drugs. NSAIDs, through their inhibition of prostaglandin synthesis, can affect the renal and cardiovascular systems. However, the majority of reported side-effects are related to the gastrointestinal (GI) system, and the occurrence of these GI events adds significantly to the disease burden. Several factors have been identified that contribute to the risk of an NSAID-associated GI event. However, when considering risk, especially in clinical trials or observational studies, it is necessary to distinguish between baseline risk and NSAID-attributable risk, since this distinction can affect the results and conclusions of the study; NSAID-attributable risk is present in subjects who have few or no risk factors for upper GI toxicity. Safer NSAIDs, such as the new specific cyclooxygenase-2 inhibitors, when targeted to the appropriate patient (i.e. those with NSAID-attributable risk), should lead to improved outcomes and reduced costs.

Age Factors↗
PubMed2000

Physical activity level is an independent predictor of the diurnal variation in blood pressure.

OBJECTIVE: The aim of this study was to define the relationship between physical activity and the magnitude of the percentage fall in blood pressure at night (nocturnal dip). METHODS: We simultaneously monitored 24-h ambulatory blood pressure and measured physical activity by actigraphy in 434 patients. Blood pressure was measured every 20 min; the actigraph integrated an activity score every 10 s. Mean daytime and night-time activity were calculated from mean scores for the 15 min preceding each blood pressure measurement. Nocturnal dip in systolic and diastolic blood pressure (SBP and DBP) were regressed on mean (log-transformed) daytime activity. Mean night-time activity, age, gender, smoking status, body mass index (BMI) and clinic blood pressure were added into a multiple linear regression. RESULTS: The patient group was heterogeneous in age, gender and mean 24-h blood pressure. Mean daytime activity level was significantly and positively associated with the magnitude of the nocturnal dip in both SBP and DBP. Increased night-time activity was significantly associated with a smaller nocturnal dip. Older patients had a smaller nocturnal dip per log unit daytime activity. Nocturnal dip in SBP was greater in males, and smaller in those taking antihypertensive medications. Smoking, BMI and clinical blood pressure level were not associated with the extent of the nocturnal dip after adjustment for other factors. CONCLUSIONS: Daytime and night-time physical activity levels are independently and significantly predictive of the magnitude of the nocturnal dip in blood pressure. Variation in activity may confound interpretation of 24-h ambulatory blood pressure monitoring, and contribute to the poor reproducibility of dipper status.

Adult↗
PubMed2000

Prevalence and aetiology of hypothyroidism in the young.

AIMS: To define the prevalence of hypothyroid disease in children and young people, and describe its aetiology. METHODS: We identified all patients on the Medicines Monitoring Unit (MEMO) database in the Tayside region of Scotland who had received two or more prescriptions for thyroxine during the study period (January 1993 to December 1995). Using this as a surrogate marker of hypothyroidism, we calculated the prevalence of hypothyroidism in those aged less than 22 years. Main outcome measures were prevalence of thyroxine prescription, estimated prevalence of hypothyroidism, and aetiology of the hypothyroidism (determined from case records, and biochemistry and immunology databases). RESULTS: Of 103,500 residents aged less than 22 years, 140 were identified as receiving thyroxine on prescription, giving a population prevalence of 0.135%. The ratio of male to female was 1:2.8. Acquired hypothyroidism was the commonest aetiology found in 73%, 66% of which had an autoimmune basis. The prevalence of congenital hypothyroidism was 0.027%. Seven had received treatment for malignancy (two primary thyroid). Fifteen per cent of patients had no record of secondary care follow up in Tayside. CONCLUSIONS: The overall prevalence of hypothyroidism in young people less than 22 years of age is 0.135%, and in the group aged 11-18 years it is 0.113%; these values are at least twice those of previous estimates. This suggests an increase in autoimmune thyroid disease, similar to the rising prevalence of type 1 diabetes, possibly indicating a rising incidence of autoimmunity in young people.

Adolescent↗
PubMed2000

Glaucoma incidence in an unselected cohort of diabetic patients: is diabetes mellitus a risk factor for glaucoma? DARTS/MEMO collaboration. Diabetes Audit and Research in Tayside Study. Medicines Monitoring Unit.

AIMS: To evaluate whether diabetes mellitus is a risk factor for the development of primary open angle glaucoma or ocular hypertension (OHT). METHODS: A historical cohort study of an unselected population comprising all residents of the Tayside region of Scotland was performed using record linkage techniques followed by case note review. Ascertainment of prevalent diabetes was achieved using the Diabetes Audit and Research in Tayside Study (DARTS) validated regional diabetes register. Glaucoma and treated OHT were defined by encashment of community prescriptions and the statutory surgical procedure coding database. RESULTS: The study population comprised 6631 diabetic subjects and 166 144 non-diabetic subjects aged >40 years without glaucoma or OHT at study entry. 65 patients with diabetes and 958 without diabetes were identified as new cases of glaucoma or treated OHT during the 24 month study period, yielding a standardised morbidity ratio of 127 (95% CI, 96-158). Case note review demonstrated non-differential misclassification of prevalent glaucoma and OHT as incident disease (diabetic cohort 20%, non-diabetic cohort 24%; p=0.56) primarily as a result of non-compliance in medically treated disease. Removing misclassified cases and adjusting for age yielded an incidence of primary open angle glaucoma in diabetes of 1.1/1000 patient years (95% CI, 0.89-1. 31) compared to 0.7/1000 patient years (95% CI, 0.54-0.86) in the non-diabetic cohort; RR 1.57 (95% CI, 0.99-2.48). CONCLUSIONS: This study failed to confirm an association between diabetes mellitus and primary open angle glaucoma and ocular hypertension. A non-significant increase in diagnosed and treated disease in the diabetic population was observed, but evidence was also found that detection bias contributes to this association.

Adult↗
PubMed2000

Regional variation in incidence and case fatality of myocardial infarction among young women in England, Scotland and Wales.

OBJECTIVES: To examine the regional variation in incidence and case fatality of myocardial infarction among young women. DESIGN: Cross sectional survey, using population based incidence data. SETTING: England, Scotland and Wales. SUBJECTS: Subjects were women aged 16-44 with a diagnosis of myocardial infarction between 1 October 1993 and 15 October 1995. OUTCOME MEASURES: Incidence of myocardial infarction per 100,000 women years, with case fatality as a percentage of total cases. RESULTS: Incidence of myocardial infarction rose steeply from age 33 upwards, (maximum = 20.2 cases per 100,000 women years at age 44). The adjusted incidence rate for myocardial infarction was 3.7 (95% CI 3.2, 4.2) times greater in Scotland than in southern England. In contrast, case fatality was significantly lower in Scotland: 18.5% (95% CI 13.1%, 25.0%), compared with 31.0% (95% CI 25.9%, 36.0%) in southern England. CONCLUSIONS: The incidence of myocardial infarction varied widely within the United Kingdom. Case fatality variation may reflect differences in ambulance response, or in diagnostic acumen, within the regions.

Adolescent↗
PubMed2000

Use of routine healthcare data in safe and cost-effective drug use.

Routine healthcare data is becoming widely available, usually as a result of administrative systems. Other related data are also often available, such as biochemistry results, mortality data, and sometimes prescribing data. These records are often linked via a common identification system or by probability matching techniques. These data sources offer many opportunities to undertake research, and where prescription data are recorded and linked, the facility to research the outcome of drug use often exists. There are now a number of research agencies around the world that use these large routine data sources to undertake drug safety and outcome studies. The purpose of this commentary is to describe some of the history behind the development of these systems, illustrate some of their uses with respect to postmarketing drug safety and to other healthcare research objectives. The review then describes the data sources necessary to develop a system that would offer an optimal system to undertake a range of studies, including population drug safety surveillance. There are both positive and negative considerations when using routine data. On the positive side, these data come from 'real life' experiences and not from the clinical trial situation. On the other hand, there are important biases to be aware of such as confounding by indication. On the whole, it is argued that large databases originating from routine healthcare procedures have an important role to play in the cost-effective prescription drug use in the postmarketing setting. These systems cannot replace other methods of drug safety evaluation but they do offer an important adjunct to spontaneous reporting systems.

Drug Monitoring↗