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Biomedical subjects

T M MacDonald

Publications and source records attributed to T M MacDonald.

At least 109 records · Page 6Linked to original sources
PubMed1997

Sample size for cohort studies in pharmacoepidemiology.

OBJECT: Cohort studies in pharmacoepidemiology can result in a unique type of study, where subjects have complex types of exposure to drugs (with periods of non-exposure as well). The object of this paper is to explain how to calculate the sample size of such a study. METHOD: It is assumed that adverse events follow Poisson distributions in the two study groups. The null hypothesis is that the two groups have equal rates of disease. Formulae are provided to calculate the sample size required to significantly reject the null hypothesis. Sample size is given as the number of events, rather than the number of subjects entered. In a Poisson study, it is the ratio of the amount of person-years exposure in the two groups that is important to calculate sample size, rather than the actual amounts of exposure (or number of subjects in the study). Some examples are included.

Journal Article↗
PubMed1997

The impact on community benzodiazepine prescribing of hospitalization.

To assess the impact of both general and psychiatric hospitalization on the community prescribing of benzodiazepines, we carried out an observational study using record linkage of prescribing prior to and following hospitalization along with a review of hospital case records at four Tayside General Practices. In a population of 29,672 subjects, 2628 general hospital and 254 psychiatric hospitalizations were studied. The main outcome measure was the change in community benzodiazepine prescribing following hospitalization. We found that admission to a general hospital resulted in 59 of the 2628 subjects (2.2%) commencing and 45 subjects (1.7%) discontinuing benzodiazepines. Admission to a psychiatric hospital resulted in 17 of 254 subjects (6.7%) commencing and 40 (16.7%) discontinuing benzodiazepines. When compared to benzodiazepine prescribing in the study population these effects were trivial. We conclude that hospitalization in both general and psychiatric hospitals had a minor effect on total community prescribing of benzodiazepines. In this study general hospital admission resulted in a small net increase and psychiatric hospitalization a small net decrease in benzodiazepine prescribing.

Adolescent↗
PubMed1997

A cohort study (with re-sampled comparator groups) to measure the association between new NSAID prescribing and upper gastrointestinal hemorrhage and perforation.

This cohort study examined the relationship between newly prescribed NSAIDs (none in the previous six months) and upper gastrointestinal hemorrhage and perforation in Tayside, Scotland. Exposure was classified by prescription duration. The study population consisted of the population of Tayside. A Comparator Group was chosen at random (within age and sex strata). Two hundred re-sampled comparator groups were created. Statistical analyses were carried out by Poisson regression (repeated for each of the re-samples). The analyses controlled for age, sex, prior hospitalization for upper gastrointestinal events, prior endoscopy, and the use of ulcer healing drugs. There were 78,191 subjects in the NSAID group, and 78,207 in each of the comparator groups. The increased risk with NSAIDs was only apparent for subjects without a history of upper gastrointestinal events; univariate rate ratio = 2.76 (1.90, 4.01). The final, re-sampled estimate of NSAID risk was rate ratio = 2.48 (1.87, 3.29).

Adult↗
PubMed1997

Do trandolapril and indomethacin influence renal function and renal functional reserve in hypertensive patients?

AIMS: To assess the effect of trandolapril (2 mg once daily) and indomethacin (25 mg three times daily), alone and in combination, on renal function and renal functional reserve in hypertensive patients (DBP 95-115 mmHg) requiring regular non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Randomized, double-blind, placebo-controlled, four way crossover design. After 3 weeks treatment renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured using the p-aminohippurate (PAH) and inulin methods. Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1) and 10% amino acid solution. RESULTS: There was no significant difference in RPF between treatments: -22.79 ml min(-1) (95% CI -54.82, 9.24) for placebo and trandolapril, -10.37 ml min(-1) (95% CI -30.7, 9.96) for placebo and indomethacin, -14.78 ml min(-1) (95% CI -50.33, 20.77) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve RPF between treatments: -34.96 ml min(-1) (95% CI -119.8, 49.88) for placebo and trandolapril, 29.78 ml min(-1), -15.18, 74.74) for placebo and indomethacin, and -25.84 ml min(-1) (95% CI -87.62, 35.94) for placebo and trandolapril with indomethacin. There was no significant difference in GFR between treatments: -1.01 ml min(-1) (95% CI -7.45, 5.42) for placebo and trandolapril, -7.88 ml min(-1) (95% CI -15.08, -0.68) for placebo and indomethacin, and -0.36 ml min(-1) (95% CI -7.58, 6.86) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve GFR between treatments: 5.13 ml min(-1) (95% CI -4.97, 15.23) for placebo and trandolapril, 6.31 ml min(-1) (95% CI -1.88, 14.5) for placebo and indomethacin, 7.21 ml min(-1) (95% CI 1.26, 13.16) for placebo and trandolapril with indomethacin. CONCLUSION: In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR.

Adult↗
PubMed1997

Influence of the angiotensin converting enzyme I/D gene polymorphisms on left ventricular diastolic filling in patients with essential hypertension.

BACKGROUND: An insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene accounts for 50% of the variance in serum ACE activity. ACE is responsible for the generation of angiotensin II, which not only has pressor and mitogenic activities but also exerts effects on left ventricular diastolic performance. OBJECTIVE: To investigate the contribution of genetic polymorphisms at the ACE gene to the development of diastolic functional abnormalities in 100 patients with essential hypertension. METHODS AND RESULTS: The left ventricular mass (LVMI) of each patient was assessed echocardiographically. We calculated peak and integral early:late left ventricular diastolic filling ratios (E:AP, and E:AI, respectively) and determined the ACE genotype from leukocyte DNA. There was no significant difference in age, sex, blood pressure and LVMI among genotype groups. Analysis of covariance modelled for indices of diastolic function, adjusted for age, sex, heart rate and LVMI, demonstrated that the E:AP interacted with age (P < 0.0001), heart rate (P < 0.001) and ACE genotype (P = 0.018). Similarly, the E:AI interacted with age (P < 0.001), heart rate (P = 0.025) and ACE genotype (P = 0.047). There was a strong correlation between the E:AP and the LVMI for the DD group (r = -0.81, P < 0.0001) but not for the ID (r = -0.03, P = 0.83) and II (r = -0.23, P = 0.23) groups. CONCLUSIONS: These findings suggest that that the I/D polymorphism of the ACE gene influences the relationship between left ventricular mass and echocardiographic left ventricular diastolic filling abnormalities in patients with essential hypertension.

Adult↗
PubMed1997

Safe withdrawal of monotherapy for hypertension is poorly effective and not likely to reduce health-care costs.

OBJECTIVE: To carry out a population-based evaluation of withdrawal of treatment in primary care using repeated ambulatory blood pressure monitoring (ABPM) assessment to avoid subjecting patients to prolonged periods of excess risk. METHOD: Patients from two community practices (total population 11 034 patients) being administered monotherapy for hypertension, were identified and invited to participate. Subjects were withdrawn from treatment if they had no significant co-morbidity and daytime ABPM blood pressure was < or = 150/90 mmHg. Antihypertensive therapy was restarted if daytime ABPM blood pressure was > 150/90 mmHg during weeks 4, 8, 12, 26, 39 and 52. RESULTS: Of 126 eligible patients 53 had a co-morbidity and 37 declined to participate. Of the 36 patients who entered the study 10 were excluded because they had elevated ABPM blood pressures during treatment and one because they had echocardiographic left ventricular hypertrophy. Of the 25 patients from whom monotherapy was withdrawn, we restarted treatment of 19 before week 52. If clinic blood pressure monitoring had been used instead of ABPM, different decisions would have been taken in eight of 25 cases. The costs of the ABPM-determined withdrawal of treatment programme were greater than the expected savings in drug costs, even assuming that all six patients from whom treatment was withdrawn remained without treatment for a further 9 years. This conclusion was not sensitive to reducing the number of ABPM measurements and to inflation in study-drug costs. However, if all patients had been treated with the most expensive drug, then even the full ABPM programme could have saved money within 9 years. CONCLUSIONS: Antihypertensive therapy could be withdrawn from only a small proportion of patients in the community on the basis of ABPM. The costs of the programme are likely to exceed savings unless the cost of drugs administered is substantially higher than that observed in this study.

Aged↗
PubMed1997

Helicobacter pylori infection status in relation to antibiotic and non-steroidal prescribing in patients on maintenance treatment for chronic duodenal ulcer.

UNLABELLED: It has been suggested that establishing Helicobacter pylori infection status is irrelevant prior to H. pylori eradication treatment in chronic duodenal ulcer, as virtually all may benefit from therapy. OBJECTIVE: The aim of the present study was (i) to determine the prevalence of active H. pylori infection in patients with proven chronic duodenal ulcer on long-term H2-antagonist prophylactic treatment and whether knowledge of this would influence the use of eradication therapy and (ii) to assess other factors which might influence the clinical diagnosis or H. pylori status, such as non-steroidal and antibiotic use. METHODS: One hundred and forty-five patients receiving long-term H2-antagonists for chronic duodenal ulcer were recruited. Their case records and a prescribing database were reviewed. Patients underwent endoscopy with biopsies for rapid urease test, histology and H. pylori culture. Serum was immunoblotted and an enzyme-linked immunosorbent assay for H. pylori was performed. RESULTS: Of the 145 patients, 128 (88%) were H. pylori biopsy positive. Twelve of the 17 H. pylori biopsy-negative patients had anti-H. pylori immunoglobulin G (IgG) antibodies and 10 of the 17 H. pylori-negative patients had previously received antibiotics for other indications. Nine patients were exposed to non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) and one had additional aspirin exposure. CONCLUSION: Only 11.7% of patients on maintenance treatment for chronic duodenal ulcer had no current infection with H. pylori, although more than 70% of these had serological evidence of previous infection. Confirmation of active infection may be indicated where there is a history of NSAID or antibiotic exposure and may result in more precise targeting of eradication therapy, thus avoiding unnecessary and potentially hazardous treatment.

Adult↗
PubMed1997

Non-steroidal anti-inflammatory drugs are associated with emergency admission to hospital for colitis due to inflammatory bowel disease.

BACKGROUND: To evaluate the relation between non-steroidal anti-inflammatory drugs (NSAIDs) and colitis due to inflammatory bowel disease. METHODS: A case-control study was conducted using a prospectively constructed, record linkage database containing hospital event and dispensed drug data (1989-93). The study population consisted of 319,465 people resident in Tayside in January 1989, and still resident (or dead) in October 1994. RESULTS: Of the 785 patients admitted to hospital as emergencies with colitis between July 1989 and June 1993, 200 fulfilled the case criterion of colitis due to inflammatory bowel disease. A further 1198 persons were used as community controls. Odds ratios were calculated for three exposure periods (current, recent, and past exposure). The overall odds ratios (with 95% confidence intervals) for current and recent exposure to NSAIDs were 1.77 (1.01 to 3.10) and 1.93 (1.20 to 3.09) respectively. Current and recent exposure to NSAIDs was also associated for incident cases, with odds ratios of 2.96 (1.32 to 6.64) and 2.51 (1.13 to 5.55). There was a trend for recent exposure among non-incident cases. CONCLUSION: The use of NSAIDs may be associated with an increased risk of emergency admission to hospital for colitis due to inflammatory bowel disease, particularly among patients with no previous history.

Adolescent↗
PubMed1997

ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside, Scotland. Medicines Monitoring Unit.

OBJECTIVE: To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship. RESEARCH DESIGN AND METHODS: The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort. RESULTS: Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2-8.3, P = 0.023), whereas use of beta-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3-3.3) and 1.7 (95% CI 0.2-2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2-16.0). CONCLUSIONS: The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.

Adolescent↗
PubMed1997

No association between non-steroidal anti-inflammatory drugs and acute appendicitis in a case-control study.

BACKGROUND: A recent case-control study reported an association between non-steroidal anti-inflammatory drug (NSAID) use and acute appendicitis. This association was investigated in a case-control study of patients, aged 30 years and over, admitted as an emergency to hospitals in Tayside between 1989 and 1992, who had appendicectomy for acute appendicitis. METHODS: A record-linkage database containing records of dispensed prescriptions and hospital admissions was used. A total of 223 patients were identified. The medical records of 161 were checked, of which 138 were valid cases, and information on white cell count and NSAID exposure was recorded. Community and hospital controls were generated. RESULTS: Some 9.0 per cent of patients were prescribed NSAIDs within 90 days of hospitalization, compared with 7.6 per cent of community controls and 11.5 per cent of hospital controls. The odds ratio was 1.21 (95 per cent confidence interval 0.73-2.01) and 0.75 (0.43-1.32) respectively. There was no significant difference in white cell count between exposed and non-exposed cases. No increased risk of appendicectomy was associated with aspirin use: odds ratio 1.67 (0.52-5.30) and 0.37 (0.12-1.13) using community and hospital controls respectively. CONCLUSION: Appendicectomy for acute appendicitis is not associated with increased prior use of NSAIDs.

Adult↗
PubMed1997

Demand for warfarin anticoagulation monitoring in Tayside, Scotland.

AIM: The aim of this study was to assess the demand for warfarin prescribing and monitoring, and to identify patients with atrial fibrillation who might benefit from warfarin therapy. The study was carried out in the population of Tayside, Scotland (400,000 people) using patient-specific dispensed prescribing and hospitalisation data from the Medicines Monitoring Unit at the University of Dundee. METHODS: The incidence and prevalence of digoxin and warfarin prescribing were calculated between 1989 and 1993. Patients dispensed digoxin in 1993 were assumed to have atrial fibrillation and they were stratified into high risk groups for an adverse thromboembolic event based on past medical history. The numbers of patients at high risk who were judged to be possible candidates for warfarin were calculated. RESULTS: The prevalence of warfarin prescribing is increasing in Tayside and is mainly for elderly patients. There were also many patients assumed to have atrial fibrillation who were at particularly high risk for an adverse thromboembolic event, who had no record of warfarin prescribing. Only 35% received warfarin. Even given the methodological limitations of this study, and the use of aspirin as an alternative prophylactic agent, it is likely that these patients have been a source of increased prevalence of warfarin prescribing since 1993 and will be in the future. Other indications for warfarin prescribing are also increasing. CONCLUSION: It is anticipated that there will be increasing demands for anticoagulant monitoring, which will need to be met either by increasing the capacity of existing clinics, or by increasing the role of primary care.

Aged↗
PubMed1996

Effects of brain natriuretic peptide on exercise hemodynamics and neurohormones in isolated diastolic heart failure.

BACKGROUND: Experimental models suggest that brain natriuretic peptide (BNP) can modify left ventricular diastolic performance. The aim of this study was to evaluate the effects of BNP on resting and exercise hemodynamics and neurohormones in patients with isolated diastolic heart failure. METHODS AND RESULTS: Six patients with isolated diastolic heart failure were studied. After baseline hemodynamic measurements were obtained with use of thermistor-tipped pulmonary artery catheters, patients were randomized to receive infusion of BNP or placebo in a single-blind, crossover study. Hemodynamic and neurohormonal parameters were measured at rest after 30 minutes of infusion and during incremental supine bicycle exercise. BNP did not significantly affect resting hemodynamics but attenuated the rise in both pulmonary capillary wedge pressure (placebo, 23 +/- 2 mm Hg; BNP, 16 +/- 2 mm Hg; P < .01) and mean pulmonary artery pressure (placebo, 34 +/- 3 mm Hg; BNP, 29 +/- 3 mm Hg; P < .05) during exercise without affecting changes in heart rate, systemic blood pressure, or stroke volume. In response to BNP, there was significant suppression of plasma aldosterone concentration (placebo, 551 +/- 107 pmol/L; BNP, 381 +/- 56 pmol/L; P < .05). CONCLUSIONS: BNP infusion causes beneficial hemodynamic and neurohormonal effects during exercise in patients with isolated diastolic heart failure.

Aged↗
PubMed1996

Impaired exercise tolerance in hypertensive patients.

PURPOSE: To review information on exercise testing in hypertensive patients and persons at risk for developing hypertension and to determine whether this type of investigation is valuable for diagnosis, prognosis, or assessment of the effect of therapy. DATA SOURCES: A MEDLINE search of English-language articles published between 1985 and 1995 and reviews of the bibliographies of textbooks. STUDY SELECTION: Primary research articles on exercise testing in patients with hypertension, with an emphasis on methods, diagnosis, prognosis, and assessment of drug therapy. DATA EXTRACTION: Study design and quality were assessed, with particular attention paid to methods and aims. Relevant data on hemodynamic responses in hypertensive patients and persons at risk for developing hypertension and correlations to end-organ damage, mortality, and exercise tolerance were analyzed. DATA SYNTHESIS: The exercise capacity of hypertensive patients was found to be reduced by as much as 30% compared with age-matched controls. This exercise impairment increases with age and end-organ damage, and its origin can be traced back to adolescence. Total peripheral resistance also progressively increases. These changes are caused by functional and structural involvement of the cardiovascular system. Diastolic dysfunction of the heart is a prominent factor in this exercise limitation. The blood pressure responses to exercise have prognostic value for the future development of hypertension, end-organ damage, and death. The adequacy of antihypertensive treatment should therefore be evaluated in terms of normalizing these stress-related blood pressure responses. CONCLUSION: Exercise testing is a simple procedure that has great potential for assessing hypertensive patients. More research is necessary, however, to determine whether controlling blood pressure during exercise is beneficial.

Age Factors↗