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Biomedical subjects

T M MacDonald

Publications and source records attributed to T M MacDonald.

At least 91 records · Page 5Linked to original sources
PubMed1998

Which drugs benefit diabetic patients for secondary prevention of myocardial infarction? DARTS/MEMO Collaboration.

UNLABELLED: Diabetic patients have increased mortality following myocardial infarction. We review the evidence for benefit in diabetic patients, of the major drug groups used as secondary prevention. Beta blockers: meta-analyses suggest a reduction in mortality of 35% with beta blockers. Diabetic patients should receive beta blockers post myocardial infarction. In many patients, the benefits of beta blockers will outweigh relative contraindications. Aspirin: meta-analyses of antiplatelet therapy in high-risk subjects have shown substantial benefits. Aspirin should be prescribed for secondary prevention. Lipid lowering with statins: subgroup analyses of the major secondary prevention trials show substantial benefits across a wide range of baseline cholesterol and LDL levels. These drugs should be prescribed as secondary prevention to patients with diabetes whose total cholesterol is > 4.0 mmol(-1). Angiotensin converting enzyme inhibitors (ACEIs): the few subgroup analyses that exist from ACEI trials suggest that diabetic and non-diabetic patients derive similar benefits. Diabetic subjects who have systolic dysfunction after myocardial infarction should receive ACEIs. Treatment combination: data exist to suggest that most of these drugs produce benefit independently. CONCLUSION: diabetic patients benefit from secondary prevention with drug treatment as much as, or more than, non-diabetic patients.

Adrenergic beta-Antagonists↗
PubMed1998

Atrial natriuretic peptide increases urinary albumin excretion in men with type 1 diabetes mellitus and established microalbuminuria.

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l-1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg-1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9% saline), low dose (2.5 pmol kg-1 min-1) or high dose (5.0 pmol kg-1 kg min-1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) micrograms min-1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) micrograms min-1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) micrograms min-1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM.

Adult↗
PubMed1998

Drug exposure risk windows and unexposed comparator groups for cohort studies in pharmacoepidemiology.

AIM: To determine the appropriate size of risk windows in both exposed and unexposed sub-cohorts. METHOD: Data was taken from a previous study of upper gastrointestinal haemorrhage and perforation. The length of each prescription for NSAIDs was estimated. The risk was calculated for the duration of a prescription plus increments of -30, -25,..., +115, +120 (i.e. 31 increments). Ten unexposed groups were re-sampled for each increment (stratified for age and sex), using the same lengths of risk window as the exposed group. Mean risks and rate-ratios were calculated (per thousand person-years). RESULTS: The NSAID risk rose from 3.52 at -30 days to a peak of 5.82 at -15 days, and then decreased gradually to 2.83 at +120 days. Unexposed risk was variable for the negative increments, and decreased gradually from 2.16 at +0 days to 1.54 at +120 days. The rate-ratio rose from 1.55 at -30 days to a peak of 2.85 at -5 days, and then decreased to 1.85 at +120 days. CONCLUSION: Risk windows should be the same as (or slightly less than) the calculated length of a prescription. Lengthy windows should not be used for unexposed comparator groups (the exposed windows may be randomly allocated).

Journal Article↗
PubMed1998

A study to determine the sensitivity and specificity of hospital discharge diagnosis data used in the MICA study.

AIMS: To determine the sensitivity and specificity of each ICD9 code for a diagnosis of definite or possible myocardial infarction (MI) from the perspective of the Myocardial Infarction Causality Study (MICA) and to use these data to estimate the likely number of MICA cases in Scotland that would be undetected were these codes omitted from the study. SETTING: Women resident and registered with general practitioners in the Tayside region of Scotland between October 1993 and October 1995. METHOD: All SMR1 records of Tayside hospitalizations containing ICD9 (International Classification of Diseases, ninth revision) codes for myocardial infarction (410) or possible myocardial infarction (411, 412, 413, 414, 427.4, 427.5, 786.5) were identified for women aged between 16 and 44 years between 1 October 1993 and 15 October 1995. Original case records were sought and each episode abstracted using a predefined form. Records were independently scrutinized by two consultant cardiologists blinded to the SMR1 code. Cases were categorized as definite MI, possible MI or unlikely MI. Where there was disagreement between the two cardiologists, the profiles for such events were examined by a third cardiologist who acted as the final adjudicator. The adjudicator's verdict was, in this study, considered dominant. The sensitivity, specificity and positive predictive value of each ICD9 code was determined. RESULTS: Two hundred and fifty-three women fulfilled the SMR1 search criteria. Case records of 204 (81%) were retrieved but four case records contained no data on the admission of interest and were classified as invalid. Forty-six of the 200 remaining patients were ineligible for the MICA study leaving 154 records for evaluation. There were 12 patients who had a discharge code for MI (ICD9 410). Of these, 11 were judged as a definite MI by both cardiologists. One event (discharge code ICD9 410) was judged as 'possible' by one cardiologist and 'unlikely' by the other. The adjudicator subsequently judged this event as 'definite'. Another six events were subsequently judged as 'possible'. Thus, after adjudication, 12 cases of definite MI and six cases of 'possible' MI were identified. The sensitivity and specificity of ICD9 code 410 was 67% and 100% respectively. The positive predictive value was 100%. The sensitivity of code 411 was 5.6%. The specificity was 99% and the positive predictive value was 50%. Code 413 had a sensitivity of 5.6% with a specificity of 94% and a positive predictive value of 9.1%. Code 414 also had a sensitivity of 5.6%. The specificity was 86% and the positive predictive value was 4.5%. Code 786.5 had a sensitivity of 17%, a specificity of 23% and a positive predictive value of 2.5%. Code 427.5 failed to identify any definite or possible cases. CONCLUSIONS: In the MICA Study, ICD9 code 410 was found to be the most robust. All 12 patients judged to have had a definite MI had the appropriate discharge code (ICD9 410). The six patients judged to have had a possible MI all had discharge codes other than that for MI (410). However, identifying these six patients required the validation of a further 160 events-giving a combined sensitivity of 33%, a specificity of 0% and a positive predictive value of only 3.8%. The use of ICD9 codes 411, 413, 414, 427.5 and 786.5 must, therefore, only be employed when circumstances fully justify the additional workload.

Journal Article↗
PubMed1998

Do H2-receptor antagonists cause acute pancreatitis?

The aim of this study was to investigate the association between H(2)-receptor antagonists and acute pancreatitis. The automated database of the Medicines Monitoring Unit (MEMO) was used to carry out a case-control study, supplemented with information on possible confounding factors from hospital and GP medical records. Cases were patients hospitalized with a computerized diagnosis of acute pancreatitis, and two sets of controls were drawn from (1) the study population and from (2) the same GP practice as the case. Current or 60-day exposure to cimetidine and ranitidine was analysed. In adjusted analyses, cimetidine exposure and ranitidine exposure were associated with an increased risk of hospitalization for acute pancreatitis, as were alcohol abuse and cholelithiasis. The risks were lower in unadjusted analyses, suggesting that the association is confounded, although they did not disappear completely. A possible explanation is that data on confounding were incomplete. This study cannot discount the existence of an association between H(2)-antagonists and acute pancreatitis, and highlights the difficulties involved in obtaining complete and accurate data on confounding factors that are not collected routinely.

Journal Article↗
PubMed1998

Isolated diastolic heart failure--what is it?

Epidemiological evidence suggests that 20 to 40% of all patients with heart failure have normal systolic function. Isolated diastolic dysfunction may be the principle pathophysiological mechanism in these patients. The diagnosis of isolated diastolic heart failure is problematic and not merely based on demonstrating normal systolic function. The prognosis in isolated diastolic heart failure is more favourable than in systolic heart failure. At the present time, there is no licensed treatment for isolated diastolic heart failure and treatment is largely empirical.

Diastole↗
PubMed1998

Aspirin, nonsteroidal anti-inflammatory drugs, and epistaxis. A regional record linkage case control study.

To assess the relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and spontaneous epistaxis in adults over 50 years old, a case control study was carried out by using a record linkage database for the population of Tayside, Scotland, which included 319,465 people. The study group consisted of 326 patients who were hospitalized with epistaxis between May 1989 and December 1992, but who had not previously been hospitalized with this diagnosis. Six community controls and 4 hospital controls, matched for age and sex to each case, were used. Previous exposure to prescribed aspirin and other NSAIDs was investigated. There was a significant association between aspirin exposure and epistaxis when either community or hospital controls were used (p < .001). Patients who had aspirin prescriptions had a relative risk of hospital admission for epistaxis of between 2.17 and 2.75, depending on the control group used. No association between non-aspirin NSAIDs and epistaxis was evident with either control group.

Aged↗
PubMed1998

Diabetes and lower-limb amputations in the community. A retrospective cohort study. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland/Medicines Monitoring Unit.

OBJECTIVE: There are few U.K. data on the incidence rates of amputation in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS: We performed a historical cohort study of first lower-extremity amputations based in Tayside, Scotland (population 364,880) from 1 January 1993 to 31 December 1994. The Diabetes Audit and Research in Tayside Scotland (DARTS) database was used to identify a prevalence cohort of 7,079 diabetic patients on 1 January 1993. We estimated age-specific and standardized incidence rates of lower-limb amputations in the diabetic and nondiabetic cohorts. Results were compared with a previous study that evaluated lower-extremity amputations in diabetic patients in Tayside in 1980-1982. RESULTS: There were 221 subjects who underwent a total of 258 nontraumatic amputations. Of the 221 subjects, 60 (27%) patients were diabetic (93% NIDDM), and 63% were first amputations. The median duration of diabetes was 6 years (range: newly diagnosed to 41 years). Nonhealing ulceration (31%) and gangrene (29%) were the two main indications for amputation in the diabetic subjects. Of the 161 nondiabetic subjects, 140 (80%) underwent first amputations. The adjusted incidences in the diabetic and nondiabetic groups were 248 and 20 per 100,000 person-years, respectively. Tayside patients with diabetes thus had a 12.3-fold risk of an amputation compared with nondiabetic residents (95% CI 8.6-17.5). The estimated proportion of diabetic patients in the population rose from 0.81% in 1980-1982 to 1.94% in 1993-1994, whereas the absolute rate of amputation in diabetic subjects was unchanged from that in 1980-1982. CONCLUSIONS: These population-based U.K. amputation data are similar to amputation rates in the U.S. Amputation rates appear to have decreased significantly since 1980-1982. The impact of diabetes education and prevention programs that target the processes leading to amputation can now be evaluated.

Adolescent↗
PubMed1998

Angiotensin II type 1 receptor blockade: a new development in cardiovascular pharmacology.

The renin-angiotensin-aldosterone system (RAS) plays a central role in blood pressure regulation and fluid and electrolyte homoeostasis. Blockade of this system with inhibitors of angiotensin-converting enzyme (ACE) has been shown to benefit several groups of patients, including those with essential hypertension, congestive heart failure, and post myocardial infarction. Inhibition of ACE also slows the progression of diabetic renal disease and diabetic retinopathy. The recent development of agents that are specific antagonists of angiotensin II (AII) has allowed us to block the RAS at receptor level. Inhibition of angiotensin II receptors has been shown to reduce blood pressure in hypertensive patients, without the side-effect profile of ACE inhibitors. It has yet to be shown whether manipulating the RAS in this way will confer the same morbidity and mortality benefits as those seen with ACE inhibition. Ongoing research will reveal whether All antagonists are beneficial in congestive heart failure, ischaemic heart disease and diabetes mellitus. The development of this new class of agent provides an exciting opportunity for clinicians to increase their understanding of the role of the RAS in health and disease.

Angiotensin II↗
PubMed1997

Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus. The DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland. Medicines Monitoring Unit.

BACKGROUND: Intensive insulin treatment effectively delays the onset and slows the progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Variable adherence to insulin treatment is thought to contribute to poor glycaemic control, diabetic ketoacidosis, and brittle diabetes in adolescents and young adults with IDDM. We assessed the association between the prescribed insulin dose and the amount dispensed from all community pharmacies with the Diabetes Audit and Research in Tayside Scotland (DARTS) database. METHODS: We studied 89 patients, mean age 16 (SD 7) years, diabetes duration 8 (4) years, and glycosylated haemoglobin (HbA1c) 8.4 (1.9)%, who attended a teaching hospital paediatric or young-adult diabetes clinic in 1993 and 1994. The medically recommended insulin dose and cumulative volume of insulin prescriptions supplied were used to calculate the days of maximum possible insulin coverage per annum, expressed as the adherence index. Associations between glycaemic control (HbA1c), episodes of diabetic ketoacidosis, and all hospital admissions for acute complications and the adherence index were modelled. FINDINGS: Insulin was prescribed at 48 (19) IU/day and mean insulin collected from pharmacies was 58 (25) IU/day, 25 (28%) of the 89 patients obtained less insulin than their prescribed dose (mean deficit 115 (68; range 9-246] insulin days/annum). There was a significant inverse association between HbA1c and the adherence index (R2 = 0.39; p < 0.001). In the top quartile (HbA1c > 10%), 14 (64%) of individuals had an adherence index suggestive of a missed dose of insulin (mean deficit 55 insulin days/annum). There were 36 admissions for complications related to diabetes. The adherence index was inversely related to hospital admissions for diabetic ketoacidosis (p < 0.001) and all hospital admissions related to acute diabetes complications (p = 0.008). The deterioration in glycaemic control observed in patients aged 10-20 years was associated with a significant reduction (p = 0.01) in the adherence index. INTERPRETATION: We found direct evidence of poor compliance with insulin therapy in young patients with IDDM. We suggest that poor adherence to insulin treatment is the major factor that contributes to long-term poor glycaemic control and diabetic ketoacidosis in this age group.

Adolescent↗
PubMed1997

Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study.

OBJECTIVES: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. DESIGN: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. SETTING: The population of Tayside, Scotland. SUBJECTS: 52,293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73,792 subjects who did not receive one during the same period (controls). MAIN OUTCOME MEASURES: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. RESULTS: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. CONCLUSION: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs.

Age Factors↗
PubMed1997

The diabetes audit and research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration.

OBJECTIVES: To identify all patients with diabetes in a community using electronic record linkage of multiple data sources and to compare this method of case ascertainment with registers of diabetic patients derived from primary care. DESIGN: Electronic capture-recapture linkage of records included data on all patients attending hospital diabetes clinics, all encashed prescriptions for diabetes related drugs and monitoring equipment, all patients discharged from hospital, patients attending a mobile unit for eye screening, and results for glycated haemoglobin and plasma glucose concentrations from the regional biochemistry database. Diabetes registers from primary care were from a random sample of eight Tayside general practices. A detailed manual study of relevant records for the 35,144 patients registered with these eight general practices allowed for validation of the case ascertainment. SETTING: Tayside region of Scotland, population 391,274 on 1 January 1996. MAIN OUTCOME MEASURES: Prevalence of diabetes; population of patients identified by different data sources; sensitivity and positive predictive value of ascertainment methods. RESULTS: Electronic record linkage identified 7596 diabetic patients, giving a prevalence of known diabetes of 1.94% (0.21% insulin dependent diabetes, 1.73% non-insulin dependent): 63% of patients had attended hospital diabetes clinics, 68% had encashed diabetes related prescriptions, 72% had attended the mobile eye screening unit, and 48% had biochemical results diagnostic of diabetes. A further 701 patients had isolated hyperglycaemia (plasma glucose > 11.1 mmol/l) but were not considered diabetic by general practitioners. Validation against the eight general practices (636 diabetic patients) showed electronic linkage to have a sensitivity of 0.96 and a positive predictive value of 0.95 for ascertainment of known diabetes. General practice lists had a sensitivity of 0.91 and a positive predictive value of 0.98. CONCLUSIONS: Electronic record linkage was more sensitive than general practice registers in identifying diabetic subjects and identified an additional 0.18% of the population with a history of hyperglycaemia who might warrant screening for undiagnosed diabetes.

Diabetes Mellitus↗
PubMed1997

Misclassification and selection bias in case-control studies using an automated database.

Automated databases are increasingly being used for pharmacoepidemiological research and fieldwork is often carried out to supplement and validate information held within them. In MEMO's case-control studies, patients are identified using computerized ICD9 diagnosis codes, the original medical records are retrieved and checked, and only patients fulfilling case inclusion criteria are used. The 20-30% of patients for whom medical records cannot be found are usually excluded. The aim is to eliminate misclassification bias. However, selection bias may be introduced if availability of medical records is associated with exposure. This investigation was therefore carried out to assess the relative importance of misclassification and selection bias. Data from four previous case-control studies, investigating the associations between NSAIDs and hospitalization for colitis, acute renal failure, appendicitis and colorectal cancer, were used. To assess misclassification, odds ratios (with 95% CI) for recent exposure to NSAIDs were compared in repeated studies that used all patients identified by ICD9 codes, with studies using validated cases only. Selection bias was assessed by comparing results in studies using patients for whom records could and could not be found. Results were plotted and the graphs indicated that misclassification bias was relatively unimportant, but that selection bias could be introduced into a study in this way.

Journal Article↗