Alex D. McMahon

Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus

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.

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.

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).

Randomised controlled double-blind trial of the calcium channel antagonist amlodipine in the treatment of acute alcoholic hepatitis

BACKGROUND/AIMS Calcium channel blockers have a hepatoprotective action in animal models of alcohol-induced liver injury but their effect in alcoholic liver disease in humans has not been previously investigated. We have conducted a randomised, placebo-controlled trial to investigate the possible benefit of the calcium channel blocker amlodipine in terms of 4-week survival in hospitalised patients with severe acute alcoholic hepatitis. METHODS Sixty-two patients with acute alcoholic hepatitis were randomised to receive 5-10 mg amlodipine each day for 1 year or an identical capsule containing placebo. In 36 (58%), acute alcoholic hepatitis was confirmed on biopsy and in the remainder on clinical and laboratory criteria. There were no statistically significant differences in clinical characteristics and disease severity in the treated and placebo groups. RESULTS Of the 32 patients receiving amlodipine, there were six deaths (19%) in the first 4 weeks compared with seven (23%) of the placebo patients (p=0.329). Causes of death were similar in the amlodipine and control groups, with liver failure predominant. Analysis by the Cox proportional hazards model after adjustment for other prognostic factors showed survival was not significantly influenced by active treatment (p=0.07). One patient in each group was withdrawn because of the development of hypotension, but this did not recur on reintroduction of the capsules. CONCLUSIONS This study shows that calcium channel blockers are well tolerated with few side effects in advanced alcoholic liver disease, but there is no conclusive evidence from this study that calcium channel blockers are helpful in the treatment of alcoholic hepatitis.

Costs Associated with Symptomatic Systolic Heart Failure

AbstractObjective: To investigate whether the extent of systolic dysfunction is a useful predictor of the costs of healthcare and social support for patients with heart failure. Design: Cross-sectional study with collection of cost data attributed to management of heart failure in the previous year. Setting: Four primary-care practices in Scotland. Patients: Patients receiving long term therapy with loop diuretics for suspected heart failure. Interventions: Two-dimensional and Doppler echocardiography. Main outcome measures and results: Two hypotheses were tested: (i) the proportion of patients incurring costs is higher in patients with abnormal left ventricular (LV) function; and (ii) the median cost per patient that incurs costs is higher in patients with abnormal LV function.Of the 226 patients in the study, 67 (30%) had abnormal systolic function. In comparison with the remaining 159 patients, they had higher healthcare costs [£560 vs £440 per patient year (1994/1995 values)], were more likely to incur hospital inpatient or outpatient costs [Odds ratio (OR): 2.02; 95% confidence interval (CI): 1.06 to 3.84] and had significantly higher primary-care costs (mean £292 vs £231 per patient year; p = 0.02, Mann Whitney test). In contrast, they were no more likely to incur social support costs (OR: 1.22; 95% CI: 0.52 to 2.86) and the mean cost of social support per patient year was lower (£234 vs £373). Conclusions: Patients with objectively measured systolic dysfunction incurred significantly higher healthcare costs in the year before diagnosis. This suggests that treatment that improves systolic function will reduce healthcare costs, even in a primary-care population with relatively mild congestive heart failure.

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.

Do H2-receptor antagonists cause acute pancreatitis?

The aim of this study was to investigate the association between H2‐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 H2‐antagonists and acute pancreatitis, and highlights the difficulties involved in obtaining complete and accurate data on confounding factors that are not collected routinely. Copyright

Patients receive an inadequate dose of antidepressants for an inadequate period.

Editor—K Milligan considers our comments on the prescribing of low doses of antidepressants to be misleading because some patients get these drugs for indications other than depression.1 2 Our study showed that less than 1% of subjects received an adequate dose of tricyclic antidepressants for an adequate period (>90 days). Our argument would stand …

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.

The effect of hip replacement on prescribing of NSAIDs, ulcer healing drugs and hospitalization--a matched cohort study.

To assess the impact of total hip replacement on prescribing of non‐steroidal anti‐inflammatory drugs (NSAIDs), ulcer healing drugs (UHDs) and hospitalization.