Maybelle Kou

Treatment of acute cortical infarct with intravenous glycerol. A double-blind, placebo-controlled randomized trial.

Background and Purpose This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infarction in whom intracerebral hemorrhage was rigorously excluded. Methods Within 48 hours of symptoms from their first ischemic stroke, 113 hospital inpatients were randomized into the trial, provided that hemorrhage was excluded by computed tomography and informed consent was obtained. Patients were stratified into alert, semicoma, and coma groups using the Glasgow Coma Scale. Treatment was allocated according to a double-blind, randomized protocol; 56 patients received 500 mL of 10% glycerol in saline over 4 hours on 6 consecutive days, and 57 patients received corresponding placebo treatment with saline. Using a variety of objective scoring systems, patient follow-up was up to 6 months. Results Corresponding measures of outcome in the glycerol and placebo groups were similar. At 6 months, respective mortality rates were 17 of 56 and 16 of 57, and mean ±SD improvements in scores were 9.98±14.40 vs 10.51±12.68 (long-term), 1.12±7.20 vs 1.57±6.30 (prognostic), −1.94±5.53 vs −2.06±5.34 (Glasgow Coma Scale), and 21.72±23.40 vs 11.94± 18.10 (Barthel Index rating in survivors). Hemolysis (generally subclinical) was the only adverse effect. Conclusions There was no clinically or statistically significant difference in outcome between the groups; a trend toward greater functional recovery among survivors was evident after treatment with glycerol.

Inability of physicians to use metered-dose inhalers.

The effectiveness of antiasthmatic therapy with metered-dose inhalers (MDIs) is usually limited by defective inhalational technique. This study surveyed the MDI inhalation performance and knowledge of 100 physicians whose performance (demarcated into six stages) and knowledge scores correlated (r = 0.33, p < 0.001). Inhalation performance scores for shaking the canister, full expiration prior to using the MDI, breath holding thereafter, and positioning of the mouth-piece correlated with their corresponding knowledge scores (p < or = 0.02). Training of physicians entailing actual instruction and supervision of inhalational maneuvers may enhance the ability of doctors to use MDIs and facilitate better patient supervision.

Increasing use of inhaled steroids associated with declining asthma mortality.

Increasing worldwide asthma prevalence and mortality has led to greater advocacy of inhaled agents, especially steroids. To determine whether corresponding drug usage trends had ensued locally, wholesale data (expressed as defined daily doses (DDDs)/1000 inhabitants/day) were compared for inclusive periods 1984–1986 and 1992–1994. Whereas absolute usage of anti-asthmatics increased by 79%, proportional inhaled usage increased markedly, especially of steroids (571%) and in hospitals. An odds ratio trend analysis revealed asthma mortality from 1992 onward had declined, particularly in males (p < 0.001). In Hong Kong, despite increasing asthma prevalence, more intensive use of anti-asthmatic drugs (especially inhaled steroids) was associated with declining asthma mortality.

An assessment of drug information sheets for diabetic patients: only active involvement by patients is helpful*

Insulin/sulphonylurea-treated diabetics attending a busy university diabetic clinic were studied to determine whether issuing drug information sheets and/or age influenced understanding and behaviour regarding their disease and its treatment, especially with respect to avoiding hypoglycaemia. Patients were each asked 10 basic questions (each correct answer scoring 1), stratified by age (20 were less than or equal to 45 years and 91 greater than 45 years). According to a single-blind randomised protocol, they were issued or not issued with drug information sheets (providing information to correctly answer all 10 questions). After 2-3 months, 107 (88 aged greater than 45 years) were retested and asked whether they recalled an information sheet, read it themselves or had it read to them. Whether or not patients received sheets, corresponding mean aggregate scores were very similar in both age groups and there was no correlation with age. Second test scores yielded clinically and statistically significant increments in both the sheet and no sheet groups, respective mean aggregate scores increasing from 4.48 to 5.80 and 5.14 to 6.27 (P less than 0.001). Among patients issued with sheets, 32 who recalled reading them achieved the greatest improvement in mean scores (4.53 to 6.16, P less than 0.001). Active interaction/communication (participation in first test, recall and reading of information sheet) had a favourable educational impact irrespective of age, but merely issuing drug information sheets had no benefit.

Lack of association between slow acetylator status and spontaneous lupus erythematosus

The Chinese in Southeast Asia are recognized as a population group that has a relatively high prevalence of rapid “acetylators” and a relatively high incidence of systemic lupus erythematosus. This study was designed to evaluate the possibility that there were environmental lupus erythematosus provocative substances eliminated by acetylation that resulted in a preponderance of slow acetylators among patients with the disease. We compared acetylator status in 36 Chinese women with mild, stable, and confirmed lupus erythematosus and 36 healthy control subjects matched for age, sex, and ethnic origin. Acetylator status was determined by use of HPLC to assay 5‐acetylanimo‐6‐formylamino‐3‐methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine). By use of parametric and nonparametric methods of analysis, the frequency distribution of AFMU/MX and AFMU/(AFMU + MX) ratios in both the patients and control subjects were determined to be very similar. Thus there was no association between slow acetylator status and lupus erythematosus in the study subjects.

Investigation of nimodipine pharmacokinetics in Chinese patients with acute subarachnoid haemorrhage

SummaryNimodipine pharmacokinetics was investigated in 12 Chinese patients with acute subarachnoid haemorrhage receiving an IV infusion of 1.6 or 2 mg/h (based on estimated body weight) for 10 days. Peripheral venous blood samples were collected for up to 4 days and plasma nimodipine was assayed by GC/ECD. The mean value was taken as the steady state concentration (Css) and Clearance (CL) (hourly dose/Css) was calculated. Eight survivors were given oral nimodipine (60 or 90 mg) every 6h (based on body weight), blood was sampled over 6 h and the plasma nimodipine level determined. The values for Css, CL and CL·kg−1 were 33.5 μg·l−1, 58 l·h−1 and 1.0 l·h−1·kg−1 respectively; in survivors receiving the drug orally, bioavailability of the 30 mg tablet was 9%. In one very sick patient given crushed tablets by naso-gastric tube, the AUC was very low; in vitro studies indicated that adsorption of nimodipine by the tubing was unlikely to have been the cause.The pharmacokinetic findings in Chinese patients are comparable to previously reported values in Caucasians.

Bronchodilator responses to salbutamol using diskhaler versus metered-dose inhaler

In adults inhaling salbutamol via metered-dose inhalers (MDls) 200 microg doses are recommended, but with diskhalers the manufacturer advocates 400 rather than 200 microg doses. To assess this advice, a partially double-blind, placebo-controlled salbutamol dose response, crossover study (also incorporating MDI doses) was conducted in 12 mild/moderate asthmatics. After active treatment, mean peak expiratory flow rate (PEFR) increments yielded no clinically or statistically significant differences; compared to placebo, respective median differences in PEFR increments (95% Cls) were 10 (-10, 50), 20 (0, 50), and 15 (0, 30) following 400 and 200 microg via diskhalers and 200 microg via MDls. Diskhalers are a suitable alternative for patients with poor MDI technique, but the use of 400 rather than 200 microg salbutamol doses is not supported by evidence.

Pattern of anti-asthmatic drug utilization in Hong Kong compared to other parts of the world

Inhaled drugs are now considered first line agents for the treatment of asthma, whereas oral beta-agonists, theophylline and its derivatives have been relegated to a secondary role. To determine whether current prescribing in Hong Kong conforms to these recommendations, we have evaluated anti-asthmatic drug utilization in the territory as reflected by 1984-86 drug sales (courtesy Medical and Health Department, Hong Kong). Sales/prescription statistics were also obtained from corresponding agencies of other governments and from published literature. If appropriate, data for comparison was expressed as defined daily doses (DDDs) per 1000 inhabitants per day. In contrast to the pattern of utilization in several developed nations, in Hong Kong (a) oral anti-asthmatic agents (particularly beta agonists) were more commonly utilized than inhaled drugs, and (b) inhaled therapy mainly consisted of non-selective beta-agonists, steroids being very rare. Further education is required to improve anti-asthmatic drug utilization patterns in the community.