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Biomedical subjects

M Kou

Publications and source records attributed to M Kou.

At least 19 recordsLinked to original sources

Curtailing unnecessary vancomycin usage in a hospital with high rates of methicillin resistant Staphylococcus aureus infections.

AIMS: To implement and monitor the effectiveness of a strategy to curb unnecessary use of vancomycin and teicoplanin for inpatients in a teaching hospital/tertiary referral centre where 33% of S. aureus isolates (72% from ICU patients) were methicillin resistant. METHODS: A sample of 182 vancomycin/teicoplanin inpatient prescriptions surveyed, revealed that only 31 (17%) conformed with Centre for Disease Control (CDC) guidelines. Following education (ward-rounds, bulletins) on appropriate CDC based guidelines for prescribing glycopeptides directed at relevant clinicians, 'Immediate Concurrent Feedback' (ICF) was gradually deployed throughout the hospital. This entailed review of respective inpatient records on the next working day. If the indication was deemed not to conform with our guidelines, the prescriber was issued a memo (copied to the supervising doctor). Each memo detailed the 'errant' incident, listed appropriate indications and explicitly advised desisting from such prescribing and suggested alternative therapy if necessary. Corresponding glycopeptide usage data for our hospital and others in Hong Kong were retrieved and analysed as were samples of records of our inpatients with staphylococcal septicaemia (pre and during ICF). RESULTS: Compared with baseline values, during 2 years of ICF, inpatient prescribing of vancomycin and teicoplanin deemed to conform increased to 71% (773/1086); difference 54% (P < 0.0001, 95% CIs 47-62%). Corresponding average monthly usage (DDDs/1000 admissions) decreased from 76 (pre-ICF) to 45; mean difference 31 (P < 0.0001, 95% CIs 24, 38). Mortality from staphylococcal bacteraemia remained unchanged. No comparable changes in glycopeptide usage ensued in comparator hospitals. CONCLUSIONS: ICF can be used safely to curb irrational overuse of vancomycin and teicoplanin in a hospital with high methicillin resistant S. aureus infection rates.

Anti-Bacterial Agents↗

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.

Administration, Inhalation↗

Antiulcer drug prescribing in hospital successfully influenced by "immediate concurrent feedback".

OBJECTIVE: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage. METHODS: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals. RESULTS: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals. CONCLUSION: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

Administration, Oral↗

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.

Adrenergic beta-Agonists↗

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.

Administration, Inhalation↗

Hospital antibiotic prescribing successfully modified by 'immediate concurrent feedback'.

1. To determine the effectiveness of ongoing immediate concurrent feedback (ICF) in minimizing 'inappropriate' sultamicillin or co-amoxiclav prescribing via the parenteral route (i.e. when the oral route was accessible and not contraindicated), a prospective controlled audit was carried out on hospital inpatients over a 20 month period. 2. After an education programme to promote oral rather than unnecessary intravenous (i.v.) use of sultamicillin, co-amoxiclav and certain other drugs, an ongoing ICF strategy was instituted. 3. ICF entailed issue of memos on the following day to prescribers of i.v. sultamicillin or co-amoxiclav for inpatients in whom this route was deemed 'inappropriate', by a specially trained nurse using strict objective criteria. The memos recommended oral prescribing (particularly of co-amoxiclav, currently the less expensive alternative). 4. After starting ICF, there were consistent, clinically and statistically significant reductions in the monthly proportions of (i) admissions prescribed i.v. sultamicillin or co-amoxiclav (38% P < 0.001), (ii) those in whom the route was 'inappropriate' (75%, P < 0.001), and (iii) corresponding ratios of i.v./oral usage and expenditure, oral sultamicillin/co-amoxiclav usage and expenditure, as well as total and per admission expenditure on i.v. forms (> or = 43%, P < 0.01). 5. For i.v. cefuroxime (for which there was no ICF) and its oral counterpart cefuroxime-axetil, there were no comparable changes in usage or expenditure. 6. This simple, ongoing ICF strategy was effective and well accepted; estimated net monthly savings being HK$26-30,000.

Anti-Bacterial Agents↗

Investigation of nimodipine pharmacokinetics in Chinese patients with acute subarachnoid haemorrhage.

Nimodipine 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 micrograms.l-1, 58 l.h-1 and 1.0 l.h-1 x 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.

Acute Disease↗

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.

Acute Disease↗

An audit of antiasthmatic drug inhalation technique and understanding.

Inhaled rather than oral antiasthmatic therapy is accepted as more advantageous but depends on patient technique and understanding. In 74 asthmatic outpatients, technique using metered-dose inhaler (MDI) was poor; in 56 patients inhaling beta-agonist, the mean peak expiratory flow rate (PEFR) increase was only 15 L/min (6%) greater than in 18 controls, p < 0.05, 95% confidence intervals 2-27 L/min or 2-11%. Tilting the head back and actuation "stopping" inspiration produced the least favorable PEFR responses; taken together, regression analysis yielded a statistically significant negative correlation with absolute or percentage PEFR change (R2 = 0.15; p < 0.02). Patients were unclear about which drugs to inhale as required or regularly. Among 19 patients reassessed inhaling beta-agonist, only 8 had baseline PEFR values within 10% of each other during both assessments. In the latter, the mean postinhalation PEFR increase was 36 L/min (or 13%) greater than the corresponding increase (or % change) at first assessment, p = 0.05 (0.08), 95% confidence intervals 0-73 L/min (-2 to 29%). Thus, MDI users should avoid tilting the head back, actuation stopping inhalation, and be more aware of prophylactic (steroid) versus symptomatic (beta-agonist) treatment.

Administration, Inhalation↗

Single-dose pharmacokinetics of intraperitoneal ofloxacin in patients on continuous ambulatory peritoneal dialysis.

The present study examines the pharmacokinetics of ofloxacin given in a single dose of 200 mg intraperitoneally (ip) in the first bag of three 2-L 8-hour exchanges. Ofloxacin was measured using high-pressure liquid chromatography (HPLC) in the serum and peritoneal effluent over 24 hours. Six patients without and 3 patients with peritonitis were studied. Ofloxacin given ip was almost completely absorbed after an 8-hour dwell, and this was not affected by peritonitis. The time required to reach peak serum concentration was longer than that reported previously following oral administration. Elimination half-life (T1/2) of ofloxacin was markedly prolonged compared to patients with normal renal function. Peritoneal clearance accounted for only one-tenth of total serum clearance. Peritonitis appeared to shorten the T1/2 of ofloxacin, but this was mainly due to an increase in total serum clearance rather than a change in peritoneal clearance. Peritoneal drug concentration > 0.5 mg/L was reached in the second and third exchange by the second hour. No side effects from ip ofloxacin were observed. We concluded that ofloxacin given in a single dose of 200 mg is safe and provides adequate therapeutic serum and peritoneal concentration for more than 24 hours in patients on continuous ambulatory peritoneal dialysis (CAPD) with 8-hour exchanges.

Aged↗

Audit exposes flawed blood sampling for "digoxin levels".

Therapeutic "digoxin level" monitoring in selected wards was audited. Time elapsing between the last dose and blood sampling was considered appropriate if greater than or equal to 6 h. If such details were not entered on the requisition, the maximum time elapsing was estimated as "appropriate" or "inappropriate" from the time samples were logged into the laboratory and the time the last dose was entered in the patient's treatment sheet. In 22 requisitions detailing sampling time, nine were considered inappropriate. In an additional 150 instances, timing was estimated as inappropriate in 45. Among the 118 requests where timing (estimated or labelled) was appropriate, available plasma digoxin concentrations yielded a mean of 1.0 nM, compared to 1.6 nM in the corresponding 54 patients with premature sampling; this difference was both clinically and statistically significant (95% confidence limits 0.8-1.2 and 1.3-1.9 nM, respectively, p less than 0.001). Premature blood sampling for digoxin levels was common and associated with higher concentrations than when appropriate. Such inappropriate timing may not have serious consequences, but digoxin levels are a matter of record and are used for teaching; due attention to timing could provide more reliable information and avoid wasting valuable resources.

Aged↗

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

BACKGROUND AND PURPOSE: Hitherto, treatment of acute cerebral hemorrhage with intravenous glycerol has not been evaluated in rigorous clinical studies with sufficient patient numbers. METHODS: We undertook a double-blind, stratified and randomized, placebo-controlled clinical trial. Only patients with a first stroke admitted to the hospital within 24 hours after onset of symptoms were recruited, provided computed tomography confirmed hemorrhage and informed consent was obtained. After stratification into alert, semicoma, and coma subgroups using the Glasgow Coma Scale, 107 patients received active treatment (500 ml of 10% glycerol in saline by intravenous infusion over 4 hours on 6 consecutive days) and 109 were given corresponding saline treatment. Using a variety of objective scoring systems, patients were followed up for up to 6 months. RESULTS: At follow-up, all measures of outcome in the treated and control groups were very similar. At 6 months, respective mortality rates were 37 of 107 and 33 of 109. Corresponding mean +/- SD improvements in Scandinavian Stroke Study Group scores were 8.35 +/- 16.9 versus 11.55 +/- 15.6 (long-term) and 0.64 +/- 7.3 versus 2.40 +/- 6.9 (prognostic), and improvements in the Barthel Index ratings were 10.72 +/- 24.7 versus 13.95 +/- 23.3, respectively. Glasgow Coma Scale score improvements in the survivors were 0.81 +/- 1.5 and 1.16 +/- 1.7 in the treated and control groups, respectively. Hemolysis (generally subclinical) was the only adverse effect of glycerol noted. CONCLUSIONS: In the absence of any clinically or statistically significant difference in outcome between the treated and control groups, this trial provides no justification for glycerol therapy following acute cerebral hemorrhage.

Acute Disease↗

Actions of FRC-8653 on smooth muscle cells of the rabbit mesenteric artery.

In ring preparations of the rabbit mesenteric artery, the Ca-contraction, but not the noradrenaline (NA)-contraction, was inhibited by FRC-8653 (10(-9)-10(-5) M) in a concentration-dependent manner, although with a potency 50-100 times weaker than that of nicardipine. The actions of FRC-8653 on Ca-contraction appeared more slowly (over 1 hr) than those of nicardipine. FRC-8653 (up to 10(-5) M) and nicardipine (up to 10(-7) M) did not change the resting membrane potential of smooth muscles. The amplitude of the evoked excitatory junction potential (e.j.p.) was inhibited by FRC-8653, but not by nicardipine, with no alteration in the facilitation process of the e.j.p.s. The inhibition by FRC-8653 of the e.j.p. appeared rapidly and was reversible. FRC-8653 inhibited the membrane depolarization of smooth muscles elicited by ATP, but not by NA or high [K+]o solution. ATP-induced contractions were also inhibited by FRC-8653. The amplitudes of action potentials evoked by current stimuli were decreased by FRC-8653, with no significant change in the electrotonic potentials. Thus, FRC-8653 has properties similar to those of the dihydropyridine Ca-antagonists, but differs from them in that 1) its inhibitory actions on Ca influx appear slowly and 2) sympathetic transmission is inhibited, possibly by inhibition of the postjunctional events for e.j.p. generation.

Animals↗

Recognition of the tRNA-like structure in tobacco mosaic viral RNA by ATP/CTP:tRNA nucleotidyltransferases from Escherichia coli and Saccharomyces cerevisiae.

The 3'-terminal tRNA-like structure of the tobacco mosaic virus RNA interacts with ATP/CTP:tRNA nucleotidyltransferases from Escherichia coli or yeast in much the same manner as do tRNAs. Primary sites of interaction cluster near the 3' end and in the loop proposed to be analogous to the psi-loop of a tRNA. Some modified bases in the tRNA-like structure inhibit interaction with nucleotidyltransferase, yet the analogous bases in a tRNA do not. The location of some of these nucleotides within the analog to the psi-loop suggests that this structure differs slightly from its counterpart in a tRNA. The location of other such bases in the helical stem near the 3' end can be explained if the pseudoknot is disrupted by these modified bases or if the tertiary structure of the RNA is altered in the enzyme-RNA complex. A partially denatured secondary structure that persists on denaturing gels is proposed.

Base Sequence↗

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-acetylamino-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.

Acetylation↗