Yoke-Lin Lo

Helicobacter pylori Infection and Non-Ulcer Dyspepsia: The Effect of Treatment with Colloidal Bismuth Subcitrate

A study was undertaken to determine the role of Helicobacter pylori in non-ulcer dyspepsia (NUD) and to determine the efficacy of colloidal bismuth subcitrate (CBS) in the treatment of NUD. Seventy-one patients were randomly allocated (double blind) to CBS or placebo, two tablets twice daily for 4 weeks. The severity of dyspepsia was scored and endoscopies performed before and after treatment, and antral biopsy specimens were taken for bacteriologic and histologic examination. Forty patients had H. pylori infection, and all had changes of chronic active gastritis. H. pylori was cleared from 17 to 21 patients (81%) treated with CBS, whereas none of the 19 patients treated with placebo cleared the bacteria. Improvement in histology was noted in 15 of 21 patients (71.4%) treated with CBS, whereas no improvement was noted in any of the placebo controls. Thirty-one patients were negative for H. pylori. All had either normal gastric histology or minor degrees of inflammation. Seventeen of these patients received CBS, and 14 received placebo. All groups reported improvement in the symptom score; however, the H. pylori-positive, CBS-treated group recorded a significantly higher improvement than the other groups (p less than 0.001). Relapse of H. pylori infection after initial clearance of the bacteria was high. Twelve of 16 patients evaluated relapsed 1 month after withdrawal of CBS.

Population Pharmacokinetics of Vancomycin in Premature Malaysian Neonates: Identification of Predictors for Dosing Determination

ABSTRACT The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates of clearance and distribution volume and the factors which affected the variability observed for the values of these parameters were obtained using a population pharmacokinetic modeling approach. The predictive performance of the population model was evaluated by visual inspections of diagnostic plots and nonparametric bootstrapping with replacement. Dosing guidelines targeting a value of ≥400 for the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) were explored using Monte Carlo simulation. Body size (weight), postmenstrual age, and small-for-gestational-age status are important factors explaining the between-subject variability of vancomycin pharmacokinetic parameter values for premature neonates. The typical population parameter estimates of clearance and distribution volume for a 1-kg premature appropriate-for-gestational-age neonate with a postmenstrual age of 30 weeks were 0.0426 liters/h and 0.523 liters, respectively. There was a 20% reduction in clearance for small-for-gestational-age infants compared to the level for the appropriate-for-gestational-age control. Dosage regimens based on a priori target response values were formulated. In conclusion, the pharmacokinetic parameter values for vancomycin in premature Malaysian neonates were estimated. Improved dosage regimens based on a priori target response values were formulated by incorporating body size, postmenstrual age, and small-for-gestational-age status, using Monte Carlo simulations with the model-estimated pharmacokinetic parameter values.

Comparison of two 1-week low-dose omeprazole triple therapies--optimal treatment for Helicobacter pylori infection?

To determine and compare the efficacy and tolerability of two 1‐week regimen comprising omeprazole, clarithromycin and amoxycillin or metronidazole in the eradication of Helicobacter pylori, and to determine the influence of bacterial resistance to metronidazole and clarithromycin on the outcome of treatment.

Postoperative sore throat and ketamine gargle

Editor—We investigated, in a double-blind randomized control study, the effect of a ketamine gargle to attenuate postoperative sore throat (POST) in 44 adult ASA I or II patients undergoing elective gynaecological procedures. The patients had 30 s gargling with either 20 ml of normal saline (Group C: control, n1⁄422) or ketamine 40 mg in 20 ml normal saline (Group K: ketamine, n1⁄422). Anaesthesia was induced with fentanyl, propofol, and rocuronium, 5–10 min after gargling. Maintenance of anaesthesia was with oxygen–air mixture and sevoflurane. Titrated boluses of morphine were given according to clinical requirements during surgery. The same anaesthetist performed all intubations and extubations. During surgery, blood samples were collected at intervals for ketamine and norketamine analysis. At the end of the study period, serum samples from five patients in Group K, randomly selected, were assayed by liquid chromatography and mass spectrometry. After extubation, POST was assessed at 0 (on arrival at the post-anaesthetic care unit), 2, and 24 h using a four-point grading scale (none, 0; mild, 1; moderate, 2; and severe, 3). POST was significantly reduced in Group K compared with Group C (P,0.05) at 0 and 2 h after surgery but not at 24 h (P1⁄40.498). There was significantly less moderate-to-severe POST in Group K at 0 h. Ketamine gargle has been reported to attenuate POST for 24 h post-surgery. We observed significant reduction in POST at 0 and 2 h post-surgery but not at 24 h. The reported ketamine level to relieve tourniquet pain after an i.v. bolus was .100 ng ml. The analgesic effect from oral administration of ketamine was at a lower mean plasma concentration of ketamine 40 ng ml, presumably due to the higher norketamine levels (160 ng ml). In this study, blood samples were obtained during intraoperatively, but POST was assessed post-surgery when ketamine concentrations are likely to be lower. Systemic absorption and the possibility of swallowing the residual solution would contribute to the ketamine in the blood. The highest average ketamine and norketamine concentrations, 16.16 and 11.43 ng ml, respectively (Table 1), were detected during surgery but would have decreased after the surgery. These low levels suggested that it was unlikely that systemic absorption played a major role for the reduction of POST. A topical effect is possible. We conclude that pre-induction ketamine gargle can attenuate POST in the early postoperative period. Drug levels detected were much lower than reported measurements for analgesia after oral and parenteral administration.

Does Helicobacter pylori infection affect gastric emptying in patients with functional dyspepsia

The objectives of the study were first, to determine if gastric emptying was altered in patients with functional dyspepsia with and without Helicobacter pylori infection compared with normal healthy volunteers; and second, to determine if there were further alterations in gastric emptying when the infection was eradicated. Gastric emptying was measured using a 99mtechnetium radiolabelled solid meal and gastric emptying time was measured as t1/2, viz. time taken for half the radiolabelled meal to be emptied from the stomach. The mean gastric emptying time for H. pylori‐positive patients (n= 20) was 56.4±24.8 min; H. pylori‐negative patients (n= 19) 67.8±31.8 min; and normal controls (n= 20) 58.8 ± 18.8 min. No significant difference was obtained between the groups (ANOVA; P= 0.348). Thirteen of 18 H. pylori‐positive patients successfully eradicated the infection following treatment with omeprazole 40 mg o.m. and amoxycillin 500 mg t.d.s. for 2 weeks. The mean difference in the gastric emptying time before and H. pylori eradication was 23.9 + 13.2 min (P= 0.556). There was no significant difference in the frequency of specific dyspeptic symptoms as well as the overall mean symptom score between the H. pylori‐positive and ‐negative patients. Gastric emptying was not different between patients with functional dyspepsia and normal controls. Helicobacter pylori infection does not appear to affect gastric emptying in patients with functional dyspepsia.

Rapid and Simultaneous Quantification of Levetiracetam and Its Carboxylic Metabolite in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry

A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV) and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.450 mL acetonitrile (ACN) containing 1 µg/mL of internal standard (IS, diphenhydramine), then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution was injected into an Agilent Zorbax SB-C18 (2.1 mm×100 mm, 3.5 µm) column with an isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and ACN (40∶60 v/v). Detection was performed using an AB Sciex API 3000 triple quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of quantification (LLOQ) for both LEV and UCB L057 was validated at 0.5 µg/mL, while their lower limit of detection (LOD) was 0.25 µg/mL. The calibration curves were linear between 0.5 and 100 µg/mL for both analytes. The inaccuracy and imprecision of both intra-assay and inter-assay were less than 10%. Matrix effects were consistent between sources of plasma and the recoveries of all compounds were between 100% and 110%. Stability was established under various storage and processing conditions. The carryovers from both LEV and UCB L057 were less than 6% of the LLOQ and 0.13% of the IS. This assay method has been successfully applied to a population pharmacokinetic study of LEV in patients with epilepsy.

Pre-admission therapy for childhood acute diarrhoea--a hospital-based study.

Acute gastroenteritis (AGE) is a common illness among infants and children contributing to significant mortality and morbidity. As such, appropriate treatment received prior to hospital admission is of utmost importance. This retrospective observational study aimed to determine preadmission management in paediatric patients prior to hospital admission. Two hundred and twenty‐two case notes of paediatric AGE patients were reviewed over a 12‐month period. One hundred and fifty‐four patients received medications prior to admission with 143 (92·9%) patients received known classes of medications. Antipyretic agents were the most commonly prescribed (69·2%), followed by antibiotics (38·5%), anti‐emetics (35·7%), oral rehydration salts (29·4%) and antidiarrhoeals (28·0%). The mean duration of stay in hospital was slightly shorter in patients, who received prior medications than those who did not (2·22 vs. 2·32 days respectively). Seventy per cent of children admitted for AGE were treated suboptimally prior to hospital admission with oral rehydration salts being largely under‐utilized, despite their proven efficacy and safety. Sex, race and age had no influence on the type of preadmission treatment. A greater effort should be made to educate the general public in the appropriate treatment of AGE.

Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge

Hearing loss has been reported with valproic acid (VPA) use. However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours. Hearing loss fully resolved after VPA discontinuation. Audiometry performed five hours after VPA rechallenge showed significant improvement in hearing thresholds. Pharmacokinetic modelling during the VPA rechallenge showed that hearing loss occurred at a level below the therapeutic range. Brainstem auditory evoked potential at three months after VPA discontinuation showed bilateral conduction defect between the cochlear and superior olivary nucleus, supporting a pre-existing auditory deficit. VPA may cause temporary hearing threshold shift. Pre-existing auditory defect may be a risk factor for VPA-induced hearing loss. Caution should be taken while prescribing VPA to patients with pre-existing auditory deficit.

Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis.

The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.

Evaluation of the predictive performance of bleeding risk scores in patients with non‐valvular atrial fibrillation on oral anticoagulants

Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant‐related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients.