Showing papers by "Shu-Chuen Li published in 2004"

Does the 12-item General Health Questionnaire contain multiple factors and do we need them?

Abstract: Background: The 12-item General Health Questionnaire (GHQ-12) is widely used as a unidimensional instrument, but factor analyses tended to suggest that it contains two or three factors. Not much is known about the usefulness of the GHQ-12 factors, if they exist, in revealing between-patient differences in clinical states and health-related quality of life. Methods: We addressed this issue in a cross-sectional survey of out-patients with psychological disorders in Singapore. The participants (n = 120) completed the GHQ-12, the Beck Anxiety Inventory, and the Short-Form 36 Health Survey. Confirmatory factor analysis was used to compare six previously proposed factor structures for the GHQ-12. Factor scores of the bestfitting model, as well as the overall GHQ-12 score, were assessed in relation to clinical and healthrelated quality of life variables. Results: The 3-factor model proposed by Graetz fitted the data better than a unidimensional model, two 2-factor models, and two other 3-factor models. However, the three factors were strongly correlated. Their values varied in a similar fashion in relation to clinical and health-related quality of life variables. Conclusions: The 12-item General Health Questionnaire contains three factors, namely Anxiety and Depression, Social Dysfunction, and Loss of Confidence. Nevertheless, using them separately does not offer many practical advantages in differentiating clinical groups or identifying association with clinical or health-related quality of life variables.

Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4.

Abstract: Cytochrome P450 (CYP) 3A4 is not only the most abundant isoform in human liver but also metabolizes approximately 60% of the therapeutic drugs. This feature renders CYP3A4 highly susceptible to both reversible and irreversible (mechanism-based) inhibition. The latter is characterized by NADPH-, time- and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive metabolites. Mechanism-based inactivation of CYP3A4 by drugs can be due to the chemical modification of the heme, the protein, or both as a result of covalent binding of modified heme to the protein. The clinical pharmacokinetic effect of a CYP3A4 inactivator is a function of its KI, kinact and partition ratio and the synthesis rate of new or replacement enzyme. Predicting drug-drug interactions involving CYP3A4 inactivation is possible when proper pharmacokinetic principles are followed. However, the prediction may become difficult, since the clinical outcomes due to CYP3A4 inactivation depend on many factors associated with the enzyme, drugs and the patients. A number of clinically important drugs have been identified to be mechanism-based CYP3A4 inhibitors. These include antibiotics (e.g. erythromycin and isoniazid), anticancer drugs (e.g. tamoxifen), antidepressants (e.g. fluoxetine and midazolam), anti-HIV agents (e.g. ritonavir and delavirdine), antihypertensives (e.g. dihydralazine and verapamil), steroids and their receptor modulators (e.g. gestodene and raloxifene), and some herbal constituents (e.g. bergamottin and glabridin). Compared to reversible inhibition, mechanismbased inhibitors of CYP3A4 more frequently cause unfavorable drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesized CYP3A4 protein. Most CYP3A4 inactivators are also PgP substrates / inhibitors, confounding the in vitro-in vivo extrapolation. Clinicians should have good knowledge on these CYP3A4 inactivators and avoid their combination use.

A cost comparison of management of chronic hepatitis B and its associated complications in Hong Kong and Singapore.

Abstract: GOALS: To estimate and compare the direct medical cost in the management of chronic hepatitis B (CHB) infection and its complications from the perspective of public health organizations in Hong Kong and Singapore. BACKGROUND: Hong Kong and Singapore are endemic hepatitis B virus areas with about 10% and 5%, respectively, of the population estimated as hepatitis B virus infected. STUDY: The medical histories of 660 patients with CHB who received medical services over 5 years from three major public hospitals in Hong Kong and Singapore were studied retrospectively. Costs were analyzed according to the five disease states and estimated in Hong Kong dollars (HKD) and Singapore dollars (SGD). RESULTS: In both Hong Kong and Singapore, the per-patient total annual cost increased with the severity of the disease. CHB cost HKD 6318 (US 810 dollars) in Hong Kong and SGD 718.15 (US 410.37 dollars) in Singapore. Compensated cirrhosis cost HKD 10,304 (US 1321 dollars) in Hong Kong and SGD 1,175.34 (US 671.62 dollars) in Singapore. Decompensated cirrhosis cost HKD 58,428 (US 7490 dollars) in Hong Kong and SGD 15,389.84 (US 8794.19 dollars) in Singapore. Hepatocellular carcinoma cost HKD 121,822 (US 15,618 dollars) in Hong Kong and SGD 12314.04 (US 7036.59 dollars) in Singapore. Each case of liver transplant was estimated to cost HKD 514,498 (US 65,961 dollars) in Hong Kong and SGD 86,369.28 (US 49,353.87 dollars) in Singapore. CHB in Hong Kong accounted for about 4% of the healthcare expenditure. CONCLUSION: This study confirms that CHB and its liver disease complications are a significant economic burden to the healthcare budgets of Hong Kong and Singapore, and indicates that effective therapy that arrests or reverses the progression of liver disease would be highly cost-effective.

Predicting pharmacokinetic herb-drug interactions.

Abstract: In vitro and in vivo studies have indicated that the induction or inhibition of cytochrome P450 (CYP) is one of the major mechanisms for some clinically important pharmacokinetic herb-drug interactions. Thus, an attempt was made to predict pharmacokinetic herb-drug interactions using the pharmacokinetic principles that are used for predicting drug-drug interactions. The expected AUC ratio was mainly dependent on unbound herbal inhibitor concentration ([I]) and inhibition constant (Ki), hepatic fraction (fh), number of inhibitory herbal constituents (n) and metabolic pathway fraction in hepatic metabolism (fm). Herb-drug interactions would be with low risk if sigma(i=1)n [[Ii]/Ki(i)] is less than 0.1, medium risk if it is between 0.1 and 1.0, and high risk if it is greater than 1. For high clearance drugs, the change of fh x fm had minor influence on AUC ratio when sigma(i=1)n [[Ii]/Ki(i)] values were fixed. Similarly, fm did not affect the AUC ratio for low clearance drugs. It appeared likely to predict a herb-drug metabolic interaction when [I], Ki, fh, fm and n could be determined. However, many herb- and drug-related factors may cause difficulties with the prediction, and well-designed human studies are always necessary.

Factors influencing health-related quality of life of Asians with anxiety disorders in Singapore.

Abstract: As little is known about health-related quality of life (HRQoL) in Asians with anxiety disorders, we assessed HRQoL in Singaporeans with anxiety disorders and identified factors influencing their HRQoL. Outpatients with anxiety disorders (n = 119) attending a hospital psychiatric clinic completed the Short Form 36 Health Survey (SF-36), Beck Anxiety Inventory (BAI) and General Health Questionnaire (GHQ-12). SF-36 score reduction from population norms (quantified as the number of standard deviations below the mean) in these subjects was compared with existing data on Singaporeans with various medical conditions and Americans with panic disorder (PD). Factors influencing HRQoL were examined using stepwise multiple linear regression models. SF-36 score reduction in these subjects (0.3–1.4 SD) was greater than that in Singaporeans with systemic lupus erythematosus or thyroid cancer survivors for seven scales but similar to that in Americans with PD (0.5–1.7 SD). BAI and GHQ-12 scores, presence of PD/generalized anxiety disorder, presence of chronic medical conditions, being married or increasing age accounted for 19–61% of the variance in six selected SF-36 scales. In conclusion, it can be said that Singaporeans with anxiety disorders experience clinically important reductions in HRQoL; both clinical and socio-demographic factors influence HRQoL in such subjects.

A retrospective drug utilization evaluation of vancomycin usage in paediatric patients.

Abstract: Summary Objective: To evaluate the appropriateness of use of vancomycin in paediatric patients at KK Women's and Children's Hospital, the major paediatric hospital in Singapore to identify potential problems in prescribing practices that may necessitate intervention to optimize vancomycin usage. Methods: A retrospective drug utilization evaluation was performed for paediatric patients who received intravenous vancomycin from 1 June 1998 to 31 June 1999. The outcome measures were consistency of vancomycin indication with recommended guidelines, dosing regimens, microbiological data, monitoring of serum drug levels, renal function, clinical outcomes and adverse drug reactions (ADRs). Results: A total of 96 cases was available for evaluation. Sixty-two (64·6%) courses of vancomycin were consistent with guidelines for indication of therapy. Eighty-six (89·6%) of the dosing regimen were consistent. All infusion times that were recorded (56·3%) were consistent with criteria. Of the patients treated with vancomycin for more than 1 day, peak and/or trough serum vancomycin levels were ordered for 70 cases. Of the 56 cases with paired levels ordered, 46 cases had at least one level that fell outside the therapeutic range. Nineteen (19·8%) cases of ADRs were documented. Fifty-eight (60·4%) cases received concurrent nephrotoxic drugs. However, a substantial portion of vancomycin courses were apparently not prescribed for appropriate indications, and there was poor recording of vancomycin administration information and sampling time. Conclusion: The majority of dosing regimens of vancomycin was consistent with guideline criteria. The most evident problem was the sub-optimal use of the monitoring of vancomycin serum levels. The information derived from this study may be used as a for further study and for the development of strategies for optimize vancomycin usage.

Drug utilization review of risperidone for outpatients in a tertiary referral hospital in Singapore.

Abstract: Background Risperidone has been used in Singapore for schizophrenia since 1996. However, little information is available on its utilization pattern. Objective To examine the risperidone utilization pattern in the Psychiatric Outpatient Clinic of the National University Hospital. Method Medical records of all outpatients with schizophrenia prescribed with risperidone from 1 September1999 to 31 August 2000 were reviewed. Results A total of 417 risperidone prescriptions were dispensed for 130 outpatients (50 male, 80 female) during the study period. The mean ± SD daily doses for prescriptions and for patients were 2.3 ± 1.3 mg and 2.1 ± 1.1 mg, respectively. Among these patients, 28 (21.5%) received at least one concomitant conventional antipsychotic and 71 (54.6%) received a concomitant anti-Parkinsonian agent. Logistic regression analysis suggested that a higher risperidone dose was associated with the greater probability of anti-Parkinsonian agent usage. Conclusions The mean risperidone dose during the study period was towards the lower end of recommendation for schizophrenia. Further study is warranted to confirm and explain the pattern of low-dose risperidone, and the high use of concomitant conventional antipsychotics and anti-Parkinsonian agents in Singapore. Elucidation of these would provide a valuable insight for the management of Asian patients with schizophrenia using risperidone. However, the current data indicate that the practice of using a lower dose of risperidone could represent better affordability and an improved cost-effectiveness ratio of risperidone compared with conventional antipsychotics in Asian patients. Copyright © 2004 John Wiley & Sons, Ltd.