Montip Tiensuwan

Genotypic resistance profiles in antiretroviral-naive HIV-1 infections before and after initiation of first-line HAART: impact of polymorphism on resistance to therapy

Genotypic testing using TRUGENE was performed for treatment-naive, human immunodeficiency virus type 1 (HIV-1)-infected patients at baseline and after initiation of protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens. The genetic diversity of HIV-1 pol sequences from 92 CRF01_AE and 21 B strains was compared. Subsequently, the impact of polymorphism on resistance to therapy was studied in CRF01_AE-infected (n=29) and subtype B-infected (n=14) patients. At baseline, the differences between CRF01_AE and B strain were mainly observed in the minor mutations L10I/V, M36I and L63P/I/H (P<0.001, chi(2)). In the reverse transcriptase sequence, M41L and T215Y/S were more common in patients infected with subtype B virus (P<0.05, chi(2)). Although all patients treated with PI-based HAART had pre-existing minor mutations, a low prevalence of resistance to PIs was observed (5/43; 11.6%). Moreover, major mutations (D30N and N88D) conferring resistance to PIs were found in patients infected with subtype B strain. In conclusion, polymorphisms at the protease region may not reduce PI susceptibility during treatment. However, this study also revealed the difference in natural mutations among subtypes, which may affect the manifestation of drug resistance.

Surveillance of Genotypic Resistance Mutations in Chronic HIV-1 Treated Individuals After Completion of the National Access to Antiretroviral Program in Thailand

Background:Due to the establishment of the National Access to Antiretroviral Program for People who have AIDS (NAPHA), approximately 80,000 Thai HIV-1 infected patients received antiretroviral drugs through the NAPHA program, which was completed at the end of 2005. The development of drug resistance is required for access to ARV drugs. The objective of this study was to determine the prevalence of antiretroviral drug resistance in Thai HIV-1 treated individuals after completing the NAPHA program.Patients and Methods:Viral genotypic resistance testing was carried out for 1,880 HIV-infected patients experiencing treatment failure, who enrolled during 2000–2005. All patients were in a follow-up treatment with ARV drugs available in clinical practice. The genotype was performed with the TRUGENE HIV-1 kit to assess resistant mutations to reverse transcriptase inhibitors and to protease inhibitors.Results:The frequency of ARV drug resistance has significantly increased after the National Access To Antiretroviral Program was implemented. The reverse transcriptase genes M184V/I (919/1,880; 48.9%) and K103S/H (416/1,880; 22.1%) were the most frequent in nucleoside reverse transcriptase and non-nucleoside reverse transcriptase, respectively. In the protease genes, minor mutations or polymorphisms were found in the majority. Thymidine analogue mutations were presented and increased over time. This study showed a sharp increase in the prevalence of mutations associated with the GPO-VIR combination; nevirapine (948/1,880; 50.4%), lamivudine (889/1,880; 47.3%), and stavudine (703/1,880; 37.4%) after the program was completed.Conclusion:With the increased availability of antiretroviral therapy in a resource-constrained country, antiretroviral drug resistance should be closely monitored. HIV-1 drug resistance testing to enable the salvage therapy will remain a priority in Thailand. Furthermore, resistance testing should also become routine before prescribing treatment, and the consequences of continuing to provide a failing regimen must be considered.

Nonnegative Unbiased Estimation of Scale Parameters and Associated Quantiles Based on a Ranked Set Sample

In this article, we are interested in estimating the scale parameter in location and scale families. It is well known that the best linear unbiased estimator (BLUE) of scale parameter based on a simple random sample (SRS) is nonnegative. However, the BLUE of scale parameter based on a ranked set sample (RSS) can assume negative values. We suggest various modifications of BLUE of scale parameter based on RSS so that the resulting estimators are unbiased as well as nonnegative. Their performances in terms of relative efficiencies are compared and some recommendations are made for normal, logistic, double exponential, two-parameter exponential and Weibull distributions. We also briefly discuss an application of the proposed nonnegative BLUE of scale parameter for quantile estimation for the above populations.

Intramyocardial Angiogenic Cell Precursors in Nonischemic Dilated Cardiomyopathy

To determine the efficacy of intramyocardial injection of angiogenic cell precursors in nonischemic dilated cardiomyopathy, 35 patients with nonischemic dilated cardiomyopathy underwent injections of angiogenic cell precursors into the left ventricle (cell group). Seventeen patients with nonischemic dilated cardiomyopathy were matched from the heart failure database to form a control group that was treated medically. Angiogenic cell precursors were obtained from autologous blood, cultured in vitro, and injected into all free-wall areas of the left ventricle in the cell group. After these injections, New York Heart Association functional class improved significantly by 1.1 ± 0.7 classes at 284.7 ± 136.2 days, and left ventricular ejection fraction improved in 71.4% of patients (25/35); the mean increase in left ventricular ejection fraction was 4.4% ± 10.6% at 192.7 ± 135.1 days. Improved quality of life was demonstrated by better physical function, role-physical, general health, and vitality domains in a short-form health survey at the 3-month follow-up. In the control group, there were no significant improvements in left ventricular ejection fraction or New York Heart Association class which increased by 0.6 ± 0.8 classes. It was concluded that intramyocardial angiogenic cell precursor injection is probably effective in the treatment of nonischemic dilated cardiomyopathy. Disclosures and Freedom of Investigation Professor Michael Belkin is an advisory board member, a minor shareholder, and receives a consulting fee from TheraVitae Co. Ltd. However, the authors had full control of the study, methods used, outcome measurements, data analysis, and production of the written report.

Cohen's Kappa Statistic: A Critical Appraisal and Some Modifications

In this paper we consider the problem of assessing agreement between two raters while the ratings are given separately in 2 - point nominal scale and critically examine some features of Cohens kappa statistic (K C ), widely and extensively used in this context. We point out some undesirahle features of K C and, in the process, propose two modified kappa statistics. Properties and features of these statistics are explained with illustrative examples.

The changing pattern of head injury in Thailand

OBJECTIVE To determine whether patterns of head injury are changing with time. MATERIALS AND METHODS A total of 3194 and 4217 consecutive trauma patients who attended the emergency room in 1985-86 and 1996 respectively were studied with respect to age, sex, cause of injury, injury severity, pathology, and outcome. RESULTS The number of patients with head injury in 1996 nearly doubled (1224/4,217:29.03%) when compared to the 1985-86 study (504/3, 194; 15.78%). This was due to an increase in the outpatient subgroup (1009/1224). The admitted patients with head injury showed a pattern of less severe injury. Severe head injury decreased from 12.4 to 7. 9%. However, acute subdural haematoma and diffuse brain injury increased from 12.2% and 9% to 32% and 16.8% respectively. The mortality rate of admitted patients increased statistically significantly from 14.4% to 21.8% between the 1985-86 and 1996 studies. CONCLUSIONS This comparative study showed attend toward less severe injury. This may be due to multiple factors. The predominant factor may be the compulsory use of motorcycle helmets. The limitation of this study was that it utilised tertiary hospital based data only. Tertiary hospital receive more and serious head injured patients from surrounding provincial hospitals this may be the major cause of the increased the mortality rate.

Major single nucleotide polymorphisms in polypoidal choroidal vasculopathy: a comparative analysis between Thai and other Asian populations.

Purpose To investigate the association in a Thai population between the major age-related macular degeneration (AMD) susceptibility loci, Y402H and I62V in the complement factor H (CFH) and A69S in the age-related maculopathy susceptibility 2 (ARMS2) genes, and polypoidal choroidal vasculopathy (PCV). Methods A case-control study included 97 PCV cases and 102 age- and gender-matched controls without any retinopathy. The genotypic profiles of the three polymorphisms were obtained using a real-time polymerase chain reaction assay. The allelic and genotypic association between the polymorphisms and PCV were compared with those from the compiled data of other Asian populations reported previously. Results Strong associations between the Y402H, I62V, and A69S polymorphisms and PCV were observed in the present study (P = 0.002, 0.003, and 0.0008 respectively) and in the compiled data (P < 0.0001 for all three polymorphisms). The risk allele frequencies of the polymorphisms in PCVs and in controls from the present study (15.0% and 5.4% for Y402H, 71.7% and 57.4% for I62V, and 54.1% and 37.3% for A69S respectively) were also comparable with the frequencies from the compiled data (10.3% and 6.4% for Y402H, 75.2% and 58.3% for I62V, and 56.8% and 36.8% for A69S respectively). The genotype distribution for each polymorphism was also comparable in both datasets. Conclusion The findings of this study support a significant genetic association between the major AMD susceptibility genes and PCV across Asian populations. This suggests that AMD and PCV, despite different phenotypic manifestation, may share common genetic risk factors.

Estimation of Location and Scale Parameters in Two-Parameter Exponential Distribution Based on Ranked Set Sample

In this article, we are interested in simultaneous comparison of the location and scale estimators of a two-parameter exponential distribution based on simple random sample (SRS) and ranked set sample (RSS) by using generalized variance (GV). We suggest various RSS strategies to estimate the scale parameter. Their performances in terms of GV are compared with SRS strategy. Finally, we illustrate the minimum values of set size, n, based on RSS, which would result in smaller GV than that based on SRS.

Modelling recurrent malaria in Thailand

Malaria is a common infectious disease in many tropical countries. Thailand is located geographically in the tropical zone and the transmission of malaria is found widely, for instance, in the Tak province. The objective of this study is to find risk factors for the number of experiences with malaria of malaria patients, i.e. repeated recurrences of the disease within an infected individual in the Tak province in the rainy season by using Poisson regression models. Among the models fitted, the best are chosen based on the analysis of deviance. The results of this study show that the risk factors are race, spraying insecticides in houses in an infectious area, number of days staying overnight without protection against mosquitoes of malaria patients, and whether or not any members of the family of the malaria patient have had malaria.

Application of log-linear models to dengue virus infection patients in Thailand

Dengue is an infectious mosquito-borne viral disease. Dengue or dengue-like epidemics ranks highly among new and newly emerging infectious diseases in public health significance and may affect persons of all ages in dengue endemic area. Dengue virus infections may lead to dengue fever (DF), dengue haemorrhagic fever (DHF) and may lead to hypovolaemic shock (dengue shock syndrome, DSS). The purpose of this study is to identify the associated factors between personal, clinical variables of dengue patients by using log-linear models. Test of independence are used (chi-square and Cramer’s V value tests) to find out the association between any two variables. In addition twoand three-dimensional log-linear models are used to obtain estimated parameters and expected frequencies for these models. Amongst the models fitted, the best are chosen based on the analysis of deviance. The results show that most paired variables of personal and clinical variables are significantly related at p-value less than 0.05. For dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) patients, the type of clinic has a strong association with gender, occupation and place of treatment that gave the highest Cramer’s V value. In addition, the type of clinic has an association with the status of the last contact. To reduce the outbreak of dengue there should be a control of mosquitoes and for treatment of patients in hospital.