[Show abstract][Hide abstract] ABSTRACT: To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.
METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm(3). The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.
CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.
TRIAL REGISTRATION: ClinicalTrials.govNCT00162682
PLoS Medicine 08/2013; 10((8):e1001494). · 15.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: To assess the treatment outcomes and to explore the determinants of clinical outcome in breast cancer patients with 1-3 positive nodes who did or did not receive postmastectomy radiotherapy (PMRT) in a tertiary care referral cancer center in Northern Thailand. Methods: We investigated a retrospective cohort of registered breast cancer patients at the Faculty of Medicine, Chiang Mai University, Thailand from 2001-2007. Analysis was performed using Cox regression models to identify factors affecting the overall survival (OS) and relapse-free survival (RFS) rates. Comparisons were made between two cohorts: women who received adjuvant PMRT (74 patients) and women who did not receive adjuvant PMRT (81 patients). Results: A total of 155 patients were included with a median follow-up period of 4.45 years. There was a statistically significant 4-year OS difference between the two groups of patients: 100% for the PMRT group and 93.1% for the non-PMRT group (P = 0.044). The 4-year RFS was 85.9% for patients receiving PMRT and 78.3% for patients who did not receive PMRT (P = 0.291). On multivariate analysis of OS, using hormonal treatment was the only significant independent factor associated with improved OS. On multivariate analysis of RFS, none of the variables were significantly associated with improved RFS. PMRT was notfound to be a prognostic variable related to the outcome of patients using a logistic regression model. Conclusion: Our retrospective, hospital-based analysis demonstrated that PMRT improved the treatment outcome in terms of OS for women with 1-3 node positive early-stage breast cancer.
Journal of Radiation Research 06/2013; · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to analyze risk factors of drug resistance in pulmonary tuberculosis patients with relapse. A total of 196 pulmonary tuberculosis patients with relapses from 2001 to 2005 were referred to the Office of Communicable Disease Prevention and Control Region 10, Thailand. Data were collected from the tuberculosis chart. Classification tree and logistic regression analysis were used to determine the risk factors of drug resistance. According to the optimal classification tree, three risk factors were determined: number of previous TB treatments, weight at baseline and shortness of breath. In the logistic regression model, four risk factors were found to be significant: underlying disease (odds ratio (OR) = 2.3; 95% CI, 1.1–4.4); cavity (OR = 2.8; 95% CI, 1.2–6.9); number of previous TB treatments ≥ 2 times (OR = 2.7; 95% CI, 1.0–7.1); and age ≥ 65 years (OR = 2.4; 95% CI, 1.1–5.1). However, the logistic regression model and optimal tree had low sensitivity, possibly due to the lack of potential risk factors that were not considered in this study. The findings underscore that the treatment of relapse patients, those with at least two previous TB treatments should be subjected to a drug susceptibility test so that an appropriate form of treatment can be prescribed.
Journal of Statistics and Management Systems. 06/2013; 13(3):535-546.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to analyze factors associated with isoniazid-resistance among pulmonary tuberculosis patients in Northern Thailand. Data was obtained from 36 hospitals in the area under supervision of The Office of Communicable Disease Prevention and Control Region 10, Chiang Mai, in which information of tuberculosis patients who had received isoniazid and was tested for resistance to the drug between 2003 and 2007 was collected. There were 504 patients who could be included in the analysis. These patients were divided into 2 groups through matching method (1:3) by using genders and age variables. There were 126 patients who were put into a “Case” group where patients showed resistance to isoniazid and 378 patients who were put into a “Control” group where patients showed no signs of resistance to the drug. Factors associated with isoniazid-resistance were assessed using univariate and multivariate conditional logistic regression analyses. It was found that 23.0% of patients in the case group and only 7.4% in the control group were relapsed patients. And, of these relapsed patients, the percentages of patients who had received treatment more than twice before were 27.6 and 10.7, respectively. After a univariate analysis, the following statistically significant factors contributing to the drug resistant condition were found: 1) type of patient 2) drug resistant tuberculosis mycobacterium infection 3) nontuberculoses mycobacterium infection 4) type of standard drugs treatment used, and 5) drugs’ side effect. When other variables were controlled, it was found that relapsed patient is 5.5 times more likely to be drug resistant than new patient. (95% confidence interval: 2.3–13.0). The results of this research indicated that doctors and healthcare personnel should be aware of whether the patient is a relapsed or a new patient and to closely monitor patient’s reaction to the treatment.
Journal of Statistics and Management Systems. 06/2013; 14(5):899-913.
[Show abstract][Hide abstract] ABSTRACT: The prognostic factors for cervical cancer has been associated with a poor treatment response and reduced survival rate. The objective of this study was to evaluate the prognostic factors for patients with cervical cancer.
Journal of Statistics and Management Systems. 06/2013; 13(1):43-57.
[Show abstract][Hide abstract] ABSTRACT: To investigate the treatment outcome in terms of relapse free survival and overall survival, and explore the determinants of the clinical outcome in HER-2/neu positive breast cancer patients who received or not received adjuvant trastuzumab.
The authors reviewed retrospectively of newly diagnosed non-metastatic breast cancer patients at the Faculty of Medicine, Chiang Mai University between January 2004 and December 2007. Comparisons were made between the two cohorts, women who did not receive adjuvant trastuzumab (100 patients) and women who received adjuvant trastuzumab (14 patients).
The median follow-up time was 4.7 years. Four-year relapse-free survival (RFS) and overall survival (OS) in patients receiving trastuzumab was 92.3% and 100%, respectively. In the cohort of HER-2 positive patients who did not receive trastuzumab, the 4-year RFS in this group was 68.2% and 4-year OS was 87.8%. The difference was not statistically significant between the 4-year RFS rates (p = 0.103) and the 4-year OS rates (p = 0.214). By multivariate Cox regression analyses, only nodal status was identified as the independent predictors for superior RFS (hazard ratio 2.93; 95% CI, 1.07 to 5.88; p = 0.034) and none of the clinical parameters were significant predictors for 4-year overall survival.
A hospital-based analysis of adjuvant Trastuzumab use in our center does not demonstrate the different treatment outcome. However there is a trend of favorable outcome in the group receiving adjuvant trastuzumab.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 06/2013; 96(6):709-15.
[Show abstract][Hide abstract] ABSTRACT: In patients receiving highly active antiretroviral therapy (HAART), increase of naive T-cell production, as measured by T-cell receptor rearrangement excision circles (TRECs), is an indicator of immune reconstitution. Our objective was to assess whether treating opportunistic infections (OIs) prior to HAART initiation affects CD4 T-cells recovery and TRECs in patients on HAART. HIV-infected patients presenting no OIs or treated OIs were prospectively enrolled prior to HAART initiation and followed-up over 12 months of HAART. CD4 T-cells and TRECs were measured at baseline, 6 and 12 months HAART and compared between patients presenting no OIs and those with treated OIs. Univariate and multivariate logistic regression models were used to identify potential factors associated with low TREC increase after 12 months HAART. Forty-four HIV-infected patients, 31 presenting no OIs and 13 with treated OIs at HAART initiation were enrolled. Patients presenting no OIs tended to have higher CD4 T-cell gain than those with treated OIs (151 vs 89 cells/μL; p = 0.05) after 6 months HAART but not after 12 months HAART (120 vs 149 cells/μL; p = 0.84). Among patients presenting no OIs, TREC levels significantly increased from baseline through 12 months HAART while among those with treated OIs, there was a trend for increase only after 12 months. Our study indicates that treatment of OIs prior to HAART does not lead to impaired CD4 T-cells recovery and thymic outputs.
Current HIV research 09/2012; 10(7):592-6. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thailand's implementation of the Directly Observed Treatment, Short course (DOTS) strategy to increase tuberculosis (TB) control program efficacy has not achieved the World Health Organization (WHO) TB key targets. We defined two TB control models in the study. Patients in Model 1 were treated with a conventional DOTS strategy and in Model 2, patients were treated the same as Model method 1 but were given a phone call reminder to take their medication. Multi-drug resistant tuberculosis (MDR-TB) and non-MDR-TB patients were randomized into either Model 1 or 2. Treatment outcomes were given as cure rates, completion rates, failure rates or success rates at 18 months in the MDR-TB group and 6 months in the non-MDR-TB group. The sputum conversion rate at 1 month were evaluated for both groups. In the MDR-TB group, the sputum conversion rate was 20% (95% CI 8-45) in Model 1 and 90% (95% CI 73-98) in Model 2 (p < 0.001). In the non-MDR-TB group, the sputum conversion rate was 52% (95% CI 36-70) in Model 1 and 37% (95% CI 22-56) in Model 2 although the difference was not significant (p = 0.221). The Model 2 success rates were significantly higher (73.7%, 96.7%) in both the MDR-TB and non-MDR-TB groups (p < 0.001, p = 0.047). The MDR-TB rate in northern Thailand decreased from 4.1% during April-September 2008 to 1.8% during April-September 2009. Further study of the association between implementation of Model 2 and MDR-TB incidence reduction needs to be carried out.
The Southeast Asian journal of tropical medicine and public health 11/2011; 42(6):1444-51. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The formation of disulphide bonds between cysteines plays a major role in protein folding, structure, function and evolution. Many computational approaches have been used to predict the disulphide bonding state ofcysteines. In our work, we developed a novel method based on Conditional Random Fields (CRFs) to predict the disulphide bonding state from protein primary sequence, predicted secondary structures and predicted relative solvent accessibilities (all-state information). Our experiments obtain 84% accuracy, 88% precision and 94% recall, using all-state information. However, our results show essentially identical results when using protein sequence and predicted relative solvent accessibilities in the absence of secondary structure.
International Journal of Data Mining and Bioinformatics 01/2011; 5(4):449-64. · 0.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The evolution of hematological parameters in HIV-1-exposed uninfected infants according to various durations of perinatal zidovudine exposure was studied. We used data prospectively collected among 1122 HIV-uninfected formula-fed infants born to HIV-infected mothers who participated in a clinical trial to prevent perinatal transmission in Thailand (PHPT-1). Infants were exposed to different durations of zidovudine both in utero and after birth. Hemoglobin level and leukocyte, absolute neutrophil, and lymphocyte counts were measured at birth and at 6 weeks of age. The association between hematological parameters at birth and the duration of zidovudine exposure in utero was studied using a linear regression model, and changes between birth and 6 weeks of age and the duration of postnatal zidovudine exposure using mixed effects models. At birth, the hemoglobin level was lower in newborns exposed to zidovudine for more than 7.5 weeks in utero (adjusted regression coefficient: -0.6 g/dl; 95% confidence interval: -1.1 to -0.1). Six weeks after birth, the hemoglobin level had decreased faster in infants administered zidovudine for more than 4 weeks (adjusted regression coefficient: -0.1 g/dl; 95% confidence interval: -0.2 to -0.1). The duration of perinatal zidovudine exposure was not associated with the evolution of leukocyte, neutrophil, and lymphocyte counts. Despite the differences in hemoglobin levels, grade 3 or 4 anemia did not significantly differ by maternal or infant zidovudine duration. The clinical impact appeared modest, but longer exposure may warrant close monitoring.
AIDS research and human retroviruses 10/2010; 26(10):1163-6. · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Radiation-induced diarrhea is frequently observed during pelvic radiotherapy. This study was performed to determine the ability of a probiotic containing live lactobacillus acidophilus plus bifidobacterium bifidum to reduce the incidence of radiation-induced diarrhea in locally advanced cervical cancer patients.
Patients who were undergoing pelvic radiotherapy concurrent with weekly cisplatin were randomly assigned to a study drug or placebo, in a double-blind study. Diarrhea was graded weekly according the Common Toxicity Criteria (CTC) system. Stool consistency and white and red blood cell count in stool were also assessed. The primary endpoint was to reduce the incidence of diarrhea, defined by a CTC grade 2 or more, and the need for anti-diarrheal medication.
A total of 63 patients were enrolled. Grade 2 -3 diarrhea was observed in 45% of the placebo group (n = 31) and 9% of the study drug group (n = 32) (p = 0.002). Anti-diarrheal medication use was significantly reduced in the placebo group (p = 0.03). The patients in the study drug group had a significantly improved stool consistency (p < 0.001).
Live lactobacillus acidophilus plus bifidobacterium bifidum reduced the incidence of radiation-induced diarrhea and the need for anti-diarrheal medication and had a significant benefits on stool consistency.
[Show abstract][Hide abstract] ABSTRACT: Several studies have shown that preterm delivery, a primary cause of perinatal mortality and morbidity, is more frequent in HIV-positive women. This study aimed to determine factors associated with prematurity in HIV-infected women and identify risks for which specific interventions could be targeted.
Data were prospectively collected in a clinical trial assessing the efficacy of different zidovudine prophylaxis durations for the prevention of perinatal HIV transmission in Thailand. Characteristics associated with prematurity - delivery before 37 weeks--were assessed using univariate and multivariate logistic regression and were subsequently used to identify subgroups of women at risk.
Among 979 women, independent prematurity risk factors were: viral load <3.5 or >4.5 log copies/mL; hemoglobin > 11.5 g/dL; weight gain <0.25 kg/week; and body mass index <20 kg/m2. These factors allowed us to define four subgroups with an expected probability of prematurity increasing from 3% to 30%. The two subgroups with the highest expected probability of prematurity were considered to be 'at risk' as opposed to the two lowest (odds ratio = 2.6, 95% confidence interval: 1.7-4.0) and the sensitivity and specificity of the prediction were 51% and 71%, respectively.
In this study, four risk factors of preterm delivery were identified allowing the identification of subgroups at increasing risk of prematurity. Adequate nutrition and the provision of highly active antiretroviral therapy during pregnancy as recommended by the World Health Organization for the prevention of perinatal transmission for immunocompromised women in resource-constrained countries may reduce the risk of premature delivery.
Journal of Obstetrics and Gynaecology Research 05/2009; 35(2):225-33. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: Each year, intrauterine growth retardation (IUGR) affects 20-30 million neonates worldwide, mostly in resource-limited settings. Increased perinatal and infant mortality has been associated with IUGR. Some studies have suggested that HIV infection could increase the risk of IUGR. To confirm this hypothesis, we examined the association between HIV-related factors and the risk of IUGR in Thailand.
Patients and Methods: Data from a cohort of 1436 HIV-infected pregnant women enrolled in the Perinatal HIV Prevention Trial-1, a clinical trial conducted from 1997 to 1999 in Thailand, were analyzed using a logistic regression, adjusting for risk factors usually associated with IUGR.
Results: The rate of IUGR was 7.6%. Adjusting for a short maternal height, low body mass index, small weight gain during pregnancy, and infant female sex, a low maternal CD4 percentage was independently associated with IUGR (odds ratio 0.96, per 1% increment, 95% confidence interval 0.93 to 0.99, P = 0.03).
Conclusions: The current World Health Organization recommendation to initiate combination antiretroviral therapy for immunocompromised women as early as possible during pregnancy for their own health and for the prevention of HIV mother-to-child transmission is likely to also decrease the incidence of IUGR. Encouraging immunocompromised HIV-infected women who plan to become pregnant to wait until immune restoration has been achieved may help to reduce the risk of IUGR.
[Show abstract][Hide abstract] ABSTRACT: TP53 mutations are observed in about 40-70% of lung cancer tissues, and the hot spot codon mutations are in exons 5 through 8. Previous studies revealed that the distinct TP53 mutational pattern between population groups may be due to different racial or exogenous factors. This research aims to identify risk factors that influence TP53 gene mutation in lung cancer patients residing areas with high lung cancer incidence, in the upper northern part of Thailand. Germline TP53 mutational analyses were also performed to determine the inherited cancer predisposition. Exons 5-8 of the TP53 gene were analyzed by sequencing DNA of cancerous tissue and peripheral blood leukocyte samples from 55 non-small lung cell cancer patients. The results showed that the TP53 germline mutation was not found in all patients, indicating that the TP53 germline mutations were not exclusively responsible for cancer predisposition in this group of lung cancer patients. A total of 19 somatic mutations were found in 18 patients. Mutations were predominantly found in exons, with only 10.53% observed at the splice sites of intron 7. No characteristic hot spot codons were observed. The data suggest that TP53 mutations in this study group are induced by exposure to substances other than tobacco smoke. Pesticide exposure or habitation in poorly ventilated houses may instead be related to the tumorigenesis of lung cancer via TP53 mutations.
Cancer genetics and cytogenetics 08/2008; 185(1):20-7. · 1.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The identification of risk factors for in utero and intrapartum transmission of human immunodeficiency virus type 1 (HIV-1) is crucial to the design and understanding of preventive interventions.
The randomized Perinatal HIV Prevention Trial-1 enrolled 1437 pregnant women and their non-breast-fed infants, to compare the efficacy of various durations of zidovudine prophylaxis. Using univariate and multivariate logistic regression analyses, we studied the role that factors known or occurring at various times during gestation or delivery play in in utero and intrapartum transmission.
Variables independently associated with in utero transmission were HIV-1 load >35,000 copies/mL (adjusted odds ratio [AOR], 4.2) and delayed initiation of maternal zidovudine prophylaxis until >31.4 weeks gestation (AOR, 3.0). Variables associated with intrapartum transmission were HIV-1 load >10,000 copies/mL (AOR, 3.8 for 10,000-35,000 copies/mL and 7.1 for >35,000 copies/mL), induction of labor (AOR, 2.6), and premature labor with tocolysis (AOR, 15.1).
With the exception of very high HIV-1 load, risk factors for in utero transmission were different from those for intrapartum transmission. Optimal prophylactic interventions must address each of the major risk factors, with appropriate timing.
The Journal of Infectious Diseases 12/2007; 196(11):1629-36. · 5.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To respond to the primary safety objective of the Perinatal HIV Prevention Trial 1 (PHPT-1) by studying the evolution of haematological parameters according to zidovudine exposure duration in HIV-1-infected pregnant women.
Multicenter, randomized, double-blind, controlled trial of different durations of zidovudine prophylaxis.
27 hospitals in Thailand.
1,436 HIV-infected pregnant women in PHPT-1.
Zidovudine prophylaxis initiation at 28 or 35 wk gestation.
Haemoglobin level, leucocytes, total lymphocyte counts, and absolute neutrophil counts were measured at 26, 32, and 35 wk and at delivery. The evolution of haematological parameters was estimated between 26 and 35 wk (zidovudine/placebo) and between 35 wk and delivery to compare a long versus short zidovudine exposure. For each parameter, linear mixed models were adjusted on baseline sociodemographic variables, HIV clinical stage, CD4 count, and viral load.
Between 26 and 35 wk, haemoglobin, leucocytes, and absolute neutrophil counts decreased in zidovudine-exposed compared to unexposed women (mean difference [95% CI] -0.4 [-0.5 to -0.3], -423 [-703 to -142], -485 [-757 to -213], respectively). However, between 35 wk and delivery, the haematological parameters increased faster in women exposed to long rather than short durations of zidovudine (0.1 [0.0 to 0.1]; 105 [18 to 191]; 147 [59 to 234], respectively). At delivery, the differences were not statistically significant, except for mean haemoglobin level, which remained slightly lower in the long zidovudine treatment group (difference: 0.2 g/dl). Zidovudine had no negative impact on the absolute lymphocyte counts.
Zidovudine initiated at 28 wk gestation rather than 35 wk had a transient negative impact on the evolution of haematological parameters, which was largely reversed by delivery despite continuation of zidovudine. This result provides reassurance about the safety of early initiation of zidovudine prophylaxis during pregnancy to maximize prevention of perinatal HIV.
[Show abstract][Hide abstract] ABSTRACT: Attempts have been made to predict the binding structures of the human immunodeficiency virus-1 protease (HIV-1Pr) with various
inhibitors within the shortest simulation time consuming. The purpose here is to improve the structural prediction by using
statistical approach. We use a combination of molecular docking and non-parametric binomial distribution test considering
the combination of binding energy, hydrogen bonding, and hydrophobic-hydrophilic interaction in term of binding residues to
select the most probable binding structure. In this study, the binding of HIV-1Pr and two inhibitors: Saquinavir and Litchi chinensis extracts (3-oxotrirucalla-7, 24-dien-21-oic acid) were investigated. Each inhibitor was positioned in the active site of
HIV-1Pr in many different ways using Lamarckian genetic algorithm and then score each orientation by applying a reasonable
evaluation function by AutoDock3.0 program. The results from search methods were screened out using non-parametric binomial
distribution test and compared with the binding structure from explicit molecular dynamic simulation. Both complexes from
statistical selected docking simulation were found to be comparable with those from X-ray diffraction analysis and explicit
molecular dynamic simulation structures.
Bioinformatics Research and Development, First International Conference, BIRD 2007, Berlin, Germany, March 12-14, 2007, Proceedings; 01/2007