Digital Innovations (Isan Cohort).

Innovations in digital procedures are discussed and highlighted in this chapter providing a comprehensive background and an overview of the Cholangiocarcinoma Screening and Care Program (CASCAP), and the innovative data base known as the Isan cohort, including the O. viverrini - CCA module, tele-radiology, databases for pathology, surgery, palliative care, and a randomized controlled trial database.

Epidemiology and Control of Opisthorchis viverrini Infection: Implications for Cholangiocarcinoma Prevention.

It is known that Opisthorchis viverrini (OV) is the most significant risk factor for the development of cholangiocarcinoma (CCA); hence, it is also known as carcinogenic parasite. Effective control and elimination of OV infection should significantly reduce O. viverrini-related CCA. This chapter includes details of the three recently developed innovative tools, namely the Isan cohort database software, an OV-RDT for screening of O. viverrini, and an ultrasound telecommunication system. Past and current control programs, i.e., education, medication, and sanitation were discussed and stressed the need for a comprehensive control program which encompasses primary, secondary, and tertiary patient care programs for confirmation and management of suspected CCA cases. The approach of mathematical modeling for control of OV and CCA was also briefly described. Additionally, we highlighted the current progress toward control of OV and CCA in Thailand and potential for expansion into nearby countries in Southeast Asia.

Survival after surgery among patients with cholangiocarcinoma in Northeast Thailand according to anatomical and morphological classification.

BACKGROUND: Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. METHODS: This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. RESULTS: Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0-3.6), with median survival time of 17.8 months (95% CI: 15.4-20.2), and 5-year survival rate of 24.6% (95% CI: 20.7-28.6). The longest median survival time was 21.8 months (95% CI: 16.3-27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8-46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9-63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4-58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01-2.09; P = 0.013) compared to ICCA+ID patients. CONCLUSIONS: Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

CKDNET, a quality improvement project for prevention and reduction of chronic kidney disease in the Northeast Thailand.

BACKGROUND: The incidence of chronic kidney disease (CKD) is high in the Northeast Thailand compared to other parts of the country. Therefore, a broad program applying all levels of care is inevitable. This paper describes the results of the first year trial of the Chronic Kidney Disease Prevention in the Northeast Thailand (CKDNET), a quality improvement project collaboratively established to curb CKD. METHODS: We have covered general population, high risk persons and all stages of CKD patients with expansive strategies such as early screening, effective CKD registry, prevention and CKD comprehensive care models including cost effectiveness analysis. RESULTS: The preliminary results from CKD screening in general population of two rural sub-districts show that 26.8% of the screened population has CKD and 28.9% of CKD patients are of unknown etiology. We have established the CKD registry that has enlisted a total of 10.4 million individuals till date, of which 0.13 million are confirmed to have CKD. Pamphlets, posters, brochures and other media of 94 different types in the total number of 478,450 has been distributed for CKD education and awareness at the community level. A CKD guideline that suits for local situation has been formulated to deal the problem effectively and improve care. Moreover, our multidisciplinary intervention and self-management supports were effective in improving glomerular filtration rate (49.57 versus 46.23 ml/min/1.73 m2; p < 0.05), blood pressure (129.6/76.1 versus 135.8/83.6 mmHg) and quality of life of CKD patients included in the program compared to those of the patients under conventional care. The cost effectiveness analysis revealed that lifetime cost for the comprehensive health services under the CKDNET program was 486,898 Baht compared to that of the usual care of 479,386 Baht, resulting in an incremental-cost effectiveness ratio of 18,702 Baht per quality-adjusted life years gained. CONCLUSION: CKDNET, a quality improvement project of the holistic approach is currently applying to the population in the Northeast Thailand which will facilitate curtailing of CKD burden in the region.

A comparison of the proportion of early stage cholangiocarcinoma found in an ultrasound-screening program compared to walk-in patients.

BACKGROUND: Patients with cholangiocarcinoma (CCA) usually have no specific symptoms until an advance stage of the disease and curative treatment is not possible. Patients with early stage, operable disease can be found using ultrasonography (US). A US-screening program was implemented in Thailand where CCA incidence is the highest worldwide. Here we evaluate the effectiveness of the program by comparing the proportion of individuals with early stage CCA in the screening group with that of the walk-in group presenting at hospitals with clinical symptoms. METHODS: All patients had a pathological diagnosis of CCA. The difference in the proportions and the 95% confidence interval (CI) were obtained using binomial regression. RESULTS: Of the 762 histologically proven CCA cases, 161 were from the screening group and 601 from the walk-in group. The proportion of early stage CCA (stages 0 to II) diagnosed was 84.5% in the screening and 21.6% in the walk-in groups. After adjustment age, gender, and liver fluke infection, there was a significantly higher proportion (P < 0.001) and higher chance (P < 0.001) of having early stage CCA in the screening group than in the walk-in group. CONCLUSIONS: US-screening is an effective tool for detecting early stage, operable CCA in high incidence areas.

ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION (APACHE) II SCORE - THE CLINICAL PREDICTOR IN NEUROSURGICAL INTENSIVE CARE UNIT.

The APACHE II scoring system is approved for its benchmarking and mortality predictions, but there are only a few articles published to demonstrate it in neurosurgical patients. Therefore, this study was performed to acknowledge this score and its predictive performance to hospital mortality in a tertiary referral neurosurgical intensive care unit (ICU). All patients admitted to the Neurosurgical ICU from February 1 to July 31, 2011 were recruited. The parameters indicated in APACHE II score were collected. The adjusted predicted risk of death was calculated and compared with the death rate observed. Descriptive statistics including the receiver operating characteristic curve (ROC) was performed. The results showed that 276 patients were admitted during the mentioned period. The APACHE II score was 16.56 (95% CI, 15.84-17.29) and 19.08 (95% CI, 15.40-22.76) in survivors and non-survivors, while the adjusted predicted death rates were 13.39% (95% CI, 11.83-14.95) and 17.49% (95% CI, 9.81-25.17), respectively. The observed mortality was only 4.35%. The area under the ROC of APACHE II score to the hospital mortality was 0.62 (95% CI, 0.44-0.79). In conclusion, not only the APACHE II score in neurosurgical patients indicated low severity, but its performance to predict hospital mortality was also inferior. Additional studies of predicting mortality among these critical patients should be undertaken.

National survey: Evaluation of cardiovascular risk factors in Thai patients with type 2 diabetes and chronic kidney disease after the development of cardiovascular disease.

AIM: The aim of the present study was to evaluate the achievement in controlling the risk factors of cardiovascular diseases (CVD) in Thai patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). METHODS: The DMHT dataset from 2011 to 2012, which was the cross-sectional study of the national survey in Thai patients with T2DM was analyzed. RESULTS: There were 1254 of 15 149 diabetic patients with estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m2 that had developed CVD for more than 12 months. The prevalence of CVD was 8.3%. The mean age in years was 68.2 with a standard deviation (SD) of 8.7. Males and females were 38.7 and 61.3%, respectively. The mean duration of diabetes was 8.5 (SD 0.2) years. The mean body mass index was 25.5 (SD 4.4) kg/m2 . The percentage of patients with the target level of blood pressure control at ≤130/80 mm Hg was 47.1%. The percentage of patients who received angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) was 58.9%. The percentage of patients with the target level of LDL control at <70 mg/dL was 17.2%. The percentage of patients with the target level of HbA1C at 7% was 39.2%. There were 63 (5.0%) patients having recurrent CVD. CONCLUSIONS: Most Thai patients with T2DM and CKD with eGFR < 60 mL/min per 1.73 m2 could not achieve the therapeutic goals after the development of CVD. The national health policy should be planned to improve the quality of care to increase the number of patients who achieve the recommended goals.

Prevalence of chronic kidney disease associated with cardiac and vascular complications in hypertensive patients: a multicenter, nation-wide study in Thailand.

BACKGROUND: Hypertension and chronic kidney disease (CKD) are common conditions and both are major risk factors for cardiovascular events. The objectives were 1) to study the prevalence of CKD in hypertensive patients and 2) to study the association of CKD with cardiac and vascular complications in a multicenter, nation-wide fashion. METHODS: This cross-sectional study evaluated patients aged 20 years or older who were diagnosed with hypertension and who had been treated for at least 12 months at 831 public hospitals in Thailand during the 2012 study period. Outcome measurements included calculated glomerular filtration rate (GFR) and cardiac and vascular complications that included coronary artery disease, stroke, peripheral arterial disease, heart failure, and atrial fibrillation. Multivariable modeling was conducted to determine independent factors associated with increased risk of cardiac and vascular complications. RESULTS: A total of 28770 patients were enrolled. Average age was 62.8 years and 37% were male. Prevalence of CKD stage 3 and 4-5 was 33.2 and 4.3%, respectively. Prevalence of cardiac and vascular complications was 10.5% (5% having coronary artery disease, 3.9% stroke, 1.7% heart failure, and 1.2% atrial fibrillation). CKD was an independent risk factor associated with each of the complications and overall cardiac and vascular complications with an adjusted Odds ratio of 1.4 for CKD stage 3 and 1.9 for CKD stage 4-5. CONCLUSION: Prevalence of CKD stage 3-5 in hypertensive population was 37.5%. CKD is an independent risk factor for adverse cardiac and vascular outcome.

Evaluating a preoperative protocol that includes magnetic resonance imaging for lymph node metastasis in the Cholangiocarcinoma Screening and Care Program (CASCAP) in Thailand.

BACKGROUND: Treatment planning especially liver resection in cholangiocarcinoma (CCA) depends on the extension of tumor and lymph node metastasis which is included as a key criterion for operability. Magnetic resonance imaging (MRI) offers a rapid and powerful tool for the detection of lymph node metastasis (LNM) and in the current manuscript is assessed as a critical tool in the preoperative protocol for liver resection for treatment of CCA. However, the accuracy of MRI to detect LNM from CCA had yet to be comprehensively evaluated. METHODS: The accuracy of MRI to detect LNM was assessed in a cohort of individuals with CCA from the Cholangiocarcinoma Screening and Care Program (CASCAP), a screening program designed to reduce CCA in Northeastern Thailand by community-based ultrasound (US) for CCA. CCA-positive individuals are referred to one of the nine tertiary centers in the study to undergo a preoperative protocol that included enhanced imaging by MRI. Additionally, these individuals also underwent lymph node biopsies for histological confirmation of LNM (the "gold standard") to determine the accuracy of the MRI results. RESULTS: MRI accurately detected the presence or absence of LNM in only 29 out of the 51 CCA cases (56.9%, 95% CI 42.2-70.7), resulting in a sensitivity of 57.1% (95% CI 34.0-78.2) and specificity of 56.7% (95% CI 37.4-74.5), with positive and negative predictive values of 48.0% (95% CI 27.8-68.7) and 65.4% (95% CI 44.3-82.8), respectively. The positive likelihood ratio was 1.32 (95% CI 0.76-2.29), and the negative likelihood ratio was 0.76 (95% CI 0.42-1.36). CONCLUSIONS: MRI showed limited sensitivity and a poor positive predictive value for the diagnosis of LNM for CCA, which is of particular concern in this resource-limited setting, where simpler detection methods could be utilized that are more cost-effective in this region of Thailand. Therefore, the inclusion of MRI, a costly imaging method, should be reconsidered as part of protocol for treatment planning of CCA, given the number of false positives, especially as it is critical in determining the operability for CCA subjects.

Is the Risk of Ovarian Malignancy Algorithm Better Than Other Tests for Predicting Ovarian Malignancy in Women with Pelvic Masses?

AIM: The study aimed to compare the risk of ovarian malignancy algorithm (ROMA) with risk of malignancy index (RMI), cancer antigen 125 (CA125), human epididymis protein 4 (HE4) and Sassone ultrasonography (US) score in predicting ovarian cancer (OC) in women who present with pelvic or adnexal masses. METHODS: Pelvic US, serum CA125 and HE4 levels were investigated preoperatively in consecutively enrolled Thai women over 18 years with clinically diagnosed pelvic or adnexal masses who were undergoing elective surgery at a super tertiary hospital in Thailand in 2012. ROMA, RMI and Sassone US score were calculated. RESULTS: Of 260 women who were evaluated, 74 had OC. Areas under the receiver operating characteristic curve (AUC) in predicting OC were ROMA, 86.2%; RMI, 87.6%; CA125, 80.6%; HE4, 82.4%; and Sassone score, 77.1%. ROMA and RMI performed similarly well (AUCs 84.4 and 85.6%) in premenopausal women but RMI outperformed ROMA in postmenopausal women (AUCs 87.9 and 84.0%, respectively). At the conventional cutoff value, ROMA and CA125 showed the highest sensitivity (83.8%) but HE4 had the highest specificity (86.0%). CONCLUSIONS: ROMA was comparable to RMI in predicting OC. Either ROMA or RMI can be applied to women with pelvic masses, stratified into low- and high-risk groups for OCs.

Rajavithi-ovarian cancer predictive score (R-OPS): A new scoring system for predicting ovarian malignancy in women presenting with a pelvic mass.

OBJECTIVE: To develop a new scoring system based on menopausal status, ultrasound (US) findings, serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to predict ovarian cancer (OC) in women presenting with a pelvic or adnexal mass. METHODS: Consecutive female patients aged over 18years with pelvic or adnexal masses investigated preoperatively by pelvic US, serum CA125 and HE4 who underwent elective surgery were enrolled. The "Rajavithi-Ovarian Cancer Predictive Score (R-OPS)" was developed using data from 2012 and validated using data from 2013 to 2014. The diagnosis of OC was based on pathological findings. Data were analyzed by logistic regression and area under the receiver operating characteristic curve (ROC-AUC). RESULTS: Based on a development set of 260 women including 74 with OC, menopausal status (M), serum CA125 and HE4, and US findings of solid lesions (U) were identified as significant predictors of OC. R-OPS=M×U×(CA125×HE4)(1/2) revealed good calibration (goodness-of-fit test, p=0.972) and discrimination (ROC-AUC=92.8%). Performance validation in 266 women, 82 with OC, showed good discrimination with ROC-AUC of 94.9%. Performance in the validation sample with a cutoff value of R-OPS>330 revealed sensitivity, specificity, and positive and negative predictive values of 93.9%, 79.9%, 67.5%, and 96.7%, respectively. CONCLUSIONS: The new R-OPS scoring system showed good discrimination between non-cancerous lesions and OC. However, a prospective study in a different setting is required to confirm these preliminary data.

Prevalence and associating factors of atrial fibrillation in patients with hypertension: a nation-wide study.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia and increases risk of ischemic stroke. Data on the prevalence of AF in Thailand is lacking especially in patients with hypertension. The objectives of this study were to determine prevalence of AF in patients with hypertension and to determine factors that are associated with increased prevalence of AF in a multicenter nationwide study. METHODS: A cross-sectional survey for the national outcome evaluation among hypertensive patients visiting 831 public hospitals in Thailand was conducted between 2011 and 2012 to evaluate status of standard care in hypertensive patients visiting public Thailand Ministry of Public Health (MoPH) hospitals. Inclusion criteria were hypertensive patients aged at least 20 years who had received medical care in the targeted hospital for at least 12 months. The main outcome measurement was AF rhythm, and was measured along with potential risk factors age, gender and cardiovascular risk factors. RESULTS: There were 13207 hypertensive patients who had ECG data recorded during the survey. AF was detected in 457 patients (3.46 %). Prevalence of AF increased with increasing age, was more common in males and in patients with chronic kidney disease (CKD). Multivariable modelling was conducted to assess which factors were most associated with increased prevalence of AF, and the results showed older age followed by male gender, low LDL-cholesterol and increased uric acid levels were the most important risk factors for AF in this population. CONCLUSIONS: Prevalence of AF in hypertensive patients was 3.46 %. Factors associated with increased risk of AF are old age, male gender, low LDL-cholesterol and elevated uric acid level.

Relation of peritubular capillary features to class of lupus nephritis.

BACKGROUND: Experimental studies have linked peritubular capillary (PTC) loss with progression of chronic kidney disease. Minimal information on PTC in lupus nephritis (LN) has been reported. We therefore evaluated the PTC area in different classes of LN and determined if specific clinical characteristics correlated with PTC changes. METHODS: Renal biopsies of 253 subjects with LN (categorized using the ISN/RPS 2003 classification) and 13 normal renal donors (the controls) were retrospectively evaluated for PTC morphology by staining for CD31 with immunohistochemistry method. The percent positive area of PTC (% PTC) was correlated with serum and urinary measures of renal function and renal pathology. RESULTS: Significant PTC loss was observed in all classes of LN compared to controls. The % PTC area was highest in controls (7.64±1.48 %) with levels of 1.95±1.50, 4.16±3.85, 4.19±4.45, 5.02±1.79, and 4.45±3.75 in classes II, III, IV, IV combined with V and V, respectively (all p values < 0.05). The lowest PTC density was observed in class II LN, but this may be because some cases with worse classes of LN showed increased PTC density due to abnormally dilated capillaries associated with acute inflammation and angiogenesis. %PTC was increased in those with hematuria (5.8±5.2 vs. 3.6±3.4 %, red blood cells 3-10 vs. < 3 cells/high power field, p < 0.05) and was reduced in those with a moderately declined renal function (3.29±3.40 vs. 4.42±4.12, eGFR 15-59 vs. ≥ 60 ml/min/1.73 m2, p < 0.05). Nephrotic-range proteinuria also trended to be associated with lower PTC density although it did not reach statistical significance (3.1±2.6 vs. 4.9±4.5, p= 0.067). CONCLUSIONS: LN is associated with PTC loss and the severity correlates with reduced renal function. Further studies are needed to investigate whether a loss of PTC can predict long term renal outcomes in LN.

Mortality and treatment costs of hospitalized chronic kidney disease patients between the three major health insurance schemes in Thailand.

BACKGROUND: Thailand has reformed its healthcare to ensure fairness and universality. Previous reports comparing the fairness among the 3 main healthcare schemes, including the Universal Coverage Scheme (UCS), the Civil Servant Medical Benefit Scheme (CSMBS) and the Social Health Insurance (SHI) have been published. They focused mainly on provision of medication for cancers and human immunodeficiency virus infection. Since chronic kidney disease (CKD) patients have a high rate of hospitalization and high risk of death, they also require special care and need more than access to medicine. We, therefore, performed a 1-year, nationwide, evaluation on the clinical outcomes (i.e., mortality rates and complication rates) and treatment costs for hospitalized CKD patients across the 3 main health insurance schemes. METHODS: All adult in-patient CKD medical expense forms in fiscal 2010 were analyzed. The outcomes focused on were clinical outcomes, access to special care and equipment (especially dialysis), and expenses on CKD patients. Factors influencing mortality rates were evaluated by multiple logistic regression. RESULTS: There were 128,338 CKD patients, accounting for 236,439 admissions. The CSMBS group was older on average, had the most severe co-morbidities, and had the highest hospital charges, while the UCS group had the highest rate of complications. The mortality rates differed among the 3 insurance schemes; the crude odds ratio (OR) for mortality was highest in the CSMBS scheme. After adjustment for biological, economic, and geographic variables, the UCS group had the highest risk of in-hospital death (OR 1.13;95 % confidence interval (CI) 1.07-1.20; p < 0.001) while the SHI group had lowest mortality (OR 0.87; 95 % CI 0.76-0.99; p = 0.038). The circumscribed healthcare benefits and limited access to specialists and dialysis care in the UCS may account for less favorable comparison with the CSMBS and SHI groups. CONCLUSIONS: Significant differences are observed in mortality rates among CKD patients from among the 3 main healthcare schemes. Improvements in equity of care might minimize the differences.

Thai nurse cohort study: cohort profiles and key findings.

BACKGROUND: Globally, the nursing profession faces shortages, high turnover, and inequitable distribution. These problems are particularly acute in South East Asia. The present paper describes the design and initial findings of the Thai Nurse Cohort Study (TNCS). METHODS: The TNCS is a longitudinal prospective cohort study comprising multiple age cohorts, initiated in 2009 and expected to run until 2027. Cohorts comprise registered nurses (RN) holding professional licenses granted by the Thailand Nursing and Midwifery Council. Follow-up is at 3-year intervals, with new (younger) TNCS cohorts introduced and older, no-longer eligible members checked out. This maintains the cohort size as representative of the Thai RN population. The first survey round (2009) used a self-administered mailed questionnaire. The second round (2012) provided follow-up of the initial cohort and formed the baseline survey of new entries. RESULTS: The sampling frame for the first round was 142,699 licensed RN; 50,200 age-stratified participants were randomly selected and mailed the questionnaire, and 18,198 questionnaires were returned owing to incorrect addresses. Of the remaining 32,002 participants, 18,756 (58.6 %) responded (average age 43.7 ± 9.8 years). About 15.4 % (equivalent to 20,000 of the current RN population), reported an intention to leave their nursing career. The second round achieved a follow-up rate of 60.2 %. This round included 3020 participants randomly selected from 6402 new RN (response rate, 38.3 %; mean age 23.1 ± 3.5 years). In this round, 11.2 % reported they intended to leave nursing in the next 2 years. CONCLUSIONS: These two survey rounds have highlighted that Thailand is facing critical nurse shortages. A high rate of nurses expressed an intention to leave the profession; the capacity to replace these potential losses is much lower.

Diagnostic Accuracy and Optimal Cutoff Value of Serum HE4 to Predict Ovarian Cancer in Thai Women with Pelvic Masses.

Background: Serum human epididymis protein 4 (HE4) is highly expressed in women with ovarian cancers (OCs), but data about its clinical application of HE4 for Thai women is limited. Objective: To evaluate the diagnostic accuracy and optimal cutoff for HE4 in distinguishing benign lesions, borderline ovarian tumor (BOTs), and OCs compared with CA125 in Thai women at Rajavithi Hospital. Material and Method: The cross-sectional study was conducted in Thai women aged older than 18 years old with pelvic masses whom underwent elective surgery at Rajavithi Hospital between 2012 and 2013. Preoperative serum HE4 and CA125 levels were measured and pathologic specimens were reviewed. Results: Of the 518 participants evaluated, 316 had benign lesions, 43 had BOTs, and 159 had OCs. Between non-cancers and OCs, area under receiver operating characteristic curve (ROC-AUC) for HE4 hardly differed from CA125 (0.85 vs. 0.83, p = 0.402) but was significantly lower in postmenopausal women (0.79 vs. 0.86, p = 0.049). The optimal cutoff value of HE4 was 72 pM/L for all menopausal status. Lower HE4 was seen in 30.8% of mucinous carcinoma and 31.7% of clear cell carcinoma. The HE4 ROC-AUC was significantly higher than CA125 ROC-AUC in distinguishing benign diseases and BOTs (0.71 vs. 0.53, p<0.001), HE4 in 70% of BOTs was 51 to 95 pM/L. Conclusion: Although the 72 pM/L cutoff for HE4 was appropriate in distinguishing between non-cancers and OCs for both pre- and postmenopausal women, the limitation for postmenopausal women, mucinous carcinomas, and clear cell carcinomas require to be complemented with CA125.

Parameters Affecting Length of Stay Among Neurosurgical Patients in an Intensive Care Unit.

AIM: to determine the predictive factors on the length of stay of neurosurgical patients in the ICU setting. METHODS: all patients admitted to the neurosurgical ICU between February 1 and July 31, 2011 were recruited. Patient demographics and clinical data for each variable were collected within 30 minutes of admission. The ICU length of stay was recorded and analyzed by linear regression model with statistical significance at p-value <0.05. RESULTS: there were 276 patients admitted, of whom 89.1% were elective cases. The mean (95% CI) and median (min-max) of ICU length of stay were 2.36 (2.09-2.63) and 2 (1-25) days. The variables associated with ICU length of stay and their percent change (95% CI) were the Glasgow Coma Scale motor subscore (GCSm), 6.72% (-11.20 to -2.01) lower for every 1 point score change; blood pH, 1.16% (0.11 to 2.21) higher for every 0.01 unit change; and emergency admission type, 58.30% (29.16 to 94.0) higher as compared to elective admission. CONCLUSION: the GCSm, pH and emergency admission were found to be the main predictive variables of neurosurgical patient length of stay in the intensive care unit, however, the model should be further explored in a larger sample size and using subgroup analysis.

Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial.

BACKGROUND: Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. METHODS: For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials.com, number ISRCTN86140460. FINDINGS: We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). INTERPRETATION: Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients. FUNDING: Thailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.

Association between praziquantel treatment and cholangiocarcinoma: a hospital-based matched case-control study.

BACKGROUND: Infection by the liver fluke, Opisthorchis viverrini, remains an important public health problem in Thailand and has resulted in the highest prevalence of infection and incidence of subsequent cholangiocarcinoma (CCA) in the world. Praziquantel (PZQ) is the antihelminthic drug of choice for treatment. Previous studies in hamsters showed that repeated infection and PZQ treatment could increase the risk of CCA. However, the few available epidemiology studies in humans have shown unclear evidence of an increased risk of CCA with frequency of PZQ intake. The present study investigated the relationship between the number of repeated PZQ treatments and CCA. METHODS: A hospital-based matched case-control study was conducted. All cases and controls were inpatients of a tertiary hospital in Northeast Thailand. During 2012-2014 a total of 210 incident cases of pathologically diagnosed CCA and 840 control subjects were selected from a hospital inpatient database (four controls per case). The four recruited controls were individually matched with CCA cases by gender, age and date of admission. Data were collected in face-to-face interviews using a standardised pre-tested questionnaire. Multivariable conditional logistic regression was used in the analysis of the data. RESULTS: The frequencies of PZQ usage among the 210 cases and 840 controls were 48.6 vs. 66.0 for never, 32.9 vs. 24.4 for once, 8.6 vs. 4.9 for twice, and 10.0% vs. 4.8% for more than twice, respectively. There was a statistically significant dose-response relationship (p < 0.001). Compared with subjects who never used PZQ, those who used the medication once, twice, and more than twice were 1.49, 1.82, and 2.30 times more likely to develop CCA (95% confidence intervals: 1.02 - 2.20, 0.92 - 3.60, and 1.20 - 4.40). These odds ratios (adjusted ORs) had already been adjusted for the effects of eating raw fish, a family history of cancer, and highest educational attainment. Additional PZQ usage increased the odds of developing CCA by 23.0% (adjusted OR = 1.23; 95% CI: 1.07 - 1.43). CONCLUSIONS: The findings show that repeated PZQ treatments are associated with an increased risk of CCA. Paradoxically, this contradicts the common belief that repeated PZQ treatments decrease the risk of CCA. The study also showed a strong association between the number of repeated PZQ treatments and the consumption of raw freshwater fish. This suggests that repeated PZQ treatments may be a surrogate marker of habit of eating raw fish.

Cohort profile: cholangiocarcinoma screening and care program (CASCAP).

BACKGROUND: Cholangiocarcinoma (CCA) is an extremely aggressive cancer that is usually fatal. Although globally morbidity and mortality are increasing, knowledge of the disease remains limited. The Mekong region of Southeast Asia, and particularly the northeast of Thailand, has by far the highest incidence of CCA worldwide with 135.4 per 100,000 among males and 43.0 per 100,000 among females being reported in Khon Kaen Province. Most patients are first seen during late stage disease with 5-year survival being less than 10%. Starting in 1984, control and prevention strategies have been focused on health education. Although early detection can substantially increase 5-year survival, there are currently no strategies to increase early diagnosis. METHODS/DESIGN: The Cholangiocarcinoma Screening and Care Program (CASCAP) is a prospective cohort study comprising two cohorts- the screening and the patient cohorts. For the screening cohort, ultrasound examination will be carried out regularly at least annually to determine whether there is current bile duct and/or liver pathology so that the optimal screening program for early diagnosis can be established. This cohort is expected to include at least 150,000 individuals coming from high-risk areas for CCA. For the patient cohort, it is estimated that about 25,000 CCA patients will be included during the 5-year recruitment period. All CCA patients will be treated according to routine clinical care and followed so that effective surgical treatment can be formulated. This cohort is indeed a conventional cancer registry. Thus, CASCAP is an ongoing project in which the number of participants changes dynamically. DISCUSSIONS: This is the first project on CCA that involves screening the at risk population at the community level. At the time of preparing this report, a total of 85,927 individuals have been enrolled in the screening cohort, 55.0% of whom have already undergone ultrasound screening, and 2661 CCA cases have been enrolled in the patient cohort. Among the participants of the screening, whose mean age was 53.8±9.8 years, 55.6% were female, 77.5% attained primary school as the highest level of education, 79.9% were farmers, 29.9%, reported having relatives with CCA, 89.1% had eaten uncooked fish, and 42.2% of those who had been tested for liver fluke were found to be infected.