Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Recent advances in uveitis therapy: focus on selected phase 2 and 3 clinical trials.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.

Longitudinal Comparative Analysis of Semi-Automated Aqueous Flare Measurements with Clinical Grading and Visual Outcomes in Uveitic Eyes.

PURPOSE: To evaluate the correlation between longitudinal changes in aqueous flare measured by laser flare photometer (LFP), best-corrected visual acuity (BCVA), and clinical grade using both Standardization of Uveitis Nomenclature (SUN) and modified SUN (MSUN) scales uveitis patients. METHODS: Patients were classified according to both SUN and MSUN grading scales. LFP measurements were acquired (Kowa FM-700) at each visit. Mean change in LFP was assessed longitudinally, comparing with those in visual acuity, SUN, and MSUN grading scales. RESULTS: Mean change in LFP was correlated to those in BCVA (p = .018), SUN scale (p < .001), and MSUN scale (p = .008). Cases within same initial SUN (0 and 1+) and MSUN (0.5+ and 1+) grades and different longitudinal flare prognosis (decreased/unchanged/increased) had significantly different initial LFP values (all p < .05). CONCLUSIONS: LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP.

Correlation of Clinical Aqueous Flare Grading to Semi-Automated Flare Measurements Using Laser Flare Photometry.

PURPOSE: To compare laser flare photometry (LFP) measurements of aqueous flare with Standardization of Uveitis Nomenclature (SUN) and modified SUN grading. METHODS: In this prospective study with multicenter design, uveitis patients were classified according to SUN and modified SUN grading scales. LFP was performed with Kowa FM-700 flaremeter. Mean LFP values were compared with SUN and MSUN scores. RESULTS: The study included 475 LFP measurements, of which 216, 48, 150, 31, 28 and 2 had 0, 0.5+, 1+, 1.5+, 2+ and 3+ flare, respectively. LFP values were significantly different between each two consecutive steps for both clinical gradings (all P < .05). Cut-off values for modified SUN grading steps were defined as 5.7, 9.7, 15.7 and 43.2 for 0/0.5+, 0.5+/ 1+, 1+/1.5+ and 1.5/2+ borders of clinical flare, respectively. CONCLUSIONS: LFP proves to be an objective measurement in analyzing aqueous flare comparable to both SUN and MSUN clinical grading systems.

Assessment of morphological and hemodynamic changes in adult atrial septal defect before and after percutaneous trans-catheter closure: the initial result in Vietnamese patient.

OBJECTIVE: This study aimed to evaluate the change of morphology and hemodynamics in a relatively large number of patients with atrial septal defect (ASD) and provide the initial result in Vietnamese patients. PATIENTS AND METHODS: This longitudinal, prospective case-control study was done at the Vietnam National Heart Institute from January 2012 to December 2017. The participants were divided into two groups: the ASD group, which included patients with ASDs, and the control group, which included healthy individuals or individuals without cardiac-related disorders. RESULTS: There were 94 participants in the ASD group and 83 participants in the control group. Most patients with ASDs in the study group were female, and the average age was 38.65 ± 14.8. The success rate of the ASD group was 98.9%. The right ventricle morphology and function showed right ventricular diameter, pulmonary trunk gradually decreased, FAC and ET increased, IVCT and IVRT decreased, and Tei index gradually decreased after each examination. Morphology and function of the left ventricle after ASD closure showed that the left ventricular diameter gradually increased, and EF% in 3 months after ASD closure increased statistically significantly. IVCT, IVRT, and LV Tei index decreased, and ET increased statistically significantly. After six months from ASD closure, the proportion of patients with NYHA I was 90.3%, with no patient with NYHA IV, and pulmonary vascular resistance gradually decreased. CONCLUSIONS: Percutaneous trans-catheter closure in Vietnamese adult atrial septal defect was an effective technique. Ventricle morphological and hemodynamic abnormalities following closure recovered statistical significance over time, particularly in the left ventricle.

Diagnostic performance of diffusion tensor imaging for preo- perative glioma grading.

BACKGROUND: This study aimed to determine the diagnostic per-formance of fractional anisotropy (FA) and mean diffusivity (MD) values for glioma grading. CONCLUSION: The tMD, rMDt/w, and rFAp/w values represent useful indices for the differentiation between LGG and HGG. The combination of these indices can improve diagnostic specificity. METHODS: A total of 42 patients who underwent biopsy or surge-ry and were histologically diagnosed with glioma from September 2019 to December 2020 were enrolled in this retrospective study. Diffusion tensor imaging (DTI) and conventional magnetic resonance imaging (MRI) were performed preoperatively using 3 Tesla MRI in all cases. The FA and MD values were measured in the solid portion of the tumor, the peritumoral area, and the normal white matter. The diagnostic performances of the absolute and relative FA and MD values for glioma grading were analyzed using the receiver operating characteristic (ROC) curve. RESULTS: The MD value in the solid portion of the tumor (tMD), the MD value of the solid portion of the tumor relative to that in the normal white matter (rMDt/w), and the FA value for the peritumoral region relative to that of the normal white matter (rFAp/w) showed significant differences between the low-grade (LGG) and high-grade glioma (HGG) groups. The combination of these three parameters provided the largest area under the curve value of 89% with sensitivity, specificity, accuracy, negative predictive, and positive predictive values of 72%, 100%, 81%, 62%, and 100%, respectively, for distinguishing between the LGG and HGG groups.

Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations.

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

Correction of perceived visual distortions using a software application and correlation to age-related macular degeneration.

PURPOSE: To investigate the use of software-generated corrections in neutralizing perceived distortions in age-related macular degeneration. METHODS: A tablet-based application was utilized to elicit distortions. Five subjects (seven eyes: neovascular age-related macular degeneration and three eyes: non-neovascular age-related macular degeneration) traced the reference lines, and their distortion traces were recorded. To counter distortion, a software-generated trace was re-traced by subjects to produce a corrected trace. Final traces were superimposed on optical coherence tomography images and following distances calculated: (a) dDT: distance between distortion trace and reference line; (b) dGT: distance between software-generated trace and corrected trace; (c) dCT: distance between corrected trace and reference line. Mean percent improvement in distortion was reported. Mean effectiveness of correction was also reported by utilizing t test to compare dDT and dCT. The number of distortion traces with underlying lesions on optical coherence tomography was also analyzed. RESULTS: Mean age of the subjects was 76.6 (±9.5) years. Each patient traced six reference lines and each was considered a separate case. Out of 30 cases, 17 (56.6%) elicited distortion. Mean percent improvement in distortion was 71.3 ± 23% (p < 0.05). Twelve cases (70.6%) had an underlying lesion (eight cases: disrupted photoreceptor layer and four cases: normal photoreceptor layer). Mean percent improvement in cases with normal photoreceptor layer (90.8 ± 5.45%) was higher than with abnormal photoreceptor layer (58.5 ± 7.17%) (p < 0.05). Five cases with distortion had no associated underlying lesion. Mean percent improvement in these subjects was significantly higher than those with photoreceptor layer disruption. CONCLUSION: Software-generated corrections can potentially correct for perceived distortions in patients with age-related macular degeneration, especially in cases with preserved photoreceptor layer.

Blue light versus green light fundus autofluorescence in normal subjects and in patients with retinochoroidopathy secondary to retinal and uveitic diseases.

PURPOSE: The aim of this study is to evaluate the differences in the fundus autofluorescence (FAF) signal between the blue light autofluorescence (BAF) from Spectralis® (Heidelberg, CA) and green light autofluorescence (GAF) 200TxTM (OPTOS, UK, in normal subjects and in patients with retinochoroidopathies (RC). METHODS: In this prospective study, FAF was performed using BL (λ = 488 nm) and GL (λ = 532 nm) on normal subjects and patients with RC. The corresponding pairs of BAF and GAF images from both groups were analyzed using Photoshop. The strength of the FAF signal was measured on a gray scale, where optic disc was a standard to indicate absence of AF. In addition, gray values obtained from three identical points (foveal center, and points of hypo and hyper autofluorescence) in the corresponding BAF and GAF images of normal and RC subjects were divided by the optic disc value to calculate autofluorescence signal ratio (R). The R values at fovea (R1), hypoautofluorescent point (R2), and hyperautofluorescent point (R3) were compared between BAF and GAF modalities, in normal and in RC subjects separately. RESULTS: One hundred six pairs (106 eyes) of FAF images analyzed (37 pairs: normal and 69 pairs: RC subjects). In normal subjects, the mean R1, R2, and R3 values for BAF were (1.5 ± 0.88, 1.23 ± 0.58, and 4.73 ± 2.85, respectively) and for GAF were (0.78 ± 0.20, 0.78 ± 0.20, and 1.62 ± 0.39, respectively). Similarly, in subjects with RC, the mean R1, R2, and R3 values for BAF were (1.68 ± 1.02, 1.66 ± 1.15, and 7.75 ± 6.82, respectively) and for GAF were (0.95 ± 0.59, 0.79 ± 0.45, and 2.50 ± 1.65, respectively). The mean difference in the R1, R2, and R3 ratios between BAF and GAF in normal and in RC subjects was statistically significant (p < 0.001). The strength of the correlation (r) between ratios for BAF and GAF was weak or not statistically significant in both normal and RC subjects (p > 0.05). CONCLUSION: The distribution and intensity of the AF signal differ in BAF and GAF and cannot be used interchangeably. In BAF, optic disc signal is always weaker than in other areas, which was not true for GAF where optic disc signal was stronger than fovea and hypoautofluorescent point in both groups.

Measuring catastrophic costs due to tuberculosis in Viet Nam.

INTRODUCTION: Progress towards ending tuberculosis (TB) in Viet Nam includes monitoring the costs borne by patients through periodic facility-based surveys. OBJECTIVE: To document the magnitude of costs incurred by TB-affected households and establish a baseline for the top End TB indicator in Viet Nam. METHODS: A national survey with retrospective data collection and projection among 735 participants in 20 stratified clusters was conducted in 2016. Each patient was interviewed on costs, time loss, coping measures and asset ownership. Total costs were expressed as a proportion of annual household income. RESULTS: In Viet Nam, 63% of households affected by TB or multidrug-resistant TB (MDR-TB) experienced costs that were >20% of their annual household income. The mean patient costs were respectively US$1054 and US$4302 per episode of TB and MDR-TB. The most significant drivers of mean costs were income loss reported and purchase of special foods, nutritional supplements, travel and accommodation. CONCLUSION: The proportion of households experiencing catastrophic total costs due to TB in Viet Nam is high, which poses a barrier to TB diagnosis and treatment. Based on study results, programme and partners need to identify key areas for policy action and work towards a national policy guide on intervention to reduce TB patient costs.

Economic burden of multidrug-resistant tuberculosis: a multicenter study across Vietnamese regions.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) has become a major worldwide health problem. Various studies have been conducted on the cost of MDR-TB treatment; however, this has remained largely unexplored in Viet Nam. OBJECTIVE: To estimate the total cost of MDR-TB treatment at several health care facilities in Viet Nam. DESIGN: A prospective, prevalence-based study was conducted at three selected centers from March to June 2016 in 204 patients, 102 of whom were treated for 9 months and 102 for 20 months. Direct medical costs were calculated using electronic hospital databases, while a questionnaire was used to interview participants for evaluating direct non-medical and indirect costs. Total costs were estimated from a societal perspective in 2017 USD. RESULTS: Patients were mostly males aged 25-44 years. The average length of hospitalization in the 9-month treatment group was 168 ± 127 days; in the 20-month group, it was 671 ± 119 days. The average treatment cost for MDR-TB was respectively US$1480.34 ± 211.61 and US$2695.58 ± 294.98 for the 9- and 20-month treatment groups. Direct medical costs generally accounted for the highest proportion of the total costs, while the cost of pharmaceuticals and materials comprised the highest direct cost. CONCLUSION: There was a significant difference in total costs among the three hospitals in the 9- and 20-month treatment groups.

Bayesian Networks to Compare Pest Control Interventions on Commodities Along Agricultural Production Chains.

The production of an agricultural commodity involves a sequence of processes: planting/growing, harvesting, sorting/grading, postharvest treatment, packing, and exporting. A Bayesian network has been developed to represent the level of potential infestation of an agricultural commodity by a specified pest along an agricultural production chain. It reflects the dependency of this infestation on the predicted level of pest challenge, the anticipated susceptibility of the commodity to the pest, the level of impact from pest control measures as designed, and any variation from that due to uncertainty in measure efficacy. The objective of this Bayesian network is to facilitate agreement between national governments of the exporters and importers on a set of phytosanitary measures to meet specific phytosanitary measure requirements to achieve target levels of protection against regulated pests. The model can be used to compare the performance of different combinations of measures under different scenarios of pest challenge, making use of available measure performance data. A case study is presented using a model developed for a fruit fly pest on dragon fruit in Vietnam; the model parameters and results are illustrative and do not imply a particular level of fruit fly infestation of these exports; rather, they provide the most likely, alternative, or worst-case scenarios of the impact of measures. As a means to facilitate agreement for trade, the model provides a framework to support communication between exporters and importers about any differences in perceptions of the risk reduction achieved by pest control measures deployed during the commodity production chain.

Latent tuberculous infection in household contacts of multidrug-resistant and newly diagnosed tuberculosis.

BACKGROUND: Differences in the prevalence of latent tuberculous infection (LTBI) and tuberculosis (TB) disease among contacts of patients with multidrug-resistant TB (MDR-TB) and drug-susceptible TB are not well understood. OBJECTIVE: To compare the prevalence of tuberculin skin test (TST) positivity in household contacts of patients with MDR-TB and in contacts of patients never previously treated for TB ('new TB'). DESIGN: Consecutive patients with MDR-TB and their household contacts at nine urban district clinics in Viet Nam were screened for TB and LTBI, and followed up for 6 months. LTBI was defined as a TST result of at least 10 mm. RESULTS: A total of 167 patients with TB and their 337 household contacts were recruited. A total of 167/180 (25.8%) contacts of new TB patients and 60/147 (40.8%) contacts of MDR-TB patients were TST-positive (odds ratio [OR] 2.0, 95%CI 1.3-3.2). Contacts of MDR-TB patients were more likely to have baseline chest radiograph findings consistent with TB (OR 2.6, 95%CI 1.4-5.0). CONCLUSION: Contacts of MDR-TB patients have a high risk of developing TB. Measures to reduce Mycobacterium tuberculosis transmission and accelerate the detection of disease among high-risk contacts should be prioritised to curb the MDR-TB epidemic.

Development of emission factors and emission inventories for motorcycles and light duty vehicles in the urban region in Vietnam.

This paper reports on a 2-year emissions monitoring program launched by the Centre for Environmental Monitoring of the Vietnam Environment Administration which aimed at determining emission factors and emission inventories for two typical types of vehicle in Hanoi, Vietnam. The program involves four major activities. A database for motorcycles and light duty vehicles (LDV) in Hanoi was first compiled through a questionnaire survey. Then, two typical driving cycles were developed for the first time for motorcycles and LDVs in Hanoi. Based on this database and the developed driving cycles for Hanoi, a sample of 12 representative test vehicles were selected to determine vehicle specific fuel consumption and emission factors (CO, HC, NOx and CO(2)). This set of emission factors were developed for the first time in Hanoi with due considerations of local driving characteristics. In particular, it was found that the emission factors derived from Economic Commission for Europe (ECE) driving cycles and adopted in some previous studies were generally overestimated. Eventually, emission inventories for motorcycles and LDVs were derived by combining the vehicle population data, the developed vehicle specific emission factors and vehicle kilometre travelled (VKT) information from the survey. The inventory suggested that motorcycles contributed most to CO, HC and NOx emissions while LDVs appeared to be more fuel consuming.

Phytochemical studies of Rehmannia glutinosa rhizomes.

2,4-Dimethoxy-2-methyl-6H-pyran-3-one (1), a hitherto unknown natural product, and the calcium salt of rehmapicroside (2) have been isolated from rhizomes of the Vietnamese variety of Rehmannia glutinosa Libosch together with a series of known compounds: norcarotenoids (3-5), 2-formyl-5-hydroxy-methylfurane (6), the iridoid rehmaglutin D (7), iridoid glycosides (8-12) and phenylethyl alcohol glycosides (13-17). Their structures were determined by mass and NMR spectroscopy.

Food intake and lipid status of three Vietnamese populations with different incomes.

In order to have basic data for dietary preventive measures against some vascular diseases caused by disorder of lipid metabolism, food intake and lipid status were investigated in three Vietnamese populations with different per capita income levels. Totally, 299 people aged over 18 were involved in this study. Among them, 98 subjects were selected from one commune with low income, 100 and 101 subjects from two urban areas with medium and high income respectively. Food intake was assessed by 24-h recall method and lipid status was evaluated by measuring serum concentration of triglyceride, total cholesterol and its subfractions. The results showed that food consumption, dietary habits and lipid status varied with income levels. In general, diet was still unbalanced in all three groups, and low in fat and protein. In the rural, fat and protein intakes were lower than in the urban. The high prevalence of low serum cholesterol was observed in all three groups, the highest in the rural (45.3%) and the lowest in the urban (11.2%). On the contrary, the prevalence of high serum cholesterol was the lowest in the rural (2%) and the highest in the urban (16%). From these data, it is suggested that the majority of the Vietnamese might be vulnerable to some vascular diseases such as stroke if the situation of low fat intake and low serum cholesterol is not a problem of concern.

Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam.

Shigellosis is an important cause of infectious diarrhea in Vietnam, caused mainly by Shigella flexneri. This study provides for the first time in the international literature, data on the development of antimicrobial resistance in Shigella between 1988 to 1998, including data reported to the National Program for Surveillance of Antimicrobial Resistance (NPSAR). Our studies show that about 80% of the Shigella strains tested were resistant to ampicillin, chloramphenicol, oxytetracycline, trimethoprim and sulfonamides. This combination of drugs was also the most common antibiogram among multiple-resistant S. flexneri (57%). Resistance to tetracyclines, sulfonamides and, in particular trimethoprim (p<0.001), increased during the study period. Our findings indicate that tetracyclines and co-trimoxazole (a combination of a sulfonamide and trimethoprim), which are recommended and commonly used drugs for the treatment of shigellosis in Vietnam, may have limited therapeutic effect. In contrast to neighboring countries, low percentages of resistance were found to nalidixic acid and norfloxacin (3-5%) and no resistance was found to ciprofloxacin, indicating that nalidixic acid with its low cost and safety in children could be recommended for the treatment of shigellosis. The NPSAR provides a useful picture of the levels and development of antimicrobial resistance in Vietnam and should receive continued support for further improvement by increasing the number of provinces covered, the numbers of isolates tested from rural areas, and the communication of results to medical practitioners and others prescribing and/or selling antimicrobials.

Development of ARI case management at primary and secondary level in southern Vietnam.

In southern Vietnam it is not uncommon that children under 5 years of age die from pneumonia. Reduction of severity and mortality has to rely on proper case management by mothers and health workers on both grass root level and referral level. The responsibility of training of clinical skills of ARI case management in the southern provinces of Vietnam has been delegated to Pediatric Hospital N1 (PHN1) Ho Chi Minh City (HCMC) by Ministry of Health. A pilot project was carried out by the Danish-Vietnamese Study Group. The immediate objects were: to provide basic epidemiological information about ARI in southern Vietnam, to develop training modules and case management intervention modules at primary and secondary level in order to enable mothers, village workers, health post staff and district hospital emergency department staff to treat moderate and severe pneumonia and acute bronchitis in accordance with the WHO management guide for ARI and to evaluate the effect of those modules after implementation in a limited number of communes. The modules were developed at PHN1. Ten commune health stations were carefully selected. The purpose of the project and the conditions for taking part had been explained to the health workers. The doctors and other commune health workers from the 10 commune health stations and doctors from the connected district hospitals attended the training courses at PHN1, HCMC and also at the belonging provincial hospitals. Essential equipment was provided and a pharmacy with essential drugs established. The registered health statistics was collected yearly during on site visits. The local doctors and commune health workers gave seminars for mothers in the villages of the 10 project communes. The mothers' knowledge, attitude and practice (KAP) was tested in interviews before and two months after the seminars had taken place. The spread of KAP was measured by random interviews of mothers six month later. In the interviews information on social conditions was obtained. The mothers' KAP had risen by 25% two months after attending the seminars. A further increase of KAP by 5-10% within the untrained group appeared in a survey 4-6 months later. It was not possible to obtain reliable statistics on morbidity or mortality of ARI in the project area.

Serum fatty acids, lipoprotein(a) and apolipoprotein composition of rural, suburban and urban populations in North Vietnam.

This study was conducted to investigate the concentrations of serum fatty acids, lipoprotein(a) and apolipoprotein of three populations in North Vietnam: rural area with low income (n = 101), suburban with average income (n = 97), and urban with high income (n = 95). The results showed the suburban and urban populations had higher fat intake than the rural. The fat intake in quality was different in these three populations. The suburban had the highest consumption of fatty foods rich in n-6 polyunsaturated fatty acid (PUFA). The rural consumed more fatty foods rich in monounsaturated fatty acid (MUFA), but less fatty foods rich in n-3 PUFA than the two other populations. The high index of thrombogenicity (IT) of the Vietnamese diet may result from their low intake of fish and vegetable oils. Risk factors for premature cardiovascular disease (CVD) assessed by serum lipoprotein(a) and apolipoprotein levels were not observed in all three populations. However, coronary heart disease (CHD) and stroke are problems that should be monitored because the increase of CVD morbidity has been reported in Vietnamese people. From a nutritional point of view, the increase of fish and vegetable oils consumption is necessary for the prevention of CVD and CHD in these Vietnamese populations.