2-year survival estimation for decompensated cirrhosis patients of prognostic scoring systems.

OBJECTIVE: Prognostic models proposed for cirrhotic patients' survival have not been satisfactorily investigated in the Vietnam population, especially in the medium-term period. PATIENTS AND METHODS: In this prospective study, we enrolled a total of 904 patients admitted to Hepato-Gastroenterology Center, Bach Mai Hospital from December 2019 to November 2021 and calculated their CP, MELD, MELD-Na score, IMELD, Refit MELD, and Refit MELD-Na after 2-year follow-up to compare their survival prognosis. RESULTS: The mean age of the patients was 53.8 ±10.8 years, and males constituted 91%. Compared with the surviving group, deceased patients had statistically significant lower albumin, higher INR, serum bilirubin, and creatinine levels with higher means of all prognostic scores. RefitMELD score had the highest AUC (0.768), followed by MELD (0.766), and the lowest belonged to RefitMELDNa (0.669). CONCLUSIONS: In conclusion, deceased patients had significantly higher values of Child-Pugh score and all MELD-based scores than survival. RefitMELD is the most reliable scoring system to predict 2-year mortality in patients with decompensated liver cirrhosis.

Virological failure and HIV drug resistance among adults living with HIV on second-line antiretroviral therapy in the Asia-Pacific.

OBJECTIVES: To assess second-line antiretroviral therapy (ART) virological failure and HIV drug resistance-associated mutations (RAMs), in support of third-line regimen planning in Asia. METHODS: Adults > 18 years of age on second-line ART for ≥ 6 months were eligible. Cross-sectional data on HIV viral load (VL) and genotypic resistance testing were collected or testing was conducted between July 2015 and May 2017 at 12 Asia-Pacific sites. Virological failure (VF) was defined as VL > 1000 copies/mL with a second VL > 1000 copies/mL within 3-6 months. FASTA files were submitted to Stanford University HIV Drug Resistance Database and RAMs were compared against the IAS-USA 2019 mutations list. VF risk factors were analysed using logistic regression. RESULTS: Of 1378 patients, 74% were male and 70% acquired HIV through heterosexual exposure. At second-line switch, median [interquartile range (IQR)] age was 37 (32-42) years and median (IQR) CD4 count was 103 (43.5-229.5) cells/µL; 93% received regimens with boosted protease inhibitors (PIs). Median duration on second line was 3 years. Among 101 patients (7%) with VF, CD4 count > 200 cells/µL at switch [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.17-0.77 vs. CD4 ≤ 50) and HIV exposure through male-male sex (OR = 0.32, 95% CI: 0.17-0.64 vs. heterosexual) or injecting drug use (OR = 0.24, 95% CI: 0.12-0.49) were associated with reduced VF. Of 41 (41%) patients with resistance data, 80% had at least one RAM to nonnucleoside reverse transcriptase inhibitors (NNRTIs), 63% to NRTIs, and 35% to PIs. Of those with PI RAMs, 71% had two or more. CONCLUSIONS: There were low proportions with VF and significant RAMs in our cohort, reflecting the durability of current second-line regimens.

Early mortality after late initiation of antiretroviral therapy in the TREAT Asia HIV Observational Database (TAHOD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Asia-Pacific.

OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific. METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count < 100 cells/µL between 2003 and 2018 were included in the study. Early mortality was defined as death within 1 year of ART initiation. PLHIV in follow-up for > 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk. RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) < 18.5 [sub-hazard ratio (SHR) 2.91; 95% confidence interval (CI) 1.60-5.32] compared to BMI 18.5-24.9, and alanine aminotransferase (ALT) ≥ 5 times its upper limit of normal (ULN) (SHR 6.14; 95% CI 1.62-23.20) compared to ALT < 5 times its ULN. A higher CD4 count (51-100 cells/µL: SHR 0.28; 95% CI 0.14-0.55; and > 100 cells/µL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/µL. CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/µL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

Diabetes, mortality and glucose monitoring rates in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD-LITE) study.

OBJECTIVES: Diabetes is a growing cause of morbidity and mortality in people living with HIV (PLHIV) receiving antiretroviral therapy (ART). We investigated the association between fasting plasma glucose (FPG) levels and mortality, and factors associated with FPG monitoring rates in Asia. METHODS: Patients from the Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) HIV Observational Database Low Intensity Transfer (TAHOD-LITE) cohort were included in the present study if they had initiated ART. Competing risk and Poisson regression were used to analyse the association between FPG and mortality, and assess risk factors for FPG monitoring rates, respectively. FPG was categorized as diabetes (FPG ≥ 7.0 mmol/L), prediabetes (FPG 5.6-6.9 mmol/L) and normal FPG (FPG < 5.6 mmol/L). RESULTS: In total, 33 232 patients were included in the analysis. Throughout follow-up, 59% had no FPG test available. The incidence rate for diabetes was 13.7 per 1000 person-years in the 4649 patients with normal FPG at ART initiation. Prediabetes [sub-hazard ratio (sHR) 1.32; 95% confidence interval (CI) 1.07-1.64] and diabetes (sHR 1.90; 95% CI 1.52-2.38) were associated with mortality compared to those with normal FPG. FPG monitoring increased from 0.34 to 0.78 tests per person-year from 2012 to 2016 (P < 0.001). Male sex [incidence rate ratio (IRR) 1.08; 95% CI 1.03-1.12], age > 50 years (IRR 1.14; 95% CI 1.09-1.19) compared to ≤ 40 years, and CD4 count ≥ 500 cells/µL (IRR 1.04; 95% CI 1.00-1.09) compared to < 200 cells/µL were associated with increased FPG monitoring. CONCLUSIONS: Diabetes and prediabetes were associated with mortality. FPG monitoring increased over time; however, less than half of our cohort had been tested. Greater resources should be allocated to FPG monitoring for early diabetic treatment and intervention and to optimize survival.

Long-term loss to follow-up in the TREAT Asia HIV Observational Database (TAHOD).

OBJECTIVES: With earlier antiretroviral therapy (ART) initiation, time spent in HIV care is expected to increase. We aimed to investigate loss to follow-up (LTFU) in Asian patients who remained in care 5 years after ART initiation. METHODS: Long-term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression. RESULTS: Under the 12-month definition, the LTFU rate was 2.0 per 100 person-years (PY) [95% confidence interval (CI) 1.8-2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub-hazard ratio (SHR) 1.64; 95% CI 1.17-2.31] compared with 31-40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16-2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06-2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self-reported adherence ≥ 95%, and in those living in high-income countries. The 6-month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9-3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006-2009: SHR 2.38; 95% CI 1.93-2.94; and 2010-2011: SHR 4.26; 95% CI 3.17-5.73) compared with 2003-2005. CONCLUSIONS: The long-term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6-month analysis, but not the 12-month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia.

Cardiovascular disease-related mortality and factors associated with cardiovascular events in the TREAT Asia HIV Observational Database (TAHOD).

OBJECTIVES: With aging of the HIV-positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD-related and other causes of death (CODs) and factors associated with CVD in a multi-country Asian HIV-positive cohort. METHODS: Patient data from 2003-2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow-up. Cumulative incidences were plotted for CVD-related, AIDS-related, non-AIDS-related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD. RESULTS: Of 8069 patients with a median follow-up of 7.3 years [interquartile range (IQR) 4.4-10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person-years (PY)], and this total included 22 CVD-related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub-hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36-3.58 for age 41-50 years; sHR 5.52; 95% CI 3.43-8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04-2.52), high total cholesterol (sHR 1.89; 95% CI 1.27-2.82), high triglycerides (sHR 1.55; 95% CI 1.02-2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12-2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle- and upper middle-income countries. CONCLUSIONS: The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle-income countries may indicate under-diagnosis of CVD in Asian-Pacific resource-limited settings.

Socio-economic status and risk of tuberculosis: a case-control study of HIV-infected patients in Asia.

SETTING: Tuberculosis (TB) is the most common human immunodeficiency virus (HIV) related opportunistic infection and cause of acquired immune-deficiency syndrome related death. TB often affects those from a low socio-economic background. OBJECTIVE: To assess the socio-economic determinants of TB in HIV-infected patients in Asia. DESIGN: This was a matched case-control study. HIV-positive, TB-positive cases were matched to HIV-positive, TB-negative controls according to age, sex and CD4 cell count. A socio-economic questionnaire comprising 23 questions, including education level, employment, housing and substance use, was distributed. Socio-economic risk factors for TB were analysed using conditional logistic regression analysis. RESULTS: A total of 340 patients (170 matched pairs) were recruited, with 262 (77.1%) matched for all three criteria. Pulmonary TB was the predominant type (n = 115, 67.6%). The main risk factor for TB was not having a university level education (OR 4.45, 95%CI 1.50-13.17, P = 0.007). Burning wood or coal regularly inside the house and living in the same place of origin were weakly associated with TB diagnosis. CONCLUSIONS: These data suggest that lower socio-economic status is associated with an increased risk of TB in Asia. Integrating clinical and socio-economic factors into HIV treatment may help in the prevention of opportunistic infections and disease progression.

Smoking and projected cardiovascular risk in an HIV-positive Asian regional cohort.

OBJECTIVES: The aim of the study was to assess the prevalence and characteristics associated with current smoking in an Asian HIV-positive cohort, to calculate the predictive risks of cardiovascular disease (CVD), coronary heart disease (CHD) and myocardial infarction (MI), and to identify the impact that simulated interventions may have. METHODS: Logistic regression analysis was used to distinguish associated current smoking characteristics. Five-year predictive risks of CVD, CHD and MI and the impact of simulated interventions were calculated utilizing the Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) algorithm. RESULTS: Smoking status data were collected from 4274 participants and 1496 of these had sufficient data for simulated intervention calculations. Current smoking prevalence in these two groups was similar (23.2% vs. 19.9%, respectively). Characteristics associated with current smoking included age > 50 years compared with 30-39 years [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.51-0.83], HIV exposure through injecting drug use compared with heterosexual exposure (OR 3.03; 95% CI 2.25-4.07), and receiving antiretroviral therapy (ART) at study sites in Singapore, South Korea, Malaysia, Japan and Vietnam in comparison to Thailand (all OR > 2). Women were less likely to smoke than men (OR 0.11; 95% CI 0.08-0.14). In simulated interventions, smoking cessation demonstrated the greatest impact in reducing CVD and CHD risk and closely approximated the impact of switching from abacavir to an alternate antiretroviral in the reduction of 5-year MI risk. CONCLUSIONS: Multiple interventions could reduce CVD, CHD and MI risk in Asian HIV-positive patients, with smoking cessation potentially being the most influential.

The Perceived Value of Passive Animal Health Surveillance: The Case of Highly Pathogenic Avian Influenza in Vietnam.

Economic evaluations are critical for the assessment of the efficiency and sustainability of animal health surveillance systems and the improvement of their efficiency. Methods identifying and quantifying costs and benefits incurred by public and private actors of passive surveillance systems (i.e. actors of veterinary authorities and private actors who may report clinical signs) are needed. This study presents the evaluation of perceived costs and benefits of highly pathogenic avian influenza (HPAI) passive surveillance in Vietnam. Surveys based on participatory epidemiology methods were conducted in three provinces in Vietnam to collect data on costs and benefits resulting from the reporting of HPAI suspicions to veterinary authorities. A quantitative tool based on stated preference methods and participatory techniques was developed and applied to assess the non-monetary costs and benefits. The study showed that poultry farmers are facing several options regarding the management of HPAI suspicions, besides reporting the following: treatment, sale or destruction of animals. The option of reporting was associated with uncertain outcome and transaction costs. Besides, actors anticipated the release of health information to cause a drop of markets prices. This cost was relevant at all levels, including farmers, veterinary authorities and private actors of the upstream sector (feed, chicks and medicine supply). One benefit associated with passive surveillance was the intervention of public services to clean farms and the environment to limit the disease spread. Private actors of the poultry sector valued information on HPAI suspicions (perceived as a non-monetary benefit) which was mainly obtained from other private actors and media.

The Effect of Resin-modified Glass-ionomer Cement Base and Bulk-fill Resin Composite on Cuspal Deformation.

OBJECTIVES: This study investigated cuspal deformation in teeth restored with different types of adhesive materials with and without a base. METHODS: Mesio-occluso-distal slot cavities of moderately large dimension were prepared on extracted maxillary premolars (n=24). Teeth were assigned to one of four groups and restored with either a sonic-activated bulk-fill resin composite (RC) (SonicFill), or a conventional nanohybrid RC (Herculite Ultra). The base materials used were a flowable nanofilled RC (Premise Flowable) and a high-viscosity resin-modified glass-ionomer cement (RMGIC) (Riva Light-Cure HV). Cuspal deflection was measured with two direct current differential transformers, each contacting a buccal and palatal cusp. Cuspal movements were recorded during and after restoration placement. Data for the buccal and palatal cusp deflections were combined to give the net cuspal deflection. RESULTS: Data varied widely. All teeth experienced net inward cuspal movement. No statistically significant differences in cuspal deflection were found among the four test groups. CONCLUSIONS: The use of a flowable RC or an RMGIC in closed-laminate restorations produced the same degree of cuspal movement as restorations filled with only a conventional nanohybrid or bulk-fill RC.

Detection of Novel Reassortant Influenza A (H3N2) and H1N1 2009 Pandemic Viruses in Swine in Hanoi, Vietnam.

From May to September 2013, monthly samples were collected from swine in a Vietnamese slaughterhouse for influenza virus isolation and serological testing. A(H1N1)pdm09 viruses and a novel H3N2 originating from reassortment between A(H1N1)pdm09 and novel viruses of the North American triple reassortant lineage were isolated. Serological results showed low seroprevalence for the novel H3N2 virus and higher seroprevalence for A(H1N1)pdm09 viruses. In addition, serology suggested that other swine influenza viruses are also circulating in Vietnamese swine.

Clinical performance of laminate and non-laminate resin composite restorations: a systematic review.

BACKGROUND: A systematic review was undertaken to determine the clinical outcomes of resin modified glass-ionomer cement or glass-ionomer cement-resin composite (RMGIC/GIC-RC) laminate restorations and flowable resin composite (FRC)-lined RC restorations compared to that of non-laminate RC restorations. METHODS: Electronic databases were searched and filtered for relevant papers by assessing titles, abstracts and full-text articles. Randomized controlled clinical trials (RCTs) were included, comparing the clinical performance of RMGIC/GIC-RC laminate restorations and FRC-lined restorations with RC restorations as the control. The articles were categorized and critically appraised. Raw data were used for a fixed effects meta-analysis. RESULTS: Thirteen articles were included in the review. Five evaluated FRC-lined restorations, and eight studies evaluated RMGIC/GIC-RC laminate restorations, comparing with non-laminate RC restorations. Three of eight RMGIC/GIC-RC laminate restorations assessed only postoperative sensitivity. A meta-analysis could only be conducted in three studies with the FRC-lined restorations as the intervention. The meta-analysis found no significant difference in clinical failures between FRC-lined RC restorations and RC restorations with no lining (p > 0.05). CONCLUSIONS: Based on current clinical evidence, a FRC lining is no more advantageous than RC restorations with no FRC lining. More long-term RCTs are required, particularly for evaluating RMGIC/GIC-RC laminate restorations.

POLG mutations in Alpers syndrome.

Described are six patients with Alpers syndrome from four unrelated families. Affected individuals harbored the following combinations of POLG mutations: 1) A467T/W1020X, 2) W748S-E1143G/G848S, 3) A467T/A467T, and 4) A467T/G848S. Homozygosity for the A467T allele in one patient was associated with a later age at onset. Mitochondrial respiratory chain studies in skeletal muscle were normal in each case. Nine combinations of mutant POLG alleles that cause Alpers syndrome are summarized.

Loss of Cul1 results in early embryonic lethality and dysregulation of cyclin E.

The sequential timing of cell-cycle transitions is primarily governed by the availability and activity of key cell-cycle proteins. Recent studies in yeast have identified a class of ubiquitin ligases (E3 enzymes) called SCF complexes, which regulate the abundance of proteins that promote and inhibit cell-cycle progression at the G1-S phase transition. SCF complexes consist of three invariable components, Skp1, Cul-1 (Cdc53 in yeast) and Rbx1, and a variable F-box protein that recruits a specific cellular protein to the ubquitin pathway for degradation. To study the role of Cul-1 in mammalian development and cell-cycle regulation, we generated mice deficient for Cul1 and analysed null embryos and heterozygous cell lines. We show that Cul1 is required for early mouse development and that Cul1 mutants fail to regulate the abundance of the G1 cyclin, cyclin E (encoded by Ccne), during embryogenesis.