Prediction of effectiveness of universal rotavirus vaccination in Southwestern Vietnam based on a dynamic mathematical model.

Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01-1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age.

Minimally invasive resection of heart valve papillary fibroelastoma: two case reports and review of the literature.

BACKGROUND: Cardiac papillary fibroelastomas are rare, accounting for approximately 10% of all cardiac tumors, with 44% of cases located on the aortic valve and only 15% of cases located on the tricuspid valve. However, the optimal management of papillary fibroelastomas remains varied. CASE PRESENTATION: We present two successful instances of treating heart valve papillary fibroelastomas through minimally invasive surgery. These cases involved heart valve papillary fibroelastomas located in two common sites: the aortic valve on the left heart, which was accessed via an upper hemi-sternotomy, and the tricuspid valve on the right heart, which was accessed via beating heart total thoracoscopy. CONCLUSION: The article consistently demonstrates the effectiveness of a minimally invasive surgical approach in managing heart valve papillary fibroelastomas. This study provides further evidence by presenting two cases of heart valve papillary fibroelastomas - one on the aortic valve and the other on the tricuspid valve - that were successfully treated using this approach, resulting in favorable outcomes.

CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial.

The oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) at two dose levels (DLs) in relapsed/refractory CLDN6-positive solid tumors. The primary endpoints were safety and tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary endpoints included objective response rate (ORR) and disease control rate. We observed manageable toxicity, with 10 out of 22 patients (46%) experiencing cytokine release syndrome including one grade 3 event and 1 out of 22 (5%) with grade 1 immune effector cell-associated neurotoxicity syndrome. Dose-limiting toxicities occurred in two patients at the higher DL, resolving without sequelae. CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR in 21 evaluable patients was 33% (7 of 21), including one complete response. The disease control rate was 67% (14 of 21), with stable disease in seven patients. Patients with germ cell tumors treated at the higher DL exhibited the highest response rate (ORR 57% (4 of 7)). The maximum tolerated dose and RP2D were not established as the trial has been amended to utilize an automated manufacturing process. A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278 .

Childhood Bacterial Meningitis Surveillance in Southern Vietnam: Trends and Vaccination Implications From 2012 to 2021.

Background: This retrospective hospital-based surveillance aimed to assess the epidemiology, causative pathogens trend, and serotypes distribution of pneumococcal meningitis among children aged under 5 years with bacterial meningitis in Southern Vietnam after the introduction of pentavalent vaccine in the Expanded Program on Immunization (EPI). Methods: From 2012 to 2021, cerebrospinal fluid samples were collected from children aged under 5 years with suspected bacterial meningitis at Children's Hospitals 1 and 2 in Ho Chi Minh City. Probable bacterial meningitis (PBM) cases were identified using biochemistry and cytology. Real-time polymerase chain reaction was used to confirm cases of confirmed bacterial meningitis (CBM) caused by Streptococcus pneumoniae, Haemophilus influenzae, or Neisseria meningitidis. Streptococcus pneumoniae serotyping was performed. Results: Of the 2560 PBM cases, 158 (6.2%) were laboratory-confirmed. The CBM proportion decreased during the 10-year study and was associated with age, seasonality, and permanent residence. Streptococcus pneumoniae was the most common pathogen causing bacterial meningitis (86.1%), followed by H influenzae (7.6%) and N meningitidis (6.3%). The case-fatality rate was 8.2% (95% confidence interval, 4.2%-12.2%). Pneumococcal serotypes 6A/B, 19F, 14, and 23F were the most prevalent, and the proportion of pneumococcal meningitis cases caused by the 10-valent pneumococcal conjugate vaccine (PCV) serotypes decreased from 96.2% to 57.1% during the PCV eras. Conclusions: Streptococcus pneumoniae is the most frequent causative agent of bacterial meningitis in children aged under 5 years in Southern Vietnam over the last decade. Policymakers may need to consider introducing PCVs into the EPI to effectively prevent and control bacterial meningitis.

Understanding the transmission dynamics of a large-scale measles outbreak in Southern Vietnam.

OBJECTIVES: Southern Vietnam experienced a large measles outbreak of over 26,000 cases during 2018-2020. We aimed to understand and quantify the measles spread in space-time dependence and the transmissibility during the outbreak. METHODS: Measles surveillance reported cases between January 2018 and June 2020, vaccination coverage, and population data at provinicial level were used. To illustrate the spatio-temporal pattern of disease spread, we employed the endemic-epidemic multivariate time series model decomposing measles risk additively into autoregressive, spatio-temporal, and endemic components. Likelihood-based estimation procedures were performed to determine the time-varying reproductive number Re of measles. RESULTS: Our analysis showed that the incidence of measles was associated with vaccination coverage heterogeneity and spatial interaction between provincial units. The risk of infections was dominated by between-province transmission (36.1% to 78.8%), followed by local endogenous transmission (4.1% to 61.5%). In contrast, the endemic behavior had a relatively small contribution (2.4% to 33.4%) across provinces. In the exponential phase of the epidemic, Re was above the threshold with a maximum value of 2.34 (95% CI: 2.20-2.46). CONCLUSION: Local vaccination coverage and human mobility are important factors contributing to the measles dynamics in Southern Vietnam, and the high risk of inter-provincial transmission is of most concern. Strengthening the disease surveillance is recommended, and further research is essential to understand the relative contribution of population immunity and control measures in measles epidemics.

Effectiveness of Hyaluronic Acid Gel and Intrauterine Devices in Prevention of Intrauterine Adhesions after Hysteroscopic Adhesiolysis in Infertile Women.

STUDY OBJECTIVE: To compare the recurrence rate, post-treatment American Fertility Society (AFS) score, ongoing pregnancy rate, and endometrial thickness of 3 secondary prevention therapies in preventing recurrent intrauterine adhesions (IUAs) and increasing pregnancy rates in infertile women after hysteroscopic adhesiolysis. DESIGN: A retrospective study. SETTING: A private fertility hospital. PATIENTS: A total of 200 consecutive infertile women, with the desire to have a baby and were diagnosed as having IUAs detected by hysterosalpingogram, who underwent hysteroscopic adhesiolysis for IUAs from January, 2018 to May, 2020. INTERVENTIONS: Women who underwent hysteroscopic adhesiolysis received hormone therapy, and one of the 3 secondary preventions: hyaluronic acid (HA) gel alone, intrauterine devices (IUDs) alone, or HA gel + IUD. MEASUREMENTS AND MAIN RESULTS: Of the 200 women included in the final analysis, 121 received HA alone, 59 were treated with IUD alone, and 20 received HA gel + IUD combination. The mean post-treatment AFS score for IUAs was significantly lower in the HA gel + IUD group than the HA alone or the IUD alone groups (adjusted p = .01 and p = .02, respectively). Multivariable analysis revealed a significantly lower recurrence rate in the women after treatment with HA gel + IUD than HA alone (adjusted odds ratio, 0.19; 95% credible interval [CreI], 0.03-0.88). Women treated with HA gel + IUD also had reduced post-treatment AFS scores compared with HA alone (ß coefficients, -0.83; 95% CreI, -1.64 to -0.01). For ongoing pregnancy rates after in vitro fertilization, the adjusted odds ratio for HA gel + IUD vs HA alone was 2.03 (95% CreI, 0.44-11.00) and for IUD alone vs HA alone was 1.13 (95% CreI, 0.41-3.29), indicating nonsignificant differences. There were no differences observed in endometrial thickness on the day of embryo transfer among the 3 groups. CONCLUSION: The investigation of the primary outcome in reducing the recurrence rate IUA after treatment demonstrated that a combination of HA gel + IUD provides greater prevention of recurrent IUAs and may decrease post-treatment AFS scores for infertile women undergoing hysteroscopic adhesiolysis. However, for the secondary outcome of increasing pregnancy rates, there was no improvement in the ongoing pregnancy rates after in vitro fertilization.

A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele.

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients ≥12 years of age with cystic fibrosis and at least one F508del-CFTR (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. Objectives: To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with F508del-minimal function or F508del-F508del genotypes. Methods: In this 24-week open-label phase 3 study, children (N = 66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 h) whereas children weighing ⩾30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h). Measurements and Main Results: The primary endpoint was safety and tolerability. The safety and pharmacokinetic profiles of ELX/TEZ/IVA were generally consistent with those observed in older patients. The most commonly reported adverse events included cough, headache, and pyrexia; in most of the children who had adverse events, these were mild or moderate in severity. Through Week 24, ELX/TEZ/IVA treatment improved the percentage of predicted FEV1 (10.2 percentage points; 95% confidence interval [CI], 7.9 to 12.6), Cystic Fibrosis Questionnaire-Revised respiratory domain score (7.0 points; 95% CI, 4.7 to 9.2), lung clearance index2.5 (-1.71 units; 95% CI, -2.11 to -1.30), and sweat chloride (-60.9 mmol/L; 95% CI, -63.7 to -58.2); body mass index-for-age z-score increased over the 24-week treatment period when compared with the pretreatment baseline. Conclusions: Our results show ELX/TEZ/IVA is safe and efficacious in children 6 through 11 years of age with at least one F508del-CFTR allele, supporting its use in this patient population. Clinical trial registered with www.clinicaltrials.gov (NCT03691779).

Rotavirus genotype trends from 2013 to 2018 and vaccine effectiveness in southern Vietnam.

OBJECTIVES: Rotavirus (RV) genotypes vary geographically, and this can affect vaccine effectiveness (VE). This study investigated the genotype distribution of RV and explored VE before introducing the RV vaccine to the national immunization programme in Vietnam. METHODS: This hospital-based surveillance study was conducted at Children's Hospital 1, Ho Chi Minh City in 2013-2018. Stool samples and relevant data, including vaccination history, were collected from children aged <5 years who were hospitalized with gastroenteritis. RV was detected using enzyme immunoassays and then genotyped. Children aged ≥6 months were included in the VE analysis. RESULTS: Overall, 5176 children were included in this study. RV was detected in 2421 children (46.8%). RV positivity decreased over the study period and was associated with age, seasonality, location and previous vaccination. Among 1105 RV-positive samples, G3P[8] was the most prevalent genotype (43.1%), followed by G8P[8] (19.7%), G1P[8] (12.9%) and G2P[4] (12.9%). Overall VE was 69.7% [95% confidence interval (CI) 53.3-80.6%] in fully vaccinated children and 58.6% (95% CI 44.1-69.4%) in children who had received at least one dose of RV vaccine. VE was highest for G3P[8] (95% CI 75.1-84.5%) and lowest for G2P[4] (95% CI 32.4-57.2%). CONCLUSIONS: RV remains a major cause of acute gastroenteritis requiring hospitalization in southern Vietnam. The RV vaccine is effective, but its effectiveness varies with RV genotype.

Estimating parameters of nonlinear dynamic systems in pharmacology using chaos synchronization and grid search.

Bridging fundamental approaches to model optimization for pharmacometricians, systems pharmacologists and statisticians is a critical issue. These fields rely primarily on Maximum Likelihood and Extended Least Squares metrics with iterative estimation of parameters. Our research combines adaptive chaos synchronization and grid search to estimate physiological and pharmacological systems with emergent properties by exploring deterministic methods that are more appropriate and have potentially superior performance than classical numerical approaches, which minimize the sum of squares or maximize the likelihood. We illustrate these issues with an established model of cortisol in human with nonlinear dynamics. The model describes cortisol kinetics over time, including its chaotic oscillations, by a delay differential equation. We demonstrate that chaos synchronization helps to avoid the tendency of the gradient-based optimization algorithms to end up in a local minimum. The subsequent analysis illustrates that the hybrid adaptive chaos synchronization for estimation of linear parameters with coarse-to-fine grid search for optimal values of non-linear parameters can be applied iteratively to accurately estimate parameters and effectively track trajectories for a wide class of noisy chaotic systems.

Self-aggregation of water-dispersible nanocollagen helices.

Inspired by nature, collagen is an outstanding polypeptide utilized to exploit its bioactivity and material design for healthcare technologies. In this study, we describe the self-aggregation of water-dispersible nanocollagen helices upon solidification to fabricate different forms of natural collagen materials. Chemically extracted native collagen fibrils are uniform anisotropic nanoparticles with an average diameter of about 50 nm and a high aspect ratio. The as-prepared collagen nanofibrils are soluble in sodium acetate-acetic acid buffer and are dispersible in water, thus generating collagen liquids that are used as distinct biopolymer precursors for materials development. Our interesting findings indicate that water-dispersible collagen-derived alcogels undergo critical point drying to self-arrange hierarchical nanofibrils into helix bundles in collagen sponge-like aerogels. Notably, using lyophilization to remove water in the biopolymer dispersion, a full regeneration of solidified fibers is achieved, producing collagen aerogels with lightweight characteristics similar to natural cottons. The self-aggregation of water-dispersible collagen occurs under freeze-drying conditions to turn individual nanofibrils into sheets with layered structures in the aerogel networks. The development of transparent, water resistant collagen bioplastic-like membranes was achieved by supramolecular self-assembly of water-dispersible collagen nanofibrils. Our efforts present a reliable concept in soft matter for creating promising collagen examples of liquids, hydrogels, aerogels, and membranes to increase utilization value of native collagen for biomedicine, pharmaceuticals, cosmetics, and nutrients.

Cholera returns to southern Vietnam in an outbreak associated with consuming unsafe water through iced tea: A matched case-control study.

BACKGROUND: After more than a decade of steadily declining notifications, the number of reported cholera cases has recently increased in Vietnam. We conducted a matched case-control study to investigate transmission of cholera during an outbreak in Ben Tre, southern Vietnam, and to explore the associated risk factors. METHODOLOGY/PRINCIPAL FINDINGS: Sixty of 71 diarrheal patients confirmed to be infected with cholera by culture and diagnosed between May 9 and August 3, 2010 in Ben Tre were consecutively recruited as case-patients. Case-patients were matched 1:4 to controls by commune, sex, and 5-year age group. Risk factors for cholera were examined by multivariable conditional logistic regression. In addition, environmental samples from villages containing case-patients were taken to identify contamination of food and water sources. The regression indicated that drinking iced tea (adjusted odds ratio (aOR) = 8.40, 95% confidence interval (CI): 1.84-39.25), not always boiling drinking water (aOR = 2.62, 95% CI: 1.03-6.67), having the main source of water for use being close to a toilet (aOR = 4.36, 95% CI: 1.37-13.88), living with people who had acute diarrhea (aOR = 13.72, 95% CI: 2.77-67.97), and little or no education (aOR = 4.89, 95% CI: 1.18-20.19) were significantly associated with increased risk of cholera. In contrast, drinking stored rainwater (aOR = 0.17, 95% CI: 0.04-0.63), eating cooked seafood (aOR = 0.27, 95% CI: 0.10-0.73), and eating steamed vegetables (aOR = 0.22, 95% CI: 0.07-0.70) were protective against cholera. Vibrio cholerae O1 Ogawa carrying ctxA was found in two of twenty-five river water samples and one of six wastewater samples. CONCLUSIONS/SIGNIFICANCE: The magnitude of the cholera outbreak in Ben Tre was lower than in other similar settings. This investigation identified several risk factors and underscored the importance of continued responses targeting cholera prevention in southern Vietnam. The association between drinking iced tea and cholera and the spread of V. cholerae O1, altered El Tor strains warrant further research. These findings might be affected by a number of limitations due to the inability to capture asymptomatic or mildly symptomatic infections, the possible underreporting of personal unhygienic behaviors, and the purposive selection of environmental samples.

R- and S-citalopram concentrations have differential effects on neuropsychiatric scores in elders with dementia and agitation.

AIMS: The aim was to determine the relationship between (R) and (S)-citalopram enantiomer exposure (AUC(0,24 h)) and therapeutic response in agitated individuals greater than 60 years old with Alzheimer's dementia (AD). METHODS: Citalopram enantiomer exposures (AUC(0,24 h)) derived from an established population pharmacokinetic analysis were utilized to explore the relationship between (R)- and (S)-citalopram area under the curve (AUC(0,24 )) and Mini-Mental State Examination (MMSE), Neurobehavioural Rating Scale-Agitation Subscale (NBRS-A), modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) and Neuropsychiatric Inventory Agitation subscale (NPIA) scores. Time dependent changes in these scores (disease progression) were accounted for prior to exploring the exposure effect relationship for each enantiomer. These relationships were evaluated using a non-linear-mixed effects modelling approach as implemented in nonmem v7.3. RESULTS: (S)-AUC(0,24 h) and (R)-AUC(0,24 h) each contributed to improvement in NBRS-A scores (k3(R) -0.502; k4(S) -0.712) as did time in treatment. However, increasing (R)-AUC(0,24 h) decreased the probability of patient response (maximum Δ -0.182%/AUC(0,24 h)) based on the CGIC while (S)-AUC(0,24 h) improved the probability of response (maximum Δ 0.112%/AUC(0,24 h)). (R)-AUC(0,24 h) was also associated with worsening in MMSE scores (-0.5 points). CONCLUSIONS: Our results suggest that citalopram enantiomers contributed differentially to treatment outcomes. (R)-citalopram accounted for a greater proportion of the adverse consequences associated with racemic citalopram treatment in patients with AD including a decreased probability of treatment response as measured by the CGIC and a reduction in MMSE scores. The S-enantiomer was associated with increased probability of response based on the CGIC.