A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Spectrum and antimicrobial resistance in acute exacerbation of chronic obstructive pulmonary disease with pneumonia: a cross-sectional prospective study from Vietnam.

BACKGROUND: Respiratory infections have long been recognized as a primary cause of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Additionally, the emergence of antimicrobial resistance has led to an urgent and critical situation in developing countries, including Vietnam. This study aimed to investigate the distribution and antimicrobial resistance of bacteria in patients with AE-COPD using both conventional culture and multiplex real-time PCR. Additionally, associations between clinical characteristics and indicators of pneumonia in these patients were examined. METHODS: This cross-sectional prospective study included 92 AE-COPD patients with pneumonia and 46 without pneumonia. Sputum specimens were cultured and examined for bacterial identification, and antimicrobial susceptibility was determined for each isolate. Multiplex real-time PCR was also performed to detect ten bacteria and seven viruses. RESULTS: The detection rates of pathogens in AE-COPD patients with pneumonia were 92.39%, compared to 86.96% in those without pneumonia. A total of 26 pathogenic species were identified, showing no significant difference in distribution between the two groups. The predominant bacteria included Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, followed by Acinetobacter baumannii and Streptococcus mitis. There was a slight difference in antibiotic resistance between bacteria isolated from two groups. The frequency of H. influenzae was notably greater in AE-COPD patients who experienced respiratory failure (21.92%) than in those who did not (9.23%). S. pneumoniae was more common in patients with stage I (44.44%) or IV (36.36%) COPD than in patients with stage II (17.39%) or III (9.72%) disease. ROC curve analysis revealed that C-reactive protein (CRP) levels could distinguish patients with AE-COPD with and without pneumonia (AUC = 0.78). CONCLUSION: Gram-negative bacteria still play a key role in the etiology of AE-COPD patients, regardless of the presence of pneumonia. This study provides updated evidence for the epidemiology of AE-COPD pathogens and the appropriate selection of antimicrobial agents in Vietnam.

Catalytic degradation of acetaminophen by Fe and N Co-doped multi-walled carbon nanotubes.

An Fe and N co-doped carbon nanotube (CNT) (Fe/N-CNT) was successfully prepared using a simple hydrothermal method. CNT, Fe doped CNTs (Fe-CNT), N doped CNTs (N-CNT), and Fe/N-CNT were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and zeta potential analysis. The catalytic activities of the materials were investigated via pharmaceutical (acetaminophen, ACT) degradation using persulfate (PS). The ACT removal rate was in the order: Fe-CNT > N-CNT > Fe-CNT > CNT, for 30 min with 10 mg/L ACT, 0.05 g/L materials, and 0.08 mM PS. The doped N existed as pyridinic-N, pyrrolic-N/N-Fe, graphitic-N, and oxidized-N, while the doped Fe existed as Fe-N, FeO/Fe3O4, and Fe2O3/FeOOH at the edge. The rates of ACT removal and PS decomposition were well correlated with pyrrolic-N/N-Fe. The ACT removal in the Fe/N-CNT + PS system was as high as >98.4% and was not significantly affected by the initial pH of 2.0-8.2 and ten consecutive uses. However, natural organic matter (NOM) inhibited ACT removal by the accumulation on Fe/N-CNT. The results of ACT removal in the presence of radical scavengers, PS decomposition, and cyclic voltammetry showed that the ACT removal was dominantly attributed to a non-radical pathway with the accelerated electron transfer from ACT to PS through the Fe/N-CNT. The results in this study strongly suggest that the Fe/N-CNT + PS system is an excellent process for the degradation of refractory organic pollutants in various water matrices with improved performance and stability attributed by non-radical pathway.

Advanced oxidative degradation of acetaminophen by carbon catalysts: Radical vs non-radical pathways.

Two representative carbon catalysts, granular activated carbon (GAC) and carbon nanotube (CNT) were selected for the degradation of acetaminophen (ACT) by persulfate (PS) activation. In this study, the materials characterization study indicated that the surface functional groups and surface area of the GAC were more abundant and larger, respectively, than the CNT. Whereas the contribution of sp2 and CO groups of the CNT was superior to the GAC; the structural defect levels and surface charging characteristics (pHPZC) were similar in both. The mass-based pseudo-first-order reaction rate constant of the CNT was 1.5 m-1 g-1, which was 50 times higher than that of the GAC (0.03 m-1 g-1). Radical and non-radical pathways were evaluated for catalytic reactions by the GAC/PS and CNT/PS systems, respectively. Experimental results using scavenger tests, linear voltammetry, and electron spin resonance (ESR) showed that the radical pathway was dominant in the GAC/PS system, whereas the non-radical pathway was dominant in the CNT/PS systems. To confirm this, the influence of affecting factors such as initial ACT concentration, the dosage of oxidant (PS), and initial pH were also investigated and compared for the two systems. The results showed that the catalytic activity of the GAC/PS system was highly dependent on initial concentrations of ACT and PS, while these were less influential in the CNT/PS system. The removal efficiency of ACT was not affected under a pH of 3-7 in both systems. Reusability experiments were conducted five times, and both the CNT/PS and GAC/PS systems demonstrated that the removal rate of ACT did not notably decrease with the number of experiment repetitions. This means that the application of a carbon catalyst to treat pharmaceutical contaminants in wastewater is effective.

Real-world analysis of afatinib as a first-line treatment for patients with advanced stage non-small-cell lung cancer with uncommon EGFR mutations: a multicenter study in Vietnam.

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X-S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

Assessing cognitive decline in Vietnamese older adults using the Montreal Cognitive Assessment-Basic (MoCA-B) and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) during the COVID-19 pandemic: A feasibility study.

Objectives: The lack of cognitive assessment tools suitable for people with minimal formal education is a barrier to identify cognitive impairment in Vietnam. Our aims were to (i) evaluate the feasibility of conducting the Montreal Cognitive Assessment-Basic (MoCA-B) and Informant Questionnaire On Cognitive Decline in the Elderly (IQCODE) remotely on the Vietnamese older adults, (ii) examine the association between the two tests, (iii) identify demographic factors correlated with these tools. Methods: The MoCA-B was adapted from the original English version, and a remote testing procedure was conducted. One hundred seventy-three participants aged 60 and above living in the Vietnamese southern provinces were recruited via an online platform during the COVID-19 pandemic. Results: IQCODE results showed that the proportions of rural participants classified as having mild cognitive impairment and dementia were substantially higher than those in urban areas. Levels of education and living areas were associated with IQCODE scores. Education attainment was also the main predictor of MoCA-B scores (30% of variance explained), with an average of 10.5 points difference between those with no formal education and those who attended university. Conclusions: It is feasible to administer the IQCODE and MoCA-B remotely in the Vietnamese older population. Education attainment played a stronger role in predicting MoCA-B scores than IQCODE, suggesting the influence of this factor on MoCA-B scores. Further study is needed to develop socio-culturally appropriate cognitive screening tests for the Vietnamese population.

Cu@Fe3O4 core-shell nanoparticle-catalyzed oxidative degradation of the antibiotic oxytetracycline in pre-treated landfill leachate.

Novel Cu@Fe3O4 core-shell nanoparticles prepared via a simple reduction method were evaluated for degradation of oxytetracycline (OTC) in pre-treated leachate (Lp-TREA) (leachate treated by conventional methods). Changes in the characteristics of dissolved organic matter (DOM) in the leachate were also investigated to gain a better understanding of the effects of DOM on the performance of Cu@Fe3O4. An excellent OTC degradation of >99% was achieved within 30 min under conditions of 1 g/L Cu@Fe3O4, 20 mg/L OTC, 20 mM H2O2, and initial pH 3.0, which was similar to the efficiency obtained in deionized water (90% even at pH 9.05). Humic acid (HA) and fulvic acid (FA) were completely degraded at initial pH 3, while aromatic protein (AP) with 32.7% of 1-3 kDa constituents were totally transformed to 0.5-1 kDa compounds, and 17% < 0.5 kDa material was degraded. The OTC removal rate decreased gradually as Cu@Fe3O4 was repeatedly used, but it was significantly enhanced when Cu@Fe3O4 was washed after five uses to remove the organic matter on its surface. The results suggest that Cu@Fe3O4 is a promising and effective catalyst for pharmaceutical and personal care product degradation in landfill leachates.

Oxidative degradation of the antibiotic oxytetracycline by Cu@Fe3O4 core-shell nanoparticles.

A core-shell nanostructure composed of zero-valent Cu (core) and Fe3O4 (shell) (Cu@Fe3O4) was prepared by a simple reduction method and was evaluated for the degradation of oxytetracycline (OTC), an antibiotic. The Cu core and the Fe3O4 shell were verified by X-ray diffractometry (XRD) and transmission electron microscopy. The optimal molar ratio of [Cu]/[Fe] (1/1) in Cu@Fe3O4 created an outstanding synergic effect, leading to >99% OTC degradation as well as H2O2 decomposition within 10min at the reaction conditions of 1g/L Cu@Fe3O4, 20mg/L OTC, 20mM H2O2, and pH3.0 (and even at pH9.0). The OTC degradation rate by Cu@Fe3O4 was higher than obtained using single nanoparticle of Cu or Fe3O4. The results of the study using radical scavengers showed that OH is the major reactive oxygen species contributing to the OTC degradation. Finally, good stability, reusability, and magnetic separation were obtained with approximately 97% OTC degradation and no notable change in XRD patterns after the Cu@Fe3O4 catalyst was reused five times. These results demonstrate that Cu@Fe3O4 is a novel prospective candidate for the pharmaceutical and personal care products degradation in the aqueous phase.