Nonadherence to oral cancer chemotherapy in hepatocellular carcinoma: prevalence and predictive factors in Vietnam.

PURPOSE: Standard oral cancer chemotherapy (OCT) or targeted therapy (OTT) has expanded the treatment methods for hepatocellular carcinoma (HCC). However, its principal nonadherence causes a reduction in efficacy. We aimed to evaluate the status of nonadherence and influencing factors among outpatient patients with HCC. PATIENTS AND METHODS: In 2021, a prospective observational study was conducted on 384 patients with either old or newly diagnosed HCC treated with OTT. Nonadherence to OCT was determined using the eight-item Morisky Medication Adherence Scale, with a score < 6 points. The patients were finished with a six-month follow-up investigation by questionnaires. RESULTS: 54,8% of HCC outpatients were nonadherent to OCT, with a mean Morisky score of 5.19. They dropped out of the treatment mainly because of drug side effects, such as fatigue (72.4%), hand-foot syndrome (42.7%), diarrhea (38.3%), nausea (25%), insomnia (24.7%), abdominal pain (12%), and anxiety about these adverse events (65.9%). Additionally, financial difficulties and low relative copayments were significantly correlated with the noncompliant treatment of patients (OR = 2.29, 95% CI = 1.32-3.98, P = 0.003; OR = 4.36, 95% CI = 0.95-19.93, P = 0.039, respectively). Moreover, inadequate individual information about the clinical course, the art of treatment, and medication usage instructions were suggestive barriers to adherence to treatment (OR = 1.96, 95% CI = 1.08-3.55, P = 0.024; OR = 1.86, 95% CI = 1.1-3.14, P = 0.02; OR = 2.34, 95% CI = 1.29-4.26, P = 0.004, respectively). Finally, a low level of trust in doctors was an essential factor in nonadherence (Mean of the Anderson Trust in Physician Scale scores counted 38.12 vs. 43.97, respectively for non-adherence vs. adherence, P = 0.00001). CONCLUSIONS: This study suggests a high rate of primary nonadherence to standard oral targeted therapy among HCC outpatient patients because of drug side effects, patient awareness of treatment, and lack of confidence in healthcare providers. Close supervision, proper medication instructions, appropriate dosage reductions, and comprehensive patient counseling might be necessary to control nonadherence.

Study on the Synthesis and Characterization of Nano Silver Loaded ZSM-5 Zeolite for Bacterial Elimination.

The synthesis of nano silver coated ZSM-5 zeolite (Ag/ZSM-5) by ion exchange method combined with anaerobic thermal treatment and its bacterial elimination performance were studied. The various Ag content of different samples was analysed by atomic absorption spectroscopy method. The Ag/ZSM-5 sample with 0.251 wt% Ag (denoted as ZAg3) was characterized by using atomic absorption spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and pulsed CO chemisorption methods. The results showed that silver nanoparticles with a small nano-size of 2-3 nm were formed and distributed on the surface of ZSM-5 zeolite with a dispersion value of 59%. The samples denoted as ZAg1, ZAg2, ZAg3, ZAg4 correspond to a Ag content of 0.064; 0.128; 0.251; 0.253 wt% Ag. In the evaluation series, after 10 min of contact time between bacterial and Ag/ZSM-5, over 99% of E.coli (initial concentration was 10(6) cfu/ml) could be eliminated by Ag/ZSM-5 with the Ag content of at least 0.251 wt% (ZAg3). In addition, over 99% of Coliform (initial concentration was 10(5) cfu/ml) could be eliminated by Ag/ZSM-5 with Ag content of at least 0.128 wt% (ZAg2). In a further evaluation series varying the contact time, ZAg3 sample could eliminate over 99% and 100% of Ecoli after 10 min and 60 min, respectively (initial concentrations of both E.coli and Coliform were 10(5) cfu/ml). In addition, it could eliminate 100% of Coliform in only 10 min of contact time.

Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions.

(R,S)-ketamine (ketamine) has rapid and sustained antidepressant (AD) efficacy at sub-anesthetic doses in depressed patients. A metabolite of ketamine, including (2R,6R)-hydroxynorketamine ((6)-HNKs) has been reported to exert antidepressant actions in rodent model of anxiety/depression. To further understand the specific role of ketamine's metabolism in the AD actions of the drug, we evaluated the effects of inhibiting hepatic cytochrome P450 enzymes on AD responses. We assessed whether pre-treatment with fluconazole (10 and 20 mg/kg, i. p.) 1 h prior to ketamine or HNKs (10 mg/kg, i. p.) administration would alter behavioral and neurochemical actions of the drugs in male BALB/cJ mice with a highly anxious phenotype. Extracellular microdialysate levels of glutamate and GABA (Gluext, GABAext) were also measured in the medial prefrontal cortex (mPFC). Pre-treatment with fluconazole altered the pharmacokinetic profile of ketamine, by increasing both plasma and brain levels of ketamine and (R,S)-norketamine, while robustly reducing those of (6)-HNKs. At 24 h post-injection (t24 h), fluconazole prevented the sustained AD-like response of ketamine responses in the forced swim test and splash test, as well as the enhanced cortical GABA levels produced by ketamine. A single (2R,6R)-HNK administration resulted in prevention of the effects of fluconazole on the antidepressant-like activity of ketamine in mice. Overall, these findings are consistent with an essential contribution of (6)-HNK to the sustained antidepressant-like effects of ketamine and suggest potential interactions between pharmacological CYPIs and ketamine during antidepressant treatment in patients.

Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout.

Allopurinol (ALP) is commonly used as a drug for gout treatment. However, ALP is known to cause cutaneous adverse reactions (CARs) in patients. The HLA-B*58:01 allele is considered a biomarker of severe CAR (SCAR) in patients with gout, with symptoms of Stevens Johnson syndrome, and with toxic epidermal necrolysis. However, in patients with gout and mild cutaneous adverse drug reactions (MCARs), the role of HLA-allele polymorphisms has not been thoroughly investigated. In this study, 50 samples from ALP-tolerant patients and ALP-induced MCARs patients were genotyped in order to examine the polymorphisms of their HLA-A and HLA-B alleles. Our results showed that the frequencies of HLA-A*02:01/HLA-A*24:02 and HLA-A*02:01/HLA-A*29:01, the dual haplotypes in HLA-A, in patients with ALP-induced MCARs were relatively high, at 33.3% (7/21), which was HLA-B*58:01-independent, while the frequency of these dual haplotypes in the HLA-A locus in ALP-tolerant patients was only 3.45% (1/29). The HLA-B*58:01 allele was detected in 38% (8/21) of patients with ALP-induced MCARs, and in 3.45% (1/29) of ALP-tolerant patients. Notably, although HLA-B*58:01 may be a cause for the occurrence of MCARs in patients with gout, this correlation was not as strong as that previously reported in patients with SCAR. In conclusion, in addition to the HLA-B*58:01 allele, the presence of the dual haplotypes of HLA-A*02:01/HLA-A*24:02 and/or HLA-A*02:01/HLA-A*29:01 in the HLA-A locus may also play an important role in the appearance of ALP-induced MCARs in the Vietnamese population. The obtained primary data may contribute to the development of suitable treatments for patients with gout not only in Vietnam but also in other Asian countries.

Alcohol use disorder and alcohol withdrawal syndrome in Vietnamese hospitalized patients.

AIMS: To identify the extent to which patients admitted to a general hospital in Vietnam meet the criteria for risky alcohol drinking, alcohol use disorder (AUD), and alcohol withdrawal syndrome (AWS), describe problems and behavior of alcohol use such as types and quantity of alcohol drinking in a hospitalized population in Vietnam, and investigate the association among age, disease-related factors, and alcohol consumption with AWS. METHODS: This study was conducted prospectively in 1340 patients admitted to a general hospital. All patients were screened for risky alcohol drinking. Risky alcohol drinkers were assessed by using the Alcohol Use Disorder Identification Test (AUDIT) to identify AUD patients. The diagnosis of AWS was based on criteria defined by Diagnostic and Statistical Manual of Mental Disorders, version 5. The AWS scale was used to quantitate AWS severity level. RESULTS: Prevalence of risky alcohol drinkers, AUD patients, and AWS patients among hospitalized patients was 15.5%, 13.1%, and 7.3%, respectively. All of the AUD and AWS patients were male. The majority of risky alcohol drinkers, patients with AUD, and patients with AWS were 40-60-year-old men. Almost all patients (98.3%) drank homemade alcohol. Hospitalized patients were more likely to develop AWS if they had liver disease or past experience with AWS. CONCLUSIONS: AUD and AWS are common in hospitalized patients. Formulating a protocol to identify and care for patients with alcohol-related disorders is urgent.

Anticancer Activities of Ricin-Liposome Complexes on SKMEL-28 Cells.

Background: Ricin has been reported as a potential chemical for cancer treatment. However, so far, the application of ricin in cancer treatment is very limited because of its non-specificity. Methods: In this study, ricin were conjugated/ encapsulated with DOTAP/DOPE liposome to form ricin-liposome complexes (ricin-lipososme1, ricin-liposome2, ricin-liposome3 and ricin-liposome4). Characteristics of ricin-liposome complexes were analyzed and their effects on survival, apoptosis, migration, invasion and tumor formation of SKMEL-28 melanoma cells were examined by carrying out the MTT assay, apoptosis assay, scratch wound healing assay, invasion assay and soft-agar colony formation assay, respectively. Results: Ricin-liposome complexes had even size-distribution with average size of around 340 nm. These ricin-liposome complexes were able to penetrate into the cells via endocytosis with the highest ability of the ricinliposome3. It also showed that ricin-liposome3 expressed very high toxicity with the IC50 of 62.4 ng/mL and followed by ricin-liposome4 (286.4 mg/mL), ricin-liposome2 (417.5 ng/mL), and ricin-liposome1 (604.3 ng/mL) to SKMEL-28 cells at 36 hours post treatment. At the concentrations of IC10 (10.1 ng/mL), ricin-liposome3 strongly induced necrosis and apoptosis of SKMEL-28 cells up to 25.6% and 11.4%, respectively. Moreover, ricin-liposome3 expressed great anticancer properties by decreasing the migration, invasion and tumor formation abilities of SKMEL-28 cells of 7.5 folds, 4.3 folds and 5.9 folds, respectively, compared with those of control SKMEL-28 cells. Conclusion: The obtained results from our study suggest that although ricin is listed as one of the most poisonous substances in nature, it can be used in the complex forms with liposome to increase its specificity to apply in treatment of melanoma and other cancers.

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice.

Radiotherapy side-effects present serious problems in cancer treatment. Melanin, a natural polymer with low toxicity, is considered as a potential radio-protector; however, its application as an agent against irradiation during cancer treatment has still received little attention. In this study, nanomelanin particles were prepared, characterized and applied in protecting the spleens of tumor-bearing mice irradiated with X-rays. These nanoparticles had sizes varying in the range of 80-200 nm and contained several important functional groups such as carboxyl (-COO), carbonyl (-C=O) and hydroxyl (-OH) groups on the surfaces. Tumor-bearing mice were treated with nanomelanin at a concentration of 40 mg/kg before irradiating with a single dose of 6.0 Gray of X-ray at a high dose rate (1.0 Gray/min). Impressively, X-ray caused mild splenic fibrosis in 40% of nanomelanin-protected mice, whereas severe fibrosis was observed in 100% of mice treated with X-ray alone. Treatment with nanomelanin also partly rescued the volume and weight of mouse spleens from irradiation through promoting the transcription levels of splenic Interleukin-2 (IL-2) and Tumor Necrosis Factor alpha (TNF-α). More interestingly, splenic T cell and dendritic cell populations were 1.91 and 1.64-fold higher in nanomelanin-treated mice than those in mice which received X-ray alone. Consistently, the percentage of lymphocytes was also significantly greater in blood from nanomelanin-treated mice. In addition, nanomelanin might indirectly induce apoptosis in tumor tissues via activation of TNF-α, Bax, and Caspase-3 genes. In summary, our results demonstrate that nanomelanin protects spleens from X-ray irradiation and consequently enhances immunoactivity in tumor-bearing mice; therefore, we present nanomelanin as a potential protector against damage from radiotherapy in cancer treatment.

The prevalence of malnutrition based on anthropometry among primary schoolchildren in Binh Dinh province, Vietnam in 2016.

OBJECTIVE: The study was conducted to determine the prevalence of malnutrition based on anthropometry among primary schoolchildren in Binh Dinh province, Vietnam. MATERIAL AND METHODS: This was a school-based cross-sectional survey using random sample technique with multistage process. Variables in malnutrition were classifed as thinness, stunting, underweight, overweight, and obesity based on z-scores according to the World Health Organization (WHO) (2007). Anthropometric measurements were taken according to WHO's standard procedures. The Chi-square test was used to compare prevalences and the Chi-square test for trend was employed to assess the trend of the prevalence of malnutrition forms by age. RESULTS: 6,514 pupils from 6 to 10 years old including 3,298 males and 3,216 females were observed. The prevalence of thinness, stunting, underweight, overweight and obesity among schoolchildren accounted for 11.19%, 6.16%, 10.79%, and 30.1%, respectively. The prevalence of underweight and that of overweight-obesity of all pupils at the age of 6 were 13.1% and 32.11%, respectively, and tended to decrease to age 10 (p < 0.01). The prevalence of thin and stunted pupils had little sign of change over ages (p > 0.05). There was a statistically significant difference in the prevalence of malnutrition in three areas of Binh Dinh (p < 0.05), in which the highest prevalence of undernutrition was in mountainous area and midland, and the highest prevalence of overweight-obesity was in urban areas. CONCLUSION: The prevalence of malnutrition of primary schoolchildren in Binh Dinh was relatively high, in which the prevalence of overweight-obesity was rather high in urban areas and the prevalence of undernutrition was pretty high in mountainous area and midland. This study has characterized an important public health challenge, highlighting the need for attention to potential interventions.

UV spectrophotometric simultaneous determination of cefoperazone and sulbactam in pharmaceutical formulations by derivative, Fourier and wavelet transforms.

Signal processing methods based on the use of derivative, Fourier and wavelet transforms were proposed for the spectrophotometric simultaneous determination of cefoperazone and sulbactam in powders for injection. These transforms were successfully applied to UV spectra and ratio spectra to find suitable working wavelengths. Wavelet signal processing was proved to have distinct advantages (i.e. higher peak intensity obtained, additional smooth function and scaling factor process eliminated) over derivative and Fourier transforms. Especially, a better resolution of spectral overlapping bands was obtained by the use of double signal transform in the sequences such as (i) spectra pre-processed by Fractional Wavelet Transform and subsequently subjected to Continuous Wavelet Transform or Discrete Wavelet Transform, and (ii) derivative - wavelet transforms combined. Calibration graphs for cefoperazone and sulbactam were recorded for the range 10-35 mg/L. Good accuracy and precision were reported for all proposed methods by analyzing synthetic mixtures of cefoperazone and sulbactam. Furthermore, these methods were statistically comparable to RP-HPLC.