Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

High-Intensity Focused Ultrasound in Dentistry: A Literature Review.

Although high-intensity focused ultrasound (HIFU) has been applied widely in medicine, utilising its non-invasive dual ablation and thermal coagulation properties, its application in dentistry has primarily remained in the research phase, predominantly in in vitro studies. Nonetheless, there has been a consistent increase in the number of publications on this subject in recent decades, focusing on areas such as remineralisation of dentine surfaces, removal of smear layers, drug delivery, and microbial elimination. The number of advantages HIFU can offer, such as its non-surgical nature, absence of ionising radiation, lack of residue, and absence of aerosols, is driving this upward trend, indicating the potential for HIFU in clinical dentistry and ongoing efforts towards developing HIFU-based devices for routine dental use. This succinct review aims to outline the historical context, operational mechanisms of HIFU, summarise recent dental research, and provide a forward-looking perspective on the role of HIFU in modern clinical dentistry.

Effect of ambient air pollution on hospital admission for respiratory diseases in Hanoi children during 2007-2019.

Air pollution poses a threat to children's respiratory health. This study aims to quantify the association between short-term air pollution exposure and respiratory hospital admissions among children in Hanoi, Vietnam, and estimate the population-attributable burden using local data. A case-crossover analysis was conducted based on the individual records where each case is their own control. The health data was obtained from 13 hospitals in Hanoi and air pollution data was collected from four monitoring stations from 2007 to 2019. We used conditional logistic regression to estimate Percentage Change (PC) and 95% Confidence Interval (CI) in odd of hospital admissions per 10 µg/m3 increase in daily average particulate matter (e.g. PM1, PM2.5, PM10), Sulfur Dioxide (SO2), Nitrogen Dioxide (NO2), 8-h maximum Ozone and per 1000 µg/m3 increase in daily mean of Carbon Monoxide (CO). We also calculated the number and fraction of admissions attributed to air pollution in Hanoi by using the coefficient at lag 0. A 10 µg/m3 increase in the concentration of PM10, PM2.5, PM1, SO2, NO2, O3 8-h maximum and 1000 µg/m3 increase in CO concentration was associated with 0.6%, 1.2%, 1.4%, 0.8%, 1.6%, 0.3%, and 1.7% increase in odd of admission for all respiratory diseases among children under 16 years at lag 0-2. All PM metrics and NO2 are associated with childhood admission for pneumonia and bronchitis. Admissions due to asthma and upper respiratory diseases are related to increments in NO2 and CO. For attributable cases, PM2.5 concentrations in Hanoi exceeding the World Health Organization Air Quality Guidelines accounted for 1619 respiratory hospital admissions in Hanoi children in 2019. Our findings show that air pollution has a detrimental impact on the respiratory health of Hanoi children and there will be important health benefits from improved air quality management planning to reduce air pollution in Vietnam.

Patients' Satisfaction with Obstetrics-Gynecology, and Pediatric Healthcare Services in Vietnam: A Multicentre Cross-Sectional Study.

Purpose: Despite improvements in maternal and child health in Vietnam, sustained efforts are required to improve healthcare quality and resolve persistent disparities, highlighting the universal significance of customer satisfaction in healthcare. This study aims to assess patient satisfaction with healthcare services and associated factors at obstetrics-gynecology and pediatric hospitals across different geographical areas in Vietnam. Patients and Methods: A cross-sectional study was conducted in 2019 among 647 patients or caregivers of hospitalized children at three major obstetrics-gynecology and pediatric hospitals, representing different geographical areas in Northern Vietnam. A Ministry of Health-approved satisfaction instrument was utilized to assess patient satisfaction. The instrument included 31 items measuring five dimensions of perceived satisfaction. Exploratory factor analysis examined the construct validity of the satisfaction measurement, and multivariate linear regression determined the factors associated with patient satisfaction. Results: Among the 643 participants, 520 were female (89.87%), and nearly half were aged 18-29 years old (43.7%). Factor analysis revealed three dimensions: "Competency and Outcomes", "Accessibility and Procedures", and "Facilities and Equipment", with mean domain scores of 4.6 ± 0.43, 4.28 ± 0.67, and 4.53 ± 0.51, respectively. The proportion of participants completely satisfied with overall service quality was 48.52%, and expectation met was 34.53%. Multivariate linear regression indicated that patients from hospitals in the Red River Delta region had higher satisfaction scores than those in the Middle region across all domains (p<0.05). Higher health insurance coverage was associated with increased satisfaction, while education level, economic status, and ethnicity also influenced satisfaction. Conclusion: The study revealed moderate to high levels of satisfaction among patients at three major obstetrics-gynecology and pediatric hospitals in northern Vietnam. The findings may provide useful evidence for implementing hospital quality control in Vietnam, focusing on patient-centered goals.

The first successful bone marrow transplantation in Vietnam for a young Vietnamese boy with chronic granulomatous disease: a case report.

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) disorder that results from defects in the respiratory burst activity in phagocytes, leading to the inability to kill bacterial and fungal microorganisms. CGD patients usually have a high incidence of morbidity such as infections and autoinflammatory diseases and a high mortality rate. Allogeneic bone marrow transplantation (BMT) is the only definitive cure for patients who suffer from CGD. Case presentation: We report the first transplant case of chronic granulomatous disease in Vietnam. A 25-month-old boy with X-linked CGD underwent bone marrow transplantation from his 5-year-old, full-matched human leukocyte antigen (HLA)-carrier sibling after myeloablative conditioning regimen with busulfan 5.1 mg/kg/day for 4 days, fludarabine 30 mg/m2/day for 5 days, and rATG (Grafalon-Fresenius) 10 mg/kg/day for 4 days. Neutrophil was engrafted on day 13 posttransplant, donor chimerism was 100% on day 30 with the dihydrorhodamine-1,2,3 (DHR 123) flow cytometric assay test that reached 38% of the normal 45 days posttransplant. Five months after transplant, the patient was free of infection with stable DHR 123 assay at 37%, and donor chimerism remained 100%. No sign of a graft-versus-host disease had been observed posttransplant. Conclusion: We suggest that bone marrow transplantation is a safe and effectual cure for CGD patients, especially for patients with HLA-identical siblings.

The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis.

BACKGROUND: Citrin deficiency (CD), a disorder caused by mutations in the SLC25A13 gene, may result in neonatal intrahepatic cholestasis. This study was purposely to explore the mutation spectrum of SLC25A13 gene in Vietnamese CD patients. METHODS: The 292 unrelated CD patients were first screened for four high-frequency mutations by PCR/PCR-RFLP. Then, Sanger sequencing was performed directly for heterozygous or undetected patients. Novel mutations identified would need to be confirmed by their parents. RESULTS: 12 pathogenic SLC25A13 mutations were identified in all probands, including three deletions c.851_854del (p.R284Rfs*3), c.70-63_133del (p.Y24_72Ifs*10), and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]), two splice-site mutations (IVS6+5G>A and IVS11+1G>A), one nonsense mutations c.1399C>T (p.R467*), one duplication mutation c.1638_1660dup (p.A554fs*570), one insertion IVSl6ins3kb (p.A584fs*585), and four missense mutation c.2T>C (p.M1T), c.1231G>A (p.V411M), c.1763G>A (p.R588Q), and c.135G>C (p.L45F). Among them, c.851_854del (mut I) was the most identified mutant allele (91.78%) with a total of 247 homozygous and 42 heterozygous genotypes of carriers. Interestingly, two novel mutations were identified: c.70-63_133del (p.Y24_72Ifs*10) and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]). CONCLUSION: The SLC25A13 mutation spectrum related to intrahepatic cholestasis infants in Vietnam revealed a quite similar pattern to Asian countries' reports. This finding supports the use of targeted SLC25A13 mutation for CD screening in Vietnam and contributed to the SLC25A13 mutation spectra worldwide. It also helps emphasize the role of DNA analysis in treatment, genetic counseling, and prenatal diagnosis.

Cerebrospinal Fluid Polymerase Chain Reaction in the Diagnosis of Neonatal Bacterial Meningitis: A Single-Center Experience From Vietnam.

OBJECTIVE: To compare the performance of cerebrospinal fluid (CSF) polymerase chain reaction (PCR) with bacterial culture for the diagnosis of neonatal bacterial meningitis (NBM). METHOD: The CSF analysis of neonate with confirmed bacterial meningitis was performed with PCR and bacterial culture, and results were compared. RESULT: Among 24 neonates, the pathogens Identified included E. coli K1, GBS, Streptococcus pneumoniae and Listeria. PCR identified 20 (83.3%) pathogens, and culture 4 (16.7%) pathogens. Prior antibiotics were administered to 20 (83.3%) neonates in whom PCR identified 17 (85%) and culture 3 (15%) pathogens. CONCLUSION: CSF PCR had a higher yield of pathogens than CSF culture in confirmed neonatal bacterial meningitis with a high rate of prior antibiotic therapy.

Efficacy of obstructive sleep apnea treatment by antileukotriene receptor and surgery therapy in children with adenotonsillar hypertrophy: A descriptive and cohort study.

Background: Prevalence of obstructive sleep apnea (OSA) in children with adenotonsillar hypertrophy is high and related to the occlusion of the upper airway. The main treatments of OSA in these children is adenotonsillectomy. However, this intervention is an invasive method with a various success rate. Thus, the indications of tonsillectomy remain debatable and non-invasive treatment is still a potential choice in these patients. Methods: It was a cross-sectional and interventional study. This study included children aged from 2 to 12 years-old who were diagnosed with OSA by respiratory polygraphy and had tonsillar hypertrophy with/without adenoid hypertrophy. All main data including age, gender, height, weight, body mass index (BMI), clinical symptoms, and medical history were recorded for analysis. Physical examination and endoscopy were done to evaluate the size of tonsillar and adenoid hypertrophy by using Brodsky and Likert classifications, respectively. The severity of OSA was done by using the classification of AHI severity for children. Results: There were 114 patients (2-12 years old) with a mean age of 5.5 ± 2.1 years included in the present study. The main reasons for consultations were snoring (96.7%), a pause of breathing (57.1%), an effort to breathe (36.8%), unrefreshing sleep (32%), doziness (28.2%), and hyperactivity (26.3%). There were 36% of subjects with tonsillar hypertrophy grade 1-2, 48.2% with grade 3, and 15.8% with grade 4 (Brodsky classification); among them, there were 46.5% of subjects with grades 1-2 of adenoid hypertrophy, 45.6% with grade 3, and 7.0% with grade 4 (Likert classification). The mean AHI was 12.6 ± 11.2 event/h. There was a significant correlation between the mean AHI and the level of tonsillar and adenoid hypertrophy severity (r = 0.7601 and r = 0.7903; p < 0.05 and p < 0.05, respectively). The improvement of clinical symptoms of study subjects was found in both groups treated with ALR (antileukotriene receptor) or ST (surgery therapy). The symptoms related to OSA at night including snoring, struggle to breathe, sleeping with the mouth open, and stopping breathing during sleep were significantly improved after treatment with ATR and with ST (p < 0.001 and p = 0.001, respectively). The mean AHI was significantly reduced in comparison with before treatment in study subjects treated with ALR (0.9 ± 1.0 vs. 3.9 ± 2.7 events/h; p = 0.001) or with ST (3.5 ± 1.4 vs. 23.4 ± 13.1 events/h; p < 0.001). Conclusion: The treatment of OSA due to adeno-tonsillar hypertrophy with ALR for moderate OSA or surgery for severe OSA might reduce the symptoms related to OSA at night and during the day.

Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports.

RATIONALE: Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5ß-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death. PATIENT CONCERNS: Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients. DIAGNOSES: The patients were diagnosed with primary Δ4-3-oxosteroid 5ß-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr). INTERVENTIONS: Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d. OUTCOMES: The patients' symptoms, signs, and primary bile acids levels improved significantly. LESSONS: Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes.

Validation of steroid ratios for random urine by mass spectrometry to detect 5α-reductase deficiency in Vietnamese children.

OBJECTIVES: The 5α-reductase-type-2 deficiency (5ARD2) is a rare autosomal recessive 46,XY disorder of sex development caused by the mutated 5α-reductase type 2 (SRD5A2) gene. In this disease, defective conversion of testosterone to dihydrotestosterone leads to variable presentations of male ambiguous genitalia during fetal development. We aimed to examine characteristics of patients presenting with 5ARD2 over a 4 year period. METHODS: Random urine samples of control and patients with suspected 5ARD2 were collected and urine steroidomic metabolites were measured by Gas chromatography-mass spectrometry (GC-MS) in the period from 2017 to 2021 at National Children's Hospital, Hanoi Vietnam. 5α- to 5ß-reduced steroid metabolite ratio, 5a-tetrahydrocortisol to tetrahydrocortisol (5α-THF/THF), was reviewed by receive operator characteristics (ROC) curve analysis. Molecular testing was offered to 25 patients who were diagnosed with 5ARD2 by GC-MS urinary steroid analysis. RESULTS: Urine steroidomic profiling was conducted for 104 male controls and 25 patients between the ages of 6 months and 13 years old. Twelve of the twenty-five 5ARD2 patients agreed to undertake genetic analysis, and two mutations of the SRD5A2 gene were detected in each patient, confirming the diagnosis. All patients showed a characteristically low ratio of 5α-THF/THF. There was no overlap of 5α-THF/THF ratio values between control and 5ARD2 groups. The ROC of 5α-THF/THF ratio at 0.19 showed 100% sensitivity and 100% specificity for boys between 6 months and 13 years of age. CONCLUSIONS: Analysis of the urine steroid metabolome by GC-MS can be used to assist in the diagnosis of 5ARD2. We recommend consideration of random urine steroid analysis as a first-line test in the diagnosis of 5ARD2.