To determine the effects of oral vitamin A supplementation on clinical outcomes in preterm infants.
We conducted the meta-analysis by searching PubMed/Medline, Scopus, Embase, CINAHL, and the ...Cochrane Library databases from inception to 12 August 2021, including reference lists of retrieved articles. Only randomized controlled trials (RCTs) evaluating the effects of oral vitamin A on premature babies were included. We used a random-effects model to calculate risk ratios (RRs) and weighted mean differences (MDs) with 95% confidence intervals (CIs). We used the GRADE approach to grade evidence quality and assess how oral vitamin A supplementation affects clinical outcomes.
The primary outcomes were respiratory outcomes, including the length of respiratory support, the need for oxygen at 36 weeks postmenstrual age (PMA), and moderate-to-severe bronchopulmonary dysplasia (BPD) at 36 weeks PMA. Secondary outcomes were hospitalization time, vitamin A status, mortality, other related outcomes, and potential adverse drug-related events.
We included four RCTs, with 800 patients total. In all trials, oral vitamin A treatment was compared to a placebo. Oral vitamin A supplementation did not significantly affect mechanical ventilation duration (MD, -1.07 days; 95% CI, -2.98 to 0.83 days), oxygen requirement at 36 weeks PMA (RR, 0.65; 95% CI, 0.33 to 1.31), or moderate-to-severe BPD at 36 weeks PMA (RR, 0.53; 95% CI, 0.07 to 4.17). However, oral vitamin A supplementation yielded a slightly shorter noninvasive ventilation duration (MD, -0.96 days; 95% CI, -1.59 to -0.33 days).
Administering oral vitamin A to preterm newborns did not alter the mechanical ventilation duration, oxygen needed at 36 weeks PMA, moderate-to-severe BPD at 36 weeks PMA, death, or short-term benefits. However, oral vitamin A supplementation may slightly affect the duration of noninvasive respiratory support without adverse drug-related events.
Background and Objectives: Meconium aspiration syndrome (MAS) is a condition caused by the aspiration of meconium-stainted amniotic fluid into the lungs, resulting in pulmonary inflammation, neonatal ...morbidity, and mortality. It is important that these MAS infants receive appropriate care to avoid further complications. Steroids have an anti-inflammatory effect and may be effective in the management of MAS. The objective of the this study was to evaluate the effect of different steroids on clinical outcomes in infants with MAS. Materials and Methods: We systematically searched of PubMed/Medline, Scopus, Embase, Clinical Trials.gov, and Cochrane Library databases from inception to 24 January 2021 without language restriction. Only randomized controlled trials (RCTs) evaluating the effects of steroids in neonates with MAS were included. We calculated relative risks and weighted mean differences (MDs) with 95% confidence intervals (CIs) using a random-effects model to determine the associations between MAS and steroids and GRADE approach was employed for quality of evidence. The main outcomes measures were duration of respiratory distress, oxygen requirement, hospitalization, need for mechanical ventilation, death, and adverse drug reactions. Results: Seven RCTs involving 397 patients were analyzed. Nebulized budesonide and intravenous (IV) methylprednisolone shortened the duration of respiratory distress (MD, −2.46 days; 95% CI, −3.09 to −1.83 and MD, −3.30 days; 95% CI, −4.07 to −2.52, respectively) (moderate certainty). There was a reduction in duration of oxygen requirement in nebulized budesonide use (MD, −2.40 days; 95% CI, −3.40 to −1.40) (low certainty) and IV methylprednisolone use (MD, −3.30 days; 95% CI, −4.07 to −2.52) (moderate certainty). Nebulized budesonide shortened hospitalization stay (MD, −4.47 days; 95% CI, −8.64 to −0.30 days) (low certainty) as IV methylprednisolone use (MD, −7.23 days; 95% CI, −8.19 to −6.07 days) (moderate certainty). None of steroids benefits in death (low certainty). Conclusions: Certain types of steroids may benefit the respiratory aspect, but there was no decrease in mortality in MAS infants.
•Adding 50 mg of fluvoxamine twice daily to favipiravir provides no benefit.•Fluvoxamine is ineffective in preventing severe COVID-19.•No anti-inflammatory effect or improved radiologic outcome was ...seen with fluvoxamine.•Cytokine changes are similar in fluvoxamine and non-fluvoxamine treatments.•The study found no immunomodulatory effect of fluvoxamine.
Fluvoxamine (FVX) is an antidepressant proposed to its immunomodulatory effects in preventing deterioration in mild and moderate COVID-19.
An open-label, 1:1 randomized controlled trial was assigned either combination therapy 50 mg twice daily of FVX for 10 days and favipiravir (FPV) or FPV alone to assess the efficacy in preventing disease progression in mild to moderate COVID-19 on the 5th day.
In total, 134 patients with mild COVID-19 received FPV and 132 received FVX/FPV, 31 patients with moderate COVID-19 received FPV/dexamethasone (FPV/Dex), and 30 received FVX/FPV/Dex. The intention-to-treat (ITT) analysis showed no difference of no clinical deterioration on the 5th day in both mild COVID-19 (100% in FPV vs 97% in FVX/FPV) and moderate COVID-19 (83.9% in FPV/Dex vs 86.7% in FVX/FPV/Dex). However, there was a low rate of oxygen supplemental, hospitalization, or intensive care in both groups and zero death in all groups. No significant difference in oxygen supplemental, hospitalization, radiological, virological, or biochemical outcomes, and the immunomodulatory effect was observed between the group.
The combined fluvoxamine treatment did not add benefit in preventing deterioration in patients with mild to moderate COVID-19 without the immunomodulatory effect observed, although it demonstrated low hospitalization rates, oxygen supplemental, intensive care needed, and zero mortality.
Thai clinical trials registry (TCTR) no. 20210615002.
The global supply of COVID-19 vaccines has been limited, and concerns have arisen about vaccine supply chain disruptions in developing countries. Heterologous prime-boost vaccination, which involves ...using different vaccines for the first and second doses, has been proposed to enhance the immune response. We aimed to compare the immunogenicity and safety of a heterologous prime-boost vaccination using an inactivated COVID-19 vaccine and AZD1222 vaccine with that of a homologous vaccination using AZD1222. This pilot involved 164 healthy volunteers without prior SARS-CoV-2 infection aged 18 years or older assigned to receive either the heterologous or homologous vaccination. The results showed that the heterologous approach was safe and well-tolerated, although the reactogenicity of the heterologous approach was higher. At 4 weeks after receiving the booster dose, the heterologous approach elicited a non-inferior immune response compared to the homologous approach in neutralizing antibody and cell-mediated immune response. The percentage of inhibition was 83.88 (79.72-88.03) in the heterologous and 79.88 (75.50-84.25) in the homologous group, a mean difference of 4.60 (−1.67-10.88). The geometric mean of interferon-gamma was 1072.53 mIU/mL (799.29-1439.18) in the heterologous group and 867.67 mIU/mL (671.94-1120.40) in the homologous group, a GMR of 1.24 (0.82-1.85). However, the binding antibody test of the heterologous group was inferior to the homologous group. Our findings suggest that the use of heterologous prime-boost vaccination with different types of COVID-19 vaccines is a viable strategy, especially in settings where vaccine supply is limited or where vaccine distribution is challenging.
Andrographis paniculata is included in ‘The National List of Essential Herbal Drugs A.D. 1999’ of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The ...therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1.
This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed.
The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10–100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined.
All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was administered at the highest dose among these four diterpenoids, 2 exhibited the highest maximum concentrations (Cmax) of 44.89ng/mL and area under the plasma concentration-time curve (AUC) of 128.17h×ng/mL. Compound 1 had the second highest Cmax and AUC as 32.41ng/mL and 55.23h×ng/mL, respectively. The relative systemic exposure, represented by the dose normalized AUC (h×ng/mL)/(mg/kg), of 2 was approximately 14 times higher than that of 1, while those of 3 and 4 were approximately 1.5 and 1.6 times higher, respectively. Cmax, AUC, apparent volume of distribution, and apparent clearance of 2 were found to be significant difference between female and male. However, when these parameters were calculated as dose normalized basis, no statistically significant difference was found.
The four major active diterpenoids in the A. paniculata capsules were soluble in all studied dissolution media. The pharmacokinetic parameters of these active diterpenoids in the present study could be applied for dose optimization of A. paniculata product in order to obtain good therapeutic efficacy and reduce the possible side effects that may occur from different active diterpenoids in this medicinal plant.
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Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in Thailand. Known etiological ...factors, such as viral hepatitis and chronic liver disease do not fully account for the country's unusually high incidence. However, the gut-liver axis, which contributes to carcinogenesis and disease progression, is influenced by the gut microbiome. To investigate this relationship, fecal matter from 44 Thai PLC patients and 76 healthy controls were subjected to whole-genome metagenomic shotgun sequencing and then analyzed by marker gene-based and assembly based methods. Results revealed greater gut microbiome heterogeneity in iCCA compared to HCC and healthy controls. Two Veillonella species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, Ruminococcus gnavus was depleted in iCCA patients and could distinguish HCC from iCCA samples. High Veillonella genus counts in the iCCA group were associated with enriched amino acid biosynthesis and glycolysis pathways, while enriched phospholipid and thiamine metabolism pathways characterized the HCC group with high Blautia genus counts. These findings reveal distinct landscapes of gut dysbiosis among Thai iCCA and HCC patients and warrant further investigation as potential biomarkers.
Rhabdomyosarcoma (RMS) exhibits varying degrees of clinical manifestations, and one of the determining factors is its primary site of origin. Ocular proptosis is an infrequent presentation of ...parameningeal RMS. The growing tumor in spacious environments such as air-filled sinuses can obscure its early detection, leading to late disease intervention. Among the four subtypes (embryonal, leiomyomatous, sclerosing and spindle cell, and alveolar), the predominant type of RMS in the paranasal sinuses is alveolar. The incidence in adult-onset RMS is relatively low compared with those of children. We herein present a rare case of a 23-year-old man with an unusual presentation of bilateral proptosis from alveolar RMS of the ethmoid sinus. In contrast to our patient, most reported cases of ocular involvement in RMS turned out to be unilateral and responded poorly to treatment. Despite the aggressive behavior of the adult-onset alveolar subtype in comparable reports, our case shows an excellent outcome. Negative FOXO1 fusion status has been recognized in recent studies as a molecular feature inclined toward a favorable outcome in alveolar RMS. The integration of molecular prognostic factors to risk stratification could be advantageous in determining different prognoses and proper management for an individual patient.
AIM To determine the role of screening and surveillance of hepatocellular carcinoma(HCC) in treatment-na?ve chronic hepatitis B(CHB) patients. METHODS We recruited 2293 CHB patients(both males and ...females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography(AUS) and serum alpha-fetoprotein(AFP) assay every 6 mo. The diagnosis,staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score < 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis.RESULTS Among 2293 treatment-na?ve CHB patients,seven cases had HCC at initial screening,giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis,all of which were Child-Pugh class A. With a median follow-up time of 42(range,3-48) mo,10 additional cases were diagnosed with HCC,resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged ≥ 40 years. Most were at an early stage(Stage 0,A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation,with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis,increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels ≥ 20 mg/L at diagnosis were observed in only 7/17 patients,most with a tumor size > 5 cm. For HCC screening and surveillance,AUS had a sensitivity and specificity of 94% and 82%,respectively,whereas the sensitivity and specificity of AFP at a cut-off value of ≥ 20 mg/L were 41% and 98%,respectively. Combined use of AUS and AFP assay did not improve effectiveness. CONCLUSION Implementation of active screening and surveillance using AUS to detect early-stage HCC in na?ve CHB patients aged ≥ 40 years in an endemic area is of benefit.
Aim
Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are considered among the most potent antiviral agents for the treatment of chronic hepatitis B infection. We aimed to compare treatment ...efficacy and safety of ETV and TDF in nucleoside‐naïve chronic hepatitis B patients.
Methods
Inclusion criteria were compensated chronic hepatitis B patients who were either hepatitis B e antigen (HBeAg)‐positive or HBeAg‐negative. Exclusion criteria were co‐infection with hepatitis C virus and/or HIV, concurrent malignancy, and decompensated cirrhosis. Virological, biochemical, and serological end‐points at week 96 and 144 were compared. Of 400 patients, 200 patients received ETV and 200 received TDF.
Results
There were no significant differences between the two groups in baseline characteristics including age (41.6 ± 11.5 vs. 41.2 ± 11.6, mean baseline hepatitis B virus DNA (5.91 ± 1.79 vs. 5.94 ± 1.68 log10 IU/mL), mean baseline alanine aminotransferase (68.1 ± 64.1 vs. 76.8 ± 79.8 U/L), and cirrhosis (15.5% vs. 14.5%). At week 144 of treatment, 91 and 94% of the ETV and TDF groups, respectively, achieved undetectable hepatitis B virus DNA. In HBeAg‐positive patients, HBeAg seroconversion could be achieved in 27.4% and 33.7% at week 144 for ETV and TDF groups, respectively. Quantitative hepatitis B surface antigen dropped significantly over 144 weeks of treatment period but only 1.0 to 1.5% experienced hepatitis B surface antigen loss. Safety profiles were consistent with previous reports of monotherapy.
Conclusion
Both ETV and TDF showed potent antiviral activity against hepatitis B. Either ETV or TDF can be recommended as a treatment of choice for patients with chronic hepatitis B. Both drugs were safe and well tolerated.
Since the introduction of hepatitis B virus (HBV) vaccines, the numbers of HBV infections and complications have significantly decreased. However, the evidence on whether primary vaccination of ...infants confers lifelong immunity varies. We aimed to assess long-term immunity among healthcare workers and medical students, and the rate of decline of HBV surface antigen antibodies (anti-HBs). Hepatitis B status among participants born after 1 January 1992 was reviewed at Chulabhorn Royal Academy, Thailand. Participants were stratified by intervals since primary vaccination. HBV immunity was determined and analyzed as anti-HBs decline rate in participants with multiple follow-ups. A total of 464 participants were analyzed, with a median age of 23. Protective immunity against HBV (anti-HBs ≥ 10 mIU/mL) at 16-20, 21-25 and 26-28 years post-primary vaccination was 28%, 51.7% and 60%, respectively. The overall declining rate of anti-HBs was -42.39 mIU/mL per year. Participants with anti-HBs levels of >100-1000 mIU/mL at baseline had a faster decline rate than those with anti-HBs levels of 10-100 mIU/mL. Primary vaccination may not provide lifelong protection since HBV immunity deteriorates over time. Individuals with higher initial HBV immunity levels may experience a faster decline rate.