Objective: Coronavirus disease (COVID-19) vaccinations have been shown to prevent infection with efficacies ranging from 50% to 95%. This study assesses the impact of vaccination on the clinical severity of COVID-19 during the second wave in Brunei Darussalam in 2021, which was due to the Delta variant. Methods: Patients included in this study were randomly selected from those who were admitted with COVID-19 to the National Isolation Centre between 7 August and 6 October 2021. Cases were categorized as asymptomatic, mild (symptomatic without pneumonia), moderate (pneumonia), severe (needing supplemental oxygen therapy) or critical (needing mechanical ventilation) but for statistical analysis purposes were dichotomized into asymptomatic/mild or moderate/severe/critical cases. Univariate and multivariable analyses were conducted to identify risk factors associated with moderate/severe/critical disease. Propensity score-matched analysis was also performed to evaluate the impact of vaccination on disease severity. Results: The study cohort of 788 cases (mean age: 42.1 + 14.6 years; 400 males) comprised 471 (59.8%) asymptomatic/mild and 317 (40.2%) moderate/severe/critical cases. Multivariable logistic regression analysis showed older age group (>45 years), diabetes mellitus, overweight/obesity and vaccination status to be associated with increased severity of disease. In propensity score-matched analysis, the relative risk of developing moderate/severe/critical COVID-19 for fully vaccinated (two doses) and partially vaccinated (one dose) cases was 0.33 (95% confidence interval [CI]: 0.16–0.69) and 0.62 (95% CI: 0.46–0.82), respectively, compared with a control group of non-vaccinated cases. The corresponding relative risk reduction (RRR) values were 66.5% and 38.4%, respectively. Vaccination was also protective against moderate/severe/critical disease in a subgroup of overweight/obese patients (RRR: 37.2%, P = 0.007). Discussion: Among those who contracted COVID-19, older age, having diabetes, being overweight/obese and being unvaccinated were significant risk factors for moderate/severe/critical disease. Vaccination, even partial, was protective against moderate/severe/critical disease.

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

Objective: To evaluate gastrointestinal (GI) patient reported outcomes (PROs) in cervical cancer patients treated with definitive radiotherapy (RT), comparing 3D conformal RT (3DCRT) vs. intensity modulated/volumetric modulated arc therapy (IMRT/VMAT). Methods: An analysis of patients treated with definitive RT between 2015–2018 was performed. GI PROs were prospectively collected at baseline, during RT (acute), ≤12 weeks after RT (subacute), and >12 weeks after RT (late). GI PROs evaluated three symptom domains: bowel problems (BPs), bowel bother (BB), and abdominal problems (APs). Multiple linear regression analysis was performed to investigate associations between mean changes of symptom scores with clinical and dosimetric variables. Results: The cohort included 167 patients. A total of 100 (60%) patients were treated with IMRT/VMAT and 67 (40%) with 3DCRT. In the subacute phase, the mean change of symptom scores from baseline in 3DCRT vs. IMRT/VMAT were +0.9 vs. −1.15 (p=0.004) for BP, +2.18 vs. −0.10 (p=0.019) for BB, and +1.41 vs. −0.38 (p=0.021) for AP. Likewise, in the late phase, mean changes were +0.72 vs. −0.82 (p=0.014) for BP, +1.98 vs. −0.03 (p=0.008) for BB, and +1.29 vs. −0.31 (p<0.001) for AP. On multiple linear regression, use of 3DCRT vs. IMRT/VMAT was associated with greater mean changes in subacute BP (p=0.023) and late phase AP (p=0.019). A higher small bowel V50Gy was associated increased symptom scores in late AP (p=0.012). Conclusion 3DCRT was associated with significantly greater worsening of GI PRO symptom scores in the subacute and late phase. These data support the ongoing use of IMRT/VMAT in routine practice.

In any infectious disease outbreak, early diagnosis, isolation of cases and quarantine of contacts are central to disease containment. In Brunei Darussalam, suspected cases of coronavirus disease 2019 (COVID-19) were quarantined either at home or at designated centres and were tested immediately for severe acute respiratory syndrome coronavirus 2. We report on 10 cases of COVID-19 that initially tested negative for COVID-19 and were positive on re-testing after becoming symptomatic. These cases comprised 3.8% of the 266 total confirmed COVID-19 cases in Brunei Darussalam as of 9 July 2021, when this study was conducted. All the cases were in quarantine at home and were tested early during their quarantine period. Since then, home quarantine has been replaced by quarantine at designated centres only, with testing on the 12th day of quarantine.

Abstract: Differences in clinical manifestations between strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. This retrospective descriptive study compares the clinical and demographic characteristics of all confirmed coronavirus disease (COVID-19) cases admitted to the National Isolation Centre (NIC) in the first wave and at the beginning of the second wave of the pandemic in Brunei Darussalam. Methods: All COVID-19 cases admitted to the NIC between 9 March and 6 May 2020 (first wave) and 7–17 August 2021 (second wave) were included. Data were obtained from NIC databases and case characteristics compared using Student’s t-tests and chi-squared tests, as appropriate. Results: Cases from the first wave were significantly older than those from the second wave (mean 37.2 vs 29.7 years, P<0.001), and a higher proportion reported comorbidities (30.5% vs 20.3%, P=0.019). Cases from the second wave were more likely to be symptomatic at admission (77.7% vs 63.1%, P<0.001), with a higher proportion reporting cough, anosmia, sore throat and ageusia/dysgeusia; however, myalgia and nausea/vomiting were more common among symptomatic first wave cases (all P<0.05). There was no difference in the mean number of reported symptoms (2.6 vs 2.4, P=0.890). Discussion Our study showed clear differences in the profile of COVID-19 cases in Brunei Darussalam between the first and second waves, reflecting a shift in the predominating SARS-CoV-2 strain. Awareness of changes in COVID-19 disease manifestation can help guide adjustments to management policies such as duration of isolation, testing strategies, and criteria for admission and treatment.

In ASEAN, the number of confirmed COVID-19 cases is reported with little information on the number of screening tests performed or the criteria for who is tested. We highlight the need for enhanced surveillance and reporting of the number of people screened and screening criteria when testing capacity is limited.

Objective: To assess the knowledge, attitudes, and practices (KAP) on Zika virus infection among pregnant women in Brunei Darussalam by a cross-sectional survey. Methods: Between February and June 2017, we recruited 234 pregnant women from all government healthcare centres at Brunei-Muara district, using a modified systematic sampling approach. A pre-tested and self-administered questionnaire was used and data analysis was conducted using descriptive statistics and multiple logistic regression analyses. Results: The study participants were mainly Malay (87.2%) and their mean age was 28.0 years. The median knowledge score was 13, out of a possible score of 28. Most participants (92.7%) knew that Zika virus was transmitted by mosquito bites whereas some (34.6%) knew that sexual transmission was also possible. Media (radio, television or newspapers) was the preferred source of updated information on Zika virus, followed by healthcare workers (44.0%), government announcements (43.2%), and social media (38.0%). Pregnant women who were 25 years old or older [Adj. OR=3.62 (95% CI: 1.57, 9.51)], not Malays [Adj. OR=3.32 (95% CI: 1.35, 8.55)], and had an average monthly household income of more than BND $3 000 [Adj. OR=4.06 (95% CI: 1.81, 19.44)] were more likely to score higher for knowledge on Zika virus. The median prevention practice score was 23, out of a possible score of 36. Most participants reported wearing covering clothes (98.3%) and kept their living surroundings clean (99.6%). Most participants (88.0%) agreed that Zika is an important issue in their community. Conclusion: We found a lack of knowledge on Zika virus infection among pregnant women attending government maternal and child healthcare centres in Brunei Darussalam, in particular that Zika virus can be sexually transmitted. Such information could be well disseminated at the healthcare centre level. Health literacy studies should be conducted to understand the facilitators and barriers of KAP on Zika virus infection among pregnant women.

PURPOSE: It aimed to find if written test results improved for advanced cardiac life support (ACLS) taught in flipped classroom/team-based Learning (FC/TBL) vs. lecture-based (LB) control in University of California-Irvine School of Medicine, USA. METHODS: Medical students took 2010 ACLS with FC/TBL (2015), compared to 3 classes in LB (2012-14) format. There were 27.5 hours of instruction for FC/TBL model (TBL 10.5, podcasts 9, small-group simulation 8 hours), and 20 (12 lecture, simulation 8 hours) in LB. TBL covered 13 cardiac cases; LB had none. Seven simulation cases and didactic content were the same by lecture (2012-14) or podcast (2015) as was testing: 50 multiple-choice questions (MCQ), 20 rhythm matchings, and 7 fill-in clinical cases. RESULTS: 354 students took the course (259 [73.1%] in LB in 2012-14, and 95 [26.9%] in FC/TBL in 2015). Two of 3 tests (MCQ and fill-in) improved for FC/TBL. Overall, median scores increased from 93.5% (IQR 90.6, 95.4) to 95.1% (92.8, 96.7, P=0.0001). For the fill-in test: 94.1% for LB (89.6, 97.2) to 96.6% for FC/TBL (92.4, 99.20 P=0.0001). For MC: 88% for LB (84, 92) to 90% for FC/TBL (86, 94, P=0.0002). For the rhythm test: median 100% for both formats. More students failed 1 of 3 tests with LB vs. FC/TBL (24.7% vs. 14.7%), and 2 or 3 components (8.1% vs. 3.2%, P=0.006). Conversely, 82.1% passed all 3 with FC/TBL vs. 67.2% with LB (difference 14.9%, 95% CI 4.8-24.0%). CONCLUSION: A FC/TBL format for ACLS marginally improved written test results.
Advanced Cardiac Life Support* ; California* ; Choice Behavior ; Humans ; Learning* ; Students, Medical* ; United States

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.
Asia* ; Blood Platelets ; Delayed-Action Preparations ; Delivery of Health Care ; Dexlansoprazole* ; Efficiency ; Esophagitis ; Gastroesophageal Reflux* ; Healthy Volunteers ; Plasma ; Prevalence ; Proton Pump Inhibitors ; Proton Pumps* ; Protons*