Impact of vaccination on COVID-19 severity during the second wave in Brunei Darussalam, 2021.

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.

Post-COVID-19 health-care utilization: one year after the 2020 first wave in Brunei Darussalam.

Objective: Patients who recover from coronavirus disease (COVID-19) infection are at risk of long-term health disorders and may require prolonged health care. This retrospective observational study assesses the number of health-care visits before and after COVID-19 infection in Brunei Darussalam. Methods: COVID-19 cases from the first wave with 12 months of follow-up were included. Health-care utilization was defined as health-care visits for consultations or investigations. Post-COVID condition was defined using the World Health Organization definition. Results: There were 132 cases; 59.1% were male and the mean age was 37.1 years. The mean number of health-care visits 12 months after recovery from COVID-19 (123 cases, 93.2%; mean 5.0 ± 5.2) was significantly higher than the prior 12 months (87 cases, 65.9%, P < 0.001; mean 3.2 ± 5.7, P < 0.001). There was no significant difference when scheduled COVID-19 visits were excluded (3.6 ± 4.9, P = 0.149). All 22 cases with moderate to critical disease recovered without additional health-care visits apart from planned post-COVID-19 visits. Six patients had symptoms of post-COVID condition, but none met the criteria for diagnosis or had alternative diagnoses. Discussion: There were significantly more health-care visits following recovery from COVID-19. However, this was due to scheduled post-COVID-19 visits as per the national management protocol. This protocol was amended before the second wave to omit post-COVID-19 follow-up, except for complicated cases or cases with no documented radiological resolution of COVID-19 pneumonia. This will reduce unnecessary health-care visits and conserve precious resources that were stretched to the limit during the pandemic.

Development and Exploration of the Effectiveness and Feasibility of a Digital Intervention for Type 2 Diabetes Mellitus (DEsireD): Protocol for a Clinical Nonrandomized Pilot Trial in Brunei Darussalam.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Digital interventions that incorporate the use of mobile phones and wearables have been getting popular. A combination of a digital intervention with support from professional management can enhance users' self-efficacy better than a digital intervention alone and provide better accessibility to a lifestyle intervention. However, there are limited studies exploring the feasibility and efficacy of applying a digital intervention in Muslim-majority countries, and none have been conducted in Brunei Darussalam. OBJECTIVE: The study aims to determine the effectiveness and feasibility of a proposed 16-week digital intervention program for T2DM self-management and to guide the rollout of a mobile app as part of a population health solution for adults with T2DM in Brunei. The primary outcome of this study is to measure the proportion of participants with a hemoglobin A1c (HbA1c) reduction of at least 0.6% from baseline, and the secondary outcomes include a change in HbA1c, BMI, lipid profile, and EQ-5D-5L score. METHODS: This single-arm nonrandomized pilot study will recruit participants using web-based (with the national health care app [BruHealth] and official social media platforms being used for outreach) and offline (in-person recruitment at health centers) approaches. A target of 180 individuals with T2DM aged between 20 and 70 years that meet the inclusion criteria will be enrolled in a 16-week digital intervention program. Baseline and postintervention markers will be evaluated. RESULTS: The study received approval from the Medical and Health Research & Ethics Committee of the Brunei Darussalam Ministry of Health (MHREC/MOH/2022/4(1)). The recruitment process is ongoing, and we anticipate that the study will conclude by April 2023. This will be followed by data analysis and the reporting of outcomes with the intention to publish. The results of this study will be disseminated through scientific publications and conferences. This study will serve as a guide to launch T2DM digital therapeutic programs and extend to other noncommunicable diseases (NCDs) if proven as an effective and feasible approach in Brunei. CONCLUSIONS: The Development and Exploration of the Effectiveness and Feasibility of a Digital Intervention for Type 2 Diabetes Mellitus (DEsireD) study will be the first study to investigate the clinical effectiveness and feasibility of the proposed 16-week T2DM digital intervention program tailored for Brunei, a Muslim-majority country. The findings of this study can potentially scale up the proposed model of care to other NCDs as a national approach for health management solutions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05364476; https://clinicaltrials.gov/ct2/show/NCT05364476. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43208.

COVID-19 patients with negative results on initial screening: Experience of Brunei Darussalam.

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.

COVID-19 symptom duration: associations with age, severity and vaccination status in Brunei Darussalam, 2021.

Objective: This retrospective, cross-sectional, observational study assessed the duration of coronavirus disease 2019 (COVID-19) symptoms during the second wave in Brunei Darussalam. Methods: Data from COVID-19 cases admitted to the National Isolation Centre during 7-30 August 2021 were included in the study. Symptom onset and daily symptom assessments were entered into a database during hospitalization and disease was categorized by severity. The time between symptom onset and hospital admission, the duration of symptoms and length of hospitalization were assessed separately by age group, disease severity and vaccination status using one-way analysis of variance with Bonferroni post hoc corrections. Results: Data from 548 cases were included in the study: 55.7% (305) of cases were male, and cases had a mean age of 33.7 years. Overall, 81.3% (446) reported symptoms at admission (mean number of symptoms and standard deviation: 2.8 ± 1.6), with cough (59.1%; 324), fever (38.9%; 213) and sore throat (18.4%; 101) being the most common. Being older, having more severe disease and being unvaccinated were significantly associated with the time between symptom onset and hospital admission, symptom duration and length of hospitalization. Discussion: Knowing which factors predict the duration of COVID-19 symptoms can help in planning management strategies, such as the duration of isolation, predict the length of hospitalization and treatment, and provide more accurate counselling to patients regarding their illness.

Challenges during the second wave of COVID-19 in Brunei Darussalam: National Isolation Centre to National COVID-19 Hospital.

Problem: Soon after the start of the second wave of coronavirus disease 2019 (COVID-19) in Brunei Darussalam, which was confirmed to be due to the more infectious Delta strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it became apparent that the National Isolation Centre (NIC) was not coping. Context: The NIC was the only isolation and treatment centre for COVID-19 in Brunei Darussalam. During the first wave and the first 11 days of the second wave, all confirmed cases were admitted to the NIC for isolation and treatment in line with the management strategy to isolate all confirmed cases to control the outbreak. Action: The Ministry of Health opened five community isolation centres and two quarantine centres to divert asymptomatic and mild cases from the NIC. The community isolation centres also functioned as triage centres for the NIC, and the quarantine centres accommodated recovered patients who did not have their own quarantine facilities. Outcome: The community isolation and quarantine centres diverted cases from the NIC and enabled recovered cases to be transferred to these step-down facilities. This reduced the NIC's occupancy to a safe level and enabled the reorganization of the NIC to function as a treatment centre and a national COVID-19 hospital. Discussion: During any disease outbreak, health facilities must be prepared to adapt to changing situations. Strong leadership, stakeholder commitments, teamwork and constant communication are important in this process.

Clinical and demographic characteristics of COVID-19 cases in Brunei Darussalam: comparison between the first and second waves, 2020 and 2021.

Objective: 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 χ2 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.

Prevalence of primary bacterial co-infections among patients with COVID-19 in Brunei Darussalam.

OBJECTIVE: Bacterial co-infections in cases of coronavirus disease 2019 (COVID-19) can lead to less favourable outcomes. The aim of this study was to determine the prevalence of primary bacterial co-infections among patients with COVID-19 in Brunei Darussalam. METHODS: Seventy-one of 180 patients admitted to the National Isolation Centre between 9 March 2020 and 4 February 2021 were screened for primary bacterial co-infection (infection occurring £48 hour from admission). We compared patients with a primary bacterial co-infection to those without. RESULTS: Of the 71 screened patients, 8 (11.2%) had a primary bacterial co-infection (sputum 37.5% [6/16], blood 2.8% [1/36], urine 1.7% [1/60]), for a period prevalence rate of 4.4% (respiratory tract infection 3.3% [6/180], bloodstream 0.6% [1/180], urine 0.6% [1/180]) among all COVID-19 patients. Older age, presence of comorbidity, symptoms at admission (fever, dyspnoea, nausea/vomiting), abnormal chest X-ray (CXR) and more severe COVID-19 (P < 0.05) were associated with primary bacterial co-infection. Primary bacterial co-infection was also associated with development of secondary infection and death (all P < 0.05). Only one patient with primary bacterial co-infection died (methicillin-sensitive Staphylococcus aureus septicaemia and multiorgan failure). CONCLUSION: Our study showed that primary bacterial co-infection affected 4.4% of patients with COVID-19 in Brunei Darussalam. Older age, presence of comorbidity, symptoms and abnormal CXR at admission and more severe disease were associated with a primary bacterial co-infection. Lower respiratory tract infection was the most common co-infection.

A randomised placebo controlled trial of VSL#3® probiotic on biomarkers of cardiovascular risk and liver injury in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk irrespective of conventional risk factors. The role of gut-liver interaction is implicated in its development. We investigated the effects of VSL#3® probiotic supplementation on biomarkers of cardiovascular risk and liver injury in patients with NAFLD. METHODS: A randomised, double-blinded, placebo-controlled, proof-of-concept study was undertaken. Patients with NAFLD were randomly allocated to take 2 sachets VSL#3® probiotic or placebo twice daily for 10 weeks. Measurements of endothelial function (digital photoplethysmography, sVCAM-1 and cGMP), oxidative stress (glutathione ratio and LHP), inflammation (hsCRP), insulin resistance (HOMA-IR) and liver injury [transaminases, fibrosis risk score and acoustic structure quantification (ASQ)] were undertaken before and after intervention. Difference in baseline characteristics between the treatment groups was analysed using independent t-test or Mann Whitney U test for non-parametric data. Independent t-test was used to compare the outcomes at the end of the study between the two treatment groups. Wilcoxon Signed Rank test was used to determine the difference in fibrosis risk scores before and after treatment. Spearman's correlation was used to determine any association between cardiovascular and hepatic markers at baseline. RESULTS: Thirty-five patients completed the study (28 males and 7 females) with a mean age of 57 ± 8 years, body mass index of 32.6 ± 5.0 kg/m2 and a relatively short duration of NAFLD (median duration 0.3 IQR 2.0 years). No significant difference was observed in biomarkers of cardiovascular risk and liver injury following VSL#3® supplementation. Significant correlations were noted between sVCAM-1 and hsCRP (rho = 0.392, p = 0.01), and HOMA-IR and AST (rho = 0.489, p < 0.01) at baseline. CONCLUSIONS: This is the first study to evaluate the effect of VSL#3® on ASQ in patients with NAFLD. VSL#3® did not significantly improve markers of cardiovascular risk and liver injury in patients with NAFLD. However, the study supports an association between endothelial dysfunction and inflammation in patients with NAFLD and suggests that NAFLD is linked with insulin resistance. TRIAL REGISTRATION: ISRCTN05474560 ( https://doi.org/10.1186/ISRCTN05474560 ) Registered 9 August 2012 (retrospectively registered).

Case Report: Right Bundle Brunch Block and QTc Prolongation in a Patient with COVID-19 Treated with Hydroxychloroquine.

Novel coronavirus disease (COVID-19) is a highly contagious disease caused by severe acute respiratory distress syndrome coronavirus-2 that has resulted in the current global pandemic. Currently, there is no available treatment proven to be effective against COVID-19, but multiple medications, including hydroxychloroquine (HCQ), are used off label. We report the case of a 60-year-old woman without any cardiac history who developed right bundle brunch block and critically prolonged corrected electrocardiographic QT interval (QTc 631 ms) after treatment for 3 days with HCQ, which resolved on discontinuation of the medication. This case highlights a significant and potentially life-threatening complication of HCQ use.

Pseudohypoparathyroidism: a rare but important cause of hypocalcaemia.

We present a 46-year-old Caucasian lady with symptomatic hypocalcaemia. Investigations revealed markedly raised parathyroid hormone (PTH) levels with vitamin D deficiency. A number of conditions causing secondary hyperparathyroidism were ruled out from her medical history and initial investigations. The main differential diagnoses were vitamin D deficiency and PTH resistance (pseudohypoparathyroidism, PHP). With high-normal serum phosphate and normal alkaline phosphatase, and a lack of symptoms associated with osteomalacia, vitamin D deficiency alone was unlikely to be the cause of hypocalcaemia. Given a normal physical appearance, genetic testing was arranged and confirmed the diagnosis of PHP type Ib. She is currently taking activated vitamin D to maintain calcium homeostasis. PTH resistance is the hallmark of PHP, a rare complex genetic disorder, which can be easily missed resulting in potentially serious consequences.