Singapore tuberculosis (TB) clinical management guidelines 2024: A modified Delphi adaptation of international guidelines for drug-susceptible TB infection and pulmonary disease.

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore's clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

Mild Neurological Manifestations Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Children During the Omicron Wave in Singapore: A Retrospective Cohort Review.

BACKGROUND: Neurological complications with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant have been reported in adults; however, there are little data in the pediatric population. We aimed to report on the prevalence and clinical characteristics of children with neurological symptoms during the SARS-CoV-2 omicron wave. METHODS: This was a single-center, retrospective cohort review of children (<18 years old) hospitalized for SARS-CoV-2 infection from December 2, 2021, to June 30, 2022. RESULTS: During the study period, 455 children (mean age 4.8 years, range 0.67 to 18, male 58.9%) were hospitalized with SARS-CoV-2 infection. A total of 108 (23.7%) children experienced neurological symptoms; most common were seizures (62.0%), headaches (32.4%) and giddiness (14.8%). Seizures included febrile seizures (64.1%), acute symptomatic seizures (17.9%), and breakthrough seizures in known epileptics (17.9%). Children with neurological manifestations were older (7.3 vs 4.0 years, P < 0.00001), more likely to have underlying epilepsy (9.3% vs 1.2%, P = 0.0002) or neurodevelopmental disorders (17.6% vs 1.7%, P < 0.00001), and presented earlier in their illness (2.1 vs 2.8 days, P < 0.00001), compared with those without neurological manifestations. Neurological symptoms fully resolved in all but one patient at discharge. There were no mortalities and no difference in duration of hospitalization (3.1 vs 3.7 days, P = 0.5) between the groups. CONCLUSIONS: One in four hospitalized children with SARS-CoV-2 infection when omicron variant was dominant experienced mild neurological symptoms. Overall risk factors for neurological symptoms associated with SARS-CoV-2 included older age, pre-existing febrile seizures/epilepsy and neurodevelopmental disorders.

The application of cardiac magnetic resonance imaging (CMR) in myocarditis after COVID-19 vaccines : Case series from single medical center in Taiwan.

During the coronavirus disease 2019 (COVID-19) pandemic, reports of vaccine-induced myocarditis, particularly messenger ribonucleic acid (mRNA)-based myocarditis, were widely spread. This case series describes various cases of COVID-19 vaccine-induced myocarditis confirmed by cardiac magnetic resonance imaging (MRI), including those who were administered rare protein-based vaccines. Eleven patients comprising eight males and three females with suspected myocarditis underwent cardiac MRI at Taichung Veterans General Hospital between October 2021 and May 2022. The median age of the patients was 33.5 years old (range: 22-57 years). The onset of myocarditis was mainly observed following mRNA vaccine inoculation. One patient received the MVC-COV1901 vaccine, a unique protein-based COVID-19 vaccine in Taiwan, and met the 2018 Lake Louise Criteria for the diagnosis of myocarditis, confirmed by cardiac MRI. Most patients reported chest discomfort after receiving various vaccine types. Among four patients with reduced left ventricular ejection fraction (LVEF), two showed LVEF restoration during the follow-up period, and the other two were lost to follow-up. Cardiac MRI characterizes myocardial features such as edema, inflammation, and fibrosis, and has been proven to diagnose myocarditis accurately with a sensitivity of 87.5% and a specificity of 96.2% according to the 2018 Lake Louise criteria. This diagnosis was achieved without invasive procedures such as endomyocardial biopsy or coronary angiography.

Anxiety in hospitalised families: lessons from the early phase of the COVID-19 pandemic.

Introduction: In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, children with COVID-19 in Singapore required hospital isolation. We aimed to explore the psychological experiences of children and their caregivers isolated in a tertiary university hospital due to COVID-19. Methods: A prospective mixed-methods design was used to evaluate the psychological status of hospitalised family units with one or more children aged <18 years who had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patient medical records were reviewed for demographic and clinical information. Parents and children ≥7 years of age underwent a psychologist-administered telephone-based interview. Self-reported, age-appropriate instruments, Short Mood and Feelings Questionnaire, and Screen for Adult/Child Anxiety-Related Disorders, were used to assess anxiety and depression, respectively. Participants were also interviewed qualitatively. Results: Fifteen family units were hospitalised between March 2020 and May 2020. Of these, 13 (73%) family units were recruited. The median age of the children and median hospitalisation duration were 57 months and 21 days, respectively. Median number of COVID-19 polymerase chain reaction swabs performed for each child was eight. All children had asymptomatic to mild SARS-CoV-2 disease. The criteria indicative of anxiety disorder were met by 40% of adults and 80% of children, while the criteria indicative of separation anxiety were met by 60% of parents and 100% of children. One child met the criteria indicative of depression. Uncertainty, separation, prolonged hospitalisation and frequent swabs caused significant reported anxiety. Conclusions: Families, especially children, had heightened anxiety while in hospital isolation. Therefore, home-based recovery from COVID-19 and psychological support for children and their families, with focus on early recognition of anxiety disorders, are recommended. We support review of paediatric isolation policy as the pandemic evolves.

Non-Tuberculous Mycobacterial Cervicofacial Lymphadenitis in Children-10-Year Experience in a Tertiary Pediatric Center.

BACKGROUND: Lymphadenitis is the most common manifestation of non-tuberculous mycobacteria (NTM) infection in children. We describe the epidemiology and clinical characteristics of NTM lymphadenitis, determine diagnostic yield from tissue sampling, and review management and outcomes. METHODS: This was a 10-year retrospective review of children aged 0-16 years diagnosed with NTM cervicofacial lymphadenitis who were seen in a pediatric infectious disease clinic in a tertiary public hospital. Data relating to patient demographics, clinical features, surgical and antimicrobial treatment, complications, and outcomes were retrieved from patients' electronic medical records and analyzed. RESULTS: There were 48 episodes of NTM cervicofacial lymphadenitis in 45 children (17 males and 28 females). Of these episodes, 43.7% manifested as a unilateral single node, mostly parotid (39.6%) and submandibular (29.2%). All patients underwent diagnostic fine-needle aspiration or surgery. Surgical excision more frequently yielded positive histological findings (P = .016). NTM was identified in 22/48 episodes (45.8%) via culture or molecular sequencing. Mycobacterium abscessus was most commonly found (47.8%). Thirty-eight children (79.2%) received antibiotics. Outcomes in 43 episodes revealed full resolution in 69.8%, while 25.6% had de novo disease and 4.6% experienced recurrence at the same site. Overlying skin changes and multiple or bilateral nodal diseases were significantly associated with de novo disease or recurrence (P = .034 and .084, respectively). Complications occurred in 11/70 (15.7%) procedures. Antibiotic-associated adverse effects occurred in 14/38 (36.8%) episodes. CONCLUSIONS: NTM lymphadenitis remains a challenging condition. More aggressive management with surgical excision and antibiotics is recommended for those with overlying skin changes and extensive nodal disease.

Immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody in the Bruneian population: Protocol for a national longitudinal study.

INTRODUCTION: Neutralising antibodies (NAbs) have been shown to be correlative of immune protection against SARS-CoV-2. We report the protocol for a national longitudinal study to assess and compare the level of NAbs generated in response to COVID-19 vaccines in Brunei Darussalam in adults 2-6 weeks post primary series (BBIBP-CorV, AZD1222, or mRNA-1273 vaccines) and their subsequent follow-up after administration of a third (booster-1) dose (BBIBP-CorV, mRNA-1273, or BNT162b2). METHODS AND ANALYSIS: Participant data will be extracted and processed from the national electronic health record system (Bru-HIMS) and the national mobile health application (BruHealth) into a research data platform. Eligible adults who have received their primary or booster vaccine will be invited using a stratified random sampling strategy based on age, gender and vaccine type (baseline target population, n=3000; 2-6 weeks post last dose). Blood serum will be isolated, and NAb levels assessed using the cPass surrogate virus neutralisation test. Baseline participants will then be screened for eligibility for subsequent longitudinal analysis. Those who have received a third dose will be followed up at 1, 3, 6, 9 and up to 12 months. NAb levels will be evaluated across the participant population according to vaccine platform/booster type, time since the last dose and correlated with demographic data. The study period is from December 2021 to January 2023 and aims to evaluate how NAb levels wane following a third vaccine dose across different vaccine platforms and determine the impact and rate of breakthrough infections. ETHICS AND DISSEMINATION: This study has been approved by the Medical and Ethical Research Committee of Ministry of Health, Brunei Darussalam. Individual NAb test results will be shared with each participant by text message. The findings from this study will help policy-makers in Brunei develop future vaccination strategies and establish regulations across multiple agencies.

Technology-assisted adaptive recruitment strategy for a large nation-wide COVID-19 vaccine immunogenicity study in Brunei.

A national study was conducted in Brunei to assess and compare the immunogenicity of the various brands of COVID-19 vaccines administered to the population as part of the National COVID-19 Vaccination Programme. Most of the population have had received at least 2 doses of BBIBP-CorV, AZD1222 or MRNA-1273 vaccines. Neutralising antibodies against SARS-CoV-2 induced by these vaccines will be analysed to infer population-level immune protection against COVID-19. During the 5-week recruitment period, 24,260 eligible individuals were invited to the study via SMS, out of which 2,712 participants were enrolled into the study. This paper describes the novel adaptive strategy used to recruit the study participants. Digital technology was leveraged to perform targeted online recruitment to circumvent the limitations of traditional recruitment methods. Technology also enabled stratified random selection of these eligible individuals who were stratified based on age, gender and vaccine brand. Data was extracted from the electronic health records, the national mobile health application and a third-party survey platform and integrated into a dedicated research platform called EVYDResearch. The instant availability and access to up-to-date data on EVYDResearch enabled the study team to meet weekly and adopt an adaptive recruitment strategy informed by behavioural science, where interventions could be quickly implemented to improve response rates. Some examples of these include incorporating nudge messaging into SMS invitations, involving the Minister of Health to make press announcements on this study, media coverage, setting up an enquiries hotline and reaching out to foreign language speaking expatriates of a local multinational company to participate in this study. Data integration from various data sources, real time information sharing and a strong teamwork led to good outcomes adaptable to the progress of recruitment, compared to the more time-consuming and static traditional recruitment methods.

In situ alginate crosslinking during spray-drying of lactobacilli probiotics promotes gastrointestinal-targeted delivery.

Alginate-based formulations have shown desirable functional characteristics for probiotic encapsulation. However, current technologies used to produce these formulations are inefficient, detrimental to probiotics viability or do not produce dry, shelf-stable products. Herein, we developed a novel spray-drying technique that combines particle formation, alginate crosslinking and drying into a single step, thereby streamlining the production of encapsulated probiotics powder. Lacticaseibacillus rhamnosus GG (LGG) encapsulated in six encapsulation formulations were characterized and compared. Among the six formulations investigated, the crosslinked alginate with sucrose formulation (Ca-Alg-Suc) was found to be most promising, achieving ~109 CFU/g of surviving LGG after spray-drying and exposure to simulated gastric fluid (SGF). The Ca-Alg-Suc formulation was further evaluated with Lactiplantibacillus plantarum and Lacticaseibacillus paracasei, and similar results of high post-spray-drying and post-SGF viabilities were obtained. Successful encapsulation of different lactobacilli probiotics via the proposed spray-drying technique highlights potential of this procedure to be scaled up for commercial applications.

Strong Moiré Excitons in High-Angle Twisted Transition Metal Dichalcogenide Homobilayers with Robust Commensuration.

The burgeoning field of twistronics, which concerns how changing the relative twist angles between two materials creates new optoelectronic properties, offers a novel platform for studying twist-angle dependent excitonic physics. Herein, by surveying a range of hexagonal phase transition metal dichalcogenides (TMD) twisted homobilayers, we find that 21.8 ± 1.0°-twisted (7a×7a) and 27.8 ± 1.0°-twisted (13a×13a) bilayers account for nearly 20% of the total population of twisted bilayers in solution-phase restacked bilayers and can be found also in chemical vapor deposition (CVD) samples. Examining the optical properties associated with these twisted angles, we found that 21.8 ± 1.0° twisted MoS2 bilayers exhibit an intense moiré exciton peak in the photoluminescence (PL) spectra, originating from the refolded Brillouin zones. Our work suggests that commensurately twisted TMD homobilayers with short commensurate wavelengths can have interesting optoelectronic properties that are different from the small twist angle counterparts.

Quantitative Measurement of Breast Tumors Using Intravoxel Incoherent Motion (IVIM) MR Images.

Breast magnetic resonance imaging (MRI) is currently a widely used clinical examination tool. Recently, MR diffusion-related technologies, such as intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI), have been extensively studied by breast cancer researchers and gradually adopted in clinical practice. In this study, we explored automatic tumor detection by IVIM-DWI. We considered the acquired IVIM-DWI data as a hyperspectral image cube and used a well-known hyperspectral subpixel target detection technique: constrained energy minimization (CEM). Two extended CEM methods-kernel CEM (K-CEM) and iterative CEM (I-CEM)-were employed to detect breast tumors. The K-means and fuzzy C-means clustering algorithms were also evaluated. The quantitative measurement results were compared to dynamic contrast-enhanced T1-MR imaging as ground truth. All four methods were successful in detecting tumors for all the patients studied. The clustering methods were found to be faster, but the CEM methods demonstrated better performance according to both the Dice and Jaccard metrics. These unsupervised tumor detection methods have the advantage of potentially eliminating operator variability. The quantitative results can be measured by using ADC, signal attenuation slope, D*, D, and PF parameters to classify tumors of mass, non-mass, cyst, and fibroadenoma types.

Low uptake of isoniazid window prophylaxis in patients exposed to a health-care worker with pulmonary tuberculosis in a paediatric ward.

AIM: A nurse on a paediatric multidisciplinary ward was diagnosed with smear-positive pulmonary tuberculosis. Children <2 years old, immunocompromised, or >40 h of contact (n = 173) were contact-traced. METHODS: Children received clinical review, chest X-ray, tuberculin skin test (TST; <5 years old) and/or an interferon-gamma release assay (Quantiferon TB-Gold, ≥5 years old). Infants <6 months old or children <5 years old screened <2 months from exposure were recommended isoniazid window prophylaxis (WP) until a repeat TST at 6 months old or 8-10 weeks after the last exposure to the index case, respectively. Empiric treatment for latent tuberculosis infection (LTBI) was individually considered for immunocompromised patients. RESULTS: Of 173 children (135 immunocompetent, 38 immunocompromised), two were uncontactable, seven refused screening and two immunocompromised children excluded. Eight of 126 immunocompetent children were diagnosed with LTBI (initial TST positive n = 7, TST conversion n = 1); seven started isoniazid. Thirty-two of 36 immunocompetent children were recommended WP; 15 accepted (one non-compliant after 1 month). Six of seven immunocompromised children accepted empiric LTBI treatment due to severe immunosuppression/initial indeterminate Quantiferon TB-Gold result. Of 15 immunocompromised children offered WP, only five accepted. CONCLUSIONS: There was high acceptance of screening but low uptake of isoniazid WP in high-risk children exposed to pulmonary tuberculosis. Perception of exposure risk and chemoprophylaxis should be explored further.

Unveiling Atomic-Scale Moiré Features and Atomic Reconstructions in High-Angle Commensurately Twisted Transition Metal Dichalcogenide Homobilayers.

Twisting the angle between van der Waals stacked 2D layers has recently sparked great interest as a new strategy to tune the physical properties of the materials. The twist angle and associated strain profiles govern the electrical and optical properties of the twisted 2D materials, but their detailed atomic structures remain elusive. Herein, using combined atomic-resolution electron microscopy and density functional theory (DFT) calculations, we identified five unique types of moiré features in commensurately twisted 7a×7a transition metal dichalcogenide (TMD) bilayers. These stacking variants are distinguishable only when the moiré wavelength is short. Periodic lattice strain is observed in various commensurately twisted TMD bilayers. Assisted by Zernike polynomial as a hierarchical active-learning framework, a hexagon-shaped strain soliton network has been atomically unveiled in nearly commensurate twisted TMD bilayers. Unlike stacking-polytype-dependent properties in untwisted structures, the stacking variants have the same electronic structures that suggest twisted bilayer systems are invariant against interlayer gliding.

Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

Evidence mapping of interactions on concomitant use of Chinese medicine and platinum-based chemotherapy: a scoping review protocol.

BACKGROUND: The utilization of Chinese herbal medicine (CHM) has gained popularity and acceptance worldwide. Increasing use of CHM either as a stand-alone or an adjunctive treatment for cancers has given rise to increasing concern on potential herbal-drug reactions. Possible combinatory effects are important to be explored in evaluating the rationality of integrating CHM and chemotherapy in clinical practice. This study aims to update the current knowledge on herbal-drug interactions (HDI) of the commonly used platinum-based chemotherapy (PtC) in cancer patients. METHODS: Systemic searches will perform on online databases (English and Chinese) to identify papers from inception until December 2019 for inclusion into the review. The search strategy will be following PRISMA Scoping Reviews Checklist as a quality assurance step. All records retrieved will be screened by 2 independent reviewers. The preclinical studies and clinical studies that involve in assessing the concurrent use of CHM and PtC will be considered. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses will be used as scoping review framework. DISCUSSION: This scoping review will explore the compatibility or combination rule of CHM-PtC and assist in understanding HDI in CHM-PtC co-treatment. Identification of active properties in CHM's HDI and understanding pharmacokinetics and pharmacodynamic of the CHM alone or as co-treatment are essential for patients' safety profile. It will provide a new insight for future practice in cancer treatment. STUDY REGISTRATION: This protocol has been registered in the Research Register (https://www.researchregistry.com/) with an unique registration number: reviewregistry790.

Enhanced ultraviolet electroluminescence from ZnO nanoparticles via decoration of partially oxidized Al layer.

We construct the ZnO-based superluminescent light-emitting diodes (SLEDs) by spin-coating ZnO nano-particles onto p-GaN/sapphire substrate. By inserting another thin Al layer to form an n-ZnO/Al/n-ZnO/p-GaN sandwich structured SLD, the intensities of the photoluminescence and electroluminescence were greatly enhanced, which can be attributed to the surface plasmon resonance of this Al layer. The tendency of the intensities of the entire electroluminescence spectra shows a super-linearly behavior with increasing the forward bias. Besides, the spectral bandwidth is narrowed down enormously owing to the achievement of the SLD. Furthermore, the interfacial emissions between ZnO/GaN are effectively suppressed by partially oxidizing the Al layer.