Access to COVID-19 vaccination by socio-economic status in older Singaporean adults: a population-based cohort study.

OBJECTIVES: Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. STUDY DESIGN: Retrospective population-based cohort study. METHODS: Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021-14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). RESULTS: 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1-2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60-69 years: 0.75 [95% CI = 0.73-0.76] for the first booster; 0.81 [95% CI = 0.79-0.84] for the second booster). CONCLUSION: While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary.

Excess mortality after hip fracture: fracture or pre-fall comorbidity?

Comorbidity and hip fracture independently increased mortality risk for 9 years in both sexes, with a significant additive interaction in the first year among women and through 6 years among men. INTRODUCTION: Hip fracture is associated with a persistently elevated mortality risk, but it is unknown whether the elevated risk is due to the fracture or to pre-fracture comorbidity. METHODS: In a population-based study in Singapore with 9 years of follow-up, patients age > 50 with first hip fracture from 2008 to 2017 were pair-matched to a cohort without hip fracture by age, sex, ethnicity, and pre-fracture Charlson Comorbidity Index (CCI). We investigated additive interaction using the relative excess risk due to interaction (RERI) and multiplicative interaction using the ratio of relative risks. RESULTS: Twenty-two thousand five hundred ninety of 22,826 patients with a first hip fracture in 2008-2017 were successfully matched. Hip fracture and comorbidity independently increased mortality risk for 9 years in both sexes. After adjustment for comorbidity, excess mortality risk continued to persist for 9 years post-fracture in both men and women. Women with a hip fracture and pre-fracture CCI > 4 had a higher relative risk (RR) of mortality at 9 years of 3.29 [95% confidence interval (CI) 3.01, 3.59] than those without comorbidity (RR 1.51, 95%CI 1.36, 1.68) compared to the referent without hip fracture or comorbidity. An additive interaction between hip fracture and pre-fracture CCI > 4 was observed in the first post-fracture year` [relative excess risk due to interaction (RERI) 1.99, 95%CI 0.97, 3.01]. For men with CCI ≥ 4, the positive additive interaction was observed through 6 years. CONCLUSIONS: Excess mortality risks post-fracture are attributable to both the fracture and pre-fracture comorbidity. Early interventions in hip fracture patients with high comorbidity could reduce their excess mortality.

Cost-effectiveness of FRAX®-based intervention thresholds for management of osteoporosis in Singaporean women.

Cost-effectiveness analysis of FRAX® intervention thresholds (ITs) in Singaporean women > 50 years of age showed that generic alendronate was cost-effective at age-dependent major osteoporotic fracture (MOF) IT from the ages of 65 years for both full and real-world adherence whilst hip fracture (HF) ITs were cost-effective from the ages of 60 and 65 years. Alendronate was cost-effective irrespective of age only at fixed MOF IT of 14% and HF IT of 3.5%. INTRODUCTION: FRAX®-based intervention thresholds (ITs) were recently identified for osteoporosis management in Singapore. This study aimed to assess the cost-effectiveness of ITs in Singaporean women over the age of 50 years. METHODS: A validated Markov microsimulation model was used to estimate the lifetime healthcare costs (SGD2019) per quality-adjusted life-years (QALY) of generic alendronate compared with no treatment. Cost-effectiveness of age-dependent FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) ITs was explored. In addition, ITs that would lead to cost-effectiveness were computed. Fracture incidence and cost data were obtained from the Ministry of Health and a previously published Singaporean study. A cost-effectiveness threshold of SGD 62,500/QALY gained was used, based conservatively on 0.7 times the Singapore GDP per capita. RESULTS: Generic alendronate was shown to be cost-effective at MOF ITs from the ages of 65 years, while HF ITs were cost-effective from the ages of 60 and 65 years, assuming full and real-world adherence, respectively. A 14% MOF and a 3.5% HF ITs were required for alendronate to be cost-effective above 50 years. CONCLUSION: This study suggests that the treatment of Singaporean women with alendronate is cost-effective at age-dependant FRAX® intervention thresholds at 65 years and older. Furthermore, identifying women at any age above 50 years with a 10-year risk of MOF or HF of 14% or 3.5% would lead to efficient use of resources. Cost-effective access to therapy for patients at high fracture probability based on FRAX® could contribute to reduce the growing burden of osteoporotic fractures in Singapore.

Energy conservation at an optical temporal boundary.

The temporal boundary appears as a novel phenomenon in a wide range of optical devices and systems, such as the photonic crystal, metamaterials, optical microcavity, and modulator, with a dynamic medium whose refractive index changes across the boundary. However, the validation of electromagnetic energy conservation was considered in violation for the optical temporal boundary traditionally. Here a new energy space-time scheme is proposed for an optical pulse in a medium with the temporal boundary. From the Poynting theory, the electromagnetic energy is investigated based on a one-dimensional model under the assumption of impedance matching. Furthermore, the results demonstrate that a more general conservation of energy is validated in a time domain for the ideal scenario. A new invariant quantity of spatial energy in the optical medium is further obtained. The numerical results are in agreement with the theory of the temporal boundary. The conservative process of energy transportation across the optical temporal boundary is clarified and confirmed.

The Long-Term Impact of Functional Disability on Hospitalization Spending in Singapore.

Singapore is one of the fastest-aging populations due to increased life expectancy and lowered fertility. Lifestyle changes increase the burden of chronic diseases and disability. These have important implications for social protection systems. The goal of this paper is to model future functional disability and healthcare expenditures based on current trends. To project the health, disability and hospitalization spending of future elders, we adapted the Future Elderly Model (FEM) to Singapore. The FEM is a dynamic Markov microsimulation model developed in the US. Our main source of population data was the Singapore Chinese Health Study (SCHS) consisting of 63,000 respondents followed up over three waves from 1993 to 2010. The FEM model enables us to investigate the effects of disability compounded over the lifecycle and hospitalization spending, while adjusting for competing risk of multi-comorbidities. Results indicate that by 2050, 1 in 6 elders in Singapore will have at least one ADL disability and 1 in 3 elders will have at least one IADL disability, an increase from 1 in 12 elders and 1 in 5 elders respectively in 2014. The highest prevalence of functional disability will be in those aged 85 years and above. Lifetime hospitalization spending of elders aged 55 and above is US$24,400 (30.2%) higher among people with functional disability compared to those without disability. Policies that successfully tackle diabetes and promote healthy living may reduce or delay the onset of disability, leading to potential saving. In addition, further technological improvements may reduce the financial burden of disability.

Hip fractures in Singapore: ethnic differences and temporal trends in the new millennium.

Despite an increase in absolute numbers, the age-standardized incidence of hip fractures in Singapore declined in the period 2000 to 2017. Among the three major ethnic groups, Chinese women had the highest fracture rates but were the only group to show a temporal decline. INTRODUCTION: A study published in 2001 predicted a 30-50% increase in Singapore hip fracture incidence rates over the ensuing 30 years. To test that prediction, we examined the incidence of hip fracture in Singapore from 2000 to 2017. METHODS: We carried out a population-based study of hip fractures among Singapore residents aged ≥ 50 years. National medical insurance claims data were used to identify admissions with a primary discharge diagnosis of hip fracture. Age-adjusted rates, based on the age distribution of the Singapore population of 2000, were analyzed separately by sex and ethnicity (Chinese, Malay, or Indian). RESULTS: Over the 18-year study period, 36,082 first hip fractures were recorded. Total hip fracture admissions increased from 1487 to 2729 fractures/year in the years 2000 to 2017. Despite this absolute increase, age-adjusted fracture rates declined, with an average annual change of - 4.3 (95% CI - 5.0, - 3.5) and - 1.1 (95% CI - 1.7, - 0.5) fractures/100,000/year for women and men respectively. Chinese women had 1.4- and 1.9-fold higher age-adjusted rates than Malay and Indian women: 264 (95% CI 260, 267) versus 185 (95% CI 176, 193) and 141 (95% CI 132, 150) fractures/100,000/year, respectively. Despite their higher fracture rates, Chinese women were the only ethnic group exhibiting a decline, most evident in those ≥ 85 years, in age-adjusted fracture rate of - 5.3 (95% CI - 6.0, - 4.5) fractures/100,000/year. CONCLUSION: Although the absolute number of fractures increased, steep drops in elderly Chinese women drove a reduction in overall age-adjusted hip fracture rates. Increases in the older population will lead to a rise in total number of hip fractures, requiring budgetary planning and new preventive strategies.

Effect of staining beverages on color and translucency of CAD/CAM composites.

This study investigated the color (ΔE) and translucency changes (ΔTP) of CAD/CAM composites after exposure to staining solutions using both spectrophotometer and shade-matching device. Direct (Filtek Z350XT [ZT]), indirect (Shofu Ceramage [CE]) and CAD/CAM (Shofu HC Block [HC], Lava Ultimate [LU], Vita Enamic [EN]) composite specimens measuring 12 × 14 × 1.5 mm were fabricated, divided into five groups (n = 8), and immersed in cola, tea, coffee, red wine, distilled water (control) at 37°C for 7 days. Color parameters were determined with both spectrophotometer and shade-taking device at baseline and 1 week. Delta E (ΔE) with white and black backgrounds, and Delta TP (ΔTP) were computed. Statistical testing was performed with ANOVA and Tukey post hoc test (P < .05). Mean ΔE (white) values ranged from 0.20 ± 0.06 to 12.26 ± 1.95 while mean ΔE (black) varied from 0.22 ± 0.11 to 14.21 ± 2.37. Mean ΔTP values ranged from 0.13 ± 0.17 to -3.87 ± 2.16. CAD/CAM composites fared better in red wine than direct and indirect materials. Clinically perceptible color changes (ΔE > 3.3) were observed for almost all materials when exposed to wine, coffee and tea. Direct, indirect, and CAD/CAM composites are all susceptible to various degrees of discoloration and translucency changes after exposure to staining beverages. Red wine caused the most discoloration and translucency changes. Limitations of these materials must be considered when placing an aesthetic restoration. CLINICAL SIGNIFICANCE: Direct, indirect, and CAD/CAM composites are all susceptible to various degrees of discoloration and translucency changes after exposure to staining beverages. Red wine generally caused the most discoloration and translucency changes. Although CAD/CAM composites were more color stable than direct and indirect materials when exposed to red wine, color changes were still clinically perceptible.

Disseminated Cutaneous Trichosporonosis in an Adult Bone Marrow Transplant Patient.

The Trichosporon species are yeast-like opportunistic pathogens in immunocompromised patients. Trichosporon asahii infections have been reported in pediatric bone marrow transplant (BMT) patients. However, its incidence is low in the adult literature. A 52-year-old Chinese woman who was diagnosed with acute myeloid leukemia received induction chemotherapy and underwent allogenic bone marrow transplant, which was complicated by a relapse and required salvage chemotherapy. She developed persistent non-neutropenic fever secondary to presumed hepatosplenic candidiasis. Antifungal therapy with fluconazole and anidulafungin was administered. She remained febrile and tender dusky nodules appeared over all the four limbs. Histopathological examination and fungal culture identified T. asahii. Oral voriconazole was initiated with complete resolution of her lesions. The Trichosporon species is a frequently isolated yeast species from cancer patients. Voriconazole has become the first choice agent against Trichosporon. We highlight the increased awareness and clinical suspicion required for diagnosis and subsequent management in similar adult patients.

Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and cationic liposome-bearing microbubbles.

We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin-avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor ß1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (P<0.01). These data suggest that delivery of an artificial miRNA targeted against CTGF using ultrasound-targeted cationic liposome-bearing microbubble destruction may be an efficacious therapeutic method to ameliorate hepatic fibrosis.

Sinonasal blue naevus: case report and clinicopathological review.

OBJECTIVE: To highlight the important clinical and histological features of sinonasal blue naevi. METHODS: A case of blue naevus of the nasal cavity is described (including endoscopic and histological pictures) and the existing literature is reviewed. RESULTS: There have been five reported cases (including the presented case). Clinically, sinonasal blue naevi are heavily pigmented lesions that are small and asymptomatic. Histopathologically, blue naevi exhibit heavily pigmented dendritic melanocytes that are never abnormal in form. CONCLUSION: Blue naevus should be a differential diagnosis for pigmented lesions within the sinonasal cavity, despite its rarity. It may be initially suspected by its small size and asymptomatic nature. However, histological examination is required for definitive diagnosis, looking for the key microscopic features described above.

In vivo and in vitro studies on the roles of neutrophil extracellular traps during secondary pneumococcal pneumonia after primary pulmonary influenza infection.

Seasonal influenza virus infections may lead to debilitating disease, and account for significant fatalities annually worldwide. Most of these deaths are attributed to the complications of secondary bacterial pneumonia. Evidence is accumulating to support the notion that neutrophil extracellular traps (NETs) harbor several antibacterial proteins, and trap and kill bacteria. We have previously demonstrated the induction of NETs that contribute to lung tissue injury in severe influenza pneumonia. However, the role of these NETs in secondary bacterial pneumonia is unclear. In this study, we explored whether NETs induced during pulmonary influenza infection have functional significance against infections with Streptococcus pneumoniae and other bacterial and fungal species. Our findings revealed that NETs do not participate in killing of Streptococcus pneumoniae in vivo and in vitro. Dual viral and bacterial infection elevated the bacterial load compared to animals infected with bacteria alone. Concurrently, enhanced lung pathogenesis was observed in dual-infected mice compared to those challenged with influenza virus or bacteria alone. The intensified NETs in dual-infected mice often appeared as clusters that were frequently filled with partially degraded DNA, as evidenced by punctate histone protein staining. The severe pulmonary pathology and excessive NETs generation in dual infection correlated with exaggerated inflammation and damage to the alveolar-capillary barrier. NETs stimulation in vitro did not significantly alter the gene expression of several antimicrobial proteins, and these NETs did not exhibit any bactericidal activity. Fungicidal activity against Candida albicans was observed at similar levels both in presence or absence of NETs. These results substantiate that the NETs released by primary influenza infection do not protect against secondary bacterial infection, but may compromise lung function.

Proliferating tricholemmal tumour: clinicopathological aspects of a case.

We report the case of a 49-year-old man who presented with an enlarging mass over his occipital scalp. The clinical impression was either a squamous cell carcinoma or an unusual adnexal tumour. A wide excision was performed with skin grafting. Gross examination revealed a large exophytic tumour mass measuring 10 cm. Histopathological examination showed a circumscribed, well-differentiated squamoproliferative lesion with a lobulated architecture. Clear cell features, pilar-type keratinisation, microcalcifications and the presence of mucinous degeneration were noted. A diagnosis of proliferating tricholemmal tumour was made. This entity incorporates a spectrum of lesions, ranging from the mostly benign proliferating tricholemmal cyst to tumours having more atypical cellular and invasive features, the latter features correlating with an increased capacity for aggressive behaviour. Management-wise, such tumours require complete excision with follow-up. As the tumours are often large in size at presentation, reconstruction is required.

The role of reactive oxygen species and autophagy in safingol-induced cell death.

Safingol is a sphingolipid with promising anticancer potential, which is currently in phase I clinical trial. Yet, the underlying mechanisms of its action remain largely unknown. We reported here that safingol-induced primarily accidental necrotic cell death in MDA-MB-231 and HT-29 cells, as shown by the increase in the percentage of cells stained positive for 7-aminoactinomycin D, collapse of mitochondria membrane potential and depletion of intracellular ATP. Importantly, safingol treatment produced time- and concentration-dependent reactive oxygen species (ROS) generation. Autophagy was triggered following safingol treatment, as reflected by the formation of autophagosomes, acidic vacuoles, increased light chain 3-II and Atg biomarkers expression. Interestingly, scavenging ROS with N-acetyl-L-cysteine could prevent the autophagic features and reverse safingol-induced necrosis. Our data also suggested that autophagy was a cell repair mechanism, as suppression of autophagy by 3-methyladenine or bafilomycin A1 significantly augmented cell death on 2-5 µM safingol treatment. In addition, Bcl-xL and Bax might be involved in the regulation of safingol-induced autophagy. Finally, glucose uptake was shown to be inhibited by safingol treatment, which was associated with an increase in p-AMPK expression. Taken together, our data suggested that ROS was the mediator of safingol-induced cancer cell death, and autophagy is likely to be a mechanism triggered to repair damages from ROS generation on safingol treatment.

Multiple idiopathic cervical resorption: case report and discussion of management options.

AIM: To present a case of cervical root resorption affecting all teeth and resulting in multiple tooth loss. SUMMARY: A healthy 33-year-old Chinese male, with no contributory medical or family/social history, presented with generalized cervical root resorption. Lesions varied in severity amongst teeth and even involved an impacted third molar. All cervical root surfaces were affected and lesions often extended coronally, undermining enamel. CBCT demonstrated that the lesions were more extensive and more widely distributed than was seen using conventional radiography. Bone extended into many resorptive defects but without clinical evidence of ankylosis. Periodontal probing, pulp testing, percussion sound and mobility were within normal limits. Key learning points • Aetiology of the generalized idiopathic cervical root resorption is uncertain. • Management is complex, and options have included surgical exposure and restoration of affected sites, extraction and submergence of affected roots. • A staged approach involving early intervention with restoration of resorptive defects, followed by progressive extraction and replacement with implant-supported prostheses is recommended.

Foetal peak systolic velocity in the middle cerebral artery: an Asian reference range.

INTRODUCTION: The aim of this study was to establish reference values of peak systolic blood flow velocity measurement in the foetal middle cerebral artery (MCA-PSV) in the local Asian obstetric population and to compare our reference ranges with those of previously-published studies. METHODS: 329 normal pregnant women attending the outpatient antenatal clinics of the Department of Obstetrics and Gynaecology in the Singapore General Hospital underwent Doppler ultrasonography at least once between 16 and 40 weeks' gestation. The blood flow velocity recordings from the foetal middle cerebral artery were obtained. New reference ranges were constructed by regressing each parameter on gestational age. RESULTS: New reference ranges for foetal middle cerebral artery with gestation were constructed for an Asian population. Our reference curves were compared with that of a previously-constructed one. CONCLUSION: MCA-PSV increases with advancing gestational age. There appear to be differences between Asian and non-Asian reference ranges for MCA-PSV.