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.

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.

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.

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.

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.

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.

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.

Nasal-type extranodal natural killer/T-cell lymphoma presenting with extensive leg ulcers.

Primary cutaneous T-cell lymphomas are rare and can be difficult to classify precisely. We present a case of extranodal natural killer (NK)/T-cell lymphoma in a previously healthy, immunocompetent man who presented with extensive necrotic leg ulcers and disseminated skin nodules. Immunohistochemical studies revealed that the tumour cells were positive for CD3, CD30, granzyme B and T-cell intracellular antigen-1, and negative for CD5 and CD56, with positive staining for Epstein-Barr virus (EBV) RNA on in situ hybridization. A diagnosis of extranodal NK/T-cell lymphoma was made, based on the presence of cytotoxic granules and positive EBV RNA staining. The patient was treated with a regimen of chemotherapy comprising corticosteroids, intravenous methotrexate, ifosphamide, L-asparaginase and etoposide with initial response.

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.

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.

Digital moiré interferometric investigations on the deformation gradients of enamel and dentine: an insight into non-carious cervical lesions.

OBJECTIVES: The objective of this study was to evaluate the biomechanical basis of non-carious cervical lesions by examining the patterns of deformation (strain) in the enamel and dentine. METHODS: The digital moiré interferometry is optics based non-destructive, whole-field experimental technique that provides whole-field strain information. Diffraction gratings (with a frequency of 1200 lines/mm) were transferred onto sagittal sections of human teeth, which were subsequently loaded compressively for loads ranging from 10 to 200 N at the incisal edge of the tooth. The acquired digital moiré fringe patterns were used to determine the in-plane deformation pattern in the enamel and the dentine in the direction parallel to the long axis (axial direction) and in the direction perpendicular to the long axis (lateral direction) of the tooth. RESULTS: It is observed that the enamel displayed marked strain gradients in the lateral direction, while the coronal dentine experienced marked strain gradients in the axial directions during compression. With the increase in applied loads, the strains in the enamel increased at the cervical edge (above the cemento-enamel junction) on the facial side, while the strains in the dentine increased below the cemento-enamel junction on the facial side. CONCLUSION: The enamel and dentine displayed unique in-plane deformation patterns in the axial and the lateral directions of the tooth. These experiments support the hypothesis that occlusal loading will contribute to cervical loss of dental hard tissues.

Nonproductive rearrangement of DNA topoisomerase I and II genes: correlation with resistance to topoisomerase inhibitors.

Topoisomerase inhibitors comprise an important group of agents that is used in cancer treatment. Because the development of resistance to cancer chemotherapeutic agents represents a major limitation of cancer chemotherapy, we investigated the mechanism of resistance by murine P388 leukemia to camptothecin (topoisomerase I inhibitor) or amsacrine (topoisomerase II inhibitor). The resistant cells contained reduced levels of topoisomerase activity and messenger RNA. The topoisomerase gene of these cells was rearranged (only in one allele) and hypermethylated. These topoisomerase gene alterations probably resulted in reduced transcription and, thus, enzyme production, which was correlated with resistance to the topoisomerase inhibitor.

Topoisomerase II alpha and topoisomerase II beta genes: characterization and mapping to human chromosomes 17 and 3, respectively.

Human cells contain two topoisomerase II isozymes named topo II alpha and topo II beta. The complementary DNAs for both enzymes have been cloned. The topo II alpha and topo II beta complementary DNAs hybridized to unique sequences of human, rodent, and chicken DNAs in Southern blots. The human topo II alpha gene has previously been mapped to chromosome 17. We confirmed the chromosomal location of topo II alpha and mapped the topo II beta gene to chromosome 3. In addition, topo II beta exhibits genetic polymorphism as has been reported for topoisomerases I and II alpha.

Nuclear tubulin of tissue culture cells.

Tubulin has been implicated as a nuclear protein because of the role it plays in mitosis. In this paper we examined the role of tubulin in the nuclei of nonmitotic cells. Tubulin was found distributed throughout the nucleus and particularly in association with the chromatin. It comprised about 6.5% of the nonhistone chromosomal proteins. Nuclear tubulin appeared to be nonmicrotubular in form. Fluorescence microscopy data on metaphase chromosomes revealed that tubulin was present on the outside of the chromosomes. These data suggest a structural role for chromatin-associated tubulin.

Studies on viral DNA protein complexes isolated at different times after infection of monkey kidney cells with simian virus 40.

The major protein components of the DNA complex, isolated from SV40-infected monkey cells, are the major viral structural polypeptide VP1 and cellular histones. At early times (24 h) after infection, VP1 is present in large amounts relative to histones, whereas at late times (48 h), the complex contains mostly histones. The amount of VP1 in the complex can be correlated to the amount of "free" VP1 present in the cells, i.e. VP1 not yet incorporated into virus particles. At early times about 40% of VP1 is "free" VP1; at late times, most of the VP1 is incorporated into virus particles. In contrast, viral DNA is produced in huge excess and only about 13% is incorporated into virions. In agreement with the above result, we find that only about 16% of the DNA in the DNA complex can be chased into virions. There is, apparently, no turnover of newly synthesized VP1 that is associated with the DNA complex at late times after infection.

Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study.

The diverse biological actions of extracellular nucleotides in tissues and cells are mediated by two distinct classes of P2 receptor, P2X and P2Y. The G protein-coupled P2Y receptors comprise at least six mammalian subtypes (P2Y(1,2,4,6,11,12)), all of which have been cloned from human tissues, as well as other species. The P2Y receptor subtypes differ in their pharmacological selectivity for various adenosine and uridine nucleotides, which overlap in some cases. Data concerning the mRNA expression patterns of five P2Y receptors (P2Y(1,2,4,6,11)) in different human tissues and cells are currently quite limited, while P2Y mRNA distribution in the human brain has not previously been studied. In this study, we have addressed this deficiency in receptor expression data by using a quantitative reverse transcription-polymerase chain reaction approach to measure the precise mRNA expression pattern of each P2Y receptor subtype in a number of human peripheral tissues and brain regions, from multiple individuals, as well as numerous human cell lines and primary cells. All five P2Y receptors exhibited widespread yet subtype-selective mRNA expression profiles throughout the human tissues, brain regions and cells used. Our extensive expression data indicate the many potentially important roles of P2Y receptors throughout the human body, and will help in elucidating the physiological function of each receptor subtype in a wide variety of human systems.

Cyclooxygenase 2 expression in nasopharyngeal carcinoma: immunohistochemical findings and potential implications.

BACKGROUND: Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials. AIMS: To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications. METHODS: Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry. RESULTS: Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p = 0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p = 0.423). CONCLUSION: COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.