Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age.

BACKGROUND: Since it was first identified in early November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread quickly and replaced the B.1.617.2 (delta) variant as the dominant variant in many countries. Data on the real-world effectiveness of vaccines against the omicron variant in children are lacking. METHODS: In a study conducted from January 21, 2022, through April 8, 2022, when the omicron variant was spreading rapidly, we analyzed data on children in Singapore who were 5 to 11 years of age. We assessed the incidences of all reported SARS-CoV-2 infections (confirmed on polymerase-chain-reaction [PCR] assay, rapid antigen testing, or both), SARS-CoV-2 infections confirmed on PCR assay, and coronavirus disease 2019 (Covid-19)-related hospitalizations among unvaccinated, partially vaccinated (≥1 day after the first dose of vaccine and up to 6 days after the second dose), and fully vaccinated children (≥7 days after the second dose). Poisson regression was used to estimate vaccine effectiveness from the incidence rate ratio of outcomes. RESULTS: A total of 255,936 children were included in the analysis. Among unvaccinated children, the crude incidence rates of all reported SARS-CoV-2 infections, PCR-confirmed SARS-CoV-2 infections, and Covid-19-related hospitalizations were 3303.5, 473.8, and 30.0 per 1 million person-days, respectively. Among partially vaccinated children, vaccine effectiveness was 13.6% (95% confidence interval [CI], 11.7 to 15.5) against all SARS-CoV-2 infections, 24.3% (95% CI, 19.5 to 28.9) against PCR-confirmed SARS-CoV-2 infection, and 42.3% (95% CI, 24.9 to 55.7) against Covid-19-related hospitalization; in fully vaccinated children, vaccine effectiveness was 36.8% (95% CI, 35.3 to 38.2), 65.3% (95% CI, 62.0 to 68.3), and 82.7% (95% CI, 74.8 to 88.2), respectively. CONCLUSIONS: During a period when the omicron variant was predominant, BNT162b2 vaccination reduced the risks of SARS-CoV-2 infection and Covid-19-related hospitalization among children 5 to 11 years of age.

Long-term Cardiovascular, Cerebrovascular, and Other Thrombotic Complications in COVID-19 Survivors: A Retrospective Cohort Study.

BACKGROUND: Growing evidence suggests that some coronavirus disease 2019 (COVID-19) survivors experience a wide range of long-term postacute sequelae. We examined the postacute risk and burden of new-incident cardiovascular, cerebrovascular, and other thrombotic complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a highly vaccinated multiethnic Southeast Asian population, during Delta predominance. METHODS: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals who had a positive SARS-CoV-2 test between 1 September and 30 November 2021 when Delta predominated community transmission. Concurrently, we constructed a test-negative control group by enrolling individuals between 13 April 2020 and 31 December 2022 with no evidence of SARS-CoV-2 infection. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular, cerebrovascular, and other thrombotic complications using doubly robust competing-risks survival analysis. Risks were reported using 2 measures: hazard ratio (HR) and excess burden (EB) with 95% confidence intervals. RESULTS: We included 106 012 infected cases and 1 684 085 test-negative controls. Compared with the control group, individuals with COVID-19 exhibited increased risk (HR, 1.157 [1.069-1.252]) and excess burden (EB, 0.70 [.53-.88]) of new-incident cardiovascular and cerebrovascular complications. Risks decreased in a graded fashion for fully vaccinated (HR, 1.11 [1.02-1.22]) and boosted (HR, 1.10 [.92-1.32]) individuals. Conversely, risks and burdens of subsequent cardiovascular/cerebrovascular complications increased for hospitalized and severe COVID-19 cases (compared to nonhospitalized cases). CONCLUSIONS: Increased risks and excess burdens of new-incident cardiovascular/cerebrovascular complications were reported among infected individuals; risks can be attenuated with vaccination and boosting.

Risks of SARS-CoV-2 JN.1 infection and COVID-19 associated emergency-department (ED) visits/hospitalizations following updated boosters and prior infection: a population-based cohort study.

INTRODUCTION: Data on protection afforded by updated COVID-19 vaccines (bivalent/XBB 1.5 monovalent) against the emergent JN.1 variant remains limited. METHODS: We conducted a retrospective population-based cohort study amongst all boosted Singaporeans aged ≥18 years during a COVID-19 wave predominantly driven by JN.1, from 26th November 2023 to 13th January 2024. Multivariable Cox regression was utilised to assess risk of SARS-CoV-2 infection and COVID-19 associated emergency-department (ED) visits/hospitalizations, stratified by vaccination status/prior infection; with individuals last boosted ≥1 year utilized as the reference category. Vaccination and infection status were classified using national registries. RESULTS: 3,086,562 boosted adult Singaporeans were included in the study population, accounting for 146,863,476 person-days of observation. During the JN.1 outbreak, 28,160 SARS-CoV-2 infections were recorded, with 2,926 hospitalizations and 3,747 ED-visits. Compared with individuals last boosted ≥1 year prior with ancestral monovalent vaccines, receipt of an updated XBB.1.5 booster 8-120 days prior was associated with lower risk of JN.1 infection (adjusted-hazard-ratio, aHR = 0.59[0.52-0.66]), COVID-19 associated ED-visits (aHR = 0.50[0.34-0.73]) and hospitalizations(aHR = 0.58[0.37-0.91]), while receipt of a bivalent booster 121-365 days prior was associated with lower risk of JN.1 infection (aHR = 0.92[0.88-0.95]) and ED-visits (aHR = 0.80[0.70-0.90]). Lower risk of COVID-19 hospitalization during the JN.1 outbreak (aHR = 0.57[0.33-0.97]) was still observed following receipt of an updated XBB.1.5 booster 8-120 days prior, even when analysis was restricted to previously infected individuals. CONCLUSION: Recent receipt of updated boosters conferred protection against SARS-CoV-2 infection and ED-visits/hospitalization during a JN.1 variant wave, in both previously infected and uninfected individuals. Annual booster doses confer protection during COVID-19 endemicity.

Cost-effectiveness analysis of continuous positive airway pressure treatment for obstructive sleep apnea in Singapore from a health system perspective.

This study assessed the cost-effectiveness of continuous positive airway pressure treatment for obstructive sleep apnea in Singapore from a health system perspective. The analysis evaluated a 5-year care pathway using a Markov model, considering per-patient costs of treatment, health system cost savings of obstructive sleep apnea and attributed conditions, the effectiveness measured in disability-adjusted life years with a discount rate of 3% and a weighted 5-year continuous positive airway pressure adherence of 74.1% from Singapore studies. Per-patient costs of treatment were from a large public hospital in Singapore. Efficacy of continuous positive airway pressure treatment, health system costs and disability-adjusted life years were obtained from literature; costs are in US dollars. We conducted probabilistic sensitivity analysis, one-way sensitivity analysis and what-if analysis. Based on a willingness-to-pay threshold of US $50,000 per disability-adjusted life year in USA, continuous positive airway pressure therapy was highly cost-effective, with an incremental cost-effectiveness ratio of $13,822 per disability-adjusted life year averted. Compared with the annual total costs of $856 for patients with continuous positive airway pressure treatment diagnosed by an inpatient sleep study, the total costs for those diagnosed by a home sleep test were $625, resulting in a remarkable 27% reduction per patient per year. One-way sensitivity analysis indicated that costs of treatment, effectiveness of continuous positive airway pressure treatment and adherence had a higher impact on the cost-effectiveness of continuous positive airway pressure therapy. The what-if analysis suggested that for continuous positive airway pressure treatment to be cost-effective, adherence rate should be at least 16.1%. These findings provide valuable insights for policymakers in making informed decisions on funding diagnosis and continuous positive airway pressure therapy within Singapore's healthcare system.

Forecasting upper respiratory tract infection burden using high-dimensional time series data and forecast combinations.

Upper respiratory tract infections (URTIs) represent a large strain on primary health resources. To mitigate URTI transmission and public health burdens, it is important to pre-empt and provide forward guidance on URTI burden, while taking into account various facets which influence URTI transmission. This is so that appropriate public health measures can be taken to mitigate strain on primary care resources. This study describes a new approach to forecasting URTIs which can be used for national public health resource planning. Specifically, using environmental and disease data comprising more than 1000 dimensions, we developed sub-models which optimizes model explainability, in-sample model fit, predictive accuracy and combines many weaker predictors over a 2-month time horizon to generate direct, point forecasts over a 1-8 week ahead forecast horizon. Predictive performance was evaluated using rolling out-of-sample forecast assessment within both periods with/without structural breaks in transmission over the period of 2012-2022. We showed that forecast combinations of 5 other forecasting models had better and more consistent predictive performance than other modelling approaches, over periods with and without structural breaks in transmission dynamics. Furthermore, epidemiological analysis on high dimensional data was enabled using post-selection inference, to show the dynamic association between lower temperature, increases in past relative humidity and absolute humidity and increased URTIs attendance. The methods proposed can be used for outbreak preparedness and guide healthcare resource planning, in both stable periods of transmission and periods where structural breaks in data occur.

Differences in virus and immune dynamics for SARS-CoV-2 Delta and Omicron infections by age and vaccination histories.

Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data.We found that Omicron had higher R0,within values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections.This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults.

INTRODUCTION: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. METHODS: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. RESULTS: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24-3.56) and 0.45 per 100 person-years (95% CI: 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62-4.84) and 0.75 per 100 person-years (95% CI: 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56-3.16) and 0.21 per 100 person-years (95% CI: 0.067-0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017). CONCLUSION: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

Percutaneous cholecystostomy in acute complicated versus uncomplicated cholecystitis; is there a difference in outcomes? A single-center experience.

BACKGROUND: Percutaneous cholecystostomy (PC) is a therapeutic intervention for acute cholecystitis. The benefits of cholecystostomy have been demonstrated in the medical literature, with up to 90% of acute cholecystitis cases shown to resolve postoperatively, and only 40% of patients subsequently undergoing an interval cholecystectomy. PURPOSE: To compare the survival outcomes between acute complicated and uncomplicated cholecystitis in patients undergoing PC as an initial intervention, as there is a paucity of evidence in the literature on this perspective. MATERIAL AND METHODS: A retrospective search was conducted of all patients who underwent PC for acute cholecystitis between August 2016 and December 2020 at a tertiary institution. A total of 100 patients were included in this study. RESULTS: The outcome, in the form of 30-day mortality, 90-day mortality, being alive after six months, and reintervention, was compared between complicated and uncomplicated cases using the chi-square test or Fisher's exact test. There was no statistically significant difference in any of the compared outcomes. The only variable that showed a statistically significant association with the risk of mortality was acute kidney injury (AKI) at admission. Patients who had stage 1, 2, or 3 AKI had a higher hazard for mortality as compared to patients with no kidney disease. CONCLUSION: Our results demonstrate that PC is a safe and effective procedure. Mortality is not affected by the presence of complications. The results have, however, highlighted the importance of recognizing and treating AKI, an independent risk factor affecting mortality.

The Addition of a Non-Steroidal Anti-Inflammatory Drug (NSAID) in Local Infiltration Analgesia During Total Knee Arthroplasty Increases the Risk of Acute Kidney Injury in Patients Who Have Renal Impairment: A Propensity-Matched Retrospective Cohort Study.

BACKGROUND: Local infiltration analgesia (LIA) is a crucial component of pain management during total knee arthroplasty (TKA). Various formulations of the LIA drug cocktail have been described, with non-steroidal anti-inflammatory drugs (NSAIDs) commonly included. Although NSAIDs are highly effective in improving postoperative pain, they are associated with adverse renal, gastrointestinal, and cardiovascular effects. This study aimed to investigate whether the addition of an NSAID in LIA affects the incidence of acute kidney injury (AKI) in TKA patients, especially those who have pre-existing renal impairment. The secondary aim was to determine overall AKI incidence. METHODS: A retrospective cohort study was conducted on elective, primary TKA patients in a single tertiary institution between January 2020 and April 2024. Data was obtained from a prospectively collected institutional knee arthroplasty registry. Patients were administered LIA intraoperatively, with or without an NSAID (30 mg of ketorolac). The study population was divided into two subpopulations, patients who did or did not have chronic kidney disease (CKD), and analyzed separately. Propensity matching was performed on the CKD group, correcting for age, sex, BMI, ASA score, and presence of diabetes mellitus/hypertension. The outcome of interest was the incidence of AKI. A t-test or Chi-square test was used, where appropriate, to determine the statistical significance of the results. RESULTS: In patients who had CKD (n = 114), the presence of ketorolac in LIA was associated with a higher AKI incidence (12.7 versus 2.0%, P = 0.041). In patients who did not have CKD (n = 870), the presence of ketorolac in LIA was not associated with a higher AKI incidence (2.0 versus 1.9%, P = 1.0). Overall AKI incidence was 2.6%. CONCLUSION: In patients who have CKD, orthopaedic surgeons should be highly cautious of administering ketorolac in LIA during TKA, as it is associated with a higher risk of AKI. Patients who have normal renal function can be safely given ketorolac in LIA without an elevated risk of AKI. Further studies are needed to examine AKI incidence when other NSAIDs are used in LIA.

Long-term Real-world Protection Afforded by Third mRNA Doses Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections, Coronavirus Disease 19-related Emergency Attendances and Hospitalizations Amongst Older Singaporeans During an Omicron XBB Wave.

BACKGROUND: Literature on long-term real-world vaccine effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster vaccines (up to and beyond 360 days) is scarce. We report estimates of protection against symptomatic infection, emergency department (ED) attendances and hospitalizations up to and beyond 360 days post-receipt of booster messenger RNA (mRNA) vaccines among Singaporeans aged ≥60 years during an Omicron XBB wave. METHODS: We conducted a population-based cohort study including all Singaporeans aged ≥60 years with no documented prior SARS-CoV-2 infection who had previously received ≥3 doses of mRNA vaccines (BNT162b2/mRNA-1273), over a 4-month period during transmission of Omicron XBB. We reported the adjusted incidence-rate-ratio (IRR) for symptomatic infections, ED attendances and hospitalizations at different time-intervals from both first and second boosters, using Poisson regression; with the reference group being those who received their first booster 90 to 179 days prior. RESULTS: In total, 506 856 boosted adults were included, contributing 55 846 165 person-days of observation. Protection against symptomatic infections among those who received a third vaccine dose (first booster) waned after 180 days with increasing adjusted IRRs; however, protection against ED attendances and hospitalizations held up, with comparable adjusted IRRs with increasing time from third vaccine doses (≥360 days from third dose: adjusted IRR [ED attendances] = 0.73, 95% confidence interval [CI] = .62-.85; adjusted IRR [hospitalization] = 0.58, 95% CI = .49-.70). CONCLUSIONS: Our results highlight the benefit of a booster dose in reducing ED attendances and hospitalizations amongst older adults aged ≥60 years with no documented prior SARS-CoV-2 infection, during an Omicron XBB wave; up to and beyond 360 days post-booster. A second booster provided further reduction.

Singapore KneE osTeoarthritis CoHort (SKETCH): protocol for a multi-centre prospective cohort study.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of global disability. The understanding of the role of psychosocial factors in knee OA outcomes is still evolving particularly in an Asian context. The primary aim of this study is to explore psychosocial factors that prognosticate short and long-term clinical outcomes, productivity, and healthcare utilization in patients with knee OA. Secondary aims are to explore the mediation and directional relationships and the role it plays in predicting the discordance between self-reported measures (SRM), physical-performance measures (PPMs) and objective clinical parameters. METHODS: A multi-centre prospective cohort study of community ambulant knee OA patients seeking treatment in the tertiary healthcare institutions in Singapore will be conducted. Patients with secondary arthritis, significant cognitive impairment, severe medical comorbidities or previous knee arthroplasty will be excluded. Primary clinical outcome measure is the Knee injury and OA Outcome Score-12 (KOOS-12). Baseline characteristics include sociodemographic status, arthritis status including symptom duration and radiographic severity, comorbidities and functional status through Charlson Comorbidities Index (CCI), Barthel Index (BI) and Parker Mobility Score (PMS). Psychosocial variables include social support, kinesiophobia, negative affect, self-efficacy, injustice, chronic illness shame and the built environment. Clinical outcomes include quality of life, physical performance, global assessment, satisfaction and physical activity levels. Productivity and healthcare utilization will be assessed by a modified OA Cost and Consequences Questionnaire (OCC-Q) and the Work Productivity and Activity Impairment Questionnaire (WPAI). Variables will be collected at baseline, 4, 12 months and yearly thereafter. Regression, mediation and structural equation modelling will be used for analysis. DISCUSSION: Results will allow contextualization, identification, and phenotyping of the critical (and potentially modifiable) psychosocial parameters that predict positive clinical outcomes in the OA population to guide optimization and refinement of healthcare and community. This will facilitate: 1. identification of high-risk knee OA subpopulations that will likely experience poor outcomes and 2. formulation of targeted multidisciplinary comprehensive approaches to address these psychosocial factors to optimize non-surgical treatment care, maximize functional outcomes and create more value-based care model for knee OA. ETHICS AND DISSEMINATION: The study has been registered under clinicaltrials.gov registry (Identifier: NCT04942236).

The economic burden of mental disorders among adults in Singapore: evidence from the 2016 Singapore Mental Health Study.

BACKGROUND: Little is known about the economic burden of mental disorders in multiethnic Asian populations. AIMS: The study aimed to estimate the economic cost of mental disorders in Singapore using data from the second Singapore Mental Health Study (SMHS 2016). METHOD: The SMHS 2016 is a nationally representative survey of the Singapore Resident population aged 18 years and above. Data on mental disorders and healthcare resource utilization were obtained from the World Mental Health Composite International Diagnostic Interview and the adapted version of the Client Service Receipt Inventory. RESULTS: The costs of visits to a restructured hospital doctor, other private health workers, accident and emergency, and intermediate and long-term care services and productivity losses tend to be much higher in those with mental disorders than those without mental disorders. The average annual excess cost associated with mental disorders per person was estimated to be S$3938.9 (95% CI, S$-100.8-S$7978.7). Extrapolation of these excess costs to the population suggests that the incremental costs of mental disorders in Singapore is about S$1.7 billion per year. CONCLUSION: This study provides evidence of the substantial burden of mental disorders on Singaporean society - both in terms of direct medical costs and loss of productivity costs.

Comparative Effectiveness of mRNA and Inactivated Whole-Virus Vaccines Against Coronavirus Disease 2019 Infection and Severe Disease in Singapore.

Compared with individuals vaccinated with Pfizer-BioNTech/Comirnaty, recipients of Sinovac-CoronaVac and Sinopharm were 2.37 (95% CI, 2.29-2.46) and 1.62 (95% CI, 1.43-1.85) times more likely to be infected with coronavirus disease 19, respectively, while individuals vaccinated with Moderna were 0.42 (95% CI, 0.25-0.70) times less likely to develop severe disease.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Pediatric Age on Delta Variant Household Transmission.

BACKGROUND: In Singapore, quarantine of all close contacts with entry and exit polymerase chain reaction testing enabled evaluation of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and pediatric age on transmission of the Delta variant. METHODS: This retrospective cohort study included all household close contacts between 1 March 2021 and 31 August 2021. RESULTS: Among 8470 Delta variant-exposed contacts linked to 2583 indices, full-vaccination of the index with BNT162b2 or mRNA-1273 was associated with reduction in acquisition by contacts (adjusted odds ratio [aOR], 0.56; 95% robust confidence interval [RCI], .44-.71 and aOR, 0.51; 95% RCI, .27-.96, respectively). Compared with young adults (aged 18-29 years), children (aged 0-11 years) were significantly more likely to transmit (aOR, 2.37; 95% RCI, 1.57-3.60) and acquire (aOR, 1.43; 95% RCI, 1.07-1.93) infection, vaccination considered. Longer duration from vaccination completion among contacts was associated with decline in protection against acquisition (first-month aOR, 0.42; 95% RCI, .33-.55; fifth-month aOR, 0.84; 95% RCI, .55-.98; P < .0001 for trend) and symptomatic disease (first-month aOR, 0.30; 95% RCI, .23-.41; fifth-month aOR, 0.62; 95% RCI, .38-1.02; P < .0001 for trend). Contacts immunized with mRNA-1273 had significant reduction in acquisition (aOR, 0.73; 95% RCI, .58-.91) compared with BNT162b2. CONCLUSIONS: Among household close contacts, vaccination prevented onward SARS-CoV-2 transmission and there was in-creased risk of SARS-CoV-2 acquisition and transmission among children compared with young adults. Time after completion of vaccination and vaccine type affected SARS-CoV-2 acquisition.

National Rates of Lower Extremity Amputation in People With and Without Diabetes in a Multi-Ethnic Asian Population: a Ten Year Study in Singapore.

OBJECTIVE: Population level data from Asia on amputation rates in people with and without diabetes are extremely limited. Hence it is unclear how the rising diabetes prevalence in Asia has affected the amputation burden. The present study examined national amputation rates in people with and without diabetes in Singapore from 2008 to 2017 in the context of increasing diabetes prevalence and health system changes. METHODS: This was a retrospective observational study using national population data for ages 16 - 100 years obtained from the Ministry of Health Singapore administrative datasets. Age sex standardised major and toe/ray amputation rates per 100 000 people with diabetes and per 100 000 people without diabetes were calculated. Rates were calculated overall and in each ethnic group (Chinese, Malay, Indian, Others), with trends over time calculated using joinpoint trend analysis. In addition, age specific rates, relative risk (RR) of amputation in diabetics compared with non-diabetics and proportion of amputations in the population attributable to diabetes were also calculated. RESULTS: Between 2008 and 2017, the database included 3.6 million unique individuals, of whom 75% were Chinese, 8.6% Malay, 7.9% Indian, and 8.4% Others. Of those, 413 486 (11%) had diabetes. Major amputation rates in people with diabetes remained stable (2008: 99.5/100 000; 2017: 95.0/100 000 people with diabetes, p = .91) as did toe/ray amputation rates. Rates in people without diabetes were substantially lower, with major amputation rates decreasing significantly (2008: 3.0/100 000; 2017: 2.1/100 000 people without diabetes, 3% annual reduction, p = .048). Diabetes related amputation rates were highest in Malays and lowest in Chinese. Diabetes related major amputation rates declined significantly among Chinese (3.1% annual reduction, p < .038). While the RR for amputations in diabetes remained stable, the proportion of major amputations attributable to diabetes increased from 63.6% in 2008 to 81.7% in 2017 (3% annual increase, p = .003). CONCLUSION: Diabetes related major and toe/ray amputation rates have remained stable but relatively high in Singapore compared with other countries, and the proportion of amputations attributable to diabetes has increased over time. More research is needed to understand the aetiopathological, sociocultural, and health system factors that may underlie the continued high rates of diabetes related amputations in this population.

The social cost of high sodium diet in Singapore.

High sodium (Na) diet is one of the leading behavioural risks of disease identified in the Singapore Burden of Disease Study. We aim to estimate the cost attributable to a high Na diet in Singapore in 2019 from a societal perspective by employing a prevalence-based approach in cost-of-illness studies. We extracted national-level healthcare data and population attributable fractions by sex and age. Costs included direct and indirect costs from inpatient treatment and productivity losses. In 2019, the annual societal cost attributable to a high Na diet was conservatively estimated to be USA$262 million (95 % uncertainty interval (UI) 218, 359 million). At least USA$67·8 million (95 % UI 48·4, 120 million) and USA$194 million (95 % UI 153, 274 million) could be saved on healthcare and indirect costs, respectively, if the daily Na intake of Singaporeans was reduced to an average of 3 g. Overall, males had higher costs compared with females at USA$221 million (95 % UI 174, 312 million) and USA$41·1 million (95 % UI 33·5, 61·7 million), respectively. Productivity loss from foregone wages due to premature mortality had the largest cost at USA$191 million (95 % UI 150, 271 million). CVD had the largest healthcare expenditure at USA$61·4 million (95 % UI 41·6, 113 million), driven by ischaemic heart disease at USA$41·0 million (95 % UI 21·4, 88·9 million). Our study found that reducing Na intake could reduce future healthcare expenditures and productivity losses. This result is vital for policy evaluation in a rapidly ageing society like Singapore, where the burden of diseases associated with high Na diet is expected to increase.

A prospective observational study exploring the association of comorbid chronic health conditions with total healthcare expenditure in people with mental health conditions in an Asian setting.

BACKGROUND: It is pertinent to focus on chronic medical condition (CMC) comorbidity with mental health conditions (MHC) as their co-occurrence has significant cost and health implications. However, current evidence on co-occurrence of MHC with CMC is mixed and mostly from Western settings. Therefore, our study aimed to (i) describe the association between MHC and total healthcare expenditure, (ii) examine the association between CMC and total healthcare expenditure and (iii) examine determinants of total and different types of healthcare expenditure in respondents with and without MHC in an Asian setting. METHODS: The data from Singapore Mental Health Study (SMHS) 2016, a nationwide epidemiological survey, were linked with the National claims record (from 2017 to 2019). Multivariable Generalized Linear Models (GLM) were used to examine the association between MHC and total and different types of healthcare expenditure. RESULTS: A total of 3077 survey respondents were included in current analysis. Respondents with MHC had a lower mean age of 38.6 years as compared to those without MHC (47.1 years). MHC was associated with increased total healthcare expenditure after adjusting for covariates (b = 0.508, p < 0.05). In respondents with MHC, presence of CMC increased the total healthcare expenditure by 35% as compared to 40% increase in those without MHC. Interestingly, 35-49 years age group with MHC had almost 3 times higher total healthcare expenditure and 7.5 times higher inpatient expenditure as compared to the 18-34 years age group. CONCLUSION: Our study highlights variations in association of CMC and age with total healthcare expenditure in those with versus without MHC in an Asian setting. Practical recommendations include appropriate planning and resource allocation for early diagnosis and management of MHC, proactive screening for CMC in those with MHC and addressing the dual issues of treatment gap and stigma to facilitate early help seeking and prevent episodic, costly healthcare utilization.

Diabetes-related lower extremity complications in a multi-ethnic Asian population: a 10 year observational study in Singapore.

AIMS/HYPOTHESIS: Diabetes progression and complication risk are different in Asian people compared with those of European ancestry. In this study, we sought to understand the epidemiology of diabetes-related lower extremity complications (DRLECs: symptomatic peripheral arterial disease, ulceration, infection, gangrene) and amputations in a multi-ethnic Asian population. METHODS: This was a retrospective observational study using data obtained from one of three integrated public healthcare clusters in Singapore. The population consisted of individuals with incident type 2 diabetes who were of Chinese, Malay, Indian or Other ethnicity. We examined incidence, time to event and risk factors of DRLECs and amputation. RESULTS: Between 2007 and 2017, of the 156,593 individuals with incident type 2 diabetes, 20,744 developed a DRLEC, of whom 1208 underwent amputation. Age- and sex-standardised incidence of first DRLEC and first amputation was 28.29/1000 person-years of diabetes and 8.18/1000 person-years of DRLEC, respectively. Incidence of both was highest in individuals of Malay ethnicity (DRLEC, 36.09/1000 person-years of diabetes; amputation, 12.96/1000 person-years of DRLEC). Median time from diabetes diagnosis in the public healthcare system to first DRLEC was 30.5 months for those without subsequent amputation and 10.9 months for those with subsequent amputation. Median time from DRLEC to first amputation was 2.3 months. Older age (p < 0.001), male sex (p < 0.001), Malay ethnicity (p < 0.001), Indian ethnicity (p = 0.014), chronic comorbidities (nephropathy [p < 0.001], heart disease [p < 0.001], stroke [p < 0.001], retinopathy [p < 0.001], neuropathy [p < 0.001]), poorer or missing HbA1c (p < 0.001), lower (p < 0.001) or missing (p = 0.002) eGFR, greater or missing BMI (p < 0.001), missing LDL-cholesterol (p < 0.001) at diagnosis, and ever-smoking (p < 0.001) were associated with higher hazard of DRLEC. Retinopathy (p < 0.001), peripheral vascular disease (p < 0.001), poorer HbA1c (p < 0.001), higher (p = 0.009) or missing (p < 0.001) LDL-cholesterol and missing BMI (p = 0.008) were associated with higher hazard of amputation in those with DRLEC. Indian ethnicity (p = 0.007) was associated with significantly lower hazard of amputation. CONCLUSIONS/INTERPRETATION: This study has revealed important ethnic differences in risk of diabetes-related lower limb complications, with Malays most likely to progress to DRLEC. Greater research efforts are needed to understand the aetiopathological and sociocultural processes that contribute to the higher risk of lower extremity complications among these ethnic groups.

Seeking healthcare services post-stroke: a qualitative descriptive study exploring family caregiver and stroke survivor perspectives in an asian setting.

AIM: Exploration of the healthcare journey post-stroke is incomplete without acknowledging the crucial role of family caregivers. With limited literature documenting the role of caregivers in the healthcare journey post-stroke, we aimed to describe the healthcare experiences of family caregivers and stroke survivors across different caregiver identities in Singapore. METHODS: We conducted a qualitative descriptive study involving semi-structured interviews with transcripts analysed using thematic analysis. 26 stroke survivors and 35 family caregivers purposively sampled from multiple settings. RESULTS: Findings were summarized into seeking care and experience of healthcare encounters. Seeking care comprised of the following themes: factors influencing seeking care, decision to seek care and role of caregiver in seeking care. Experience of healthcare encounters comprised of the following themes: service around the patient, service with care and role of caregiver in healthcare encounters. CONCLUSION: Multi-dimensional role of caregivers in healthcare experience emerged as a major finding. Unique to our Asian context, as per the participants' accounts, family caregivers seemed to be central in healthcare decision-making for stroke survivors, with adult-child caregivers commonly reported being engaged in collaborative decision-making. While spousal caregivers preferred a relational healthcare experience, adult-child caregivers preferred a transactional one. Practical implications include equipping caregivers with skillset to make healthcare decisions, provision of supportive decision-making environment for caregivers and reinforcing communication aspects in the medical, nursing and allied healthcare curriculum to improve healthcare experience.

Mapping the PHQ-8 to EQ-5D, HUI3 and SF6D in patients with depression.

BACKGROUND: There is limited evidence of mapping clinical instruments to a generic preference-based instrument in Asian patient populations. The current study aims to map the eight-item Patient Health Questionnaire depression scale (PHQ-8) onto the EuroQol Five-Dimension (EQ-5D), the Health Utilities Index Mark 3 (HUI3) and the Short Form Six-Dimension (SF-6D) which helps to inform future cost-utility analyses of treatments for depression. METHODS: A total of 249 participants who had completed PHQ-8, EQ-5D, SF-6D and HUI3 questionnaires were included in the analyses. A beta regression mixture model was used to map the utility scores as a function of PHQ-8 total scores, PHQ-squared, age and gender. The predictive accuracy of the models was examined using mean absolute error and root mean square error. RESULTS: The results were compared against two common regression methods including Ordinary Least Square (OLS) and Tobit regression models. The mean age of the sample was 36.2 years (SD = 11.1). The mean EQ-5D-3L, EQ-5D-5L, HUI3 and SF-6D utility scores were 0.615, 0.709, 0.461 and 0.607, respectively. The EQ-5D-3L, EQ-5D-5L and SF-6D utility scores were best predicted by the beta mixture regression model consisting of PHQ-8 total sores, PHQ-squared, and covariates including age and gender. The HUI3 was best predicted by the OLS regression model. CONCLUSIONS: The current study provides important evidence to clinicians and researchers about the mapping algorithms that can be used in economic evaluation among patients with depression.