Impact of COVID-19 national response on primary care utilisation in Singapore: an interrupted time-series analysis.

Since the start of the pandemic, many national responses, such as nationwide lockdowns, have been implemented to curb the spread of COVID-19. We aim to assess the impact of Singapore's national responses on primary care utilisation. We performed an interrupted time series using acute and chronic primary care data of 3 168 578 visits between 1 September 2019 and 31 August 2020 over four periods: before any measures were put in place, during Disease Outbreak Response System Condition (DORSCON) Orange, when Circuit Breaker was instituted, and when Circuit Breaker was lifted. We found significant mean reductions in acute and chronic primary care visits immediately following DORSCON Orange and Circuit Breaker. DORSCON Orange was associated with - 2020 mean daily visits (95% CI - 2890 to - 1150). Circuit Breaker was associated with a further - 2510 mean daily visits (95% CI - 3660 to - 1360). Primary care utilisation for acute visits remained below baseline levels even after the Circuit Breaker was lifted. These significant reductions were observed in both acute and chronic visits, with acute visits experiencing a steeper drop during DORSCON Orange. Understanding the impact of COVID-19 measures on primary care utilisation will be useful for future public health planning.

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.

Empiric treatment with aspirin and ticagrelor is the most cost-effective strategy in patients with minor stroke or transient ischemic attack.

BACKGROUND: Patients with minor ischemic stroke or transient ischemic attacks (TIAs) are often treated with dual antiplatelet therapy regimens as part of secondary stroke prevention. Clopidogrel, an antiplatelet used in these regimens, is metabolized into its active form by the CYP2C19 enzyme. Patients with loss of function (LOF) mutations in CYP2C19 are at risk for poorer secondary outcomes when prescribed clopidogrel. AIMS: We aimed to determine the cost-effectiveness of three different treatment antiplatelet regimens in ischemic stroke populations with minor strokes or TIAs and how these treatment regimens are influenced by the LOF prevalence in the population. METHODS: Markov models were developed to look at the cost-effectiveness of empiric treatment with aspirin and clopidogrel versus empiric treatment with aspirin and ticagrelor, versus genotype-guided therapy for either 21 or 30 days. Effect ratios were obtained from the literature, and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). RESULTS: Empiric treatment with aspirin and ticagrelor was the most cost-effective treatment. Genotype-guided therapy was more cost-effective than empiric aspirin and clopidogrel if the LOF was above 48%. Empiric ticagrelor and aspirin was cost saving when compared to genotype-guided therapy. Results in models of dual antiplatelet therapy for 30 days were similar. CONCLUSION: This study suggests that in patients with minor stroke and TIA planned for dual antiplatelet regimens, empiric ticagrelor and aspirin is the most cost-effective treatment regimen. If ticagrelor is not available, genotype-guided therapy is the most cost-effective treatment regimen if the LOF prevalence in the population is more than 48%.

Long-term neuropsychiatric sequelae of Delta versus Omicron SARS-CoV-2 infection.

OBJECTIVES: Studies have reported increased rates of long-term neuropsychiatric sequelae after SARS-CoV-2 infection using electronic health-record (EHR) data; however, the majority were conducted before Omicron and booster rollout. We estimated the long-term risks and excess burdens of pre-specified new-incident neuropsychiatric diagnoses after Delta versus Omicron BA.1/2 infection in a highly-vaccinated and boosted cohort of adult Singaporeans. METHODS: The national SARS-CoV-2 testing registry was used to construct cohorts of Singaporean adults infected during periods of Delta and Omicron BA.1/2 predominance and a contemporaneous test-negative control group. New-incident neuropsychiatric diagnoses recorded in the national health care claims database were identified up to 300 days postinfection. Risks and excess burden were estimated using a doubly robust competing-risks survival analysis. RESULTS: 104 179 and 375 903 infected cases were assigned to Delta and Omicron cohorts and compared against test-negative controls (Delta: N = 666 575 and Omicron: N = 619 379). Elevated risk of cognition or memory disorders was consistently reported across Omicron (Adjusted hazards ratio [aHR], 1.24; 95% CI, 1.12-1.38) and Delta cohorts (aHR, 1.63; 95% CI, 1.39-1.92). Delta-variant infection was associated with an increased risk of anosmia or dysgeusia (aHR, 4.53; 95% CI, 2.78-7.41) and psychosis (aHR, 1.65; 95% CI, 1.22-2.22). By contrast, Omicron-variant infection was associated with a risk of abnormal involuntary movements (aHR, 1.93; 95% CI, 1.32-2.83). Risks of neuropsychiatric sequelae predominantly accrued in hospitalized individuals. DISCUSSIONS: A modestly increased risk of cognition and memory disorders at 300 days after SARS-CoV-2 infection was observed among adult Singaporeans infected during the Delta/Omicron BA.1/2 transmission. There was no overall increased risk of neuropsychiatric sequelae observed across other domains. Variant-specific differences were also observed in individual neuropsychiatric sequelae, including an elevated risk of anosmia or dysgeusia after Delta-variant infection.

mRNA SARS-CoV-2 Vaccination Before vs During Pregnancy and Omicron Infection Among Infants.

Importance: Infants younger than 6 months are at risk of severe SARS-CoV-2 infection. Data are lacking on the optimum timing for maternal vaccination and estimated effectiveness against Omicron variants, including XBB, for infants. Objective: To investigate maternal vaccination against Omicron variants, including XBB, and the association of vaccination timing during pregnancy vs prior to pregnancy and risks of SARS-CoV-2 infection among infants aged 6 months or younger. Design, Setting, and Participants: This population-based cohort study was conducted between January 1, 2022, and March 31, 2023. Singapore's national dataset was used to study infants born at greater than 32 weeks' gestation between January 1, 2022, and September 30, 2022. The study included infants whose parents had a confirmed SARS-CoV-2 infection from the date of birth up to 6 months of age. Of 21 609 infants born during this period, 7292 (33.7%) had at least 1 parent infected with SARS-CoV-2 before the age of 7 months. Statistical analysis was performed from April to July 2023. Exposure: Infants' mothers were unvaccinated, vaccinated prior to pregnancy, or vaccinated with a messenger RNA (mRNA) SARS-CoV-2 vaccine during pregnancy. Main Outcome and Measure: Infants were considered infected if they had a positive polymerase chain reaction test. Results: Among 7292 infants included in this study, 4522 (62.0%) had mothers who were Chinese, 527 (7.2%) had mothers who were Indian, 2007 (27.5%) had mothers who were Malay, and 236 (3.2%) had mothers who were other ethnicity; 6809 infants (93.4%) were born at full term, and 1272 infants (17.4%) were infected during the study period. There were 7120 infants (97.6%) born to mothers who had been fully vaccinated or boosted as of 14 days prior to delivery. The crude incidence rate was 174.3 per 100 000 person-days among infants born to mothers who were unvaccinated, 122.2 per 100 000 person-days among infants born to mothers who were vaccinated before pregnancy, and 128.5 per 100 000 person-days among infants born to mothers who were vaccinated during pregnancy. The estimated vaccine effectiveness (VE) was 41.5% (95% CI, 22.8% to 55.7%) among infants born to mothers vaccinated during pregnancy. Infants of mothers who received vaccination prior to pregnancy did not have a lower risk for infection (estimated VE, 15.4% [95% CI, -17.6% to 39.1%]). A lower risk for Omicron XBB infection was only observed among mothers vaccinated with the third (booster) dose antenatally (estimated VE, 76.7% [95% CI, 12.8% to 93.8%]). Conclusions and Relevance: In this population-based cohort study, maternal mRNA vaccination was associated with a lower risk of Omicron SARS-CoV-2 infection among infants up to 6 months of age only if the vaccine was given during the antenatal period. These findings suggest that mRNA vaccination during pregnancy may be needed for lower risk of SARS-CoV-2 infection among newborns.

Predictors of 10-year Mortality After Hip Fracture Surgery in a Pre-Pandemic Cohort.

Introduction: Though hip fractures are associated with significant mortality and morbidity, increasing life expectancy in developed countries necessitates an analysis of mortality trends and factors predicting long term survival. The aim of this study is to identify the predictors of 10-year mortality as well as assess the correlation of Age-adjusted Charlson comorbidity index (ACCI) with 10-year mortality in a surgically treated Asian geriatric hip fracture population. Materials and Methods: From January 1, 2007 to December 31, 2009, 766 patients who underwent surgery for hip fracture with a minimum follow up of 10-years were recruited to the study (92% follow-up rate). A review of the patient's electronic hospital records was performed to glean the following data: patient demographics, pre-existing comorbidities, operation duration, length of stay, fracture configuration, as well as mortality data up to 10 years. CCI scores and individual co-morbidities were correlated with inpatient, 30-day, 1-year, 5-year and beyond 10-year mortality. Results: Of the 766 patients, the mortality rate for 30-day, 1-year, 5-year and 10-years was 2.9%, 12.0%, 38.9% and 61.6% respectively. The average ACCI was 5.31. The 10-year mortality for patients with ACCI ≤ 3, ACCI 4-5 and ACCI ≥ 6 are 29.4%, 57.4% and 77.5% respectively. End-Stage-Renal Failure (ESRF), liver failure and COPD were dominant predictors of mortality at 10 years, whereas cancer was the predominant predictor at 1 year. Discussion: ACCI significantly correlates with the 10-year mortality after surgically treated hip fractures with a shift of the dominant predictors from cancer to ESRF and COPD. This could inform future health policy and resource planning. This data also represents recently available pre-pandemic survival trends after hip fracture surgery and serves as a baseline for post-pandemic outcome surveillance of interventions for fragility fractures. Conclusion: This study demonstrates that ACCI correlated with 10-year mortality after surgical treatment of hip fractures.

Factors associated with delayed diagnosis of symptomatic adult COVID-19 cases presenting to primary care: a population-wide study during transition from Delta to Omicron BA.1 in Singapore.

Background: During pandemics, avoiding time delay in diagnosing infection is crucial. We evaluated factors associated with delayed diagnosis of symptomatic SARS-CoV-2 infection in a national cohort of adult Singaporeans, during which emergence of the more transmissible Omicron variant shifted pandemic management towards endemicity. Methods: Retrospective cross-sectional study amongst all adult Singaporeans diagnosed with symptomatic SARS-CoV-2 infection during the transition from Delta to Omicron BA.1 (September 2021-February 2022). SARS-CoV-2 testing was fully subsidised and compulsory for all symptomatic individuals presenting at primary care. Results and demographic information were extracted from national databases. Time to diagnosis was defined as days from symptom-onset to diagnosis (date of first positive SARS-CoV-2 test); dichotomising into no delay (≤24 h from symptom-onset) and delay >24 h. Multivariable logistic regression was utilised to assess factors associated with delay >24 h, and association of delay >24 h with progression to severe COVID-19. Findings: Of 149,063 Singaporean adults presenting with symptomatic SARS-CoV-2 infection, 75.9% (113,195/149,063) were diagnosed within 24 h of symptom-onset. On multivariable analysis, female gender, older age (>60 years), Chinese (vs. Malay) ethnicity, socioeconomic status (housing type), primary care characteristics, presentation during Omicron BA.1 (vs. Delta), symptom-onset on Friday/Saturday (vs. Monday), and not having completed a primary vaccination series were independently associated with higher odds of delay >24 h. Delay >24 h was independently associated with severe COVID-19 (adjusted odds-ratio, aOR = 1.45, 95% CI = 1.27-1.65, p < 0.001). Interpretation: At-risk populations (unvaccinated, age >60 years) had higher odds of delay in diagnosis. Delay >24 h in diagnosis was independently associated with severe COVID-19. Funding: This study was not grant-funded.

Effectiveness of Monovalent mRNA Vaccines Against Omicron XBB Infection in Singaporean Children Younger Than 5 Years.

Importance: Literature on vaccine effectiveness of SARS-CoV-2 messenger RNA (mRNA) vaccines for children younger than 5 years is limited. Objective: To report the effectiveness of monovalent mRNA vaccines against SARS-CoV-2 infection among Singaporean children aged 1 through 4 years during a COVID-19 pandemic wave of the Omicron XBB variant. Design, Setting, and Participants: This was a population-based cohort study, conducted over a 6-month study period from October 1, 2022, through March 31, 2023, after the implementation of community vaccination among all Singaporean children aged 1 through 4 years. The study period was dominated by the Omicron XBB subvariant. Exposure: Receipt of SARS-CoV-2 mRNA vaccines. Main Outcome Measure: Vaccine effectiveness against confirmed SARS-CoV-2 infection. The adjusted incidence rate ratio for confirmed infections using Poisson regression was reported, with the reference group being those who were unvaccinated. Analyses were stratified by prior documented SARS-CoV-2 infection. Results: A total of 121 628 children (median [IQR] age, 3.1 [2.2-3.9] years; 61 925 male [50.9%]) were included in the study, contributing 21 015 956 person-days of observation. The majority of children (11 294 of 11 705 [96.5%]) received the mRNA-1273 COVID-19 vaccine (Moderna). Vaccine effectiveness against confirmed infection was 45.2% (95% CI, 24.7%-60.2%) in partially vaccinated, infection-naive children and 63.3% (95% CI, 40.6%-77.3%) in fully vaccinated, infection-naive children compared with the unvaccinated group. Among previously infected children, vaccine effectiveness against reinfections in those with at least 1 vaccine dose was estimated at 74.6% (95% CI, 38.7%-89.5%). Conclusions and Relevance: Study results suggest that completion of a primary mRNA vaccine series provided protection against SARS-CoV-2 infection in children aged 1 through 4 years. Although incidence of hospitalization and severe illness is low in this age group, there is potential benefit of vaccination in preventing infection and potential sequelae.

Chronic wounds in a multiethnic Asian population: a cost of illness study.

OBJECTIVE: To estimate the 'cost of illness' arising from chronic wounds in Singapore. DESIGN: Incidence-based cost of illness study using evidence from a range of sources. SETTING: Singapore health services. PARTICIPANTS: We consider 3.49 million Singapore citizens and permanent residents. There are 16 752 new individuals with a chronic wound in 2017, with 598 venous ulcers, 2206 arterial insufficiency ulcers, 6680 diabetic ulcers and 7268 pressure injuries.Primary outcome measures expressed in monetary terms are the value of all hospital bed days lost for the population; monetary value of quality-adjusted life years (QALYs) lost in the population; costs of all outpatient visits; and costs of all poly clinic, use of Community Health Assist Scheme (CHAS) and emergency departments (EDs) visits. Intermediate outcomes that inform the primary outcomes are also estimated. RESULTS: Total annual cost of illness was $350 million (range $72-$1779 million). With 168 503 acute bed days taken up annually (range 141 966-196 032) that incurred costs of $139 million (range 117-161 million). Total costs to health services were $184 million (range $120-$1179 million). Total annual costs of lost health outcomes were 2077 QALYs (range -2657 to 29 029) valued at $166 million (range -212 to 2399 million). CONCLUSIONS: The costs of chronic wounds are large to Singapore. Costs can be reduced by making positive investments for comprehensive wound prevention and treatment programmes.

Effectiveness of bivalent mRNA vaccines against medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission among SARS-CoV-2-naive and previously infected individuals: a retrospective cohort study.

BACKGROUND: Emergence of the SARS-CoV-2 omicron (B.1.1.529) variant with high immune evasion has led to the development and roll-out of bivalent mRNA vaccines targeting original and omicron strains. However, real-world observational data on effectiveness of bivalent vaccines are scarce. We aimed to assess the relative effectiveness of a fourth vaccine dose with the BA.1-adapted or BA.4/BA.5-adapted bivalent vaccines against medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission among SARS-CoV-2-naive and previously infected individuals in Singapore. METHODS: We conducted a retrospective cohort study among Singapore residents aged 18 years and older who had received three monovalent mRNA vaccine doses and were eligible for a fourth dose. Data were collected from official databases on COVID-19 cases and vaccinations maintained by the Singapore Ministry of Health. We analysed the incidence of medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission between Oct 14, 2022, and Jan 31, 2023, by previous infection status and type of fourth vaccine dose received. Inverse probability-weighted Cox regressions were used to estimate hazard ratios (HRs). FINDINGS: 2 749 819 individuals were included in the analysis. For the SARS-CoV-2-naive group, a fourth monovalent vaccine dose did not confer additional protection over three monovalent doses against symptomatic infection (HR 1·09 [95% CI 1·07-1·11]), whereas the bivalent vaccine did provide additional protection (0·18 [0·17-0·19]). Among individuals with previous infection, the HR was 0·87 (95% CI 0·84-0·91) and 0·14 (0·13-0·15) with receipt of the fourth monovalent and bivalent doses, respectively. Against COVID-19-related hospital admission, the bivalent vaccine (HR 0·12 [95% CI 0·08-0·18] in SARS-CoV-2-naive participants and 0·04 [0·01-0·15] in previously infected participants) conferred greater benefit compared with the fourth monovalent dose (0·84 [0·77-0·91] in SARS-CoV-2-naive participants and 0·85 [0·69-1·04] in previously infected participants). INTERPRETATION: A fourth dose with the bivalent vaccine was substantially more effective against medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission than four monovalent doses among both SARS-CoV-2-naive and previously infected individuals. Boosters with the bivalent vaccine might be preferred in this omicron-predominant pandemic, regardless of previous infection history. FUNDING: None.

COVID-19 Severity and Waning Immunity After up to 4 mRNA Vaccine Doses in 73 608 Patients With Cancer and 621 475 Matched Controls in Singapore: A Nationwide Cohort Study.

Importance: Despite patients with cancer being at risk of poor outcomes from COVID-19, there are few published studies for vaccine efficacy in this group, with suboptimal immunogenicity and waning vaccine efficacy described in small studies being a concern. Objective: To assess the incidence rate of severe COVID-19 disease outcomes associated with the number of vaccine doses received and the waning of protection over time. Design, Setting, and Participants: A prospective multicenter observational cohort study was carried out over 2 time periods (September 15, 2021, to December 20, 2021 [delta wave], and January 20, 2022, to November 11, 2022 [omicron wave]) predominated by SARS-CoV-2 delta and omicron variants, respectively. Overall, 73 608 patients with cancer (23 217 active treatment, 50 391 cancer survivors) and 621 475 controls matched by age, sex, race and ethnicity, and socioeconomic status were included. Exposure: Vaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose. Outcomes: Competing-risk regression analyses were employed to account for competing risks of death in patients with cancer. Main outcomes were incidence rate ratios (IRRs) of COVID-19 infection, hospitalization, and severe disease (defined as requirement for supplemental oxygen, intensive care, or death). The IRRs stratified by time from last vaccine dose served as indicators of waning of vaccine effectiveness over time. Results: The mean (SD) age of actively treated patients with cancer, cancer survivors, and controls were 62.7 (14.7), 62.9 (12.6), and 61.8 (14.7) years, respectively. Of 73 608 patients with cancer, 27 170 (36.9%) were men; 60 100 (81.6%) were Chinese, 7432 (10.1%) Malay, 4597 (6.2%) Indian, and 1479 (2.0%) were of other races and ethnicities. The IRRs for the 3-dose and 4-dose vs the 2-dose group (reference) for COVID-19 hospitalization and severe disease were significantly lower during both the delta and omicron waves in cancer and control populations. The IRRs for severe disease in the 3-dose group for active treatment, cancer survivors, and controls were 0.14, 0.13, and 0.07 during the delta wave and 0.29, 0.19, and 0.21 during omicron wave, respectively. The IRRs for severe disease in the 4-dose group during the omicron wave were even lower at 0.13, 0.10 and 0.10, respectively. No waning of vaccine effectiveness against hospitalization and severe disease was seen beyond 5 months after a third dose, nor up to 5 months (the end of this study's follow-up) after a fourth dose. Conclusion: This cohort study provides evidence of the clinical effectiveness of mRNA-based vaccines against COVID-19 in patients with cancer. Longevity of immunity in preventing severe COVID-19 outcomes in actively treated patients with cancer, cancer survivors, and matched controls was observed at least 5 months after the third or fourth dose.

Density forecasting of conjunctivitis burden using high-dimensional environmental time series data.

As one of the most common eye conditions being presented at clinics, acute conjunctivitis puts substantial strain on primary health resources. To reduce this public health burden, it is important to forecast and provide forward guidance to policymakers by estimating conjunctivitis trends, taking into account factors which influence transmission. Using a high-dimensional set of ambient air pollution and meteorological data, this study describes new approaches to point and probabilistic forecasting of conjunctivitis burden which can be readily translated to other infectious diseases. Over the period of 2012 - 2022, we show that simple models without environmental data provided better point forecasts but the more complex models which optimized predictive accuracy and combined multiple predictors demonstrated superior density forecast performance. These results were shown to be consistent over periods with and without structural breaks in transmission. Furthermore, ecological analysis using post-selection inference showed that increases in SO2, O3 surface concentration and total precipitation were associated to increased conjunctivitis attendance. The methods proposed can provide rich and informative forward guidance for outbreak preparedness and help guide healthcare resource planning in both stable periods of transmission and periods where structural breaks in data occur.

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.

Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalizations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5, and XBB transmission.

OBJECTIVES: Real-world data on continued effectiveness of nirmatrelvir/ritonavir against hospitalization and severe COVID-19 in the context of widespread booster mRNA vaccine uptake and more immune-evasive Omicron sub-variants are lacking. We conducted a retrospective cohort study in adult Singaporeans aged ≥60 years presenting to primary care with SARS-CoV-2 infection, during waves of Omicron BA.2/4/5/XBB transmission. METHODS: Binary logistic regression was used to estimate the effect of treatment (receiving nirmatrelvir/ritonavir) on outcomes (hospitalization, severe COVID-19). Additional sensitivity analyses, including inverse-probability-of-treatment-weighting-adjusted analysis and adjustment using overlap weights, were performed to account for observed differences in baseline characteristics among treated/untreated cohorts. RESULTS: We included 3959 nirmatrelvir/ritonavir recipients and 139 379 untreated controls. Almost 95% received ≥3 doses of mRNA vaccines; 5.4% had preceding infection. Overall 26.5% of infections occurred during the Omicron XBB period and 1.7% were hospitalized. On multivariable logistic regression, receipt of nirmatrelvir/ritonavir was independently associated with lower odds of hospitalization (adjusted odds ratio [aOR] = 0.65, 95% CI = 0.50-0.85). Consistent estimates were obtained after inverse-probability-of-treatment-weighting adjustment (aOR for hospitalization = 0.60, 95% CI = 0.48-0.75) and adjustment using overlap weights (aOR for hospitalization = 0.64, 95% CI = 0.51-0.79). Although receipt of nirmatrelvir/ritonavir was associated with lower odds of severe COVID-19, it was not statistically significant. DISCUSSION: Outpatient usage of nirmatrelvir/ritonavir was independently associated with reduced odds of hospitalization amongst boosted older community-dwelling Singaporeans during successive waves of Omicron transmission, including Omicron XBB; however, it did not significantly reduce the already low risk of severe COVID-19 in a highly vaccinated population.

Genesis, evolution and effectiveness of Singapore's national sorting logic and home recovery policies in handling the COVID-19 Delta and Omicron waves.

Singapore developed several novel strategies to transition towards "living with COVID-19", while protecting hospital capacity. The Home Recovery Programme (HRP) was a national, centrally-administered programme that leveraged technology and telemedicine to allow low-risk individuals to safely recover at home. The HRP was subsequently expanded by partnering primary care doctors in caring for more cases in the community. A key enabler was the National Sorting Logic (NSL), a multi-step triage algorithm allowing risk-stratification of large numbers of COVID-19 patients at a national-level. At the core of the NSL was a risk assessment criterion, comprising of Comorbidities-of-concern, Age, Vaccination status, Examination/clinical findings and Symptoms (CAVES). The NSL sorted all COVID-19 cases into the various levels of care - Primary Care, HRP, COVID-19 Treatment Facility and Hospital. By adopting a national approach towards managing healthcare capacities and triaging COVID-19 patients, Singapore was able to prioritize healthcare resources for high-risk individuals and prevent hospital capacities from being overwhelmed. As part of the national response strategy to tackle COVID-19, Singapore set up and integrated key national databases to enable responsive data analysis and support evidence-based policy decisions. Using data collected between 30 August 2021 to 8 June 2022, we conducted a retrospective cohort study to evaluate the outcomes and effectiveness of vaccination policies, NSL and home-based recovery. A total of 1,240,183 COVID-19 cases were diagnosed during this period, spanning both Delta and Omicron waves, Overall, Singapore experienced very low severity (0.51%) and mortality (0.11%) rates. Vaccinations significantly lowered severity and mortality risks across all age groups. The NSL was effective in predicting risk of severe outcomes and was able to right-site >93% of cases into home-based recovery. By leveraging high vaccination rates, technology and telemedicine, Singapore was able to safely navigate through two COVID-19 waves without impacting severity/mortality rates nor overwhelming hospital capacities.

Mapping the schizophrenia quality of life scale to EQ-5D, HUI3 and SF-6D utility scores in patients with schizophrenia.

OBJECTIVES: The current study aimed to map the disease-specific Schizophrenia Quality of Life Scale (SQLS) onto the three- and five-level EuroQol five-dimension (EQ-5D-3 L and EQ-5D-5 L), Health Utility Index Mark 3 (HUI3) and Short Form six-dimensional (SF-6D) preference-based instruments to inform future cost-utility analyses for treatment of patients with schizophrenia. METHODS: Data from 251 outpatients with schizophrenia spectrum disorders was included for analysis. Ordinary least square (OLS), Tobit and beta regression mixture models were employed to estimate the utility scores. Three regression models with a total of 66 specifications were determined by goodness of fit and predictive indices. Distribution of the original data to the distributions of the data generated using the preferred estimated models were then compared. RESULTS: EQ-5D-3 L and EQ-5D-5 L were best predicted by the OLS model, including SQLS domain scores, domain-squared scores, age, and gender as explanatory predictors. The models produced the best performance index and resembled most closely with the observed EQ-5D data. HUI3 and SF-6D were best predicted by the OLS and Tobit model respectively. CONCLUSION: The current study developed mapping models for converting SQLS scores into generic utility scores, which can be used for economic evaluation among patients with schizophrenia.

Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).