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Objective: The aim of this study was to describe the time series of broad-spectrum antibiotic utilisation and incidence of antibiotic-resistant organisms during the implementation of antimicrobial stewardship programmes (ASP) in Singapore. Methods: An observational study was conducted using data from 2011 to 2020 in seven acute-care public hospitals. We applied joinpoint regressions to investigate changes in antibiotic utilisation rate and incidence density of antibiotic-resistant organisms. Results: Across the seven hospitals, quarterly broad-spectrum antibiotic utilisation rate remained stable. Half-yearly incidence density of antibiotic-resistant organisms with two joinpoints at first half (H1) of 2012 and second half (H2) of 2014 decreased significantly in the second and third period with a half-yearly percentage change (HPC) of -2.9% and − 0.5%, respectively. Across the five hospitals with complete data, half-yearly broad-spectrum antibiotic utilisation rate with one joinpoint decreased significantly from H1 of 2011 to H2 of 2018 (HPC − 4.0%) and H2 of 2018 to H2 2020 (HPC − 0.5%). Incidence density of antibiotic-resistant organisms decreased significantly in the two joinpoint periods from H1 of 2012 to H2 of 2014 (HPC − 2.7%) and H2 of 2014 to H2 of 2020 (HPC − 1.0%). Ceftriaxone with one joinpoint decreased significantly from H1 of 2011 to H1 of 2014 (HPC − 6.0%) and H1 of 2014 to H2 of 2020 (HPC − 1.8%) and ceftriaxone-resistant E. coli and K. pneumoniae decreased significantly in later periods, from H2 of 2016 to H2 of 2020 (HPC − 2.5%) and H1 of 2012 to H2 of 2015 (HPC − 4.6%) respectively. Anti-pseudomonal antibiotics with one joinpoint decreased significantly from H1 of 2011 to H2 of 2014 (HPC − 4.5%) and H2 of 2014 to H2 of 2020 (HPC − 0.8%) and that of quinolones with one joinpoint at H1 of 2015 decreased significantly in the first period. C. difficile with one joinpoint increased significantly from H1 of 2011 to H1 of 2015 (HPC 3.9%) and decreased significantly from H1 of 2015 to H2 of 2020 (HPC − 4.9%). Conclusions: In the five hospitals with complete data, decrease in broad-spectrum antibiotic utilisation rate was followed by decrease in incidence density of antibiotic-resistant organisms. ASP should continue to be nationally funded as a key measure to combat antimicrobial resistance in acute care hospitals. [ABSTRACT FROM AUTHOR]

Objective: Abnormal liver tests have been associated with worse clinical outcomes in patients infected with COVID-19. This retrospective observational study from Singapore aims to elucidate simple clinical predictors of abnormal alanine aminotransferase (ALT) in COVID-19 infections. Design: 717 patients hospitalised with COVID-19 at the National Centre for Infectious Diseases (NCID), Singapore, from 23 January–15 April 2020 were screened, of which 163 patients with baseline normal alanine transferase (ALT) and at least two subsequent ALTs performed were included in the final analysis. Information on baseline demographics, clinical characteristics and biochemical laboratory tests were collected. Results: 30.7% of patients developed abnormal ALT. They were more likely to be older (60 vs. 55, p = 0.022) and have comorbidities of hyperlipidaemia and hypertension. The multivariate logistic regression showed that R-factor ≥1 on admission (adjusted odds ratio (aOR) 3.13, 95% Confidence Interval (CI) 1.41–6.95) and hypoxia (aOR 3.54, 95% CI 1.29–9.69) were independent risk factors for developing abnormal ALT. The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58% vs. 18.6%, p < 0.0005), admission to the Intensive Care Unit (ICU)/High Dependency Unit (HDU) (32% vs. 11.5%, p = 0.003) and intubation (20% vs. 2.7%, p < 0.0005). There was no difference in death rate between the two groups. Conclusions: Liver injury is associated with poor clinical outcomes in patients with COVID-19. R-factor ≥1 on admission and hypoxia are independent simple clinical predictors for developing abnormal ALT in COVID-19. [ABSTRACT FROM AUTHOR]

Background: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks. [ABSTRACT FROM AUTHOR]

Background: The paediatric massive transfusion protocol (MTP) is activated in the paediatric population for both trauma and non-trauma related indications. While it helps to improve the efficiency and efficacy of the delivery of blood products, it can also result in increased wastage. We aimed to evaluate the wastage rates from our paediatric MTP activations from 2013 to 2018. Method: As part of an audit, we retrospectively reviewed the records of the paediatric patients who had MTP activations. We collected the following data: reason for MTP activation, weight of patient, number of cycles of MTP required, blood products used, blood products wasted, deviation from our institution's recommended MTP blood product ratio, and reason for wastage. Result: We had 26 paediatric MTP activations within the audit period. There was an overall wastage rate of 1.5%, with wastage occurring in 3 out of 26 patients. The reason for all wastage was demise of the patient. Most patients' transfusion ratios deviated from our institution's MTP protocol. Conclusion: Our wastage rates are low likely because of clear MTP activation guidelines and a flexible MTP workflow. [ABSTRACT FROM AUTHOR]

Background: There is currently insufficient long-term data on costs of treatment in patients with Parkinson's disease (PD), which is chronic and progressive, and associated with substantial healthcare costs. Identifying patterns in healthcare utilization and cost may illuminate further discussion on early intervention. Objective: To characterize long-term healthcare utilization and costs of PD in newly diagnosed patients managed by movement disorder specialists. Methods: Using a longitudinal matched-cohort study of linked data from the National Neuroscience Institute Parkinson's disease and Movement Disorder and healthcare administrative databases in Singapore from 2008–2017, we compared healthcare utilization and costs between patients and controls matched on age, sex, race, and Charlson Comorbidity Index score. Results: 1,162 patients met study inclusion criteria and 1,157 matched controls were identified. The total mean annual healthcare cost (at 2017 costs) was significantly increased in patients compared to controls from years 1–9 post-diagnosis. The increased cost was observed 2 years before diagnosis (USD2322 vs. 2052; p < 0.001). Mean annual cost attributable to PD increased from USD1854 at 1-year post-diagnosis to USD2652 at 9 years. Over 9 years, average costs were significantly higher across all domains of healthcare utilization except primary care—cost of intermediate and long-term care was increased by a factor of 2.5, specialist care by 2.3, emergency department visits by 1.6, and hospital admissions by 1.3. Conclusion: PD results in higher healthcare utilization and costs. Pre-diagnosis increase in healthcare utilization observed in patients supports the presence of prodromal PD symptoms and may present an opportunity for early diagnosis. [ABSTRACT FROM AUTHOR]

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background Previously treated (ie, recurrent) tuberculosis (TB) cases account for approximately 7%–8% of incident TB globally and in Singapore. Molecular fingerprinting has enabled the differentiation of these patients into relapsed or reinfection cases. Methods Patient demographics, disease characteristics, and treatment information were obtained from the national TB notification registry and TB Control Unit. We performed a retrospective, case-control study to evaluate factors associated with recurrent TB disease in Singapore citizens and permanent residents with culture-positive TB from 2006 to 2013 and who developed a second episode of culture-positive TB up to 2016 using multivariable logistic regression analyses. Results Ninety-one cases with culture-positive first and recurrent TB disease episodes were identified. Recurrent TB was associated with age ≥60 years (adjusted odds ratio [aOR], 1.98 [95% confidence interval {CI}, 1.09–3.61), male sex (aOR, 2.29 [95% CI, 1.22–4.51]), having concomitant pulmonary and extrapulmonary TB (aOR, 3.10 [95% CI, 1.59–6.10]) and extrapulmonary TB alone (aOR, 3.82 [95% CI, 1.12–13.31]), and was less likely in non-Malays (aOR, 0.52 [95% CI,.27–.99]). DNA fingerprinting results for both episodes in 49 cases differentiated these into 28 relapsed and 21 reinfection cases. Relapse was associated with having concomitant pulmonary and extrapulmonary TB (aOR, 9.24 [95% CI, 2.50–42.42]) and positive sputum acid-fast bacilli smear (aOR, 3.95 [95% CI, 1.36–13.10]). Conclusions Relapse and reinfection contributed to 57% and 43%, respectively, of recurrent TB in Singapore. Our study highlights the underappreciated association of concomitant pulmonary and extrapulmonary TB as a significant risk factor for disease relapse. [ABSTRACT FROM AUTHOR]

Background: While the use of combination antiretroviral therapy (cART) has conferred significant reduction in morbidity and mortality, there are growing concerns about the metabolic complications of antiretroviral regimens in HIV-infected patients. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) among people living with HIV (PLHIV) in Singapore. Methods: We conducted a retrospective study using the clinical database maintained by the Clinical HIV Programme at the National Centre for Infectious Diseases, Singapore. Treatment-experienced PLHIV on follow-up during 2015–2017 were included. MetS was defined as having three or more of the following five abnormalities: hypertriglyceridemia, HDL hypocholesterolemia, hypertension, obesity, and diabetes. Results: A total of 2,231 PLHIV were included in this study. 93.9% were men, and the median age at latest follow-up was 48 years. The median duration of HIV infection and duration of exposure to cART was 6.8 years and 5.7 years, respectively. All had been exposed to nucleoside reverse transcriptase inhibitors (NRTIs) as the first line of treatment, 93.9% to non-NRTIs, 28.6% to protease inhibitors (PIs) and 12.8% to integrase strand transfer inhibitors. The most common metabolic abnormality among PLHIV was HDL hypocholesterolemia (60.2%) followed by hypertriglyceridemia (45.5%). Of all the 2,231 individuals, 68.8% had at least one component of MetS. The overall prevalence of MetS was 23.6% (95% confidence interval 21.9%–25.4%). Of the 526 with MetS, the most common combination was HDL hypocholesterolemia, hypertriglyceridemia and hypertension (51.0%), followed by HDL hypocholesterolemia, hypertriglyceridemia, hypertension and diabetes (25.1%). Compared with PLHIV without MetS, a significantly higher proportion of those with MetS were ever on protease inhibitors (33.5% vs. 27.1%). Conclusion: MetS is common in PLHIV. In view of the progressive aging of HIV-infected population and long-term use of cART, regular monitoring for metabolic abnormalities, surveillance of drug effects and behavioural interventions are needed to optimize management and prevention of metabolic disorders in PLHIV. [ABSTRACT FROM AUTHOR]

Background: Ceftriaxone is the preferred treatment for bacteraemia caused by non-MDR (antibiotic-susceptible) Klebsiella pneumoniae. Excessive and widespread ceftriaxone use creates selection pressure for ESBLs. Cefazolin is an alternative, although there are theoretical concerns that SHV-1 β-lactamase in K. pneumoniae may inactivate cefazolin in an inoculum-dependent manner.Objectives: In this retrospective study, we investigated the outcomes in K. pneumoniae bacteraemia patients treated with IV cefazolin versus IV ceftriaxone as definitive therapy.Methods: A total of 917 patients infected with K. pneumoniae from 1 January to 31 December 2016 in three public acute care hospitals in Singapore were screened for study eligibility. Consecutive unique episodes of monomicrobial bacteraemia caused by cefazolin- and/or ceftriaxone-susceptible K. pneumoniae were analysed (n = 284).Results: There were 143 patients (50.4%) in the cefazolin group and 141 patients (49.6%) in the ceftriaxone group. Demographics, baseline illness severity and risk factors for healthcare-associated bacteraemia were comparable in the two treatment groups. The primary outcome of 28 day all-cause mortality was not significantly different between the cefazolin and ceftriaxone groups (10.5% versus 7.1%, P = 0.403). Both in the crude analysis and using a multivariable logistic regression model with inverse probability weighting based on propensity score, cefazolin treatment was not associated with increased risk of 28 day mortality (OR 1.51 with ceftriaxone as the reference group, 95% CI 0.67-3.53; adjusted OR 1.55, 95% CI 0.33-7.40).Conclusions: Cefazolin may be a ceftriaxone-sparing alternative treatment for antibiotic-susceptible K. pneumoniae bacteraemia. This observation may provide sufficient clinical equipoise for a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Background The epidemiology of hepatitis C virus (HCV) infection in people living with HIV has been evolving, with increasing evidence of permucosal (sexual) transmission identified predominantly in HIV-positive men who have sex with men (MSM). The aim of this study was to estimate the incidence rate and elucidate epidemiological factors associated with HCV infection among HIV-infected men in Singapore from 2006 to 2018.Methods: A retrospective cohort study was conducted using a clinical database maintained by the Clinical HIV Program at the National Centre for Infectious Diseases, Singapore. Factors associated with incident HCV infections were identified using Cox proportional hazards regression analyses.Results: Among 1348 HIV-infected male patients who were HCV seronegative at baseline, 64 (4.7%) subsequently tested positive for HCV, giving an incidence of 0.88 per 100 person-years of follow-up (PYFU) (95% confidence interval (CI) 0.69-1.13). The incidence rate of HCV seroconversion increased from 0.33 (95% CI 0.12-0.71) per 100 PYFU in 2010-2012 to 1.93 (95% CI 1.36-2.67) in 2016-2018. Independent factors associated with incident HCV infection were younger age groups at HIV diagnosis versus ≥45 years, HIV acquisition via MSM or via both sexual contact and intravenous drug use versus heterosexual transmission, HIV diagnosis in later periods versus 2006-2009, and recent syphilis acquisition.Conclusions: An increasing trend of incident HCV infection was seen in HIV-infected men, particularly for MSM. Preventive and behavioural interventions should be targeted at HIV-infected individuals engaged in high-risk sexual behaviour. [ABSTRACT FROM AUTHOR]

Purpura fulminans is a serious condition that can result in severe morbidity in the pediatric population. Although autologous skin grafts remain the gold standard for the coverage of partial- to full-thickness wounds, they have several limitations in pediatric patients, including the lack of planar donor sites, the risk of hemodynamic instability, and the limited graft thickness. In Singapore, an in-house skin culture laboratory has been available since 2005 for the use of cultured epithelial autografts (CEAs), especially in burn wounds. However, due to the fragility of CEAs, negative-pressure wound therapy (NPWT) dressings have been rarely used with CEAs. With several modifications, we report a successful case of NPWT applied over a CEA in an infant who sustained 30% total body surface area full-thickness wounds over the anterior abdomen, flank, and upper thigh secondary to purpura fulminans. We also describe the advantages of using NPWT dressing over a CEA, particularly in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis is crucial in securing optimal outcomes in the HIV care cascade. Recent HIV infection (RHI) serves as an indicator of early detection in the course of HIV infection. Surveillance of RHI is important in uncovering at-risk groups in which HIV transmission is ongoing. The study objectives are to estimate the proportion of RHI among persons newly-diagnosed in 2013-2017, and to elucidate epidemiological factors associated with RHI in Singapore.Methods: As part of the National HIV Molecular Surveillance Programme, residual plasma samples of treatment-naïve HIV-1 positive individuals were tested using the biotinylated peptide-capture enzyme immunoassay with a cutoff of normalized optical density ≤ 0.8 for evidence of RHI. A recent infection testing algorithm was applied for the classification of RHI. We identified risk factors associated with RHI using logistic regression analyses.Results: A total of 701 newly-diagnosed HIV-infected persons were included in the study. The median age at HIV diagnosis was 38 years (interquartile range, 28-51). The majority were men (94.2%), and sexual route was the predominant mode of HIV transmission (98.3%). Overall, 133/701 (19.0, 95% confidence interval [CI] 16.2-22.0%) were classified as RHI. The proportions of RHI in 2015 (31.1%) and 2017 (31.0%) were significantly higher than in 2014 (11.2%). A significantly higher proportion of men having sex with men (23.4, 95% CI 19.6-27.6%) had RHI compared with heterosexual men (11.1, 95% CI 7.6-15.9%). Independent factors associated with RHI were: age 15-24 years (adjusted odds ratio [aOR] 4.18, 95% CI 1.69-10.31) compared with ≥55 years; HIV diagnosis in 2015 (aOR 2.36, 95% CI 1.25-4.46) and 2017 (aOR 2.52, 95% CI 1.32-4.80) compared with 2013-2014; detection via voluntary testing (aOR 1.91, 95% CI 1.07-3.43) compared with medical care; and self-reported history of HIV test(s) prior to diagnosis (aOR 1.72, 95% CI 1.06-2.81).Conclusion: Although there appears to be an increasing trend towards early diagnosis, persons with RHI remain a minority in Singapore. The strong associations observed between modifiable behaviors (voluntary testing and HIV testing history) and RHI highlight the importance of increasing the accessibility to HIV testing for at-risk groups. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is an important respiratory pathogen that affects people of all ages. Objectives: We examined the patterns of RSV circulation in 2014‐2018, and investigated their age‐specific differences in tropical Singapore. Methods: Nasopharyngeal and/or throat swabs were taken from outpatient attendees for the national influenza virological surveillance among those who presented with acute respiratory illness in the community. Specimens tested negative for influenza were then tested for RSV and other respiratory pathogens. Results: Among 8436 influenza‐negative specimens tested during the five‐year period, 5.8% (95% confidence interval 5.3%‐6.3%) were positive for RSV. The peak of RSV activity occurred around middle of the year. The age‐specific proportion of RSV detections showed a reverse J‐shaped pattern; RSV positivity was the highest in young children ≤2 years of age (10.9%), followed by those aged 3‐5 years (6.4%) and persons aged ≥65 years (5.3%), while the nadir was observed in the age group of 15‐24 years (1.2%). RSV type A was predominantly circulating in children ≤5 years of age from 2014 to 2015 and 2017, whereas in 2016, they were more affected by type B. Conclusion: Respiratory syncytial virus was more frequently detected among the two age groups that have been recommended for influenza vaccination; persons ≥65 years of age and children 6 months to <5 years of age. Characterisation of RSV activity in the community helps to better inform public health policies for effective prevention and control interventions. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study is to compare Parkinson's disease (PD) treatment practices by movement disorder (MD) specialists across a decade, and to determine the factors that influence drug choice for the motor symptoms of PD in newly diagnosed drug-naïve patients. Methods. This prospective temporal analysis included patients seen at the National Neuroscience Institute in Singapore and diagnosed with PD by MD specialists in the years 2007 and 2017. Primary outcomes were use of specific PD drugs and changes in drug-prescribing patterns. Descriptive analyses and multivariable logistic regression models determined the extent to which patient characteristics were associated with type of PD treatment. Results. Of 230 patients with PD (mean (SD) age, 66.7 (10.3) years), 131 (57.0%) were male. From 2007 to 2017, the use of ergot dopamine agonists and anticholinergics decreased from 19.3% to 2.0% (P < 0.001) and from 12.0% to 2.7% (P = 0.004), respectively. The use of monoamine oxidase B inhibitors (MAOBI) increased from 13.3% to 25.2% (P = 0.033). The use of levodopa (LD)-sparing strategies decreased nonsignificantly from 33.7% to 24.5% (P = 0.133). Overall, 196 (85.2%) patients were initiated on symptomatic monotherapy, with LD being the most commonly prescribed. MAOBI was the most common drug used in combination therapy. Age ≤70 (adjusted OR, 11.9; 95% CI, 4.5–31.5) and Hoehn and Yahr (HY) stage <2 (adjusted OR, 3.4; 95% CI, 1.5–7.7) were independent factors for LD-sparing strategies. Non-LD prescriptions (13 of 92; 14.1%) were more likely to be discontinued compared to LD ones (6 of 149; 4.0%) (P = 0.005). Conclusions. Drug-prescribing patterns in PD have changed significantly through the last decade, influenced by emerging evidence and reports of adverse drug effects. Choosing drugs based on the patient's age and disease severity remain sound guiding principles across the years. It is important that international and national guidelines for pharmacotherapy in PD be updated consistently throughout different socioeconomic settings to optimize care. [ABSTRACT FROM AUTHOR]

Surveillance and reporting of epidemiological features of seasonal influenza mostly are aggregates across all‐ages. We investigated age‐specific differences in distribution of influenza virus (sub)types in tropical Singapore, using laboratory‐confirmed virological data collected under the national influenza surveillance programme from 2011 to 2017. The proportion of influenza‐positive specimens from outpatients with influenza‐like illness was used as an indicator of influenza activity in the community. The highest influenza positivity for age groups of 5 to 14 years and 15 to 64 years coincided in the same month in 5 out of the 7 years under study. Influenza positivity was lowest in young children <5 years of age compared with older age groups. Influenza A(H3N2) was most prevalent in the community except in 2012 when a predominance of influenza B was observed. The dominant virus (sub)type varied across the years in children <5 years and 5 to 14 years of age. Influenza A(H3N2) was the predominant circulating virus subtype among elderly persons aged ≥65 years during the 7‐year period, and among adults aged 15 to 64 years since 2013. Knowledge about the age‐specific differences in distribution of influenza virus (sub)types helps to facilitate better understanding of seasonal epidemics and to inform targeted strategies in prevention and control of influenza virus transmission. Highlight: Influenza peak for age groups of 5–14 years and 15–64 years mostly coincided in the same month.Influenza positivity was lowest in young children <5 years of age.Children <5 years of age experienced a mixture of influenza A and B viruses as the predominant types.Age groups of 5–14 years and 15–64 years were mostly affected by A(H3N2) followed by influenza B.Influenza A(H3N2) was particularly prevalent in elderly persons aged ≥65 years. [ABSTRACT FROM AUTHOR]

National data on dengue notifications do not capture all dengue infections and do not reflect the true intensity of disease transmission. To assess the true dengue infection rate and disease control efforts in Singapore, we conducted age-stratified serosurveys among residents after a 2013 outbreak that was the largest dengue outbreak on record. The age-weighted prevalence of dengue immunoglobulin G among residents was 49.8% (95% confidence interval: 48.4, 51.1) in 2013 and 48.6% (95% confidence interval: 47.0, 50.0) in 2017; prevalence increased with age. Combining these data with those from previous serosurveys, the year-on-year estimates of the dengue force of infection from 1930 to 2017 revealed a significant decrease from the late 1960s to the mid-1990s, after which the force of infection remained stable at approximately 10 per 1,000 persons per year. The reproduction number (R 0) had also declined since the 1960s. The reduction in dengue transmission may be attributed to the sustained national vector program and partly to a change in the age structure of the population. The improved estimated ratio of notified cases to true infections, from 1:14 in 2005–2009 to 1:6 in 2014–2017, signifies that the national notification system, which relies on diagnosed cases, has improved over time. The data also suggest that the magnitudes of dengue epidemics cannot be fairly compared across calendar years and that the current disease control program remains applicable. [ABSTRACT FROM AUTHOR]

Introduction: Patients may be symptomatic, resulting in lower quality of life (QOL), despite L-thyroxine (LT4) therapy for hypothyroidism or having normal thyroid function. We hypothesized that their clinical symptoms of hypothyroidism and co-morbidities were associated with QOL.Objective: The study aimed to determine the association between the hypothyroid-related symptoms of Asian patients on LT4 treatment, their co-morbidities and their QOL.Method: A questionnaire survey was conducted from November 2015 to July 2016 on consecutive multi-ethnic Asian patients on LT4 treatment for their hypothyroidism in a public primary care clinic in Singapore. Data on their demography, clinical symptoms, morbidity status, QOL scores based on the EQ5D instrument and thyroid function tests were computed and analysed, including logistic regression analysis to identify factors associated with lower QOL.Results: Complete data of 226 Asian patients (79.0% women; 74.2% Chinese, 10.0% Malay, 13.1% Indian and 2.6% other minority groups; median age 57 years; 27.5% had previous thyroid surgery) were analysed. Their QOL was not associated with their socio-demographic profiles, clinical parameters and latest thyroid-stimulating hormone and free thyroxine levels. Patients reporting weight gain, dry or coarse skin, leg swelling, feeling weak and carpal tunnel syndrome had significantly lower QOL; 53.6% of them with any single symptom had lower QOL. More patients had lower QOL if they had two or more symptoms and multiple medical conditions.Conclusion: In Asian patients with hypothyroidism, weight gain, feeling tired, feeling weak, having dry or coarse skin, leg swelling and increased number of co-morbidities and symptoms were significantly associated with poorer QOL. [ABSTRACT FROM AUTHOR]

Objectives: Since the 1990s, Singapore has experienced periodic dengue epidemics of increasing frequency and magnitude. In the aftermath of the 2004–2005 dengue epidemic, hospitals refined their admission criteria for dengue cases to right-site dengue case management and reduce the burden of healthcare utilization and negative outcomes. In this study, we describe the national trends of hospital admissions for dengue and disease severity in terms of length of stay (LOS), admission to the intensive care unit (ICU) and death in hospital, and case fatality rate (CFR) in Singapore. Methods: We conducted a retrospective study of notified cases and laboratory confirmed dengue patients admitted to all public and private hospitals between 2003 and 2017. Case notifications for dengue and hospitalization records were extracted from national databases. Results: The proportion of dengue cases hospitalized was lower in recent years; 28.9% in the 2013–2014 epidemic, compared to 93.2% in the 2004–2005 epidemic, and 58.1% in the 2007 epidemic. Median LOS remained stable over the years; overall LOS was 3 to 4 days and ICU stay was 2 to 3 days. Less than 2% of hospitalized patients were admitted to the ICU. Overall CFR was low and remained below 0.5%. The proportions of dengue cases hospitalized and patients admitted to the ICU were highest in the elderly aged 65 years and older. Conclusions: While the proportion of dengue cases hospitalized saw a drastic decline due to more selective admission criteria, there was no concomitant increase in adverse outcomes, suggesting that admission criteria were appropriate to focus on severe dengue cases. Further studies are needed to optimize dengue management in older adults who are more likely to be hospitalized with greater disease severity, given the higher proportions of hospitalizations and severe disease among older adults. [ABSTRACT FROM AUTHOR]

Acoustic signalling is the most important form of communication in anuran amphibians. Here we recorded and analysed the calls of 18 male Guenther's frogs (Hylarana guentheri) from the wild during the breeding season. The advertisement calls of H. guentheri were composed of from a single note to five notes, with three-note calls the most recorded. All individuals produced calls around 600 Hz but calls ranged from 470 to 2600 Hz. Comparing the differences between individuals calls, we found within-male coefficients of variation (CVw) of call intensity, the fundamental frequency, the first formant, the second formant, the third formant and the fourth formant were static (less than 5% variation), whereas those of note duration, call duration, call interval, numbers of pulses and dominant frequency were dynamic (larger than 15% variation). Comparisons of the call characteristics of H. guentheri in this study with other studies from China, Singapore and Vietnam found call characteristics varied greatly between the five different locations. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates the demographics of paediatric pedestrian injuries with the aim of identifying the group of children who is most vulnerable and the risk factors for major trauma (MT).Methods: Data was extracted from the integrated trauma system of a regional paediatric referral hospital. All paediatric cases involving road traffic accidents from January 2011 to December 2013 were studied. Demographics, injury mechanism, treatment and outcome were evaluated. Patients were categorised as MT or non-MT (NMT) based on their Injury Severity Score, admission to the intensive care unit, type of surgery (e.g. life/limb-saving) and death. Data analysis was done using nonparametric tests and Fisher's exact test.Results: A total of 261 children were admitted for pedestrian injuries during the study period. The median age was ten years (range 14 months-16 years) and the median weight was 42.4 (range 8.6-93.7) kg. Half (i.e. 50.2%) of the children were primary-schoolers. The majority of the accidents occurred on roads (i.e. 83.1%), between 12 pm and 6 pm (i.e. 52.8%). Among the 261 children, 177 (67.8%) were unaccompanied by an adult at the time of the accident; 17 (6.5%) children sustained MT, while 244 (93.5%) suffered NMT. MT patients were more likely to have lost consciousness (p < 0.001) and been flung (p = 0.001).Conclusion: Most paediatric pedestrian injuries involved primary-schoolers walking home from school unaccompanied by adults. This information should inform future road safety campaigns. Being flung and loss of consciousness predicted MT in children who sustained pedestrian injuries. [ABSTRACT FROM AUTHOR]

Aims: In Singapore, pneumococcal vaccination is recommended for the elderly (i.e. those ≥65 years of age) and people with chronic medical conditions. We investigated epidemiological characteristics associated with the uptake of pneumococcal vaccine based on a nationally representative cross-sectional sample of community-living adults aged ≥50 years. Methods: The data were obtained from the National Health Surveillance Survey (NHSS) 2013. Associations between pneumococcal vaccination and sociodemographic and health-related variables were analysed using univariable and multivariable logistic regression models. Results: Among 3672 respondents aged ≥50 years in the NHSS, 7.8% had taken the pneumococcal vaccination. A higher level of education and higher monthly household income were sociodemographic characteristics independently associated with pneumococcal vaccine uptake. Health-related characteristics predictive of pneumococcal vaccine uptake were better self-rated health and having a regular family doctor/general practitioner. Among those who responded to the two questions on vaccinations, 3.9% had been vaccinated against both seasonal influenza and pneumococcal infection, while 11.1% had taken only seasonal influenza vaccination in the past year. Conclusions: There is a need to boost pneumococcal vaccination coverage among community-dwelling older adults. These findings provide insights into reviewing and tailoring public-health strategies and programmes to increase vaccine uptake in at-risk population groups. [ABSTRACT FROM AUTHOR]

Objectives: We determined the seroprevalence of chikungunya virus (CHIKV) infection in the adult resident population in Singapore following local outbreaks of chikungunya fever (CHIKF) in 2008–2009. Methods: Our cross-sectional study involved residual sera from 3,293 adults aged 18–79 years who had participated in the National Health Survey in 2010. Sera were tested for IgG antibodies against CHIKV and dengue virus (DENV) and neutralizing antibodies against CHIKV. Results: The prevalence of CHIKV-neutralizing antibodies among Singapore residents aged 18–79 years was 1.9% (95% confidence interval: 1.4%– 2.3%). The CHIKV seroprevalence was highest in the elderly aged 70–79 years at 11.5%, followed by those aged 30–39 years at 3.1%. Men had significantly higher CHIKV seroprevalence than women (2.5% versus 1.3%, p = 0.01). Among the three main ethnic groups, Indians had the highest seroprevalence (3.5%) compared to Chinese (1.6%) and Malays (0.7%) (p = 0.02 and p = 0.01, respectively). Multivariable logistic regression identified adults aged 30–39 years and 70–79 years, men, those of Indian ethnicity and ethnic minor groups, and residence on ground floor of public and private housing apartments as factors that were significantly associated with a higher likelihood of exposure to CHIKV. The overall prevalence of anti-DENV IgG antibodies was 56.8% (95% CI: 55.1%– 58.5%), while 1.5% (95% CI: 1.1%– 2.0%) of adults possessed both neutralizing antibodies against CHIKV and IgG antibodies against DENV. Conclusions: Singapore remains highly susceptible to CHIKV infection. There is a need to maintain a high degree of vigilance through disease surveillance and vector control. Findings from such serological study, when conducted on a regular periodic basis, could supplement surveillance to provide insights on CHIKV circulation in at-risk population. [ABSTRACT FROM AUTHOR]

Influenza is a major cause of mortality and morbidity. We aimed to examine the influenza-associated hospitalization rates and proportions for cardiovascular disease (CVD) in tropical Singapore. Hospital admissions for ischemic heart disease (IHD), congestive heart failure (CHF), and overall CVD were obtained from the national inpatient database for the period of 2010--2014. We used, as the key indicator of influenza virus activity, the overall proportion of specimens from outpatients with influenza-like illness in the community that tested positive for influenza as part of the national influenza surveillance program. The annual influenza-associated hospitalization rates per 100,000 personyears ranged from 9.5 to 12.2 for IHD, 7.7 to 9.1 for CHF, and 15.8 to 19.2 for overall CVD. The influenza-associated hospitalization rates increased with increasing age. Influenza was significantly associated with excess hospitalizations in elderly persons aged ≥80 years, with an excess hospitalization rate per 100,000 person-years of 242.7 for IHD (P = 0.02), 271.8 for CHF (P = 0.01), and 497.2 for overall CVD (P < 0.001). In the tropics, influenza accounts for excess cardiovascular-related hospitalizations, especially in the elderly. [ABSTRACT FROM AUTHOR]

Objective In line with regional and global goals for the elimination of rubella and congenital rubella syndrome (CRS), we reviewed the epidemiological situation in Singapore, based on surveillance reports on rubella and CRS, national immunization coverage and seroprevalence surveys. The aim of our review was to identify current gaps and steps taken to achieve the targets set by the World Health Organization (WHO) Western Pacific Regional Office (WPRO). Methods Epidemiological data on clinical and laboratory-confirmed rubella cases, including CRS, notified to the Communicable Diseases Division, Ministry of Health, Singapore, from 2003 to 2013 were collated and analyzed. Vaccination coverage against rubella was obtained from the National Immunization Registry and School Health Services of the Health Promotion Board. The changing prevalence of rubella was determined from periodic serological surveys. Findings The incidence of indigenous rubella cases per million population decreased from 37.2 in 2008 to 7.6 in 2013 and there had been no indigenous case of CRS in 2012 and 2013. Therapeutic abortions performed due to rubella infections had become uncommon. The annual measles, mumps, and rubella (MMR) vaccination coverage in childhood population remained high ranging from 93% to 96%. The overall susceptibility to rubella in women aged 18–44 years had reduced significantly from 15.8% in 2004 to 11.0% in 2010. The prevalence of IgG antibody against rubella among Singapore children aged 1–17 years was maintained at 87.3% in 2008–2010. Conclusion All available data indicated that Singapore has made good progress towards the elimination of rubella and CRS. It has attained the targets set by the WHO WPRO for 2015. In preparation for verification of rubella elimination, an enhanced surveillance system has been implemented to ensure that all reported cases are laboratory confirmed, and genotyping of rubella virus strains isolated is carried out to provide evidence for interruption of endemic transmission. [ABSTRACT FROM AUTHOR]

Objective. Wearable and wireless motion sensor devices have facilitated the automated computation of speed, amplitude, and rhythm of hand motion tasks. The aim of this study is to determine if there are any biological influences on these kinematic parameters. Methods. 80 healthy subjects performed hand motion tasks twice for each hand, with movements measured using a wireless motion sensor device (Kinesia, Cleveland Medical Devices Inc., Cleveland, OH). Multivariate analyses were performed with age, gender, and height added into the model. Results. Older subjects performed poorer in finger tapping (FT) speed (r=0.593, p<0.001), hand-grasp (HG) speed (r=0.517, p<0.001), and pronation-supination (PS) speed (r=0.485, p<0.001). Men performed better in FT rhythm p<0.02, HG speed p<0.02, HG amplitude p<0.02, and HG rhythm p<0.05. Taller subjects performed better in the speed and amplitude components of FT p<0.02 and HG tasks p<0.02. After multivariate analyses, only age and gender emerged as significant independent factors influencing the speed but not the amplitude and rhythm components of hand motion tasks. Gender exerted an independent influence only on HG speed, with better performance in men p<0.05. Conclusions. Age, gender, and height are not independent factors influencing the amplitude and rhythm components of hand motion tasks. The speed component is affected by age and gender differences. [ABSTRACT FROM AUTHOR]

Coxsackieviruses A6 (CV-A6) and A16 (CV-A16) and Enterovirus 71 (EV-A71) have caused periodic epidemics of hand, foot and mouth disease (HFMD) among children in Singapore. We conducted a cross-sectional study to estimate the seroprevalence of these enteroviruses among Singapore children and adolescents. The study was conducted between August 2008 and July 2010. It involved 700 Singapore residents aged 1–17 years whose residual sera were obtained following the completion of routine biochemical investigations in two public acute-care hospitals. The levels of neutralizing antibodies (NtAb) against CV-A6, CV-A16 and EV-A71 were analyzed by the microneutralization test. The age-specific geometric mean titer (GMT) of antibodies against each of the three enteroviruses and the 95% confidence intervals (CI) were calculated. The seroprevalence of CV-A6 and CV-A16 was high at 62.7% (95% CI: 59.1–66.2%) and 60.6% (95% CI: 56.9–64.1%), respectively. However, the seroprevalence of EV-A71 was significantly lower at 29.3% (95% CI: 26.0–32.8%). About 89.7% of the children and adolescents had been infected by at least one of the three enteroviruses by 13–17 years of age. About half (52.3%) were seropositive for two or all three enteroviruses, while only 16.1% had no NtAb against any of the three enteroviruses. High NtAb levels were observed in the younger age groups. CV-A6 and CV-A16 infections are very common among Singapore children and adolescents, while EV-A71 infections are less common. Infection is continually acquired from early childhood to adolescent age. [ABSTRACT FROM AUTHOR]

Background/objectives Singapore is a tropical country with influenza seasons occurring bi-annually. We compared the profile of severely ill patients with laboratory confirmed influenza A(H1N1)pdm09 infection in Singapore during the pandemic and post-pandemic periods, and studied their risk factors associated with mortality. Patients/methods Three periods were defined for this study; pandemic period from 18 June to 29 August 2009, early post-pandemic period from 30 August 2009 to 12 February 2010, and late post-pandemic period from 13 February to 10 August 2010. Results A total of 172 severely ill patients were admitted to hospitals from 18 June 2009 to 10 August 2010, of whom 23.8% died. The median age in the late post-pandemic period was significantly older than that in the early post-pandemic period (52 years versus 35 years, P = 0.02). The median age of patients who died was significantly older than those who survived (52 years versus 44 years, P < 0.01). The median length of stay under intensive care in the late post-pandemic period was twice that in the early post-pandemic (6 days versus 3 days, P = 0.045). The proportion who died in the late post-pandemic period was more than 2.5 times that in the early post-pandemic period (29.8% versus 11.1%, P = 0.043). Conclusions Severely ill patients were of older age in the late post-pandemic period. Older age was also significantly associated with mortality. It is important to maintain heightened vigilance and continue the surveillance of severely ill patients with influenza post-pandemic, so that patients with suspected infections could be promptly identified for early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Incense burning is common in many parts of the world. Although it is perceived that particulate matter from incense smoke is deleterious to health, there is no epidemiologic evidence linking domestic exposure to cardiovascular mortality. Objective: We examined the association between exposure to incense burning and cardiovascular mortality in the Singapore Chinese Health Study. Methods: We enrolled a total of 63,257 Singapore Chinese 45–74 years of age during 1993–1998. All participants were interviewed in person to collect information about lifestyle behaviors, including the practice of burning incense at home. We identified cardiovascular deaths via record linkage with the nationwide death registry through 31 December 2011. Results: In this cohort, 76.9% were current incense users, and most of the current users (89.9%) had burned incense daily for ≥ 20 years. Relative to noncurrent users, current users had a 12% higher risk of cardiovascular mortality [multivariable adjusted hazard ratio (HR) = 1.12; 95% CI: 1.04, 1.20]. The HR was 1.19 (95% CI: 1.03, 1.37) for mortality due to stroke and 1.10 (95% CI: 1.00, 1.21) for mortality due to coronary heart disease. The association between current incense use and cardiovascular mortality appeared to be limited to participants without a history of cardiovascular disease at baseline (HR = 1.16; 95% CI: 1.07, 1.26) but not linked to those with a history (HR = 1.00; 95% CI: 0.86, 1.17). In addition, the association was stronger in never-smokers (HR = 1.12; 95% CI: 1.02, 1.23) and former smokers (HR = 1.19; 95% CI: 1.00, 1.42) than in current smokers (HR = 1.05; 95% CI: 0.91, 1.22). Conclusions: Long-term exposure to incense burning in the home environment was associated with an increased risk of cardiovascular mortality in the study population. [ABSTRACT FROM AUTHOR]

We evaluated a disease management and education programme delivered via telephone support (TS) to patients with poorly controlled diabetes (HbA1c >7%). All eligible patients were invited to participate in the programme, which involved education on lifestyle modification and disease management delivered via three scheduled monthly calls by trained nurses. Patients who declined or could not be contacted acted as the controls (usual care, UC). A per protocol analysis was conducted using a mixed effect model for two subgroups with different baseline HbA1c levels (i.e. baseline HbA1c <8.0% and HbA1c ≥8.0%). A total of 2646 patients with diabetes were eligible for enrolment. Of these, 1391 participants had HbA1c measurements available. The study comprised 633 patients (46%) who completed the programme (TS), 598 (43%) who were not contactable or refused to participate at the first telephone call (UC) and 160 patients who dropped out. In the patients with HbA1c ≥8%, TS reduced the adjusted mean HbA1c by 0.38% (P = 0.022) but the reduction in diabetes-related admissions (4.2% lower adjusted mean admission rate) was not significant. In patients with HbA1c <8%, TS had no additional effect on glycaemic control or diabetes-related admission. Telephone support appeared effective in improving glycaemic control in patients with poor diabetes control. [ABSTRACT FROM AUTHOR]

Background Limited information is available about seasonal influenza vaccine effectiveness ( VE) in tropical communities. Objectives Virus subtype-specific VE was determined for all military service personnel in the recruit camp and three other non-recruit camp in Singapore's Armed Forces from 1 June 2009 to 30 June 2012. Methods Consenting servicemen underwent nasal washes, which were tested with RT- PCR and subtyped. The test positive case and test negative control design was used to estimate the VE. To estimate the overall effect of the programme on new recruits, we used an ecological time series approach. Results A total of 7016 consultations were collected. The crude estimates for the VE of the triavalent vaccine against both influenza A( H1 N1)pdm09 and influenza B were 84% (95% CI 78-88%, 79-86%, respectively). Vaccine efficacy against influenza A( H3 N2) was markedly lower ( VE 33%, 95% CI −4% to 57%). An estimated 70% ( RR = 0·30; 95% CI 0·11-0·84), 39% ( RR = 0·61;0·25-1·43) and 75% ( RR = 0·25; 95% CI 0·11-0·50) reduction in the risk of influenza A( H1 N1)pdm09, influenza A( H3 N2) and influenza B infections, respectively, in the recruit camp during the post-vaccination period compared with during the pre-vaccination period was observed. Conclusions Overall, the blanket influenza vaccine programme in Singapore's Armed Forces has had a moderate to high degree of protection against influenza A( H1 N1)pdm09 and influenza B, but not against influenza A( H3 N2). Blanket influenza vaccination is recommended for all military personnel. [ABSTRACT FROM AUTHOR]

Summary: Objective: To understand the seroepidemiology of varicella zoster virus (VZV) in the Singaporean population, based on a paediatric survey conducted in 2008–2010 and the 2010 National Health Survey. The findings were compared with previous studies carried out in 1989–1990, 1993, 1998, and 2004. Methods: The paediatric survey involved 1200 subjects; residual diagnostic serum samples were collected from Singapore residents aged 1–17 years at two hospitals. The adult survey involved 3293 subjects; residual serum samples were obtained from Singapore residents aged 18–79 years who had participated in the 2010 National Health Survey. Results: The seroprevalence in children under 5 years of age increased from 4% in 1989/1990 to 11.7% in 1998 and 33.2% in 2008–2010. For children aged 5–14 years, the corresponding seroprevalences were 22.8%, 59.5%, and 58.0%. The seroprevalence in children aged 5–14 years in 2008–2010 was not significantly different from that in 1998 (p =0.721). Among Singapore adults over 25 years of age, the seroprevalence remained consistently high at around 88% from 1998/1990 to 2010. Conclusions: Nearly two-thirds of pre-school children, 39.5% of primary school children, and 29% of adolescents aged 13–17 years are susceptible to VZV infection. At this level of immunity, it can be expected that outbreaks will continue to occur unless the varicella vaccine is introduced into the national childhood immunization programme. [Copyright &y& Elsevier]

Introduction A regionalized trauma system must be tailored to the trauma epidemiology and the trauma care resources of the population it serves. Pediatric trauma system in Singapore differs from others because of its geographic compactness and relatively low incidence of severe trauma. The scarcity of polytrauma highlights the need of a reliable screening system to identify injured children who necessitate urgent transport to emergency department (ED) with pediatric resuscitation capacity as well as activation of trauma team upon their arrival. In this study, the validity of Pediatric Trauma Score (PTS), Glasgow Come Scale (GCS), and respiratory rate (RR) in identifying pediatric patients with major trauma and receipt of resuscitation is evaluated. Patients and Methods After obtaining Institutional Review Board approval, a retrospective analysis was performed using data obtained from our trauma registry between January 2011 and December 2012. Information pertaining to the demographics, causative mechanism, and injury description, resuscitation, admitting disciplines, surgical intervention, and outcome were analyzed. The sensitivity and specificity of PTS, GCS, and RR to predict outcomes of interest are calculated. Results A total of 92 patients were recruited. From the 92 patients, 26 sustainedmajor trauma, and 21 patients received ED resuscitation. Themean age was 4 years 9 months. Sensitivity and specificity of PTS ⩽ 8, GCS ⩽ 10, and abnormal RR for predicting major trauma were 61.5, 77.3; 26.9, 100; and 53.8, 60.6%; respectively. When the reliability to identify patients received ED resuscitation was evaluated the sensitivity and specificity of PTS ⩽ 8, GCS ⩽ 10, and abnormal RR were 90.5, 83.1; 28.6, 98.6; and 76.2, 66.2%; respectively. Conclusion The parameters of PTS need to be further refined to improve its accuracy and minimize the undertriage rate. If a combined physiologic and anatomic scoring system such as PTS is used, other physiologic parameters such as GCS and RR may become redundant. The evaluation of the validity of PTS, GCS, and RR in predicting pediatric major trauma indicated poor reliability. [ABSTRACT FROM AUTHOR]

Highlights: [•] We assessed the changing seroprevalence of hepatitis B virus (HBV) markers in adults in Singapore. [•] Hepatitis B vaccination in the national childhood immunisation programme was extended to all newborns on 1 September 1987. [•] The national childhood HBV immunisation and catch-up programmes in 2001–2004 raised the immunity of those aged 18–29 years. [•] The prevalence of hepatitis B surface antigen (HBsAg) was 3.6% in 2010, within the range of intermediate HBV endemicity. [•] HBsAg prevalence among permanent residents who were foreign-born was 1.4 times that of Singapore citizens. [ABSTRACT FROM AUTHOR]

Summary: Objectives: We undertook an epidemiological review to determine the trend and characteristics of acute hepatitis E in Singapore over the last 12 years. Methods: We analysed the epidemiological records of all laboratory-confirmed cases of acute hepatitis E maintained at the Communicable Diseases Division, Ministry of Health, from 2000 to 2011. Results: A total of 540 laboratory-confirmed cases of acute hepatitis E was reported with more than half imported, mainly from India and Bangladesh. Among the indigenous cases, the mean annual incidence per 100,000 population increased from 0.05 in 2000–2002 to 0.92 in 2009–2011. There was a male predominance and the median age was 46 years. Among the 3 major ethnic groups of Singapore residents, Chinese and Indians had higher mean annual incidence rate compared to Malays. All the indigenous cases occurred singly and sporadically and could not be epidemiologically linked to one another by person, place or time. No common food item was implicated. Conclusions: Indigenous acute hepatitis E has emerged as a major cause of acute viral hepatitis in Singapore. While epidemiological investigations are ongoing to elucidate the risk factors and modes of transmission, travellers should be reminded to practise a high standard of personal and food hygiene when visiting endemic countries. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the epidemiological features of the 2007 dengue outbreak to determine the factors that could have triggered it two years after the previous large outbreak in 2005. Methods: All laboratory-confirmed cases of dengue reported during the year, as well as entomological and virological data, were analysed. Results: A total of 8826 cases including 24 deaths were reported in 2007, giving an incidence of 192.3 cases per 100 000 residents and a case-fatality rate of 0.27%. The median age of the cases was 37 years (interquartile range 25 to 50), with an age range from two days to 101 years, which was higher than the median age of 31 years (interquartile range 20 to 42), with a range from four days to 98 years, in 2005. The overall Aedes premises index in 2007 was 0.68%, lower than the 1.15% observed in 2005. The predominant dengue serotype in 2007 was dengue virus DENV-2 which re-emerged with a clade replacement in early 2007, and overtook the predominant serotype (DENV-1) of 2005. Seroprevalence studies conducted in the three largest outbreak clusters revealed that 73.2% of residents with recent infection were asymptomatic. Discussion: With the exception of an increase in the median age of the cases, and a change in the predominant dengue serotype, the epidemiological features of the 2007 epidemic were largely similar to those of 2005. Singapore remains vulnerable to major outbreaks of dengue, despite sustained vector control measures to maintain a consistently low Aedes premises index. [ABSTRACT FROM AUTHOR]

To determine trends and clinical and epidemiologic features of legionellosis in Singapore, we studied cases reported during 2000-2009. During this period, 238 indigenous and 33 imported cases of legionellosis were reported. Cases were reported individually and sporadically throughout each year. Although the annual incidence of indigenous cases had decreased from 0.46 cases per 100,000 population in 2003 to 0.16 cases per 100,000 in 2009, the proportion of imported cases increased correspondingly from 6.2% during 2000-2004 to 27.3% during 2005-2009 (p<0.0005). The prevalence of Legionella bacteria in cooling towers and water fountains was stable (range 12.1%-15.3%) during 2004-August 2008. [ABSTRACT FROM AUTHOR]

Summary: Objectives: We conducted an epidemiological review of the chikungunya fever situation in Singapore and described the measures taken to prevent the chikungunya virus from becoming entrenched in the tropical city-state. Methods: All laboratory-confirmed cases and outbreak investigation reports maintained by the Communicable Diseases Division, Ministry of Health, and Aedes mosquito surveillance data obtained by the National Environment Agency during the period 2006 and 2009 were reviewed and analysed. Results: Sporadic cases were imported into Singapore until the first local transmission occurred in an urban area where Aedes aegypti was the predominant vector. Subsequent introduction of a mutant viral strain (A226V) in early 2008 resulted in the rapid spread to suburban and rural areas where Aedes albopictus was the primary vector. 1072 cases including 812 (75.7%) indigenous cases were reported. The main sources of importation were India and Malaysia. Foreign contract workers were identified as high-risk for indigenous infections. Conclusions: The disease was successfully brought under control through aggressive vector control measures directed at A. albopictus. Although the incidence has sharply declined since January 2009, a high degree of vigilance is maintained to prevent a recurrence of epidemic transmission which can occur even with a well-established nationwide mosquito control programme. [ABSTRACT FROM AUTHOR]

The article focuses on HIV infection and AIDS in Singapore. The first case of HIV infection in Singapore was detected in May 1985. The number of new cases of HIV and AIDS reported to Singapore Ministry of Health increased steadily until 1990. The number of new cases has stabilized since then, with between 200 and 240 new cases reported annually. The mode of HIV transmission at the beginning of the epidemic had been predominantly homosexual or bisexual. Heterosexual transmission, however, has been the main mode of HIV transmission in Singapore since the early 1990s. The vast majority of infections occurred among men, with the ratio between men and women being seven to one. Almost 80% of cases were between the ages of 20 and 49 years at the time of diagnosis.

The incidence of melioidosis in Singapore decreased during 1998-2007, with the exception of the first quarter of 2004. After heavy rainfalls, an increase in pneumonic cases with a high case-fatality rate was detected. We show that melioidosis has the potential to reemerge following adverse climate events. [ABSTRACT FROM AUTHOR]

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.Objective: To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management.Design, Setting, and Participants: Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020.Exposures: Confirmed SARS-CoV-2 infection.Main Outcomes and Measures: Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir.Results: Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results.Conclusions and Relevance: Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent. [ABSTRACT FROM AUTHOR]

Objective: There have been recent reports globally on substantial increase in syphilis diagnoses particularly among high-risk men. The aim of this study was to assess temporal trends of incident syphilis and associated risk factors among HIV-infected men in Singapore.Methods: We conducted retrospective cohort analysis using the clinical database maintained by the Clinical HIV Programme at the National Centre for Infectious Diseases, Singapore. HIV-infected men with a negative syphilis result at baseline who had undergone at least one subsequent test in 2006-2017 were included. Factors associated with incident syphilis were investigated using Cox proportional hazards regression analyses.Results: A total of 1069 HIV-infected men were tested for syphilis at least once following their negative baseline test during the 12-year period, and they contributed 4284 person-years of follow-up (PYFU). There were 266 cases of incident syphilis, giving an overall incidence of 6.21 per 100 PYFU (95% CI 5.49-7.00). The incidence of syphilis per 100 PYFU increased from 1.21 (95% CI 0.33 to 3.10) in 2010 to 26.04 (95% CI 19.97 to 33.40) in 2017. In the multivariable model, risk factors for syphilis seroconversion were: age 15-24 years at HIV diagnosis (adjusted HR (aHR) 1.64, 95% CI 1.05 to 2.56) versus ≥45 years, being Chinese (aHR 1.82, 95% CI 1.01 to 3.29) versus Indian and other minority ethnic groups, men having sex with men (MSM) (aHR 3.29, 95% CI 2.22 to 4.87) versus heterosexuals, and HIV diagnosis in later periods of 2009-2011 (aHR 1.96, 95% CI 1.41 to 2.74), 2012-2014 (aHR 3.96, 95% CI 2.68 to 5.83) and 2015-2017 (aHR 7.94, 95% CI 4.52 to 13.95) versus 2006-2008.Conclusion: The annual incidence rate of syphilis in HIV-infected men was on the rise, and it was consistently higher among MSM than in heterosexual men. The findings supported regular screening for syphilis and enhanced behavioural interventions in Singapore. [ABSTRACT FROM AUTHOR]

Objective We describe the epidemiological trends of measles in Singapore in relation to its progress towards measles elimination and identify gaps in fulfilling the World Health Organization Western Pacific Regional Office regional measles elimination criteria. Methods Epidemiological data on measles maintained by the Communicable Diseases Division, Ministry of Health from 1981 to 2012 were collated and analysed. Data on measles vaccination coverage were obtained from the National Immunization Registry and School Health Services, Health Promotion Board. To assess the seroprevalence of the population, the findings of periodic seroepidemiological surveys on measles were traced and reviewed. Findings With the successful implementation of the National Childhood Immunization Programme using the monovalent measles vaccine, measles incidence declined from 88.5 cases per 100,000 in 1984 to 6.9 per 100,000 in 1991. Resurgences were observed in 1992, 1993 and 1997. A ‘catch-up’ vaccination programme using the trivalent measles, mumps and rubella (MMR) vaccine was conducted in 1997, followed by introduction of the two-dose vaccination schedule in January 1998. Measles incidence subsequently declined sharply to 2.9 per 100,000 in 1998. Vaccination coverage was maintained at 95% for the first dose and 92–94% for the second dose. Seroprevalence surveys showed seropositivity for measles IgG antibodies in over 95% of adults in 2004, and in 83.1% of children aged 1–17 years in 2008–2010. Sporadic cases with occasional clusters of two or more cases continued to occur among the unvaccinated population, especially children aged below 4 years. The predominant measles virus genotype has shifted from D9 to the B3 and G3 genotypes, which are endemic in neighbouring countries. Conclusion Singapore has made good progress towards the elimination of endemic measles. To further eliminate sporadic cases of measles, the national immunisation schedule has recently been amended to vaccinate children with 2 doses of MMR vaccine before 2 years of age. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection.Methods: We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study-a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed.Findings: Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14-28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00-0·48]) compared with infection with wild-type virus only.Interpretation: The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines.Funding: National Medical Research Council Singapore. [ABSTRACT FROM AUTHOR]

• A seroprevalence survey was conducted among Singapore's children and adolescents. • Seroprevalence of measles and rubella antibodies were 98.2% and 94.8% respectively. • Seroprevalence for diphtheria and tetanus were 97.1% and 89.3% respectively. • Seroprevalence for varicella and anti-HBs were 52.9% and 45.7% respectively. • Concordance between vaccination status and seroprevalence was generally observed. The Ministry of Health (MOH), Singapore, conducted the National Paediatric Seroprevalence Survey 2018 (NPSS 2018) to estimate the latest immunity levels against measles, rubella, varicella, diphtheria, tetanus and hepatitis B, and the seroprevalence of chronic hepatitis B virus (HBV) carriage in children and adolescents in Singapore. The survey involved prospective collection of residual sera from 1,200 children and adolescents aged 1–17 years in two public acute hospitals. Enzyme-linked immunosorbent assays (EIA) or plague reduction neutralisation tests (PRNT) were used to determine the seroprevalence of the vaccine-preventable diseases. Overall prevalence of measles and rubella antibodies among Singaporean children and adolescents aged 1–17 years were 98.2% (95% CI: 91.2–98.8%) and 94.8% (95% CI: 93.4–95.9%) respectively. 97.1% (95% CI: 96.0–97.9%) of subjects had at least basic protection against diphtheria, while 89.3% (95% CI: 87.5–91.0%) were protected against tetanus. The prevalence of chronic HBV carriage was 0.4% (95% CI: 0.2–1.0%), while 45.7% (95% CI: 42.9–48.5%) were immune against HBV. The seroprevalence for varicella antibodies was 52.9% (95% CI: 50.1–55.7%). Concordance between vaccination status and seroprevalence was observed for measles, rubella, diphtheria and tetanus. Singapore's children and adolescents are well-protected against measles, rubella, diphtheria and tetanus. Continual efforts in ensuring high vaccination coverage should be sustained. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Although multiple studies of cost-effectiveness of pneumococcal conjugate vaccines have been conducted, no such study has examined Singapore''s situation nor compared the licensed conjugate vaccines in an Asian population. This paper estimates the costs and public health impacts of pneumococcal conjugate vaccine programs, varying estimates of serotype replacement and herd immunity effects as key parameters in the analysis. Based in part on a 2008 analysis also presented here, Singapore has approved the PCV-7, PHiD-10, and PCV-13 pneumococcal conjugate vaccines as part of its National Childhood Immunisation Programme. Methods: An economic evaluation was performed using a Markov simulation model populated with Singapore-specific population parameters, vaccine costs, treatment costs, and disease incidence data. The vaccinated infant and child cohort of 226,000 was 6% of the Singapore resident population of 3.8 million. Vaccine efficacy estimates were constructed for PCV-7, PHiD-10, and PCV-13 vaccines based on their serotype coverage in Singapore and compared to ‘no vaccination’. The model estimated impacts over a five-year time horizon with 3% per year discounting of costs and health effects. Costs were presented in 2010 U.S. dollars (USD) and Singapore dollars (SGD). Sensitivity analyses included varying herd immunity, serotype replacement rates, vaccine cost, and efficacy against acute otitis media. Results: Under base case assumptions for the revised analysis (i.e., herd effects in the unvaccinated population equivalent to 20% of direct effects) PCV-13 prevented 834 cases and 7 deaths due to pneumonia, meningitis, and bacteremia in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population over the 5-year time horizon. Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 (SGD $51,854) per QALY. Without herd effects, however, the ratio was USD $204,535 (SGD $281,743) per QALY. The PCV-7 cost per QALY including herd effects was USD $43,275 (SGD $59,610) and for PHiD-10 the ratios were USD $45,100 (SGD $62,125). The original 2008 analysis, which had higher estimates of pneumonia prevention due to herd immunity and lower estimates of cost per dose, had found a cost-effectiveness ratio of USD $5562 (SGD $7661) per QALY for PCV-7. Conclusions: When compared to cost-effectiveness thresholds recommended by the World Health Organization (WHO), our 2008 analysis found that vaccination of infants in Singapore with PCV-7 was very cost-effective if herd immunity effects were present. However, knowledge on herd immunity and serotype replacement that emerged subsequent to this analysis changed our expectations about indirect effects. Given these changed inputs, our current estimates of infant vaccination against pneumococcal disease in Singapore find such programs to be moderately cost-effective compared to WHO thresholds. The different findings from the 2008 and 2011 analyses suggest that the dynamic issue of serotype replacement should be monitored post-licensure and, as changes occur, vaccine effectiveness and cost-effectiveness analyses should be re-evaluated. [Copyright &y& Elsevier]

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson's disease (PD), reducing dyskinesia and time spent in the "OFF" state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore., Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery., Results: A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the "OFF" state by 36.9% at 1 year ( P =0.034) and 40.9% at 5 years ( P =0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years ( P <0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild., Conclusion: STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.

Objectives: We aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics., Methods: We used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into "epidemic quarters", i.e. periods corresponding to each quartile of RSV cases. Multinomial logistic regression models were fitted to evaluate whether the likelihood of RSV cases being aged <1 or ≥5 years (vs. 1 to <5) changed over time within a season., Results: In all countries, RSV cases were significantly more likely to be aged <1 year in the 4th vs. 1st epidemic quarter; the relative risk ratio [RRR] ranged between 1.35 and 2.56. Likewise, RSV cases were significantly more likely to be aged ≥5 years in the 4th vs. 1st epidemic quarter (except in Singapore); the RRR ranged from 1.75 to 6.70. The results did not change when stratifying by level of care or moving the lower cut-off to 6 months., Conclusions: The age profile of RSV cases shifts within a season, with infants and adolescents, adults, and the elderly constituting a higher proportion of cases in the later phases of annual epidemics. These findings may have implications for RSV prevention policies with newly approved vaccines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.B. and R.K. are Sanofi employees and may hold shares and/or stock options in the company. J.P. reports that Nivel has received RSV research grants from the Foundation for Influenza Epidemiology and Sanofi. The remaining authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Differences in disease behaviour and genotypes are described in Asian and Western interstitial lung disease (ILD) cohorts. Short leukocyte telomere length (LTL) correlates with poor outcomes in Western ILD cohorts but its significance in Asian populations is unknown. We aim to characterise the burden and clinical implications of short LTL in Singaporean ILD patients., Methods: Patients diagnosed with ILD at Singapore General Hospital were prospectively recruited and compared against 36 healthy controls. The primary outcome was transplant-free survival. Genomic DNA from peripheral blood was extracted and LTL measured using quantitative polymerase chain reaction assay (qPCR)., Results: Amongst 165 patients, 37% had short LTL. There was a higher proportion of combined pulmonary fibrosis and emphysema (CPFE) patients with short LTL (n = 21, 34.4% vs n = 16, 15.4%; p < 0.001). Short LTL patients had reduced survival at 12-, 24- and 36-months and median survival of 24 months (p < 0.001) which remained significant following adjustment for smoking, GAP Stage and radiological UIP pattern (Hazard Ratio (HR), 2.74; 95%CI:1.46, 5.11; p = 0.002). They had increased respiratory-related mortality and acute exacerbation incidences. Despite similar baseline lung function, short LTL patients had a faster decline in absolute forced vital capacity (FVC) of -105.3 (95% CI: 151.4, -59.1) mL/year compared to -58.2 (95% CI: 82.9, -33.6) mL/year (p < 0.001) in normal LTL patients., Conclusion: Short LTL correlated with increased mortality and faster lung function decline in our Singaporean ILD cohort with a magnitude similar to that in Western ILD cohorts. Further research is needed to integrate LTL assessment into clinical practice., Competing Interests: Declaration of competing interest MLW Kam reports having received research funding from Singapore General Hospital, Singapore and Singapore Health Services (Singhealth), Singapore and having received speaker honorarium from Boehringer Ingelheim, Singapore. YH Tan reports having received speaker honorarium from Boehringer Ingelheim, Singapore. SY Low reports having received research funding, consulting fees, speaker honorarium and support for meetings and travel from Boehringer Ingelheim, Singapore and speaker honorarium from Astra Zeneca, Singapore. JYY Ngeow reports having received research funding from Astra Zeneca, Singapore and the National Medical Research Council Clinician Scientist Award, Singapore. The other authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Introduction: We aim to investigate the functional outcomes and long-term health-related quality of life (HRQOL) in children with major trauma associated with traumatic brain injury (TBI)., Method: We performed a retrospective review of records among patients >2 and ≤16 years old in a tertiary paediatric hospital between January 2014 and October 2019 with major trauma (Injury Severity Score of ≥16) and TBI of all severities. We recorded each child's Glasgow Outcome Scale-Extended Pediatric Version (GOS-E Peds) at 12 months post-injury and Pediatric Quality of Life Inventory (PedsQL) scores at 6 and 12 months post-injury based on the parent proxy-report scales., Results: We included 53 patients with a median age of 9.0 years old (interquartile range 2.3-15.5). Most injuries were due to falls (30, 56.6%) or road traffic collisions (15, 28.3%); 41 patients (77.3%) required intensive care while 30 patients (56.6%) underwent neurosurgical intervention. Most patients (43, 81.1%) had GOS-E Peds scores of ≤2 at 12 months post-injury. We reported a significant mean difference between the 6- and 12-month parent-reported scores for physical functioning (6.6, 95% confidence interval [CI] 0.3-12.8, P=0.041), psychosocial functioning (4.1, 95% CI 1.0-7.2, P=0.012) and overall scores (5.0, 95% CI 1.4-8.7, P=0.008). Compared with the validated PedsQL scores, our mean scores were higher across all domains at 12 months., Conclusion: With current standard of care, parents of children with major trauma and TBI reported gains in quality of life, physical, psychosocial and overall function between 6 and 12 months post-injury., Competing Interests: The authors report no conflict of interest.

Objective: To determine the distribution of major fetal congenital heart diseases (CHDs) diagnosed antenatally during routine second-trimester obstetric anatomical scans in an unselected population at a single tertiary centre and to characterise and stratify risk factors, genetic diagnosis and long-term health at 4 years old., Method: A single-centre cohort study of all major fetal CHDs detected on routine obstetric fetal anatomical ultrasound scans between January 2014 and December 2017 was performed in an unselected population. Demographic details, fetal echocardiogram reports, genetic test results, delivery outcomes and postnatal progress were stratified by CHD subtype., Results: Of 20,031 screened pregnancies, 109 pregnancies (0.53%) had major fetal CHDs. The most common subtypes were coarctation of aorta (17.4%), transposition of great arteries (16.5%), and tetralogy of Fallot and univentricular hearts (13.8% each). Of the 60.5% that underwent confirmatory genetic testing-mostly conventional karyotyping and testing for 22q11 microdeletion-about a quarter had abnormalities, of which 22q microdeletion was the most common. We had complete obstetric data in 85 pregnancies (78%), of which 76.5% progressed to live birth. Among these, 92.1% of postnatal echocardiograms concurred with antenatal ones. At 4 years old, 43.2% of offspring had no medical or developmental issues, 20.0% had mild medical or developmental issues, 21.5% had major medical or developmental issues, and 12.3% had deceased., Conclusion: Fetal echocardiograms accurately diagnose CHDs. Future studies should evaluate the roles of chromosomal microarray and next-generation sequencing in diagnosing CHD.