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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]

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.

Objective: To describe the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) and factors associated with its transmission in Singapore., Methods: Spoligotyping, 24-loci mycobacterial interspersed repetitive units - variable number of tandem repeats (MIRU-VNTR) typing and demographic data from the national TB notification registry of MTBC culture-positive cases notified from January 2011 to December 2017 were analysed., Results: Of the 12,046 culture-positive cases notified, complete spoligotyping and MIRU-VNTR typing results were available for 8690 (72.1%) belonging to 4950 (57.0%) local-born and 3740 (43.0%) foreign-born persons. From these, 4810 (55.3%) were identified in 883 clusters. The proportion of recent transmission was 45.2%. The East-Asian Lineage 2 accounted for 4045 (47.1%) of isolates, and disproportionately accounted for large clusters. Clustered cases were more likely to be older than 50 years, male, Malay, local-born, Singapore citizens or Permanent Residents, of lower socioeconomic status, imprisoned; to harbour East-Asian Lineage 2 strain; to have cavitary pulmonary TB, positive sputum smear or be recalcitrant treatment defaulters. They were less likely to have multidrug-resistant, or isoniazid or rifampicin mono-resistant TB., Conclusion: We demonstrated the diversity of MTBC strains and, notwithstanding the likely over-estimation of clustering using these genotyping methods, elucidated factors associated with TB transmission in Singapore., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: COVID-19 is a novel pandemic affecting almost all countries leading to lockdowns worldwide. In Singapore, locally-acquired cases emerged after the first wave of imported cases, and these two groups of cases may have different health-seeking behavior affecting disease transmission. We investigated differences in health-seeking behavior between locally-acquired cases and imported cases, and within the locally-acquired cases, those who saw single versus multiple healthcare providers., Methods: We conducted a retrospective study of 258 patients who were diagnosed with COVID-19 from 23 January to 17 March 2020. Variables related to health-seeking behavior included number of visits prior to hospitalization, timing of the first visit, duration from symptom onset to admission, and places where the cases had at least one visit., Results: Locally-acquired cases had longer duration from onset of symptoms to hospital admission (median 6 days, interquartile range [IQR] 4-9) than imported cases (median 4 days, IQR 2-7) (p < 0.001). Singapore residents were more likely to have at least one visit to private clinics and/or government-subsidized public clinics than non-residents (84.0% vs. 58.7%, p < 0.001). Among locally-acquired cases, those who sought care from a single healthcare provider had fewer visits before their hospital admissions compared with those who went to multiple providers (median 2 vs. 3, p = 0.001)., Conclusion: Our study indicates the need to encourage individuals to seek medical attention early on in their patient journey, particularly from the same healthcare provider. This in turn, would facilitate early detection and isolation, hence limiting local transmission and enabling better control of the COVID-19 outbreak., (© 2022. The Author(s).)

Background: In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore., Methods: Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT)., Results: A total of 2234 migrant workers aged 20-49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2-91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965-1989 than those born in 1990-1999 (95.3% vs. 86.6%, p < 0.0005), whereas there was no significant difference by gender (90.8% in men vs. 89.9% in women, p = 0.508). 195 out of 213 samples with equivocal or negative ELISA results were tested positive using PRNT., Conclusion: The IgG seroprevalence in migrant workers was below the herd immunity threshold of 95% for measles. Sporadic outbreaks may occur in susceptible individuals due to high transmissibility of measles virus. Seroprevalence surveys can help identify susceptible subgroups for vaccination., (© 2022. The Author(s).)