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It is important to understand the temporal trend of the paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined the differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. Serial cycle threshold values of SARS-CoV-2 from the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral loads (mean cycle threshold on day 7 of illness 28.6 vs. 36.7, P = 0.02). Peak SARS-CoV-2 viral loads occurred around day 2 of illness in infected children. Although we were unable to directly demonstrate infectivity, the detection of significant amount of virus in the upper airway of asymptomatic children suggest that they have the potential to shed and transmit SARS-CoV-2. Our study highlights the importance of contact tracing and screening for SARS-CoV-2 in children with epidemiological risk factors regardless of their symptom status, in order to improve containment of the virus in the community, including educational settings.
There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness.
Prospective data from 505 mother–child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models.
Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034).
Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children.
Studies have shown that mental health problems during pregnancy have adverse effects on fetal growth. The impact of depressive and anxiety symptoms during pregnancy on the fetus have not yet been examined in Singapore.
To examine the association between mental health problems during the second trimester of pregnancy on the quality of the pregnancy, reflected by birth weight and birth length of the newborn.
This study aims to understand the importance of mental health during pregnancy on the development of the child in an Asian population.
Preliminary data of a prospective cohort study of pregnant women (GUSTO), were followed from pregnancy onwards. At 26 weeks of the pregnancy, the Edinburgh Postnatal Depression Scale (EPDS), the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI) were administered. Data on birth parameters were collected from medical records.
Linear regression analyses of preliminary data show negative correlations between depressive symptoms measured with EPDS (n = 1025, P = 0.54), BDI (n = 1012, P = 0.001), and anxiety symptoms measured with STAI (n = 1023, P = 0.002) and birth length (corrected for gestational age and gender). No associations were found for birth weight.
There is an association between depressive and anxiety symptoms reported at the end of the second trimester of the pregnancy and birth length, but not birth weight, of the newborn. As it is known that fetal length increases mainly in the second trimester, it suggests that stress of the mother influences the development of the fetus during this trimester.
Mental health stigma is a multidimensional concept that encompasses many different themes and definitions. Public stigma is defined as the degree to which the general public holds negative views and discriminates against a specific group.
To understand the context and correlates of stigma in multi-ethnic Singapore.
The current study aimed to (i) explore the factor structure of the Depression Stigma Scale and the Social Distance Scale using an exploratory structural equation modelling approach and (ii) examine the correlates of the identified dimensions of stigma in the general population of Singapore.
Data for the current study came from a larger nation-wide cross-sectional study of mental health literacy conducted in Singapore. All respondents were administered the Personal and Perceived scales of the Depression Stigma Scale and the Social Distance scale to measure personal stigma and social distance respectively.
The findings from the factor analysis revealed that personal stigma formed two distinct dimensions comprising “Weak-not-Sick” and “Dangerous/Unpredictable” components while social distance stigma items loaded strongly into a single factor. Those of Malay and Indian ethnicity, lower education, lower income status and those who were administered the depression and alcohol abuse vignette were significantly associated with higher weak-not-sick scores. Those of Indian ethnicity, 6 years of education and below, lower income status and those who were administered the alcohol abuse vignette were significantly associated with higher dangerous/unpredictable scores.
There is a need for well-planned and culturally relevant anti-stigma campaigns in this population.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
The second Singapore Mental Health Study (SMHS) – a nationwide, cross-sectional, epidemiological survey - was initiated in 2016 with the intent of tracking the state of mental health of the general population in Singapore. The study employed the same methodology as the first survey initiated in 2010. The SMHS 2016 aimed to (i) establish the 12-month and lifetime prevalence and correlates of major depressive disorder (MDD), dysthymia, bipolar disorder, generalised anxiety disorder (GAD), obsessive compulsive disorder (OCD) and alcohol use disorder (AUD) (which included alcohol abuse and dependence) and (ii) compare the prevalence of these disorders with reference to data from the SMHS 2010.
Door-to-door household surveys were conducted with adult Singapore residents aged 18 years and above from 2016 to 2018 (n = 6126) which yielded a response rate of 69.0%. The subjects were randomly selected using a disproportionate stratified sampling method and assessed using World Health Organization Composite International Diagnostic Interview version 3.0 (WHO-CIDI 3.0). The diagnoses of lifetime and 12-month selected mental disorders including MDD, dysthymia, bipolar disorder, GAD, OCD, and AUD (alcohol abuse and alcohol dependence), were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
The lifetime prevalence of at least one mood, anxiety or alcohol use disorder was 13.9% in the adult population. MDD had the highest lifetime prevalence (6.3%) followed by alcohol abuse (4.1%). The 12-month prevalence of any DSM-IV mental disorders was 6.5%. OCD had the highest 12-month prevalence (2.9%) followed by MDD (2.3%). Lifetime and 12-month prevalence of mental disorders assessed in SMHS 2016 (13.8% and 6.4%) was significantly higher than that in SMHS 2010 (12.0% and 4.4%). A significant increase was observed in the prevalence of lifetime GAD (0.9% to 1.6%) and alcohol abuse (3.1% to 4.1%). The 12-month prevalence of GAD (0.8% vs. 0.4%) and OCD (2.9% vs. 1.1%) was significantly higher in SMHS 2016 as compared to SMHS 2010.
The high prevalence of OCD and the increase across the two surveys needs to be tackled at a population level both in terms of creating awareness of the disorder and the need for early treatment. Youth emerge as a vulnerable group who are more likely to be associated with mental disorders and thus targeted interventions in this group with a focus on youth friendly and accessible care centres may lead to earlier detection and treatment of mental disorders.
This article analyses Euripides’ mythopoetics in what survives of the first quarter of his fragmentary Hypsipyle: prologue, parodos, and first episode. It examines Euripides’ innovation in joining two myths (the Seven Against Thebes and the story of Hypsipyle and the Argonauts) into one, and the representation of Hypsipyle herself. In her private moments, the thoughts that preoccupy her mind are focused on other-places and other-times, in vivid contrast to the naturalistically presented world of the present where, as a slave, she must interact with men. Euripides uses the language of serving (θɛραπɛύɛιν) and doing a ‘favour’ (χάρις), as well as the word ἐρῆμος (‘lonely,’ ‘deserted’) and homoeophonic language (e.g. Argo and Argos) to indicate that, in helping the Argives, Hypsipyle repeats typologically her hospitality to the Argonauts. There is a circularity in Hypsipyle's story that creates suspense, since by doing a favour for the Argive leader, she is reunited with the sons she bore to Argonauts’ leader, who themselves are sent to find her by their grandfather whom she saved; and by losing the infant in her care (Opheltes, later named Archemorus), she is reunited with her former infants. By the end of Hypsipyle's first conversation with Amphiaraus, Euripides has invented a theme of ‘parallel worlds’ that he will resolve at the play's end.
The Single Ventricle Reconstruction trial randomised neonates with hypoplastic left heart syndrome to a systemic-to-pulmonary-artery shunt strategy. Patients received care according to usual institutional practice. We analysed practice variation at the Stage II surgery to attempt to identify areas for decreased variation and process control improvement.
Prospectively collected data were available in the Single Ventricle Reconstruction public-use database. Practice variation across 14 centres was described for 397 patients who underwent Stage II surgery. Data are centre-level specific and reported as interquartile ranges across all centres, unless otherwise specified.
Preoperative Stage II median age and weight across centres were 5.4 months (interquartile range 4.9–5.7) and 5.7 kg (5.5–6.1), with 70% performed electively. Most patients had pre-Stage-II cardiac catheterisation (98.5–100%). Digoxin was used by 11/14 centres in 25% of patients (23–31%), and 81% had some oral feeds (68–84%). The majority of the centres (86%) performed a bidirectional Glenn versus hemi-Fontan. Median cardiopulmonary bypass time was 96 minutes (75–113). In aggregate, 26% of patients had deep hypothermic circulatory arrest >10 minutes. In 13/14 centres using deep hypothermic circulatory arrest, 12.5% of patients exceeded 10 minutes (8–32%). Seven centres extubated 5% of patients (2–40) in the operating room. Postoperatively, ICU length of stay was 4.8 days (4.0–5.3) and total length of stay was 7.5 days (6–10).
In the Single Ventricle Reconstruction Trial, practice varied widely among centres for nearly all perioperative factors surrounding Stage II. Further analysis may facilitate establishing best practices by identifying the impact of practice variation.
By contrast to infantile spinal muscular atrophy, which usually links to deletions in the SMN genes, fetal onset motor neuron disease is poorly reported. We collected a series of twelve cases of fetal arthrogryposis (16-31 weeks gestational age) with fetal motor neuron disease and excluded infectious diseases, lysosomal storage disease and neuroaxonal dystrophy. Of these twelve, 3 were thought to be ischemic in nature with microvascular alterations and systemic or central nervous system ischemic injury. The remaining 9 all displayed marked reduction in anterior horn motor neurons. Of these 9, four demonstrated mineralised neurons, four demonstrated either neuronal loss or cavitation in the globus pallidus, and in two, degenerating neurons were detectable in the brainstem or globus pallidus. Specific sequencing of SMN1 was performed in 6 of 9 and was reported as normal. Whole exome sequencing was performed in 4 without definitive diagnosis. We conclude that fetal motor neuron disease can be distinguished from ischemic injury, is morphologically heterogeneous, may affect the globus pallidus and is rarely linked to SMN1 mutations.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.
The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.
The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.
Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.
The quality of prenatal maternal mental health, from psychological stress and depressive symptoms to anxiety and other nonpsychotic mental disorders, profoundly affects fetal neurodevelopment. Despite the evidence for the influence of positive mental well-being on health, there is, to our knowledge, no research examining the possible effects of positive antenatal mental health on the development of the offspring. Using exploratory bifactor analysis, this prospective study (n = 1,066) demonstrated the feasibility of using common psychiatric screening tools to examine the effect of positive maternal mental health. Antenatal mental health was assessed during 26th week of pregnancy. The effects on offspring were assessed when the child was 12, 18, and 24 months old. Results showed that positive antenatal mental health was uniquely associated with the offspring's cognitive, language and parentally rated competences. This study shows that the effects of positive maternal mental health are likely to be specific and distinct from the sheer absence of symptoms of depression or anxiety.
Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia and is associated with encapsulated organisms, most commonly Streptococcus pneumoniae, but also Haemophilus influenzae and Neisseria meningitidis. We aimed to estimate the risk of infection in this patient group. We reviewed data collected by the Victorian Spleen Registry in Australia. On registration, all patients are asked about significant infections requiring admission to hospital for intravenous antibiotics; those requiring admission to ICU were defined as OPSI. In the 3274 asplenic patients registered 492 patients reported at least one episode of infection. There were 47 episodes of OPSI requiring intensive care (incidence rate 1·11/1000 patient-years). The risk of OPSI was highest in older patients, and there were no statistically significant differences in incidence by reason for splenectomy except for a higher rate in patients with medical hyposplenia. This study reinforces that post-splenectomy infection is a clinically significant but uncommon complication, and that fulminant infection requiring intensive care is a minority of all infections.
The current study aimed to: (i) describe the extent of overall stigma as well as the differences in stigma towards people with alcohol abuse, dementia, depression, schizophrenia and obsessive compulsive disorder, as well as (ii) establish the dimensions of stigma and examine its correlates, in the general population of Singapore, using a vignette approach.
Data for the current study came from a larger nation-wide cross-sectional study of mental health literacy conducted in Singapore. The study population comprised Singapore Residents (Singapore Citizens and Permanent Residents) aged 18–65 years who were living in Singapore at the time of the survey. All respondents were administered the Personal and Perceived scales of the Depression Stigma scale and the Social Distance scale to measure personal stigma and social distance, respectively. Weighted mean and standard error of the mean were calculated for continuous variables, and frequencies and percentages for categorical variables. Exploratory structural equation modelling and confirmatory factor analysis were used to establish the dimensions of stigma. Multivariable linear regressions were conducted to examine factors associated with each of the stigma scale scores.
The mean age of the respondents was 40.9 years and gender was equally represented (50.9% were males). The findings from the factor analysis revealed that personal stigma formed two distinct dimensions comprising ‘weak-not-sick’ and ‘dangerous/unpredictable’ while social distance stigma items loaded strongly into a single factor. Those of Malay and Indian ethnicity, lower education, lower income status and those who were administered the depression and alcohol abuse vignette were significantly associated with higher weak-not-sick scores. Those of Indian ethnicity, 6 years of education and below, lower income status and those who were administered the alcohol abuse vignette were significantly associated with higher dangerous/unpredictable scores. Those administered the alcohol abuse vignette were associated with higher social distance scores.
This population-wide study found significant stigma towards people with mental illness and identified specific groups who have more stigmatising attitudes. The study also found that having a friend or family member with similar problems was associated with having lower personal as well as social distance stigma. There is a need for well-planned and culturally relevant anti-stigma campaigns in this population that take into consideration the findings of this study.
Toxoplasmosis affects a third of the global population and is of particular concern for immunologically compromised individuals. Toxoplasmosis induces host physiological events ranging from immunological to metabolic responses across multiple biological compartments. To understand the sequence of host responses during acute and chronic Toxoplasma gondii infection, eight male BALB/c mice were infected with 2000 T. gondii ME49 tachyzoites with a further eight uninfected mice used as controls. Plasma cytokines status, urinary metabolic profiling and fecal microbial profiles were characterized to monitor temporal variation related to T. gondii infection. The results showed elevated serum interferon-γ (IFN-γ), interleukin-12p40 and necrosis factor-α during acute phase of infection with concomitant perturbation in host energy metabolism and host-gut microbiome co-metabolism of phenolics and a shift in microbial composition. However, the differences were less pronounced during the putative chronic phase of infection with elevated IFN-γ, differences in urinary N-acetyls and O-acetyls of glycoproteins with no shift in gut microbial composition. Structural equation modelling on the current data showed host immune responses as the main driver for changes observed in urinary metabolites and gut microbial composition. Such an approach can be applied to other models of infectious diseases to aid understanding of host–pathogen interactions and potential biomarker discovery.
Three epidemic waves of human influenza A(H7N9) were documented in several different provinces in China between 2013 and 2015. With limited understanding of the potential for human-to-human transmission, it was difficult to implement control measures efficiently or to inform the public adequately about the application of interventions. In this study, the human-to-human transmission rate for the epidemics that occurred between 2013 and 2015 in Zhejiang Province, China, was analysed. The reproduction number (R), a key indicator of transmission intensity, was estimated by fitting the number of infections from poultry to humans and from humans to humans into a mathematical model. The posterior mean R for human-to-human transmission was estimated to be 0·27, with a 95% credible interval of 0·14–0·44 for the first wave, whereas the posterior mean Rs decreased to 0·15 in the second and third waves. Overall, these estimates indicate that a human H7N9 pandemic is unlikely to occur in Zhejiang. The reductions in the viral transmissibility and the number of poultry-transmitted infections after the first epidemic may be attributable to the various intervention measures taken, including changes in the extent of closures of live poultry markets.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.