Evaluating quasi-experimental approaches for estimating epidemiological efficacy of non-randomised field trials: applications in Wolbachia interventions for dengue.

BACKGROUND: Wolbachia symbiosis in Aedes aegypti is an emerging biocontrol measure against dengue. However, assessing its real-world efficacy is challenging due to the non-randomised, field-based nature of most intervention studies. This research re-evaluates the spatial-temporal impact of Wolbachia interventions on dengue incidence using a large battery of quasi-experimental methods and assesses each method's validity. METHODS: A systematic search for Wolbachia intervention data was conducted via PUBMED. Efficacy was reassessed using commonly-used quasi-experimental approaches with extensive robustness checks, including geospatial placebo tests and a simulation study. Intervention efficacies across multiple study sites were computed using high-resolution aggregations to examine heterogeneities across sites and study periods. We further designed a stochastic simulation framework to assess the methods' ability to estimate intervention efficacies (IE). RESULTS: Wolbachia interventions in Singapore, Malaysia, and Brazil significantly decreased dengue incidence, with reductions ranging from 48.17% to 69.19%. IEs varied with location and duration. Malaysia showed increasing efficacy over time, while Brazil exhibited initial success with subsequent decline, hinting at operational challenges. Singapore's strategy was highly effective despite partial saturation. Simulations identified Synthetic Control Methods (SCM) and its variant, count Synthetic Control Method (cSCM), as superior in precision, with the smallest percentage errors in efficacy estimation. These methods also demonstrated robustness in placebo tests. CONCLUSIONS: Wolbachia interventions exhibit consistent protective effects against dengue. SCM and cSCM provided the most precise and robust estimates of IEs, validated across simulated and real-world settings.

Correlates of lifestyle patterns among children in Singapore aged 10 years: the growing up in Singapore towards healthy outcomes (GUSTO) study.

OBJECTIVE: To characterise lifestyle patterns (comprising dietary and movement behaviour aspects) of children in Singapore and examine the correlates of these patterns. DESIGN: An observational study approach was used. Children recorded their diet and activities over two weekdays and two weekend days on a validated web-based assessment, My E-Diary for Activities and Lifestyle (MEDAL). Lifestyle patterns were derived using principal component analysis, and the correlations of these with multiple known determinants organised by distal, intermediate, and proximal levels of influence were studied. SETTING: Children of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. PARTICIPANTS: Ten-year-old children (n = 397). RESULTS: Three lifestyle patterns, "high snacks and processed food", "balanced" and "mixed", were identified. We focused on the more health-promoting "balanced" pattern, characterised by lower screen-viewing and higher consumption of fruits, vegetables, wholegrains, and dairy. Among the distal factors, girls were more adherent to the "balanced" pattern compared to boys, and children of parents with lower education levels were less adherent to this pattern. Among intermediate factors, children of mothers with higher diet quality were more adherent to the "balanced" pattern. Among the proximal factors, engagement in active transport, leisure sports, and educational activities outside of school were positively associated with the "balanced" pattern, whereas screen-viewing while travelling was negatively associated with this pattern. Having siblings, pet ownership, mother's physical activity, parenting style, parental bonding, child's outdoor time, and breakfast consumption were not associated with children's lifestyle patterns. CONCLUSIONS: These findings provide direction for future interventions by identifying vulnerable groups and contexts that should be prioritised.

Prevalence of dermatoses in geriatric singaporeans in the community - a cross-sectional study.

BACKGROUND: Little is known about the prevalence of dermatoses in "skin-well" geriatric Singaporeans. We aim to identify the prevalence of dermatoses and their associations within the geriatric population in Singapore, and to understand the distribution of dermatological encounters presenting to primary care physicians, and the resultant referral behaviour. METHODS: A joint quantitative-qualitative study was performed across 8 months. Patients aged 65 years and above who visited a local polyclinic for management of non-dermatological chronic diseases were recruited. They were administered questionnaires, and underwent full skin examinations. Online surveys were disseminated to polyclinic physicians under the same healthcare cluster. RESULTS: 201 patients and 53 physicians were recruited. The most common dermatoses identified in patients were benign tumours and cysts (97.5%), and asteatosis (81.6%). For every 1-year increase in age, the odds of having asteatosis increased by 13.5% (95% CI 3.4-24.7%, p = 0.008), and urticarial disorders by 14.6% (95% CI 0.3-30.9%, p = 0.045). Patients who used any form of topical preparations on a daily basis had higher odds of having eczema and inflammatory dermatoses (OR 2.51, 95% CI 1.38 to 4.56, p = 0.003). Physicians reported dermatological conditions involving 20% of all clinical encounters. Eczema represented the most commonly reported dermatosis within the first visit. 50% of dermatology referrals were done solely at the patient's own request. CONCLUSION: The prevalence of dermatoses in the elderly in Singapore is high, especially asteatosis. Prompt recognition by the primary healthcare provider potentially prevents future morbidity. Outreach education for both primary care physicians and the general public will be key. ETHICS APPROVAL: National Healthcare group (NHG) Domain Specific Review Board (DSRB), Singapore, under Trial Registration Number 2020/00239, dated 11 August 2020.

Medical students' experience and learning outcomes of overseas community involvement project: a qualitative study.

BACKGROUND: Medical students in Singapore engage in short term medical missions, locally known as Overseas Community Involvement Projects (OCIPs). Little is known about the learning outcomes of an OCIP and how this complements their medical education back home. Understanding this can help the medical educators structure the OCIP to optimise its learning value. OBJECTIVES: This study aims to gain an in-depth understanding of the experiences and learning outcomes of the medical students who participated in the OCIP. METHODS: This was a qualitative study involving Singaporean students from one medical school travelling to Nepal. Data was collected from reflective journals, overall group reflections and two focus group discussions. The data was thematically analysed using the Accreditation Council for Graduate Medical (ACGME) core competencies for medical professionals. RESULTS: The data could be classified under various themes within the six domains of the ACGME framework. The study revealed themes of: humanism, socioeconomic and cultural determinants of health under the domain of patient care, application of medical knowledge, investigating and evaluating the needs of a population and feedback to drive improvement under the domain of practice-based learning and improvement, use of non-verbal cues and communicating across language barriers under the domain of interpersonal and communication skills, healthcare systems and delivery, resourcefulness and adaptability, health equity and accessibility under the domain of systems-based practice, ethics, role-modelling, teamwork and leadership skills, interprofessional skills and resilience under the domain of professionalism. Understanding the students' motivations, utilising reflections, and following the patients' journey facilitated attainment of these outcomes. CONCLUSIONS: This OCIP experience translated to learning outcomes aligned with the ACGME framework. There is great potential for the experiential learning from a well-structured OCIP to help with personal and professional development and global health education.

Validation of a Major and Clinically Relevant Nonmajor Bleeding Phenotyping Algorithm on Electronic Health Records.

PURPOSE: Bleeding is an important health outcome of interest in epidemiological studies. We aimed to develop and validate rule-based algorithms to identify (1) major bleeding and (2) all clinically relevant bleeding (CRB) (composite of major and all clinically relevant nonmajor bleeding) within real-world electronic healthcare data. METHODS: We took a random sample (n = 1630) of inpatient admissions to Singapore public healthcare institutions in 2019 and 2020, stratifying by hospital and year. We included patients of all age groups, sex, and ethnicities. Presence of major bleeding and CRB were ascertained by two annotators through chart review. A total of 630 and 1000 records were used for algorithm development and validation, respectively. We formulated two algorithms: sensitivity- and positive predictive value (PPV)-optimized algorithms. A combination of hemoglobin test patterns and diagnosis codes were used in the final algorithms. RESULTS: During validation, diagnosis codes alone yielded low sensitivities for major bleeding (0.16) and CRB (0.24), although specificities and PPV were high (>0.97). For major bleeding, the sensitivity-optimized algorithm had much higher sensitivity and negative predictive values (NPVs) (sensitivity = 0.94, NPV = 1.00), however false positive rates were also relatively high (specificity = 0.90, PPV = 0.34). PPV-optimized algorithm had improved specificity and PPV (specificity = 0.96, PPV = 0.52), with little reduction in sensitivity and NPV (sensitivity = 0.88, NPV = 0.99). For CRB events, our algorithms had lower sensitivities (0.50-0.56). CONCLUSIONS: The use of diagnosis codes alone misses many genuine major bleeding events. We have developed major bleeding algorithms with high sensitivities, which can ascertain events within populations of interest.

Disease progression in Parkinson's disease patients with mild cognitive impairment: 5-year longitudinal study from the early Parkinson's disease longitudinal Singapore (PALS) cohort.

AIM: To investigate motor, non-motor and cognitive progression in early Parkinson's disease (PD) patients with Mild Cognitive Impairment (MCI). METHODS: PD patients were recruited within 1 year of diagnosis and were classified into PD-MCI group and PD with normal cognition (PD-NC) group. H&Y staging scale, MDS-UPDRS part III were used to assess disease severity and motor progression. Non-motor symptom scale (NMSS) was used to evaluate the NMS progression. Cognitive progression was assessed from 5 cognitive domains. Annual progression changes in the longitudinal outcomes were examined via linear mixed model with random intercept effect. False discovery rate (FDR) method was performed to control for multiple testing comparison and q-value was calculated. We set the threshold of q-values as 0.1. RESULT: A total of 205 PD patients, including 107 PD-MCI and 98 PD-NC patients were assessed prospectively over a 5-year period. PD-MCI patients, compared to PD-NC group, had a significantly higher progression rate in H&Y score (0.11 vs. 0.06, p=0.03, q=0.08), MDS-UPDRS motor score (3.11 vs. 1.90 p<0.001, q=0.06) and postural instability gait difficulty (PIGD) score (0.40 vs. 0.20, p=0.02, q=0.07). PD-MCI group also exhibited significantly faster deterioration in NMSS perceptual domain (PD-MCI vs. PD-NC: 0.38 vs. -0.04, p=0.01, q=0.06) and cognitive visuospatial domain (PD-MCI vs. PD-NC: 0.13 vs. -0.06, p=0.048, q=0.09) after adjustment for confounders and multiple comparisons. CONCLUSIONS: PD-MCI patients had faster decline in motor functions, visuo-perceptual and visuospatial performance. These findings provide a more comprehensive prognosis of PD-MCI, which could be helpful for clinician to manage PD-MCI patients.

A cross sectional study of role of technology in health for middle-aged and older adults in Singapore.

Telemedicine has gained popularity due to the increasing use of technology in our lives. However, no studies have explored the demographic factors affecting acceptability, desirability and adherence (ADA) to telemedicine in Singapore. Our study aims to evaluate the level of ADA of telemedicine services within demographic factors and to explore the association of potential demographic factors with the degree of acceptability, desirability and adherence of telemedicine among older adults in Singapore. A cross-sectional study was conducted with Singapore citizens or permanent residents aged 40-99 years, who were able to provide informed consent. Interviewers conducted door-to-door surveys in 67 Blocks of Housing & Development Board flats in Singapore, offering a self-administered electronic questionnaire available in four languages. Random sampling without replacement determined the order of blocks, floors and units visited. The questionnaire utilised Qtelemediab scoring and covered sociodemographic data, usage of telemedicine, as well as ADA towards telemedicine. A total of 324 valid responses were analysed. Increased age was associated with a significant decrease across all three domains of ADA namely acceptability (ß = - 0.02, 95%CI - 0.03; - 0.02, p-value = 0.002), desirability (ß = - 0.02, 95%CI - 0.02; - 0.02, p-value < 0.001) and adherence (ß = - 0.02, 95%CI - 0.03; - 0.0.02, p-value < 0.001). Additionally, lower education was associated with a decrease in all domains of ADA. Conversely, employment and increased household income were associated with higher ADA scores across all three domains. These associations were independent of gender, chronic health conditions and smoking history. Older participants with lower income and lesser education demonstrated lower levels of acceptability, desirability and adherence towards telemedicine. Our study highlights the importance of considering these factors in the implementation and promotion of telemedicine solutions.

Screen time and social-emotional skills in preschoolers with developmental, behavioural or emotional issues in Singapore.

Introduction: This study aimed to determine patterns of screen viewing time (SVT) in preschool children with developmental, behavioural or emotional (DBE) issues, and to identify its relationship with social-emotional development. Method: This cross-sectional study involved children aged 0-5 years who were referred to a developmental paediatric clinic for DBE issues. Parents completed a screen time questionnaire, and the Devereux Early Childhood Assessment-Clinical (DECA-C) question-naire which assessed the social-emotional competence of the children. Data were analysed using logistic regression, correlational analyses and tests of comparison. Results: Among 225 children (mean age: 32.4 months), mean daily SVT was 138 minutes. More than half (51.1%) of the children had clinical features of language delay, while 26.6% had features suggestive of autism spectrum disorder. Screen time was first introduced at a mean age of 13.8 months, with 32.4% of children previously experiencing higher SVT. Compared to SVT introduction after 1 year of age, SVT in the first 12 months was primarily to facilitate feeding (P<0.05). Children with higher past SVT had poorer attention, more aggression, and increased behavioural concerns. Children with DBE issues have significantly more screen time than same-aged peers. Conclusion: Children with DBE issues are exposed to SVT at a very young age and have significantly more screen time than their peers. It is crucial to guide parents to reduce SVT in early childhood, particularly around mealtimes.

Trends in fluid overload-related hospitalisations among patients with diabetes mellitus The impact of chronic kidney disease.

Introduction: Fluid overload is a known complication in patients with diabetes mellitus, particularly those with cardiovascular and/or chronic kidney disease (CKD). This study investigates the impact of fluid overload on healthcare utilisation and its association with diabetes-related complications. Method: Electronic medical records from the SingHealth Diabetes Registry (2013-2022) were analysed. Hospitalisations due to fluid overload were identified using International Classification of Diseases, 10th Revision (ICD-10) discharge codes. Trends were examined using Joinpoint regression, and associations were assessed with generalised estimating equation models. Results: Over a period of 10 years, 259,607 individuals treated at primary care clinics and tertiary hospitals were studied. The incidence of fluid overload-related hospitalisations decreased from 2.99% (n=2778) in 2013 to 2.18% (n=2617) in 2017. However, this incidence increased from 2.42% (n=3091) in 2018 to 3.71% (n=5103) in 2022. The strongest associations for fluid overload-related hospitalisation were found with CKD stages G5 (odds ratio [OR] 6.61, 95% confidence interval [CI] 6.26-6.99), G4 (OR 5.55, 95% CI 5.26-5.86) and G3b (OR 3.18, 95% CI 3.02-3.35), as well as with ischaemic heart disease (OR 3.97, 95% CI 3.84-4.11), acute myocardial infarction (OR 3.07, 95% CI 2.97-3.18) and hypertension (OR 3.90, 95% CI 3.45-4.41). Additionally, the prevalence of stage G5 CKD among patients with fluid overload increased between 2018 and 2022. Conclusion: Our study revealed a significant increase in fluid overload-related hospitalisations and extended lengths of stay, likely driven by severe CKD. This underscores an urgent need for initiatives aimed at slowing CKD progression and reducing fluid overload-related hospitalisations in diabetes patients.

Demographic diversity of participants in clinical trials conducted in Singapore.

Introduction: The under-representativeness of participants in clinical trials limits the generalisability of results. This review evaluates the representative-ness within pharmaceutical randomised controlled trials (RCTs) in Singapore. Method: Four bibliographic databases were searched for papers on pharmaceutical RCTs which included Singapore adults (≥18 years old), published between 2017 and 2022. The demographic characteristics of study participants were compared against the population in the 2020 Singapore census. Recruitment strategies and authors' comments on the generalisa-bility of their findings were reviewed. Results: Thirty-three publications were included (19 Singapore-only studies and 14 multiregional trials which included Singapore). Where data were available, we found that females and Indians were under-represented compared to the census (41.3% versus [vs] 51.1%, P<0.05; 7.3% vs 9.0%, P<0.05). Ethnic diversity varied between individual studies, and almost half (46.2%) of Singapore-only studies achieved census levels. However, more than one-third of the trials provided no data (31.6%) or partial data (5.3%) on ethnicity. Half of the multiregional publications stated the number of participants recruited from Singapore, but only 1 reported any detail beyond Asian participants. Recruitment strategies were mentioned in fewer than half (42.4%), and less than a quarter (24.2%) commented on sample representative-ness or the external validity of the evidence generated. Conclusion: There is room for improvement regarding the recruitment of RCT participants in Singapore, with particular attention to female gender and Indian ethnicity. Demographic data should also be presented in full. RCTs should be designed and reported such that clinicians can ascertain the generalisability to the Singapore population and the potential benefits from the studied interventions in clinical practice.

Hospitalised patients as stewards of their own antibiotic therapy: a qualitative analysis informing the strategic design of interventions to encourage shared decision-making in tertiary hospital settings in Singapore.

Background: Shared decision-making (SDM) on antibiotic therapy may improve antibiotic use in tertiary hospitals, but hospitalised patients are apprehensive about being involved in it. Understanding the facilitators and barriers to SDM can inform the design and implementation of interventions to empower these patients to engage in SDM on their antibiotic therapies. Methods: We conducted qualitative interviews with 23 adult patients purposively sampled with maximum variation from the three largest tertiary-care hospitals in Singapore (April 2019─October 2020). Thematic analysis was conducted using the Theoretical Domains Framework and Capability, Opportunity, Motivation, Behaviour (COM-B) model to identify areas for intervention. Results: Hospitalised patients lacked comprehensive knowledge of their antibiotic therapies and the majority did not have the skills to actively query their doctors about them. There was a lack of opportunities to meet and interact with doctors, and patients were less motivated to engage in SDM if they had a self-perceived paternalistic relationship with doctors, trusted their doctors to provide the best treatment, and had self-perceived poor knowledge to engage in SDM. To empower these patients, they should first be educated with antibiotic knowledge. Highlighting potential side effects of antibiotics could motivate them to ask questions about their antibiotic therapies. Environment restructuring, as facilitated by nurses and visual cues to nudge conversations, could create opportunities for interactions and motivating patients into SDM on their antibiotic therapies. Conclusion: Education and environmental restructuring should be explored to empower hospitalised patients to engage in SDM on their antibiotic therapies.

Pediatric trauma during the COVID-19 lockdown: caregiver abuse and self-harm in a vulnerable population.

PURPOSE: This retrospective cohort study explores the impact of the COVID-19 pandemic on pediatric trauma cases in Singapore's National University Hospital from January 2015 to July 2021. The pandemic prompted unprecedented measures, altering societal dynamics. The study hypothesizes a reduction in major trauma incidents during the pandemic period. METHODS: This is a single-center retrospective study including all pediatric patients presenting with trauma-related ICD-9 codes, and an Injury Severity Score (ISS) greater than 8. Patients were stratified into two time periods: pre-pandemic (January 2015 to March 2020) and pandemic (April 2020 to July 2021) periods. RESULTS: Out of 254 pediatric trauma cases, 201 occurred pre-pandemic, and 53 during the pandemic. While overall trauma incidence remained similar, the pandemic period saw a shift in injury patterns. Home-based falls increased, vehicular accidents decreased, while deliberate self-harm and caregiver abuse rose significantly. The incidence of serious trauma attributed to non-accidental injury increased during the pandemic. CONCLUSION: The study reveals changing trauma patterns, emphasizing the importance of understanding societal impacts during pandemics. Notably cases of deliberate self-harm and caregiver abuse surged, echoing global concerns highlighted in other studies during the pandemic. The study underscores the need to preempt physical and psychological stressors in vulnerable populations during future pandemics.

Housing status is protective of neuropsychiatric symptoms among dementia-free multi-ethnic Asian elderly.

BACKGROUND: Housing has been associated with dementia risk and disability, but associations of housing with differential patterns of neuropsychiatric symptoms (NPS) among dementia-free older adults remain to be explored. The present study sought to explore the contribution of housing status on NPS and subsyndromes associated with cognitive dysfunction in community-dwelling dementia-free elderly in Singapore. METHODS: A total of 839 dementia-free elderly from the Epidemiology of Dementia in Singapore (EDIS) study aged ≥ 60 were enrolled in the current study. All participants underwent clinical, cognitive, and neuropsychiatric inventory (NPI) assessments. The housing status was divided into three categories according to housing type. Cognitive function was measured by a comprehensive neuropsychological battery. The NPS were assessed using 12-term NPI and were grouped into four clinical subsyndromes: psychosis, hyperactivity, affective, and apathy. Associations of housing with composite and domain-specific Z-scores, as well as NPI scores, were assessed using generalized linear models (GLM). Binary logistic regression models analysed the association of housing with the presence of NPS and significant NPS (NPI total scores ≥ 4). RESULTS: Better housing status (5-room executive apartments, condominium, or private housing) was associated with better NPS (OR = 0.49, 95%CI = 0.24 to 0.98, P < 0.05) and significant NPS profile (OR = 0.20, 95%CI = 0.08 to 0.46, P < 0.01), after controlling for demographics, risk factors, and cognitive performance. Compared with those living in 1-2 room apartments, older adults in better housing had lower total NPI scores (ß=-0.50, 95%CI=-0.95 to -0.04, P = 0.032) and lower psychosis scores (ß=-0.36, 95%CI=-0.66 to -0.05, P = 0.025), after controlling for socioeconomic status (SES) indexes. Subgroup analysis indicated a significant correlation between housing type and NPS in females, those of Malay ethnicity, the more educated, those with lower income, and those diagnosed with cognitive impairment, no dementia (CIND). CONCLUSIONS: Our study showed a protective effect of better housing arrangements on NPS, especially psychosis in a multi-ethnic Asian geriatric population without dementia. The protective effect of housing on NPS was independent of SES and might have other pathogenic mechanisms. Improving housing could be an effective way to prevent neuropsychiatric disturbance among the elderly.

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

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

Understanding the preferences of young adults with type 2 diabetes mellitus with regard to diabetes self-management education: a qualitative study.

AIM: Young-onset type 2 diabetes (YOD) is associated with poorer clinical outcomes. To support the development of more effective diabetes self-management education (DSME) programmes, this study aimed to understand the preferences of young adults with YOD in relation to the modality, content and qualities of DSME. METHODS: Maximal variation sampling was employed to recruit participants of varied age, ethnicity and marital status. In-depth interviews using a semistructured questionnaire were conducted. Subsequently, thematic analysis with coding and conceptualisation of data was applied to identify the main themes regarding DSME. RESULTS: 21 young adult participants aged 22-39 years were interviewed from three polyclinics in Singapore. The most used modalities for DSME included education from healthcare providers, information and support from family and friends and information from internet sources. Participants were most interested in information regarding diet, age-specific diabetes-related conditions and medication effects. Additionally, participants valued DSME that was credible, accessible, individualised and empathetic. Conversely, absence of the above qualities and stigma hindered participants from receiving DSME. CONCLUSION: Our study explored the preferences of young adults with YOD with regard to DSME, identifying the most used modalities, preferred content and qualities that were valued by young adults. Our findings will help inform the development of DSME programmes that can better meet the needs and preferences of young adults with YOD.