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Prevalence of hearing loss in children with autism spectrum disorder (ASD) is uncertain, as it is more challenging to assess hearing function in children with developmental difficulties (DD). We aimed to determine the prevalence and profiles of hearing loss in preschool children with ASD in a Southeast-Asian population who passed newborn hearing screening. A retrospective study of preschool children with DD (ASD, Global Developmental Delay (GDD), and Speech and Language Delay (SLD)) attending the Child Development Unit (CDU) at our hospital was performed. Three hundred and thirty-three children (ASD: n = 129; GDD: n = 110; and SLD: n = 94) underwent hearing assessments. Of these, 10.8% of children (n = 36, comprising 15 with ASD, 12 with GDD and 9 with SLD) had confirmed hearing loss. Hearing loss was predominantly bilateral in children with ASD and GDD; in those with SLD, unilateral and bilateral hearing loss were equally common. Conductive hearing loss occurred as frequently as sensorineural hearing loss in children with ASD and SLD, but was the dominant subtype in those with GDD. Moderate to severe hearing loss (n = 2) was noted only in children with ASD. Children with ASD and GDD required significantly more audiology visits and procedures to obtain conclusive hearing test results, compared to those with SLD. The need to identify hearing loss and monitor for resolution is particularly important in vulnerable populations with communication deficits, such as in those with ASD.

Adolescent idiopathic scoliosis is the most common paediatric spinal deformity, impacting 1 in 300 children.1 In Singapore and other countries, national screening programmes have been established to detect scoliosis early, with the aim of using bracing to prevent progression to moderate or severe scoliosis, which may require surgical intervention.1,2 Whole spine radiography is crucial for accurately diagnosing scoliosis using the Cobb method, where scoliosis is defined by a Cobb angle of at least 10°.3 This method requires precise identification of the most tilted vertebral endplates above and below the curve apex, leading to a classification of mild (10–25°), moderate (25–40°) or severe scoliosis (>40°).4

Background: This study was carried out to compare the concurrent validity of the Kaufman Brief Intelligence Test – Second Edition (KBIT-2) with that of two Wechsler Intelligence Scales (Wechsler Intelligence Scale for Children – Fifth Edition (WISC-V) and the Wechsler Preschool and Primary Scale of Intelligence – Fourth Edition (WPPSI-IV)) in an Asian setting. Methods: A retrospective study reviewed the medical records of 101 children with developmental disorders who were being followed up at a tertiary child development unit. Pearson product moment correlation coefficients were calculated between the KBIT-2 and Wechsler assessment scores. Simple regression analysis was used to calculate standard errors of estimation to assess the accuracy of predicting Wechsler scores using KBIT-2 scores. Results: A strong positive correlation was observed between KBIT-2's Intelligence Quotient (IQ) Composite and WISC-V's Full-Scale IQ (FSIQ) scores (r = 0.722, p

BackgroundAging is a risk factor for falls, frailty, and disability. The utility of wearables to screen for physical performance and frailty at the population level is an emerging research area. To date, there is a limited number of devices that can measure frailty and physical performance simultaneously. ObjectiveThe aim of this study is to evaluate the accuracy and validity of a continuous digital monitoring wearable device incorporating gait mechanics and heart rate recovery measurements for detecting frailty, poor physical performance, and falls risk in older adults at risk of falls. MethodsThis is a substudy of 156 community-dwelling older adults ≥60 years old with falls or near falls in the past 12 months who were recruited for a fall prevention intervention study. Of the original participants, 22 participants agreed to wear wearables on their ankles. An interview questionnaire involving demographics, cognition, frailty (FRAIL), and physical function questions as well as the Falls Risk for Older People in the Community (FROP-Com) was administered. Physical performance comprised gait speed, timed up and go (TUG), and the Short Physical Performance Battery (SPPB) test. A gait analyzer was used to measure gait mechanics and steps (FRAIL-functional: fatigue, resistance, and aerobic), and a heart rate analyzer was used to measure heart rate recovery (FRAIL-nonfunctional: weight loss and chronic illness). ResultsThe participants’ mean age was 74.6 years. Of the 22 participants, 9 (41%) were robust, 10 (46%) were prefrail, and 3 (14%) were frail. In addition, 8 of 22 (36%) had at least one fall in the past year. Participants had a mean gait speed of 0.8 m/s, a mean SPPB score of 8.9, and mean TUG time of 13.8 seconds. The sensitivity, specificity, and area under the curve (AUC) for the gait analyzer against the functional domains were 1.00, 0.84, and 0.92, respectively, for SPPB (balance and gait); 0.38, 0.89, and 0.64, respectively, for FRAIL-functional; 0.45, 0.91, and 0.68, respectively, for FROP-Com; 0.60, 1.00, and 0.80, respectively, for gait speed; and 1.00, 0.94, and 0.97, respectively, for TUG. The heart rate analyzer demonstrated superior validity for the nonfunctional components of frailty, with a sensitivity of 1.00, specificity of 0.73, and AUC of 0.83. ConclusionsAgreement between the gait and heart rate analyzers and the functional components of the FRAIL scale, gait speed, and FROP-Com was significant. In addition, there was significant agreement between the heart rate analyzer and the nonfunctional components of the FRAIL scale. The gait and heart rate analyzers could be used in a screening test for frailty and falls in community-dwelling older adults but require further improvement and validation at the population level.

Introduction: Children from low-income (LI) families often suffer from poor health, with sub-optimal health practices. This cross-sectional study examined the differences in health habits and health-related quality of life (HRQoL) of LI preschool children compared to non-low-income preschool peers (PPG). Method: Using data from the social-health Circle of Care-Health Development Screening Programme (CoC-HDSP) in Singapore, 118 LI children and 304 PPG children aged 18 months to 6 years old and their families were recruited from 13 government-funded preschools. Health practices examined included screen time habits, sleep, nutrition, dental health and the children’s HRQoL using PedsQL 4.0 Generic Core Scales. Results: Majority of the children were aged 4–6 years in kindergarten 1 and 2. There were more Malay children in the LI than the PPG (61.9% versus [vs] 29.3%, P

Abstract Background Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. Methods This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. Results There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p

To develop and assess the preliminary effectiveness of Ontological Coaching Intervention for nursing undergraduates. Design: A pilot randomized controlled trial with a two-group pre-test and post-test followed by process-evaluation qualitative interviews. An Ontological Coaching Intervention was developed through an integration of prior literature and the collective the research team’s experience, consisting of 4-6 sessions over 6-months, each lasting 30-60 minutes. Sessions encompassed exploring ontological coaching concepts, empowering nursing undergraduates to choose topics, and tailoring sessions to individual needs. Sixty undergraduates were recruited; ten were excluded for not completing the baseline questionnaires. Twenty-one nursing undergraduates were randomly assigned to the intervention group and twenty-nine undergraduates to the control group (standard academic support only). Primary (psychological well-being) and secondary (social support quantity and satisfaction, goal-setting, resilience) outcomes were measured at baseline, 3-months, and 6-months. Semi-structured interviews captured post-intervention experiences. Between-group analyses revealed a significant difference in goal-setting scores at 3-months (U = 325.5, p = 0.013), favoring the intervention group (median = 70.50, IQR = 64.25, 76.75). At 6-months, a significant difference in social support satisfaction scores (U = 114.5, p = 0.028) was found between the intervention (median = 33.00, IQR = 29.50, 35.25) and control (median = 30.00, IQR = 30.00, 35.00) groups. However, no significant between-group differences were noted in other outcome measures. Significant within-group differences were found in goal-setting scores at 3- and 6-months in the intervention group and social support quantity scores at 3- and 6-months in the control group. However, no significant within-group differences were noted in other outcome measures. Three themes were identified: Enhanced Holistic Development, Keys to Successful Coaching, and Future Directions for Successful Coaching. There is urgent need to advance research on Ontological Coaching Intervention, particularly, enhancing study rigor, broadening examinations to diverse healthcare student populations and cultural contexts, and addressing identified limitations.

Aims To study the risk factors for burnout among doctors in a tertiary general hospital in Singapore. We hypothesized that burnout would be associated with singles, young age, females, foreign born staff who had recently moved to this country unaccompanied by family, and those showing less resilience. We hypothesised perceived support and satisfaction with leisure would mitigate against burnout. Methods An anonymised survey was carried out, with questionnaires sent to all staff via email. Survey instruments included the Oldenburg Burnout Inventory, Connor Davidson Resilience Scale, Brief Form of Perceived Social Support Questionnaire, Patient Health Questionnaire-4 items (PHQ-4), Leisure Time Satisfaction Survey and the Demand Control Support Questionnaire (DCSQ). Descriptive statistics for normally-distributed numerical variables were presented as mean (SD or standard deviation), and for categorical variables, median and n (%). One-way ANOVA was performed to determine differences in total burnout scores across categorical variables and simple linear regression was used to assess for binary and numerical outcomes in terms of resilience, PHQ, DSCQ, satisfaction with leisure time and perceived social support, with significance set as p < 0.05. Results A total of 129 doctors responded to the survey. Over half were male, and nearly 70% were married. Nearly half were below age 40 and only about 5% had no immediate family living in Singapore. Burnout was associated with young age (p < 0.004) and those with anxiety 2.39 (2.13 to 2.64) p = 0.038, and depressive symptoms 2.71 (2.44 to 2.97) p < 0.001. Psychological demand was positively associated with burnout (1.52 (1.32 to 1.71) p < 0.001; whereas decision latitude −0.69 (−0.85 to −0.52), social support at work −1.35 (−1.49 to −1.21), and high resilience −0.56 (−0.63 to −0.48), were negatively associated (all p < 0.001). Satisfaction with leisure time was negatively correlated with burnout (p < 0.001). Contrary to hypothesis, singlehood, gender, overseas staff recently joined with no accompanying family were not associated with burnout (p > 0.05). In addition, perceived social support from outside work did not mitigate against burnout (p > 0.05). Conclusion Young age, anxiety and depression, and psychological demands were risk factors, whereas resilience, decision latitude, satisfaction with leisure, and social support at work were protective factors against burnout. Reducing workload, improving work schedules, promoting self-management, teaching physical, mental, and emotional self-care, and other stress management activities are among the effective techniques shown to reduce burnout. Interventions should be made available for all staff, but specifically focusing on those at greatest risk.

BackgroundParents experience many challenges during the perinatal period. Mobile app–based interventions and chatbots show promise in delivering health care support for parents during the perinatal period. ObjectiveThis descriptive qualitative process evaluation study aims to explore the perinatal experiences of parents in Singapore, as well as examine the user experiences of the mobile app–based intervention with an in-built chatbot titled Parentbot—a Digital Healthcare Assistant (PDA). MethodsA total of 20 heterosexual English-speaking parents were recruited via purposive sampling from a single tertiary hospital in Singapore. The parents (control group: 10/20, 50%; intervention group: 10/20, 50%) were also part of an ongoing randomized trial between November 2022 and August 2023 that aimed to evaluate the effectiveness of the PDA in improving parenting outcomes. Semistructured one-to-one interviews were conducted via Zoom from February to June 2023. All interviews were conducted in English, audio recorded, and transcribed verbatim. Data analysis was guided by the thematic analysis framework. The COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist was used to guide the reporting of data. ResultsThree themes with 10 subthemes describing parents’ perceptions of their parenting journeys and their experiences with the PDA were identified. The main themes were (1) new babies, new troubles, and new wonders; (2) support system for the parents; and (3) reshaping perinatal support for future parents. ConclusionsOverall, the PDA provided parents with informational, socioemotional, and psychological support and could be used to supplement the perinatal care provided for future parents. To optimize users’ experience with the PDA, the intervention could be equipped with a more sophisticated chatbot, equipped with more gamification features, and programmed to deliver personalized care to parents. Researchers and health care providers could also strive to promote more peer-to-peer interactions among users. The provision of continuous, holistic, and family-centered care by health care professionals could also be emphasized. Moreover, policy changes regarding maternity and paternity leaves, availability of infant care centers, and flexible work arrangements could be further explored to promote healthy work-family balance for parents.

ABSTRACT Background The prevalence and healthcare cost of metabolic dysfunction–associated steatotic liver disease (MASLD) has increased alongside the epidemic surge in obesity and Type 2 diabetes. Weight loss through lifestyle modification remains the primary effective therapy for MASLD. Incorporation of mobile technology in lifestyle interventions has been previously found to be efficacious and cost‐effective in facilitating weight loss. However, there is a paucity of studies that have successfully translated lifestyle research into clinical service for weight loss to alleviate disease burden. Our study aimed to describe the process of translating a mobile technology–enabled trial into a tertiary hospital outpatient dietetics service for patients with MASLD. Methods The Iowa Model of Evidence‐Based Practice to Improve Quality Care was used as a framework for this paper to guide implementation at the organizational level. Results Regular engagement of key operational staff and the hospital management team facilitated open discussions of the challenges faced and enabled rapid implementation of strategies that contributed to the smooth piloting of the service. A service adoption rate of 81% was achieved. Preliminary outcome evaluation found that the percentage of patients achieving ≥ 5% weight loss from baseline at 6 months was comparable at 54% and 52% for the service and trial groups, respectively. Conclusions Evaluation of the implementation process found that a hybrid model of care (in‐person consultation supplemented with app coaching) preserved interpersonal connections while maximizing the convenience and scalability of mobile app–enabled service. Although high digital acceptance and adoption rates propelled by COVID‐19‐supported telehealth, it is prudent to assess patient's access to technology and digital literacy and offer resources to help them benefit from telehealth services.

IntroductionIt is challenging to prognosticate hospitalised older adults. Delayed recognition of end-of-life leads to failure in delivering appropriate palliative care and increases healthcare utilisation. Most mortality prediction tools specific for older adults require additional manual input, resulting in poor uptake. By leveraging on electronic health records, we aim to create an automatable mortality prediction tool for hospitalised older adults.MethodsWe retrospectively reviewed electronic records of general medicine patients ≥75 years at a tertiary hospital between April–September 2021. Demographics, comorbidities, ICD-codes, age-adjusted Charlson Comorbidity Index (CCI), Hospital Frailty Risk Score, mortality and resource utilization were collected. We defined early deaths, late deaths and survivors as patients who died within 30 days, 1 year, and lived beyond 1 year of admission, respectively. Multivariate logistic regression analyses were adjusted for age, gender, race, frailty, and CCI. The final prediction model was created using a stepwise logistic regression.ResultsOf 1,224 patients, 168 (13.7%) died early and 370 (30.2%) died late. From adjusted multivariate regression, risk of early death was significantly associated with ≥85 years, intermediate or high frail risk, CCI > 6, cardiovascular risk factors, AMI and pneumonia. For late death, risk factors included ≥85 years, intermediate frail risk, CCI >6, delirium, diabetes, AMI and pneumonia. Our mortality prediction tool which scores 1 point each for age, pneumonia and AMI had an AUC of 0.752 for early death and 0.691 for late death.ConclusionOur mortality prediction model is a proof-of-concept demonstrating the potential for automated medical alerts to guide physicians towards personalised care for hospitalised older adults.

IntroductionPeriodontitis as a comorbidity in systemic lupus erythematosus (SLE) is still not well recognized in the dental and rheumatology communities. A meta-analysis and network meta-analysis were thus performed to compare the (i) prevalence of periodontitis in SLE patients compared to those with rheumatoid arthritis (RA) and (ii) odds of developing periodontitis in controls, RA, and SLE.MethodsPooled prevalence of and odds ratio (OR) for periodontitis were compared using meta-analysis and network meta-analysis (NMA).ResultsForty-three observational studies involving 7,800 SLE patients, 49,388 RA patients, and 766,323 controls were included in this meta-analysis. The pooled prevalence of periodontitis in SLE patients (67.0%, 95% confidence interval [CI] 57.0-77.0%) was comparable to that of RA (65%, 95% CI 55.0-75.0%) (p>0.05). Compared to controls, patients with SLE (OR=2.64, 95% CI 1.24-5.62, p

BackgroundDecline in intrinsic capacity (IC) has been shown to accelerate progression to disability. The study aims to explore association of IC composite score with functional ability, sarcopenia and systemic inflammation in pre-frail older adults.MethodsCross-sectional study of pre-frail older adults ≥60 years old recruited from the community and primary care centers. Composite scores of four domains of IC were measured: locomotion, vitality, cognition and psychological. FRAIL scale was used to define pre-frailty. Muscle mass was measured using the bioelectrical impedance analysis. Systemic inflammation biomarkers [Interleukin-6 (IL-6), Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), and Growth differentiated factor 15 (GDF-15)] were measured. Participants in the lowest tertile (T1) exhibited greater decline in IC.ResultsA total of 398 pre-frail older adults were recruited, mean age was 72.7 ± 5.8 years, 60.1% female, education level 7.8 years, and 85.2% were of Chinese ethnicity. A total of 75.1% had decline in locomotion, 40.5% in vitality, 53.2% in cognition and 41.7% in psychological domain. A total of 95% had decline in at least one domain. T1 was significantly associated with ADL impairment (aOR 3.36, 95% CI 1.78–6.32), IADL impairment (aOR 2.37, 95% CI 1.36–4.13), poor perceived health (aOR 0.96, 95% CI 0.95–0.98), fall (aOR 1.63, 95% CI 1.05–2.84), cognitive impairment (aOR 8.21, 95% CI 4.69–14.39), depression (aOR 101.82, 95% CI 33.62–308.37), and sarcopenia (aOR 2.40, 95% CI 1.60–5.45). T1 had significant associations with GDF-15, IL-10, and IL-10 to TNF-α ratio.ConclusionDecline in IC composite score among pre-frail older adults was associated with functional limitation, sarcopenia, and systemic inflammation.

BackgroundWomen are less likely to have classic cardiovascular risk factors than men, and events during their reproductive and menopausal years may increase hypertension risk. The aim of this study is to examine woman-specific factors, including menstrual, reproductive and pregnancy complications, in relation to the prevalence of hypertension in mid-life Asian women.MethodsThis is a cross-sectional study of 1146 healthy women aged 45-69 years, from a multi-ethnic Asian cohort. The women completed an extensive questionnaire that included their sociodemographic details, medical history, lifestyle and physical activity, and reproductive and menopausal history. They also underwent objectively measured physical performance tests and a dual X-ray absorptiometry scan. Hypertension was defined as a systolic BP ≥140 and/or diastolic BP ≥90mm Hg, past diagnosis by a physician, or use of antihypertensive medications. Multivariable logistic regression was used to assess the independent risk factors for hypertension.ResultsThe average age of the 1146 women analysed was 56.3 (SD 6.2) years, and 55.2 percent of them were hypertensive. The prevalence of gestational diabetes and gestational hypertension was 12.6% and 9.4%, respectively. Besides age, abnormal menstrual cycle length at 25 years of age (OR:2.35, CI:1.34-4.13), preeclampsia (OR:2.46, CI:1.06-5.74), increased visceral adiposity (OR:4.21, CI:2.28-7.79) and reduced physical performance (OR:2.83, CI:1.46-5.47) were independently associated with hypertension in Asian women.ConclusionsOur findings highlight the necessity of including features of menstrual and reproductive history as possible indicators of hypertension risk in cardiovascular disease risk assessment and prevention among Asian women. Reducing visceral adiposity and exercise to improve physical performance may help women avoid developing hypertension.

Objective: To examine factors associated with poor sleep quality in community-dwelling midlife women. Methods: Healthy women (aged 45–69 years) of Chinese, Malay and Indian ethnicities attending well-women clinics at the National University Hospital, Singapore, completed the Pittsburgh Sleep Quality Index (PSQI). A PQSI score >5 denoted poor sleep quality. The women filled out validated questionnaires covering menopausal and genito-urinary symptoms, and mental health. Physical performance was measured. Bone mineral density and visceral adiposity were assessed by dual energy X-ray absorptiometry. Binary logistic regression analyses assessed independent factors for poor sleep. Results: Poor sleep quality was reported in 38.2% of women (n = 1094, mean age: 56.4 ± 6.2 years). Indian women had higher sleep disturbance scores than Chinese women (mean ± SD: 1.33 ± 0.58 vs 1.17 ± 0.49). Malays experienced more daytime dysfunction (0.54 ± 0.60 vs 0.33 ± 0.55) and had a higher overall PSQI score (6.00 ± 3.31 vs 5.02 ± 2.97) than the Chinese. A low education level (aOR: 1.76, 95% CI: 1.01–3.05), feelings of irritability (2.67, 1.56–4.60) and vaginal dryness (1.62, 1.03–2.54) were associated with poor sleep quality in the adjusted multivariable model. Women with moderate to severe disability were ∼3 times (2.99, 1.20–7.44) more likely to experience less than ideal sleep quality, while urinary incontinence (1.53, 1.08–2.17) and breast cancer history (2.77, 1.36–5.64) were also associates of poor sleep quality. Conclusion: Self-reports of education level, irritability, vaginal dryness, disability, urinary incontinence, and breast cancer history were independently related to poor sleep. Ethnic differences suggest the need for targeted interventions among the ethnic groups.

IntroductionSurgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore.MethodsThis is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 – 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups.ResultsThere was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p

BackgroundOne of the core features of autism spectrum disorder (ASD) is restricted, repetitive patterns of behavior, interests and activities (RRBs). RRBs are known to adversely affect cognition and adaptive functioning. We explored the relationship of RRBs with cognition and adaptive functioning in children with ASD in an Asian setting.MethodsThis cross-sectional study was conducted at a tertiary developmental pediatrics center in Singapore from September 2019 to October 2021. Parent-child dyads (parents and their children ≤7 years old diagnosed with ASD) were recruited. Parents completed the Repetitive Behavior Questionnaire-2 (RBQ-2), which reports total score and two subscales – Motor/Sensory Behaviors (RBQ-2 MS) and Rigidity/Routines/Preoccupation with Restricted Interests (RBQ-2 RRPRI). Standardized assessments included Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS-II). Data analysis utilized descriptive statistics and Pearson’s correlation.ResultsParents of 113 children [75.2% male, mean (SD) age 5.0 (1.2) years] participated. Median (IQR) RBQ-2 score was 29.0 (11.0). Significant negative correlations (adjusted for age, gender and family history of ASD) were observed for total RBQ-2 scores with MSEL ELC scores (r = −0.248, n = 101, p = 0.014) and VABS-II ABC scores (r = −0.281, n = 88, p = 0.009). Specifically, these correlations of fair strength were seen only with the RBQ-2 MS subscale for both ELC (r = −0.321, n = 101, p = 0.001) and ABC (r = −0.3478, n = 88, p = 0.001).ConclusionIn children with ASD, severity of RRBs correlated with adverse cognition and adaptive functioning measures in our study, consistent with Western literature. While our study does not show causality, it adds to literature serving as a foundation for further research for both clinicians and researchers to target RRBs in improving outcomes with children in ASD.

Botulinum toxin type A (Botox®) is thought to have antipruritic effects through inhibition of pruritic factors, including acetylcholine, substance P, and glutamate. The aim of this randomized, single-blind, placebo-controlled trial was to test the effect of botulinum toxin type A on cowhage, a non-histaminergic model for chronic itch. Botulinum toxin type A was injected into the arm of 35 healthy subjects, with a saline control injected into the contralateral arm. Thermal sensory parameters (warmth and heat thresholds and heat pain intensity) and itch intensity after cowhage application were examined on test areas. Botulinum toxin type A reduced itch intensity, overall perceived itch (area under the curve (AUC); percentage change from baseline), and peak itch intensity compared with the control at 1 week, 1 month, and 3 months. Botulinum toxin type A had no effect on thermal thresholds or heat pain intensity. In conclusion, botulinum toxin type A reduced cowhage itch for at least 3 months, which suggests that botulinum toxin type A is a potential long-lasting treatment for localized, non-histaminergic itch.

BackgroundExercise and a protein-enriched diet are essential for muscle protein synthesis, cellular growth, mitochondrial function, and immune function. The U.S. Food and Nutrition Board's current guideline on recommended dietary allowance for protein in older adults is 0.8 g/kg per day, which may not be sufficient in vulnerable pre-frail older adults.AimsThis study aimed to evaluate the impact of leucine-enriched protein supplementation with or without exercise over 3 months in pre-frail older adults who consumed ≤1 g/kg/day of protein on improving (i) physical function, (ii) body composition measures, and (iii) inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α).MethodsA non-randomized cluster quasi-experimental study guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist of 178 pre-frail older adults [112 control, 44 nutrition (Nu), and 22 in the nutrition with exercise (Nu+Ex) group] comparing the effect of Nu+Ex and Nu on physical function, body composition, and inflammation. At 0, 3, and 6 months, questionnaires on demographics, depression, perceived health, and cognition were administered. Physical function assessment (short physical performance battery [SPPB] test, gait speed, handgrip strength, 5× sit-to-stand [STS]) was conducted, and body composition analysis was performed using a bioelectrical impedance analysis machine. IL-6 and TNF-α were measured at 0 and 3 months.ResultsAt 3 months, there were significant improvements in gait speed, 5× STS, SPPB scores, depression, perceived health, fat-free mass, and appendicular skeletal muscle mass indices in the Nu+Ex group. Both Nu+Ex and Nu groups had improvements in body cell mass and reductions in IL-6 and TNF-α. The improvements were not sustained after 6 months.ConclusionOur study results need to be validated in future longitudinal randomized studies with a larger sample size focusing on populations at risk.

We recently reported that messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination was associated with flares in 9% of patients with systemic lupus erythematosus (SLE). Herein, we focused our analysis on patients from a multi-ethnic Southeast Asian lupus cohort with the intention of identifying distinct phenotypes associated with increased flares after mRNA COVID-19 vaccination. Methods: Six hundred and thirty-three SLE patients from eight public healthcare institutions were divided into test and validation cohorts based on healthcare clusters. Latent class analysis was performed based on age, ethnicity, gender, vaccine type, past COVID-19 infection, interruption of immunomodulatory/immunosuppressive treatment for vaccination, disease activity and background immunomodulatory/immunosuppressive treatment as input variables. Data from both cohorts were then combined for mixed effect Cox regression to determine which phenotypic cluster had a higher risk for time to first SLE flare, adjusted for the number of vaccine doses. Results: Two clusters were identified in the test (C1 vs. C2), validation (C1′ vs. C2′) and combined (C1″ vs. C2″) cohorts, with corresponding clusters sharing similar characteristics. Of 633 SLE patients, 88.6% were female and there was multi-ethnic representation with 74.9% Chinese, 14.2% Malay and 4.6% Indian. The second cluster (C2, C2′ and C2″) was smaller compared to the first. SLE patients in the second cluster (C2 and C2′) were more likely to be male, non-Chinese and younger, with higher baseline disease activity. The second cluster (C2″) had more incident flares (hazard ratio = 1.4, 95% confidence interval 1.1–1.9, p = 0.014) after vaccination. A higher proportion of patients in C2″ had immunomodulatory/immunosuppressive treatment interruption for vaccination as compared to patients in C1″ (6.6% vs. 0.2%) (p < 0.001). Conclusion: We identified two distinct phenotypic clusters of SLE with different patterns of flares following mRNA COVID-19 vaccination. Caution has to be exercised in monitoring for post-vaccination flares in patients with risk factors for flares such as non-Chinese ethnicity, young age, male gender and suboptimal disease control at the time of vaccination.

Abstract Objectives To evaluate dentition status amongst community-dwelling older adults and its association with frailty and cognitive impairment. Methodology One thousand forty-seven community-dwelling older adults aged ≥65 years were surveyed in an epidemiologic population-based cohort study in Singapore between April 2015 and August 2016. Data on demographics, dentition status, chronic diseases, activities and instrumental activities on daily-living, cognition (age- and education-specific MMSE cut-offs), frailty (FRAIL scale), perceived health and functional status were collected. Multiple logistic regression was performed to examine the association between dentition, frailty and cognition. Results Mean age of participants was 71.2 ± 5.5 years. The prevalence of denture use was 70.7% and edentulism 7.9%. Compared to edentulousness, having teeth was associated with lower odds of cognitive impairment and higher odds of being robust or pre-frail. Denture-wearers compared with edentulous persons were less likely to be male, had higher education level and more likely be robust or pre-frail. Conclusion and implications There were significant associations between dentition status, frailty and cognition in our study where those with remining teeth and / or dentures had better overall outcomes. As oral health, frailty and cognitive impairments are all modifiable risk factors for healthy ageing, countries should consider population level screening for oral health, frailty and cognitive impairment.

IntroductionMetastatic spinal cord compression (MSCC) is a disastrous complication of advanced malignancy. A deep learning (DL) algorithm for MSCC classification on CT could expedite timely diagnosis. In this study, we externally test a DL algorithm for MSCC classification on CT and compare with radiologist assessment.MethodsRetrospective collection of CT and corresponding MRI from patients with suspected MSCC was conducted from September 2007 to September 2020. Exclusion criteria were scans with instrumentation, no intravenous contrast, motion artefacts and non-thoracic coverage. Internal CT dataset split was 84% for training/validation and 16% for testing. An external test set was also utilised. Internal training/validation sets were labelled by radiologists with spine imaging specialization (6 and 11-years post-board certification) and were used to further develop a DL algorithm for MSCC classification. The spine imaging specialist (11-years expertise) labelled the test sets (reference standard). For evaluation of DL algorithm performance, internal and external test data were independently reviewed by four radiologists: two spine specialists (Rad1 and Rad2, 7 and 5-years post-board certification, respectively) and two oncological imaging specialists (Rad3 and Rad4, 3 and 5-years post-board certification, respectively). DL model performance was also compared against the CT report issued by the radiologist in a real clinical setting. Inter-rater agreement (Gwet’s kappa) and sensitivity/specificity/AUCs were calculated.ResultsOverall, 420 CT scans were evaluated (225 patients, mean age=60 ± 11.9[SD]); 354(84%) CTs for training/validation and 66(16%) CTs for internal testing. The DL algorithm showed high inter-rater agreement for three-class MSCC grading with kappas of 0.872 (p

Summary: Background: Malnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030. Methods: Using data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed. Findings: In 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507–895) per 100,000 population. DALY rates decreased from 2000 to 2019 (−2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277–2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries. Interpretation: The ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further. Funding: None.

Abstract Background Hepatic resection (HR) for hepatocellular carcinoma (HCC) is safe with good perioperative and long-term oncologic outcomes. There is a paucity of data with regards to intermediate-term outcomes (i.e., beyond 90-day and within 1-year mortality). This paper studies the risk factors for within 1-year mortality after elective HR with curative intent in patients with HCC. Methods An audit of patients who underwent curative HR for HCC from January 2007 to April 2016 was conducted. Univariate and multivariate analysis were sequentially performed on perioperative variables using Cox-regression analysis to identify factors predicting intermediate-term outcomes defined as within 1-year mortality. Kaplan–Meier survival curves and hazard ratios were obtained. Results Three hundred forty-eight patients underwent HR during the study period and 163 patients had curative hepatectomy for HCC. Fifteen patients (9.2%) died within 1-year after HR. Multivariate analysis identified Child-Pugh class B/C (HR 5.5, p = 0.035), multinodularity (HR 7.1, p = 0.001), macrovascular invasion (HR 4.2, p = 0.04) postoperative acute renal failure (HR 5.8, p = 0.049) and posthepatic liver failure (HR 9.6, p = 0.009) as significant predictors of 1-year mortality. Conclusion One-year mortality following HR for HCC remains high and can be predicted preoperatively by multinodularity, Child-Pugh class, and macrovascular invasion. Postoperative acute renal failure and liver failure are associated with 1-year mortality.

Abstract Background Data from certain subgroups of clinical interest may not be presented in primary manuscripts or conference abstract presentations. In an effort to enable secondary data analyses, we propose a workflow to retrieve unreported subgroup survival data from published Kaplan-Meier (KM) plots. Methods We developed KMSubtraction, an R-package that retrieves patients from unreported subgroups by matching participants on KM plots of the overall cohort to participants on KM plots of a known subgroup with follow-up time. By excluding matched patients, the opposing unreported subgroup may be retrieved. Reproducibility and limits of error of the KMSubtraction workflow were assessed by comparing unmatched patients against the original survival data of subgroups from published datasets and simulations. Monte Carlo simulations were utilized to evaluate the limits of error of KMSubtraction. Results The validation exercise found no material systematic error and demonstrates the robustness of KMSubtraction in deriving unreported subgroup survival data. Limits of error were small and negligible on marginal Cox proportional hazard models comparing reconstructed and original survival data of unreported subgroups. Extensive Monte Carlo simulations demonstrate that datasets with high reported subgroup proportion (r = 0.467, p

Background: To characterize the nature and severity of feeding difficulties in Asian young children with Autism Spectrum Disorders (ASD) and identify potential predictors of poorer feeding outcomes. Methods: Cross sectional study of children aged 1–7 years with ASD. Parents completed the following: demographic information, brief autism mealtime behavior inventory, aberrant behavior checklist (ABC), behavioral pediatrics feeding assessment scale (BPFAS) and caregiver feeding style questionnaire. Additional information (medical data, cognitive and developmental assessment results, e.g., Autism Diagnostic Observation Schedule Second Edition, Autism Diagnostic Interview, Revised, Vineland Adaptive Behaviour Scales, etc.) were subsequently obtained from electronic medical records retrospectively by one of the study team members. Results: Of the 67 children, 28.4% had feeding difficulties (high BPFAS total frequency score). Caregiver feeding styles were authoritarian (34.8%) or indulgent (39.4%). Child characteristics did not significantly predict for the severity of feeding difficulties. Univariate analysis revealed that authoritarian feeding style (p = 0.001) and ABC hyperactivity score (p = 0.006) were significantly associated with BPFAS severity score. Multivariate analysis revealed that ABC hyperactivity score remained significantly associated with BPFAS severity score after controlling for all other ABC subscale scores. A final regression model including all child characteristics and ABC scores did not reveal any significant predictors of BPFAS total frequency score (R2 = 0.557). Conclusion: Our findings suggest an association between hyperactivity, authoritarian feeding style and feeding difficulties. Children with ASD who have significant hyperactivity behaviors in the context of parents with an authoritarian feeding style should be actively screened for problematic feeding behaviors.

BackgroundPrevious studies have investigated the various effects of parenting on infant developmental outcomes. In particular, parental stress and social support have been found to significantly affect the growth of the newborn. Although many parents today use mobile apps to obtain more support in parenting and perinatal care, few studies have examined how these apps could affect infant development. ObjectiveThis study aimed to examine the effectiveness of the Supportive Parenting App (SPA) in improving infant developmental outcomes during the perinatal period. MethodsThis study adopted a 2-group parallel prospective longitudinal design and recruited 200 infants and their parents (N=400 mothers and fathers). The parents were recruited at 24 weeks of gestation for a randomized controlled trial conducted from February 2020 to July 2022. They were randomly allocated to either the intervention or control group. The infant outcome measures included cognition, language, motor skills, and social-emotional development. Data were collected from the infants when they were aged 2, 4, 6, 9, and 12 months. Linear and modified Poisson regressions were used to analyze the data to examine between- and within-group changes. ResultsAt 9 and 12 months post partum, the infants in the intervention group were found to have better communication and language skills than those in the control group. An analysis of motor development revealed that a larger proportion of the infants in the control group fell under the at-risk category, where they scored approximately 2 SDs below the normative scores. The control group infants scored higher on the problem solving domain at 6 months post partum. However, at 12 months postpartum, the infants in the intervention group performed better on cognitive tasks than those in the control group. Despite not being statistically significant, the intervention group infants were found to have consistently scored better on the social components of the questionnaires than the control group infants. ConclusionsOverall, the infants whose parents had received the SPA intervention tended to fare better in most developmental outcome measures than those whose parents had received standard care only. The findings of this study suggest that the SPA intervention exerted positive effects on the communication, cognition, motor, and socioemotional development of the infants. Further research is needed to improve the content and support provided by the intervention to maximize the benefits gained by infants and their parents. Trial RegistrationClinicalTrials.gov NCT04706442; https://clinicaltrials.gov/ct2/show/NCT04706442

BackgroundAdjusting to new or additional parenting responsibilities increases stress and affects parental well-being. Existing research has highlighted both parents’ desire to receive more support. It has also been found that receiving sufficient social support enhances parenting outcomes. With the increasing popularity of mobile health apps, a Supportive Parenting App (SPA) intervention was developed to fulfill the support needs of parents during the perinatal period. ObjectiveThis study aimed to examine the effectiveness of the SPA on parental outcomes during the perinatal period. MethodsA 2-group pretest and repeated posttest randomized controlled trial was conducted wherein 200 couples (N=400 mothers and fathers) were recruited from 2 public health care institutions in Singapore. Parents were randomly assigned to intervention (100/200, 50%) or control (100/200, 50%) groups. The SPA intervention consisted of a mobile app–based psychoeducation and peer support program to support parents from pregnancy to 6 months post partum. The outcome measures included postnatal depression, anxiety, parental bonding, parental self-efficacy, perceived social support, and parenting satisfaction. Data were collected at baseline (at >24 weeks of gestation—age of viability in Singapore) and at the first, second, fourth, sixth, ninth, and 12th month post partum. Linear mixed models were used to compare parental outcomes between the groups, and a linear mixed model for repeated measures was used to examine within-group changes. ResultsParents in the intervention group mostly showed better outcomes compared with those in the control group. Parents in the intervention group had higher perceived social support than those in the control group at the first (effect size=1.59, 95% CI 0.38-2.80; Cohen standardized effect size=1.31; P=.01), second (effect size=1.98, 95% CI 1.09-2.88; Cohen standardized effect size=2.21; P=.003), and fourth (effect size=2.57, 95% CI 1.62-3.51; Cohen standardized effect size=2.72; P=.048) months post partum. However, parents in the intervention group showed significantly poorer parental bonding (effect size=1.67, 95% CI 0.24-3.11; Cohen standardized effect size=1.16; P=.02). The other parental outcomes did not differ significantly between groups. The scores of mothers and fathers also differed significantly for all outcomes except parental self-efficacy. ConclusionsParents in the intervention group generally fared better, especially regarding perceived social support. However, the lack of statistical significance in most outcomes showed the limited effectiveness of the SPA intervention, which may be because of the COVID-19 pandemic. Parental differences in outcome scores suggest that mothers and fathers have different support needs; therefore, interventions should be tailored accordingly. Further improvements and evaluations are needed to examine the effectiveness of the SPA intervention in enhancing parental outcomes. Despite statistically insignificant results, limitations should be considered to further improve mobile health app–based interventions such as SPA, as they could serve as reliable and convenient sources of support for parents. Trial RegistrationClinicaltrails.gov NCT4706442; https://clinicaltrials.gov/ct2/show/NCT04706442

Introduction. Growth differentiation factor 15 (GDF-15) has been shown to be a metabolic and appetite regulator in diabetes mellitus (DM) and obesity. We aimed to investigate (i) the association between GDF-15 and DM with and without poor physical function independent of inflammation and (ii) the prediction model for poor physical function in prefrail older adults. Methods. A cross-sectional study of 108-prefrail participants ≥60 years recruited for multidomain interventions. Data was collected for demographics, cognition, function, frailty, nutrition, handgrip strength (HGS), short physical performance battery (SPPB), and gait speed. Serum concentrations of GDF-15, IL-6, and TNF-α were measured. GDF-15 was classified into tertiles (T1, T2, and T3), and its association was studied with DM and physical function (DM poor physical function, DM no poor physical function, no DM poor physical function, and no DM no poor physical function). Results. Compared with T1, participants in T3 were significantly older, had a lower education level, had almost three times higher prevalence of DM, slower gait speed, longer chair-stand time, and lower SPPB scores. On multivariate analysis, the odds of having both DM and poor physical performance compared to having no DM and no poor physical performance were significantly higher in GDF-15 T3 vs. GDF-15 T1 (aOR 9.7, 95% CI 1.4-67.7; p=0.021), and the odds of having DM no poor physical function compared to having no DM and no poor physical performance were significantly higher in GDF-15 T2 (aOR 12.7, 95% CI 1.1-143.7; p=0.040) independent of BMI, IL-6, TNF-α, nutrition, physical function, education, age, and gender. Conclusion. The association of GDF-15 with DM-associated poor physical function is independent of inflammation in prefrail older adults. Its causal-association link needs to be determined in longitudinal studies.

BackgroundThe contribution of language preference and ethnicity to muscle strength and physical performance is unclear. We examined the associations of reading language preferences with muscle strength and performance in Chinese women and compared them to other ethnicities.MethodsThe Integrated Women's Health Programme (IWHP) cohort comprised community-dwelling, midlife Singaporean women aged 45-69. Ethnic Chinese women could choose between the English or Chinese versions of the questionnaire. Malay and Indian women were presented with the English version. Sociodemographic, reproductive, anthropometric characteristics were obtained. Hand grip strength and physical performance were objectively assessed. Visceral adiposity (VAT) was determined by Dual-energy X-ray Absorptiometry. Multivariable logistic regression models were used to determine independent associations of language preference/ethnicity with muscle strength and physical performance.ResultsThe cohort comprised 1164 women (mean age: 56.3±6.2 years); 84.1% Chinese, 5.6% Malay, and 10.3% Indian. 315 Chinese participants (32.2%) had a Chinese-language reading preference (CLP). CLP women tended to be parous, of a lower socioeconomic status (lower proportions received tertiary education, lower employment rates and lower household income), and engaged in less physical activity compared to Chinese women with an English-language preference (ELP). This translated to a weaker hand grip strength (aOR: 1.56; 95%CI: 1.07-2.27), slower repeated chair stand (1.55; 1.12-2.13), poorer balance on tandem stand (2.00; 1.16-3.47), and a slower gait speed (1.62; 1.06-2.47). Compared to ELP women, Malay women had higher odds of poor hand grip strength (1.81; 1.12-2.93) while Indians had a higher odd of poor balance on one-leg stand (2.12; 1.28-3.52) and slow gait speeds on usual (1.88; 1.09-3.25) and narrow walks (1.91; 1.15-3.17).ConclusionsChinese language reading preference was associated with inferior muscle strength and physical performance. Such disparities were largest and most consistent in the CLP group, followed by Indian and Malay women compared to the ELP group. Further studies should determine if CLP-associated muscle weakness can predict adverse health outcomes.

This study aimed to examine sarcopenia prevalence using the Asian Working Group for Sarcopenia 2019 (AWGS) and the Foundation for the National Institutes of Health (FNIH) definitions, and their associations with important health conditions affecting midlife Singaporean women. Muscle mass and function were objectively assessed in 1201 healthy community-dwelling subjects aged 45-69 years under the Integrated Women's Health Program (IWHP). Dual-energy X-ray absorptiometry (DXA), handgrip strength and the Short Physical Performance Battery (SPPB) were measured, and the relationship between sarcopenia with hypertension, type 2 diabetes (T2DM), osteoporosis, depression/anxiety, and urinary incontinence were examined using binary logistic regression models. Sarcopenia prevalence was 18.0% and 7.7% by the AWGS and FNIH criteria respectively. Osteoporosis (aOR: 1.74, 95% CI: 1.02, 2.94) and T2DM (aOR: 1.98, 95% CI: 1.14, 3.42) was positively associated with AWGS- and FNIH-defined sarcopenia respectively, while hypertension was not, after adjustment for age, ethnicity, education levels and menopausal status. A negative percent agreement of 95.6% suggests good agreement between the criteria in the absence of sarcopenia. Even though they represent a single concept, sarcopenia by either criterion differed in their relationships with diabetes and osteoporosis, suggesting the need for further rationalization of diagnostic criteria.

BackgroundExercise is the pillar for healthy aging. “Non-responders” may be due to a mismatch in exercise prescription. A latent cluster analysis (LCA) profile can be useful to uncover subpopulations sharing similar profiles or outcomes. We aim to use the LCA to develop a response prediction model for older adults who would benefit from The Healthy Aging Promotion Program for You, a community-embedded dual-task exercise program.MethodsA total of 197 participants completed the 3-month follow-up, and the complete data were available for 136 community-dwelling older adults. Inclusion criteria were age ≥60 years, pre-frail or frail and ambulant, mild cognitive impairment, and ability to provide consent. Data collected include demographics, education, falls, physical function (Katz ADL scale and Lawton's IADL scale), physical activity (rapid assessment of physical activity), cognition (Montreal Cognitive Assessment; MoCA), frailty (FRAIL scale), and perceived health, pain, anxiety/depression, fear of falling, and social isolation (Lubben Social Network Scale). The body mass index (BMI), handgrip strength, and short physical performance battery (SPPB) were measured. Those who improved in frailty, anxiety/depression, pain, Lubben, MoCA, SPPB, fear-of-falling, physical activity, falls, and HGS were classified as responders.ResultsThe mean age was 74.7 years, BMI 23.5 kg/m2, 23.5% were male, 96.3% were of Chinese ethnicity, 61% were pre-frail, education level of 4.3 years, and the MoCA score of 23.3 ± 4.8. Two clusters were identified: non-responders (61.8%) and responders (38.2%). Responders had significant improvement in cognition (44.2% vs. 0, p < 0.001) and SPPB (gait:28.8% vs. 0, p < 0.001; balance:42.3% vs. 15.5%, p = 0.001; chair-stand:65.4% vs. 4.8%, p < 0.001). Responders were significantly older (76.9 vs. 73.3 years, p = 0.005), had higher BMI (24.8 vs. 22.8 kg/m2, p = 0.007), lower education (3.4 vs. 4.9 years, p = 0.021), lower MoCA scores (21.8 vs. 24.3, p = 0.002), and lower SPPB scores (8.7 vs. 10.6, p < 0.001). The predictive variables for the responder cluster were age ≥75 years, BMI ≥23 kg/m2, robust, no anxiety, pain, fear of falling, MoCA ≤22, Lubben ≤12, SPPB score: chair-stand ≤2, balance ≤2, gait >2, handgrip strength 3. With an optimal cut-off of ≥12, this prediction model had sensitivity of 76.9%, specificity of 70.2%, positive predictive value 61.5%, and negative predictive value of 83.1%.ConclusionResponse to dual-task exercise was influenced by age, SPPB, BMI, and cognition. Prospective longitudinal studies are needed to validate this LCA model and guide the development of public health strategies.

Background: The COVID 19 pandemic has had its impact on tuberculosis notification, incidence, and management, particularly in the context of rifampicin-resistant TB. We set out to determine the trends in rifampicin resistant tuberculosis between the pre-COVID and COVID era in a resource-constrained setting. Methods: This was a retrospective review of single early morning sputum from presumed tuberculosis between January 2016 and May 2022 in a regional TB referral and treatment centre in South-western, Nigeria. We used a molecular beacon to detect Mycobacterium tuberculosis (MTB) and mutations in the rpoB gene using a real-time polymerase chain reaction (PCR). Results: We analyzed 19,892 of 20,589 presumptive TB with complete data. Most subjects were in the age group 18–45 years (10,594; 53.3 %) and were males (11,492; 57.8 %). Of the 19,892 presumptive TB, 4,526 (22.8 %) were in pre-COVID-19 era (Jan 2016-December 2019) and 15,366 (77.2 %) cases were in COVID-19 era (Jan 2020-May 2022). The MTB notification declined during the COVID-19 era compared with the pre-COVID-19 era (10.5 % vs 12.9 %, p

Abstract Background Enhancers are distal cis-regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity—however, most predicted enhancer regions remain to be functionally tested. Methods We analyzed 132 epigenomic histone modification profiles of 18 primary gastric cancer (GC) samples, 18 normal gastric tissues, and 28 GC cell lines using Nano-ChIP-seq technology. We applied Capture-based Self-Transcribing Active Regulatory Region sequencing (CapSTARR-seq) to assess functional enhancer activity. An Activity-by-contact (ABC) model was employed to explore the effects of histone acetylation and CapSTARR-seq levels on enhancer-promoter interactions. Results We report a comprehensive catalog of 75,730 recurrent predicted enhancers, the majority of which are GC-associated in vivo (> 50,000) and associated with lower somatic mutation rates inferred by whole-genome sequencing. Applying CapSTARR-seq to the enhancer catalog, we observed significant correlations between CapSTARR-seq functional activity and H3K27ac/H3K4me1 levels. Super-enhancer regions exhibited increased CapSTARR-seq signals compared to regular enhancers, even when decoupled from native chromatin contexture. We show that combining histone modification and CapSTARR-seq functional enhancer data improves the prediction of enhancer-promoter interactions and pinpointing of germline single nucleotide polymorphisms (SNPs), somatic copy number alterations (SCNAs), and trans-acting TFs involved in GC expression. We identified cancer-relevant genes (ING1, ARL4C) whose expression between patients is influenced by enhancer differences in genomic copy number and germline SNPs, and HNF4α as a master trans-acting factor associated with GC enhancer heterogeneity. Conclusions Our results indicate that combining histone modification and functional assay data may provide a more accurate metric to assess enhancer activity than either platform individually, providing insights into the relative contribution of genetic (cis) and regulatory (trans) mechanisms to GC enhancer functional heterogeneity.

IntroductionThe concept of participation restriction was first described by the World Health Organization in 2001 as a component of The International Classification of Functioning, Disability and Health Framework. Both falls and fear of falling (FOF) are associated with social isolation, depression, anxiety, poor quality of life and cognitive impairment resulting in participation restriction. Life-space mobility (LSM) is an important indicator for participation restriction which depends on multiple inter-related factors. We aimed to determine participation patterns using latent cluster analysis (LCA) in older adults at risk of falls, its relationship with intrinsic capacity (IC) and its risk prediction.MethodsCross-sectional study of 154 community dwelling older adults ≥ 60 years with falls or risk of falls was conducted. Questionnaires were administered on demographics, hearing, LSM, frailty (FRAIL scale), anorexia of aging (SNAQ), cognition (Montreal Cognitive Assessment, MoCA), FOF (Falls Efficacy Scale-International), physical function, and assessment for handgrip strength (HGS), gait speed, 5-times sit to stand (STS), vision and times-up-and-go (TUG) were performed. Six IC domains (vision and hearing, cognition, nutrition, mobility and depression) were measured.ResultsThree pattern of participation cluster were identified, high (n = 63, 40.9%), moderate (n = 83, 53.9%) and low (n = 8, 33 5.2%). Individuals in the high participation cluster were significantly younger, had higher LSM scores and lower FES-I scores, more robust, fewer ADL and IADL limitations, lower prevalence of low HGS, higher gait speed and shorter TUG. In the fully adjusted model compared to the high participation cluster, moderate participation was significantly associated with low MoCA scores (OR 4.2, 95% CI 1.7–10.4, p = 0.02), poor STS (OR 7.1, 95% CI 3.0–17.0, p < 0.001) whereas low participation was associated with anorexia of aging (OR 9.9, 95% CI 1.6–60.9, p = 0.014), poor STS (OR 19.1, 95% CI 2.0–187.5, p = 0.011) and hearing impairment (OR 9.8, 95% CI 1.4–70.8, p = 0.024). Participants with 3 out of 6 IC decline had a probability of greater than 80% to belong to the low/moderate participation class.DiscussionPhysical function, cognition, hearing and nutrition were significantly associated with low and/or moderate participation class. Future studies are needed to evaluate improvement in participation of those with falls or at risk for falls through restoration of IC.

BackgroundMobile health apps are increasingly used as early intervention to support behavior change for diabetes prevention and control, with the overarching goal of lowering the overall disease burden. ObjectiveThis prospective cohort study conducted in Singapore aimed to investigate app engagement features and their association with weight loss and improved glycemic control among adults with diabetes and prediabetes from the intervention arm of the Diabetes Lifestyle Intervention using Technology Empowerment randomized controlled trial. MethodsDiabetes and prediabetes participants (N=171) with a median age of 52 years, BMI of 29.3 kg/m2, and glycated hemoglobin (HbA1c) level of 6.5% and who were being assigned the Nutritionist Buddy Diabetes app were included. Body weight and HbA1c were measured at baseline, 3 months, and 6 months. A total of 476,300 data points on daily app engagement were tracked via the backend dashboard and developer’s report. The app engagement data were analyzed by quartiles and weekly means expressed in days per week. Linear mixed model analysis was used to determine the associations between the app engagements with percentage weight and HbA1c change. ResultsThe median overall app engagement rate was maintained above 90% at 6 months. Participants who were actively engaged in ≥5 app features were associated with the greatest overall weight reduction of 10.6% from baseline (mean difference −6, 95% CI −8.9 to −3.2; P5.9 days per week and choosing healthier food options for >4.3 days per week had the most impact, eliciting weight loss of 9.1% (mean difference −5.2, 95% CI −8.2 to −2.2; P=.001) and 8.8% (mean difference −4.2, 95% CI −7.1 to −1.3; P=.005), respectively. Among the participants with diabetes, those who had a complete meal log for >5.1 days per week or kept within their carbohydrate limit for >5.9 days per week each achieved greater HbA1c reductions of 1.2% (SD 1.3%; SD 1.5%), as compared with 0.2% (SD 1%; SD 0.6%). in the reference groups who used the features

Motoric cognitive risk syndrome (MCR) is defined by the presence of slow gait and subjective cognitive decline. It is well recognized as a prodrome for dementia, but the biological mechanism and trajectory for MCR are still lacking. The objective of this study was to explore the association of MCR with body composition, including sarcopenia and systemic inflammation, in pre-frail older adults in a cross-sectional study of 397 pre-frail community-dwelling older adults. Data on demographics, physical function, frailty, cognition (Montreal Cognitive Assessment (MoCA)), perceived health and depression were collected. Body composition was measured using a bioelectrical impedance analyzer. Systemic inflammatory biomarkers, such as progranulin, growth differentiation factor-15 (GDF-15), interleukin-10 (IL-10), interleukin-6 and tumor necrosis factor-α (TNF-α), were collected. Univariate and multivariate logistic regression were used to analyze the association between MCR, body composition, sarcopenia and systemic inflammatory biomarkers. The prevalence of MCR was 14.9%. They were significantly older and there were more females, depression, functional impairment, lower education, physical activity and MoCA scores. Body fat percentage (BF%), fat mass index, fat to fat free mass ratio (FM/FFM) and sarcopenia prevalence were significantly higher in MCR. Serum GDF-15 and TNF-α levels were highest with progranulin/TNF-α and IL-10/TNF-α ratio lowest in MCR. Compared to healthy patients, MCR was significantly associated with sarcopenia (aOR 2.62; 95% CI 1.46–3.17), BF% (aOR 1.06; 95% CI 1.01–1.12), FMI (aOR 1.16; 95% CI 1.02–1.30) and FM/FFM (aOR 6.38; 95% CI 1.20–33.98). The association of IL-10 to TNF-α ratio (aOR 0.98, 95% CI 0.97–0.99) and IL-10 (aOR 2.22, 95% CI 0.05–0.98) with MCR were independent of sarcopenia and BF%. Longitudinal population studies are needed to understand the role of body fat indices and IL-10 in pre-frail older adults with MCR and trajectory to dementia.

Abstract Background The current Berlin definition of acute respiratory distress syndrome (ARDS) uses the PaO2/FiO2 (P/F) ratio to classify severity. However, for the same P/F ratio, a patient on a higher positive end-expiratory pressure (PEEP) may have more severe lung injury than one on a lower PEEP. Objectives We designed a new formula, the P/FP ratio, incorporating PEEP into the P/F ratio and multiplying with a correction factor of 10 [(PaO2*10)/(FiO2*PEEP)], to evaluate if it better predicts hospital mortality compared to the P/F ratio post-intubation and to assess the resultant changes in severity classification of ARDS. Methods We categorized patients from a dataset of seven ARDS network trials using the thresholds of ≤ 100 (severe), 101–200 (moderate), and 201–300 (mild) for both P/F (mmHg) and P/FP (mmHg/cmH2O) ratios and evaluated hospital mortality using areas under the receiver operating characteristic curves (AUC). Results Out of 3,442 patients, 1,057 (30.7%) died. The AUC for mortality was higher for the P/FP ratio than the P/F ratio for PEEP levels > 5 cmH2O: 0.710 (95% CI 0.691–0.730) versus 0.659 (95% CI 0.637–0.681), P

Abstract Background Graves’ disease is the most common cause of hyperthyroidism. It results in accelerated tissue metabolism with multi-organ involvement ranging from cardiovascular to neuropsychological function. This results in a negative impact on the quality of life (QOL) of the individual patient. We aim to evaluate the psychometric properties of ThyPRO, a Thyroid-related Patient Reported Outcome questionnaire, and validate its use in our multi-ethnic Asian patients with Graves’ hyperthyroidism. Methods Forty-seven consecutive Graves’ hyperthyroidism patients answered the ThyPRO questionnaire at baseline and at 4 months after treatment initiation. Data were recorded for thyroid related symptoms and signs, thyroid function tests and thyroid volume. We analyzed the internal consistency using Cronbach’s alpha, construct validity by evaluating relationship between clinical variables and ThyPRO scales, ceiling and floor effects, and responsiveness of ThyPRO to treatment based on Cohen’s effect size. Results Correlations between individual scale scores and free thyroxine concentrations were moderate and statistically significant: 0.21–0.64 (p 0.7 for all scales. ThyPRO was responsive to the changes in QOL after treatment (Effect Size: 0.20–0.77) in 9 of the 14 scales including the hyperthyroid symptoms and psychosocial scales (Tiredness, Cognitive complaints, Anxiety, Emotional susceptibility, Impact on Social, Daily and Sex life). Conclusion This study provides evidence that ThyPRO has satisfactory measurement properties in hyperthyroid Graves’ disease patients in Singapore population with the potential to complement clinical care.

Background: Allergic sensitization is linked to allergy development, with early sensitization often associated with worse outcomes. We aimed to identify if distinct allergic sensitization trajectories existed within a diverse and multi-ethnic Asian cohort. Methods: We administered modified ISAAC questionnaires in the first 8 years and conducted skin prick testing at ages 18 months, 3, 5 and 8 years in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. We used latent class analysis to derive allergic sensitization trajectories, and adjusted odds ratios (AOR) to evaluate predictive risk factors and associations with allergic comorbidities. Results: Among 997 children, three trajectories were identified: early food and mite sensitization (16.2%), late mite sensitization (24.2%) and no/low sensitization (59.6%). Early food and mite sensitization was associated with early eczema by 6 months [AOR (95%CI) 4.67 (1.78–12.28)], increased risk of wheeze by 3–8 years (ARR 1.72–1.99) and eczema in the first 8 years of life (ARR 1.87–2.41). Late mite sensitization was associated with female sex [AOR 0.58 (0.35–0.96)], cesarean section [AOR 0.54 (0.30–0.98)], early eczema by 6 months [AOR 3.40 (1.38–8.42)], and increased risk of eczema by 18 months [ARR 1.47 (1.03–2.08)] and 8 years [ARR 1.35 (1.05–1.73)]. Conclusion: Early onset of eczema and early allergic sensitization were strongly associated. Early sensitization, especially to house dust mites, was associated with increased risks of developing wheeze and eczema, pointing to the importance of developing preventive perinatal interventions and effective therapeutics for sensitized toddlers.

IntroductionWhile hospitalist and internist inpatient care models dominate the landscape in many countries, geriatricians and internists are at the frontlines managing hospitalized older adults in countries such as Singapore and the United Kingdom. The primary aim of this study was to determine outcomes for older patients cared for by geriatricians compared with non-geriatrician-led care teams.Materials and MethodsA retrospective cohort study of 1,486 Internal Medicine patients aged ≥75 years admitted between April and September 2021 was conducted. They were either under geriatrician or non-geriatrician (internists or specialty physicians) care. Data on demographics, primary diagnosis, comorbidities, mortality, readmission rate, Hospital Frailty Risk Score (HFRS), Age-adjusted Charlson Comorbidity Index, Length of Stay (LOS), and cost of hospital stay were obtained from the hospital database and analyzed.ResultsThe mean age of patients was 84.0 ± 6.3 years, 860 (57.9%) females, 1,183 (79.6%) of Chinese ethnicity, and 902 (60.7%) under the care of geriatricians. Patients under geriatrician were significantly older and had a higher prevalence of frailty, dementia, and stroke, whereas patients under non-geriatrician had a higher prevalence of diabetes and hypertension. Delirium as the primary diagnosis was significantly higher among patients under geriatrician care. Geriatrician-led care model was associated with shorter LOS, lower cost, similar inpatient mortality, and 30-day readmission rates. LOS and cost were lower for patients under geriatrician care regardless of frailty status but significant only for low and intermediate frailty groups. Geriatrician-led care was associated with significantly lower extended hospital stay (OR 0.73; 95% CI 0.56–0.95) and extended cost (OR 0.69; 95% CI 0.54–0.95).ConclusionGeriatrician-led care model showed shorter LOS, lower cost, and was associated with lower odds of extended LOS and cost.

Abstract Background A diagnosis of Polycystic Ovary Syndrome (PCOS) and its related phenotypic features including increased hair growth can affect a woman’s social and emotional well-being. We aim to determine firstly, if excess body weight affects menstrual cycle length, excessive hair growth and other phenotypic features in healthy women without PCOS and secondly, whether having PCOS exacerbates the effects of high body mass index (BMI). Methods A prospective cross-sectional study involving healthy women (21–45 years) recruited at an annual health screen for hospital staff and volunteers from the university community, and PCOS cases referred to tertiary gynecological clinics in Singapore. To dissect the independent and/or combinatorial effects of PCOS and BMI on the phenotypic features, subjects were divided into four categories: non-PCOS (normal BMI), non-PCOS (high BMI), PCOS (normal BMI), and PCOS (high BMI). General linear modelling was performed to compare clinical, ovarian, hormonal and metabolic parameters across these four categories. Results Of 389 participants, 134 (34.4%) were classified as PCOS and the remaining 255 (65.6%), as the non-PCOS population. Overall 45.2% of women had high BMI (≥ 23). Compared to non-PCOS subjects, women with PCOS had a higher BMI (mean (SD): 25.14 ± 6.46 vs 23.08 ± 4.36, p

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) questionnaire 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. [ABSTRACT FROM AUTHOR]

Introduction: Clinical assessment is pivotal in diagnosing acute coronary syndrome. Our study aimed to identify clinical characteristics predictive of major adverse cardiac events (MACE) in an Asian population and to derive a risk score for MACE. Methods: Patients presenting to the emergency department (ED) with chest pain and non-diagnostic 12-lead electrocardiograms were recruited. Clinical history was recorded in a predesigned template. Random glucose and direct low-density lipoprotein measurements were taken, in addition to serial troponin. We derived the age, coronary risk factors (CRF), sex and symptoms (ACSS) risk score based on multivariate analysis results, considering age, CRF, sex and symptoms and classifying patients into very low, low, moderate and high risk for MACE. Comparison was made with the ED Assessment of Chest Pain Score (EDACS) and the history, electrocardiogram, age, risk factors, troponin (HEART) score. We also modified the HEART score with the CRF that we had identified. The outcomes were 30-day and 1-year MACE. Results: There were a total of 1689 patients, with 172 (10.2%) and 200 (11.8%) having 30-day and 1-year MACE, respectively. Symptoms predictive of MACE included central chest pain, radiation to the jaw/neck, associated diaphoresis, and symptoms aggravated by exertion and relieved by glyceryl trinitrate. The ACSS score had an area under the curve of 0.769 (95% confidence interval [CI]: 0.735-0.803) and 0.760 (95% CI: 0.727-0.793) for 30-day and 1-year MACE, respectively, outperforming EDACS. Those in the very-low-risk and low-risk groups had <1% risk of 30-day MACE. Conclusion: The ACSS risk score shows potential for use in the local ED or primary care setting, potentially reducing unnecessary cardiac investigations and admission. [ABSTRACT FROM AUTHOR]

Abstract Background Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation. Hence, the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies. In this longitudinal study, we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers. Methods We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer’s Network according to their mutation carrier status. The interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q), age, and estimated years to symptom onset (EYO) as a function of metabolism measured by [18F]flurodeoxyglucose ([18F]FDG) positron emission tomography, were evaluated by the mixed-effects regression model with family-level random effects in DIAD mutation carriers and non-carriers. Exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q sub-components. Then the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression model. Results A total of 119 mutation carriers and 102 non-carriers were studied. The interaction of higher NPI-Q and shorter EYO was associated with more rapid declines of global and regional [18F]FDG uptake in the posterior cingulate and ventromedial prefrontal cortices, the bilateral parietal lobes and the right insula in DIAD mutation carriers. The neuropsychiatric subsyndromes of agitation, disinhibition, irritability and depression interacted with the EYO to drive the [18F]FDG uptake decline in the DIAD mutation carriers. The interaction of NPI and EYO was not associated with [18F]FDG uptake in DIAD mutation non-carriers. Conclusions The NPS in cognitively intact DIAD mutation carriers may be a clinical indicator of subsequent metabolic decline in brain networks vulnerable to AD, which supports the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD. Further studies using different methodological approaches to identify NPS in preclinical AD are needed to validate our findings.

BackgroundMetastatic epidural spinal cord compression (MESCC) is a devastating complication of advanced cancer. A deep learning (DL) model for automated MESCC classification on MRI could aid earlier diagnosis and referral.PurposeTo develop a DL model for automated classification of MESCC on MRI.Materials and MethodsPatients with known MESCC diagnosed on MRI between September 2007 and September 2017 were eligible. MRI studies with instrumentation, suboptimal image quality, and non-thoracic regions were excluded. Axial T2-weighted images were utilized. The internal dataset split was 82% and 18% for training/validation and test sets, respectively. External testing was also performed. Internal training/validation data were labeled using the Bilsky MESCC classification by a musculoskeletal radiologist (10-year experience) and a neuroradiologist (5-year experience). These labels were used to train a DL model utilizing a prototypical convolutional neural network. Internal and external test sets were labeled by the musculoskeletal radiologist as the reference standard. For assessment of DL model performance and interobserver variability, test sets were labeled independently by the neuroradiologist (5-year experience), a spine surgeon (5-year experience), and a radiation oncologist (11-year experience). Inter-rater agreement (Gwet’s kappa) and sensitivity/specificity were calculated.ResultsOverall, 215 MRI spine studies were analyzed [164 patients, mean age = 62 ± 12(SD)] with 177 (82%) for training/validation and 38 (18%) for internal testing. For internal testing, the DL model and specialists all showed almost perfect agreement (kappas = 0.92–0.98, p < 0.001) for dichotomous Bilsky classification (low versus high grade) compared to the reference standard. Similar performance was seen for external testing on a set of 32 MRI spines with the DL model and specialists all showing almost perfect agreement (kappas = 0.94–0.95, p < 0.001) compared to the reference standard.ConclusionA DL model showed comparable agreement to a subspecialist radiologist and clinical specialists for the classification of malignant epidural spinal cord compression and could optimize earlier diagnosis and surgical referral.