Experiences of living with overweight/obesity and early type 2 diabetes in Singapore-a qualitative interview study.

OBJECTIVES: To understand the lived experience of adults with overweight/obesity and early type 2 diabetes in a modern urban environment, and the interrelations among the various aspects of these experiences and participants' attitudes to weight management. DESIGN: Qualitative inductive approach to analysing data thematically from semistructured interviews and interpreted from a socioecological perspective. SETTING: Primary care clinics located in northern and central Singapore. PARTICIPANTS: 21 patients between 29 and 59 years old who are living with overweight/obese (Body Mass Index of 25.3-44.0kg/m2) and type 2 diabetes for 6 years or less. RESULTS: The main themes - everyday life, people around me and within me - pointed to a combination of barriers to weight and health management for participants. These included environmental factors such as easy physical and digital access to unhealthy food, and high-stress work environments; social factors such as ambiguous family support and dietary practices of peers; and individual factors such as challenges with self-regulation, prioritising work, dealing with co-existing medical conditions and the emotional significance of food. While lack of motivation and cultural dietary practices are hard to change, a problem-solving attitude, and presence of role models, may enable behaviour change. CONCLUSION: An exploration of the lifeworld of patients with overweight/obese and early type 2 diabetes revealed that work demands, dietary practices in the workplace and at home, and the easy availability of calorie-dense foods afforded by a technology-infused environment hindered the individual's efforts at maintaining a healthy weight and lifestyle. Policy and initiatives promoting work-life balance as well as individualised interventions can support participants' stress management, and problem-solving capability for behaviour change. These barriers stemmed from the various domains of the environmental, interpersonal and intrapersonal but were interrelated. They underscored the need for an integrated approach to weight and diabetes management.

Identifying primary care clinicians' preferences for, barriers to, and facilitators of information-seeking in clinical practice in Singapore: a qualitative study.

BACKGROUND: The growth of medical knowledge and patient care complexity calls for improved clinician access to evidence-based resources. This study aimed to explore the primary care clinicians' preferences for, barriers to, and facilitators of information-seeking in clinical practice in Singapore. METHODS: A convenience sample of ten doctors and ten nurses was recruited. We conducted semi-structured face-to-face in-depth interviews. The interviews were recorded, transcribed verbatim, and analysed using thematic content analysis. RESULTS: Of the 20 participants, eight doctors and ten nurses worked at government-funded polyclinics and two doctors worked in private practice. Most clinicians sought clinical information daily at the point-of-care. The most searched-for information by clinicians in practice was less common conditions. Clinicians preferred evidence-based resources such as clinical practice guidelines and UpToDate®. Clinical practice guidelines were mostly used when they were updated or based on memory. Clinicians also commonly sought answers from their peers. Furthermore, clinicians frequently use smartphones to access the Google search engine and UpToDate® app. The barriers to accessing clinical information included the lack of time, internet surfing separation of work computers, limited search functions in the organisation's server, and limited access to medical literature databases. The facilitators of accessing clinical information included convenience, easy access, and trustworthiness of information sources. CONCLUSION: Most primary care clinicians in our study sought clinical information at the point-of-care daily and reported increasing use of smartphones for information-seeking. Future research focusing on interventions to improve access to credible clinical information for primary care clinicians at the point-of-care is recommended. TRIAL REGISTRATION: This study has been reviewed by NHG Domain Specific Review Board (NHG DSRB) (the central ethics committee) for ethics approval. NHG DSRB Reference Number: 2018/01355 (31/07/2019).

Reduced skeletal muscle mass to visceral fat area ratio is independently associated with reduced cognitive function in type 2 diabetes mellitus.

AIM: Skeletal muscle mass to visceral fat area ratio (SVR) has been recognised as an index of sarcopenic obesity. SVR is associated with type 2 diabetes mellitus (T2DM), metabolic syndrome and arterial stiffness which are known risk factors for cognitive dysfunction. We aimed to investigate association between SVR and cognitive function in patients with T2DM. METHODS: This was a cross-sectional study of 1326 patients with T2DM and mean age 61.3 ± 8.0 years. SVR was assessed based on bioelectrical impedance measurements of muscle mass and visceral fat area (VFA). Cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Linear regression was used to examine the association between SVR in quartiles and RBANS score, adjusting for demographics, education, presence of depressive symptoms, clinical covariates and medications. RESULTS: The lower SVR quartiles were negatively associated with RBANS total score in the unadjusted analysis. The corresponding coefficients for Quartiles 1 and 2 SVR were -3.79 (95 % CI -5.39 to -2.19; p < 0.001) and -1.47 (95 % CI -2.86 to -0.07; p = 0.039) in fully adjusted analysis. The negative association between Quartile 1 SVR and RBANS score was evident in immediate memory, delayed memory, visuo-spatial construction, language and attention domains. Muscle mass and VFA alone had weaker associations with RBANS scores. CONCLUSION: Our study demonstrated, for the first time, an independent association between reduced SVR and lower cognitive function. This is evident in global and multiple cognitive domains. The synergistic effects of reduced muscle mass and visceral obesity may be more pronounced than their independent effects on cognitive function.

Association between Plasma LRG1 and Lower Cognitive Function in Asians with Type 2 Diabetes Mellitus.

CONTEXT: Leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of diabetic complications, but its association with cognitive function remains unclear. OBJECTIVE: Our primary objective is to investigate the longitudinal association between LRG1 and cognitive function in patients with type 2 diabetes mellitus (T2DM). Secondarily, we determine the causal relationship using Mendelian Randomization (MR), and the role of arterial stiffness as a potential mediator. METHODS: T2DM patients (n = 1039; age = 64.1 ± 6.4 years) were followed-up for 5.3 ± 1.2 years. Plasma LRG1 was measured at baseline using enzyme-linked immunosorbent assay. Baseline and follow-up cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). One-sample MR was performed with rs4806985 as plasma LRG1-associated single-nucleotide polymorphism (SNP). Mediation analysis was performed to examine if pulse wave velocity (PWV), an arterial stiffness index, mediated the association between plasma LRG1 and follow-up cognitive function. RESULTS: Elevated baseline natural log (Ln)-transformed LRG1 was inversely associated with baseline and follow-up RBANS total score with adjusted coefficients -1.38 (95%CI -2.55 to -0.21; p = 0.021) and -1.38 (95%CI -2.70 to -0.07; p = 0.039), respectively. Genetically-predicted higher levels of plasma LRG1 was associated with lower follow-up RBANS total score with coefficient -7.44 (95%CI -14.14 to -0.74; p = 0.030) per unit increase in LnLRG1. Higher PWV accounted for 27.7% of the association between LnLRG1 and follow-up RBANS total score. CONCLUSIONS: Baseline plasma LRG1 was associated with lower cognitive function at follow-up in patients with T2DM, mediated by PWV. MR analysis provided evidence of an association between genetically influenced plasma LRG1 and lower cognitive function at follow-up.

Longitudinal profiling and tracking stability in the Singapore study of macro-angiopathy and microvascular reactivity in type 2 diabetes cohort.

INTRODUCTION: The Singapore Study of Macro-Angiopathy and microvascular Reactivity in Type 2 Diabetes (SMART2D) is a prospective cohort study which was started in 2011 to investigate the effect of risk factors on vascular function and diabetes-related complications in Asians. We aimed to compare the longitudinal change in risk factors by accounting for batch effect and assess the tracking stability of risk factors over time in patients recruited for SMART2D. In this study, we (1) described batch effect and its extent across a heterogenous range of longitudinal data parameters; (2) mitigated batch effect through statistical approach; and (3) assessed the tracking stability of the risk factors over time. METHODS: A total of 2258 patients with type 2 diabetes mellitus (T2DM) were recruited at baseline. The study adopted a three-wave longitudinal design with intervals of 3 years between consecutive waves. The changes in a few selected risk factors were assessed after calibration, assuming patients with similar demographic and anthropometry profile had similar physiology. The tracking pattern of the risk factors was determined with stability coefficients derived from generalised estimating equations. RESULTS: The medians of the longitudinal differences in risk factors between the waves were mostly modest at <10%. Larger increases in augmentation index (AI), aortic systolic blood pressure (BP) and aortic mean BP were consistently observed after calibration. The medians of the longitudinal differences in AI, aortic systolic BP and aortic mean BP between the waves were <2% before calibration, but increased slightly to <5% after calibration. Most of the risk factors had moderate to high tracking stability. Muscle mass and serum creatinine were among those with relatively high tracking stability. CONCLUSIONS: The longitudinal differences in parameters between the waves were overall modest after calibration, suggesting that calibration may attenuate longitudinal differences inflated by non-biological factors such as systematic drift due to batch effect. Changes of the hemodynamic parameters are robust over time and not entirely attributable to age. Our study also demonstrated moderate to high tracking stability for most of the parameters.

Associations of non-invasive indices of liver steatosis and fibrosis with progressive kidney impairment in adults with type 2 diabetes.

AIMS: Longitudinal data linking non-alcoholic fatty liver disease to kidney dysfunction in type 2 diabetes (T2D) are limited. This study evaluated the associations of non-invasive indices of liver steatosis and liver fibrosis with kidney impairment, and the mediatory role of the pro-angiogenic factor leucine-rich α-2 glycoprotein 1 (LRG1). METHODS: T2D adults (n = 2057) were followed for a mean period of 6.1 ± 1.6 years. Baseline liver steatosis [(hepatic steatosis index (HSI) and Zhejiang University index (ZJU)] and liver fibrosis [aspartate transaminase/alanine transaminase ratio (AAR) and BARD] indices derived from composite scoring systems were calculated. Plasma LRG1 levels were quantified using immunoassay. The study outcomes were progressive kidney function decline defined as estimated glomerular filtration rate (eGFR) decline of ≥ 40% and albuminuria progression defined as an increase in albuminuria category. RESULTS: Cross-sectionally, liver steatosis and liver fibrosis indices were associated with increased albuminuria (urinary albumin/creatinine ratio ≥ 30 µg/mg) and reduced renal function (eGFR < 60 mL/min/1.73 m2) after covariate adjustment, respectively. Approximately 32% of the participants experienced progressive kidney function decline, while 38% had albuminuria worsening over time. Longitudinal analysis revealed that baseline AAR (hazard ratio: 1.56; 95% CI 1.15-2.11) and BARD (hazard ratio: 1.16, 95% CI 1.04-1.28) predicted progressive kidney function decline, partly mediated by LRG1. In contrast, liver steatosis (HSI and ZJU) but not liver fibrosis (AAR and BARD) indices were independently associated with albuminuria progression. CONCLUSIONS: Increased liver steatosis scores were associated with albuminuria deterioration. Conversely, liver fibrosis indices may be associated with progressive kidney function decline, potentially driven by increased inflammation and angiogenesis.

An Evidence-Based Serious Game App for Public Education on Antibiotic Use and Antimicrobial Resistance: Protocol of a Randomized Controlled Trial.

BACKGROUND: The misuse and overuse of antibiotics contribute to the acceleration of antimicrobial resistance (AMR), but public knowledge on appropriate antibiotic use and AMR remained low despite ongoing health promotion efforts. App gamification has gained traction in recent years for health promotion and to affect change in health behaviors. Hence, we developed an evidence-based serious game app "SteWARdS Antibiotic Defence" to educate the public on appropriate antibiotic use and AMR and address knowledge gaps. OBJECTIVE: We aim to evaluate the effectiveness of the "SteWARdS Antibiotic Defence" app in improving the knowledge of, attitude toward, and perception (KAP) of appropriate antibiotic use and AMR among the public. The primary objective is to assess the changes in KAP of antibiotic use and AMR in our participants, while the secondary objectives are to assess the extent of user engagement with the app and the level of user satisfaction in using the app. METHODS: Our study is a parallel 2-armed randomized controlled trial with a 1:1 allocation. We plan to recruit 400 participants (patients or their caregivers) aged 18-65 years from government-funded primary care clinics in Singapore. Participants are randomized in blocks of 4 and into the intervention or control group. Participants in the intervention group are required to download the "SteWARdS Antibiotic Defence" app on their smartphones and complete a game quest within 2 weeks. Users will learn about appropriate antibiotic use and effective methods to recover from uncomplicated upper respiratory tract infections by interacting with the nonplayer characters and playing 3 minigames in the app. The control group will not receive any intervention. RESULTS: The primary study outcome is the change in participants' KAP toward antibiotic use and AMR 6-10 weeks post intervention or 6-10 weeks from baseline for the control group (web-based survey). We will also assess the knowledge level of participants immediately after the participant completes the game quest (in the app). The secondary study outcomes are the user engagement level (tracked by the app) and satisfaction level of playing the game (via the immediate postgame survey). The satisfaction survey will also collect participants' feedback on the game app. CONCLUSIONS: Our proposed study provides a unique opportunity to assess the effectiveness of a serious game app in public health education. We anticipate possible ceiling effects and selection bias in our study and have planned to perform subgroup analyses to adjust for confounding factors. The app intervention will benefit a larger population if it is proven to be effective and acceptable to users. TRIAL REGISTRATION: ClinicalTrials.gov NCT05445414; https://clinicaltrials.gov/ct2/show/NCT05445414. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45833.

Prevalence of health literacy and its correlates from a national survey of older adults.

BACKGROUND: Health literacy (HL) is an important determinant of health. Sub-optimal HL can have profound consequences for individuals and health systems. However, little is known about the HL of older Singaporeans. OBJECTIVE: This study determined the prevalence, socio-demographic and health-related correlates of limited and marginal HL among older Singaporeans (≥65 years). METHODS: Data from a national survey were analysed (n = 2327). HL was measured using the 4-item BRIEF with a 5-point response scale (range 4-20), and classified as limited, marginal, and adequate. Multinomial logistic regression models were applied to identify correlates of limited and marginal HL versus adequate HL. RESULTS: The weighted prevalence of limited HL was 42.0%, marginal HL was 20.4% and adequate HL was 37.7%. In adjusted regression analysis, older adults in advanced age groups with lower education and those living in 1-3 room flats had higher risk of limited HL. Furthermore, having ≥3 chronic diseases (Relative Risk Ratio [RRR] = 1.70, 95% Confidence Interval [95% CI] = 1.15, 2.52), poor self-rated health (RRR = 2.07, 95% CI = 1.56, 2.77), vision impairment (RRR = 2.08, 95% CI = 1.55, 2.80), hearing impairment (RRR = 1.57, 95% CI = 1.15, 2.14) and mild cognitive impairment (RRR = 4.87, 95% CI = 2.12, 11.19) were also associated with limited HL. The likelihood of marginal HL was higher among those with lower education, ≥2 chronic diseases, poor self-rated health (RRR = 1.48, 95% CI = 1.09, 2.00), vision impairment (RRR = 1.45, 95% CI = 1.06, 1.99) and hearing impairment (RRR = 1.50, 95% CI = 1.08, 2.08). CONCLUSIONS: Over two-thirds of older adults faced difficulties in reading, understanding, exchanging, and using health information and resources. There is a pressing need to create awareness about the issues that could result from the mismatch between healthcare system demands and the HL of older adults.

Implementation and use of technology-enabled blood pressure monitoring and teleconsultation in Singapore's primary care: a qualitative evaluation using the socio-technical systems approach.

BACKGROUND: Telemedicine is becoming integral in primary care hypertension management, and is associated with improved blood pressure control, self-management and cost-effectiveness. This study explored the experiences of patients and healthcare professionals and their perceived barriers and facilitators in implementing and using a technology-enabled blood pressure monitoring intervention with teleconsultation in the Singapore primary care setting. METHODS: This was a qualitative study embedded within the Primary Technology-Enhanced Care Hypertension pilot trial. Patients were selected purposively and invited to participate by telephone; healthcare professionals involved in the trial were invited to participate by email. Individual semi-structured interviews were conducted in English or Mandarin with thirteen patients and eight healthcare professionals. Each interview was audio-recorded and transcribed verbatim. Data were analyzed inductively to identify emergent themes which were then grouped into the dimensions of the socio-technical systems model to study the interactions between the technical, individual and organizational factors involved in the process. RESULTS: Several emergent themes were identified. The factors involved in the implementation and use of the intervention are complex and interdependent. Patients and healthcare professionals liked the convenience resulting from the intervention and saw an improvement in the patient-provider relationship. Patients appreciated that the intervention helped form a habit of regular blood pressure monitoring, improved their self-management, and provided reassurance that they were being monitored by the care team. Healthcare professionals found that the intervention helped to manage workload by freeing up time for other urgent matters. Nevertheless, participants highlighted challenges with usability of the equipment and management portal, data access, and some expressed technology anxiety. Participants suggested patient segmentation for the intervention to be more targeted, wished for a more user-friendly equipment and proposed allocating more resources to the intervention. CONCLUSIONS: The implementation and use of telemedicine for hypertension management can engender various benefits and challenges to patients, healthcare professionals and the healthcare system. Stakeholder feedback gathered on the sociotechnical aspects of the technology should be taken into consideration to guide the design, implementation and evaluation of future telemedicine interventions in primary care. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on October 9, 2018. ID: NCT03698890.

Challenges encountered by pharmacy staff in using prescription medication labels during medication counselling with older adults and solutions employed: A mixed-methods study.

Background: Prescription medication labels (PMLs) predominantly dispensed in English, are an important adjunct to medication counselling. PMLs are routinely used by pharmacy staff to counsel older adults about their medications. This study sought to identify challenges that pharmacy staff observe older adults face in using their PMLs, and to identify and quantify solutions employed by pharmacy staff during medication counselling to address such challenges. Methods: Ten in-depth interviews were done with primary care pharmacy staff to gather the range of challenges and solutions. Subsequently, a quantitative survey, informed by the qualitative findings, was administered to 121 pharmacy staff to assess if the reported solutions were commonly used. Results: The two main challenges were incongruity between PML language (English) and older adults' language proficiency, and poor PML legibility. The solutions, classified under three themes, were simplifying medication information on PMLs, supplementing PMLs with additional medication information and mitigating poor readability. Conclusions: Pharmacy staff observed challenges faced by older adults in using PMLs during medication counselling. Ad-hoc improvisations by pharmacy staff to PMLs were pervasive. System-level PML improvements, such as provision of legible bilingual medication instructions, pharmaceutical pictograms and additional medication information, through patient information leaflets or using quick response (QR) codes on PMLs, should be considered. This will facilitate patient-provider communication, especially in settings with language dissonance between PMLs and patients.

Trust and Uncertainty in the Implementation of a Pilot Remote Blood Pressure Monitoring Program in Primary Care: Qualitative Study of Patient and Health Care Professional Views.

BACKGROUND: Trust is of fundamental importance to the adoption of technologies in health care. The increasing use of telemedicine worldwide makes it important to consider user views and experiences. In particular, we ask how the mediation of a technological platform alters the trust relationship between patient and health care provider. OBJECTIVE: To date, few qualitative studies have focused on trust in the use of remote health care technologies. This study examined the perspectives of patients and clinical staff who participated in a remote blood pressure monitoring program, focusing on their experiences of trust and uncertainty in the use of technology and how this telehealth intervention may have affected the patient-provider relationship. METHODS: A secondary qualitative analysis using inductive thematic analysis was conducted on interview data from 13 patients and 8 staff members who participated in a remote blood pressure monitoring program to elicit themes related to trust. RESULTS: In total, 4 themes were elicited that showed increased trust (patients felt reassured, patients trusted the telehealth program, staff felt that the data were trustworthy, and a better patient-provider partnership based on the mutually trusted data), and 4 themes were elicited that reflected decreased trust (patients' distrust of technology, clinicians' concerns about the limitations of technologically mediated interactions, experiences of uncertainty, and institutional risk). CONCLUSIONS: Managing trust relationships plays an important role in the successful implementation of telemedicine. Ensuring that trust building is incorporated in the design of telehealth interventions can contribute to improved effectiveness and quality of care.

Urine Leucine-Rich α-2 Glycoprotein 1 (LRG1) Predicts the Risk of Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes.

OBJECTIVE: Leucine-rich α-2 glycoprotein 1 (LRG1) was recently identified as an amplifier of transforming growth factor-ß (TGF-ß)-induced kidney fibrosis in animal models. We aimed to study whether urine LRG1 is associated with risk of progression to end-stage kidney disease (ESKD) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,837 participants with type 2 diabetes and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were recruited from a regional hospital and a primary care facility. Association of urine LRG1 with risk of ESKD (progression to sustained eGFR <15 mL/min/1.73 m2, dialysis, or death resulting from renal causes) was assessed by survival analyses. RESULTS: During a median follow-up of 8.6 (interquartile range 5.8-9.6) years, 134 incident ESKD events were identified. Compared with those in the lowest tertile, participants with baseline urine LRG1 in the highest tertile had a 1.91-fold (95% CI 1.04-3.50) increased risk of progression to ESKD, after adjustment for cardiorenal risk factors, including eGFR and albuminuria. As a continuous variable, 1 SD increment in urine LRG1 was associated with a 1.53-fold (95% CI 1.19-1.98) adjusted risk of ESKD. Of note, the association of urine LRG1 with ESKD was independent of plasma LRG1. Moreover, urine LRG1 was associated with rapid kidney function decline and progression to macroalbuminuria, two common pathways leading to ESKD. CONCLUSIONS: Urine LRG1, a TGF-ß signaling modulator, predicts risk of progression to ESKD independently of clinical risk factors in patients with type 2 diabetes, suggesting that it may be a novel factor involved in the pathophysiological pathway leading to kidney disease progression.

Prevalence of IgE-mediated cow milk, egg, and peanut allergy in young Singapore children.

Background: The rising prevalence of food allergy reported in the United States, UK, and Australia may be attributable to the rise in peanut allergy prevalence. The food allergy prevalence in other parts of the world such as Asia is, however, less well documented. Objective: This study aimed to evaluate the prevalence of cow's milk, egg, and peanut allergies in a general population of Singaporean children below 30 months of age. Methods: A total of 4,115 children from the general population who attended well-baby visits between 2011 and 2015 completed standardized questionnaires to elicit a convincing history of food allergy to estimate the population prevalence of food allergies. Results: The prevalence of a convincing history of cow's milk allergy was 0.51% (95% confidence interval [CI], 0.3-0.7), hen's egg allergy 1.43% (95% CI, 1.1-1.8), and peanut allergy 0.27% (95% CI, 0.12-0.42). Of the 15 of 59 children with a convincing history of hen's egg allergy who consented, 12 (80%) had corroborative positive skin prick tests. Conclusion: The prevalence of food allergy, in particular peanut allergy, in children below 2 years of age is lower in this South East Asian population than reported in Western cohorts. Further research should focus on deciphering differential risk factors for food allergy across different geographical locations.

Decline in skeletal muscle mass is associated with cognitive decline in type 2 diabetes mellitus.

AIMS: To examine the longitudinal association between skeletal muscle mass (SMM) loss and cognitive decline over time in type 2 diabetes mellitus (T2DM). METHODS: We conducted a prospective cohort study of 453 patients from SMART2D cohort with follow-up intervals of 1.6 to 6.4 years. Baseline and follow-up measurements included bio-impedance analysis (BIA) measure of skeletal muscle mass index (SMI) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measure of cognitive function. We examined the association between annual rate of SMI and RBANS scores using linear regression, adjusting for demographics, education, depression, clinical co-variables and presence of apolipoprotein E4 (APOE) Ɛ4 allele. RESULTS: The mean age of participants was 60.3 ± 7.4 years. Compared to patients with Tertile 1 SMI change, the group with greater SMI decline (Tertile 3 SMI change) experienced 0.30 decline in RBANS total score (95%CI -0.57 to -0.03; p = 0.030) in the adjusted analysis. RBANS scores for subdomains in immediate memory and visuo-spatial/construction were lower in Tertile 3 SMI change group with corresponding coefficients -0.54 (95%CI -1.01 to -0.06; p = 0.026), and -0.71 (95%CI -1.30 to -0.12; p = 0.019) respectively. CONCLUSION: In patients with T2DM, BIA measure of muscle mass loss over time was independently associated with cognitive decline globally and in the domains of memory and visuo-spatial/construction.

Association of early-onset Type 2 diabetes with cognitive impairment is partially mediated by increased pulse pressure.

AIMS: Type 2 diabetes mellitus (T2DM) has been shown to be associated with cognitive decline and dementia. As earlier onset of diabetes implies a longer disease duration and an increased risk to complications, we sought to investigate the effect of T2DM onset on cognitive function of our patients. METHODS: We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to T2DM patients aged 45-85 from our SMART2D cohort. We assessed the association of the T2DM onset age (both continuous and stratified into 3 groups: early-onset ≤40 (n = 326), middle-aged onset 41-64 (n = 703) and late-onset ≥65 years old (n = 38)) and RBANS cognitive indices in 1067 patients. Potential mediation of this association by vascular compliance using mediation analysis was investigated. RESULTS: T2DM onset associates significantly with RBANS total score. Patients with early T2DM onset have lower RBANS total score as compared to patients with middle-aged onset (ß = -2.01, p = 0.0102) and those with late-onset (ß = -5.80, p = 0.005). This association was partially mediated by pulse pressure index (25.8%), with indirect effect of 0.028 (Bootstrapped-CI: 0.008-0.047). CONCLUSIONS: Association of early-onset T2DM with cognitive impairment is partly mediated by diminished vascular compliance. Appropriate screening and assessment of cognitive function is important for early intervention and management of cognitive impairment.

Clinical variable-based cluster analysis identifies novel subgroups with a distinct genetic signature, lipidomic pattern and cardio-renal risks in Asian patients with recent-onset type 2 diabetes.

AIMS/HYPOTHESIS: We sought to subtype South East Asian patients with type 2 diabetes by de novo cluster analysis on clinical variables, and to determine whether the novel subgroups carry distinct genetic and lipidomic features as well as differential cardio-renal risks. METHODS: Analysis by k-means algorithm was performed in 687 participants with recent-onset diabetes in Singapore. Genetic risk for beta cell dysfunction was assessed by polygenic risk score. We used a discovery-validation approach for the lipidomics study. Risks for cardio-renal complications were studied by survival analysis. RESULTS: Cluster analysis identified three novel diabetic subgroups, i.e. mild obesity-related diabetes (MOD, 45%), mild age-related diabetes with insulin insufficiency (MARD-II, 36%) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII, 19%). Compared with the MOD subgroup, MARD-II had a higher polygenic risk score for beta cell dysfunction. The SIRD-RII subgroup had higher levels of sphingolipids (ceramides and sphingomyelins) and glycerophospholipids (phosphatidylethanolamine and phosphatidylcholine), whereas the MARD-II subgroup had lower levels of sphingolipids and glycerophospholipids but higher levels of lysophosphatidylcholines. Over a median of 7.3 years follow-up, the SIRD-RII subgroup had the highest risks for incident heart failure and progressive kidney disease, while the MARD-II subgroup had moderately elevated risk for kidney disease progression. CONCLUSIONS/INTERPRETATION: Cluster analysis on clinical variables identified novel subgroups with distinct genetic, lipidomic signatures and varying cardio-renal risks in South East Asian participants with type 2 diabetes. Our study suggests that this easily actionable approach may be adapted in other ethnic populations to stratify the heterogeneous type 2 diabetes population for precision medicine.

Understanding the journeys of patients with an asthma exacerbation requiring urgent therapy at a primary care clinic.

BACKGROUND: Asthma is a significant health issue in primary care. We examined the journeys of patients with asthma exacerbations requiring urgent therapy at a primary care clinic in Singapore. METHODS: Face-to-face semi-structured interviews were conducted with patients who received urgent therapy for asthma exacerbation at a primary care clinic. Data collected was used to construct themes. RESULTS: Fifteen multi-ethnic adult patients were recruited. Participants cited treatment cost, underuse of preventer medication, difficulties attending routine asthma care due to work, and stigma as barriers to asthma control. Reasons for delay in seeking urgent care for asthma were: inability to access medical care out of hours, competing priorities, perception that an exacerbation was 'not serious enough', difficulty recognizing symptoms of asthma exacerbation, and being tired or despondent. Participants were triggered to seek care due to failure of reliever inhalers, duration of symptoms, sleep disturbance, inability to work, or advice from others. During an exacerbation, participants often initiated other self-management measures besides using reliever medication. This included over-the-counter medications and non-pharmacological interventions (e.g. drinking water). Of the 15 patients interviewed, only one stepped up preventer inhaler adequately, according to their Asthma Action Plan (AAP). CONCLUSIONS: In caring for patients with asthma, primary care providers should address patients' asthma self-management skills, such as recognizing symptoms of asthma exacerbations and regular preventer use, and provide clear instructions on how to respond to asthma symptoms (AAP). Minimizing direct (medication and consultation fees) and indirect costs (loss of earnings and adverse impact on employment prospects) are also important considerations.

Ethnic-Specific Type 2 Diabetes Risk Factor PAX4 R192H Is Associated with Attention-Specific Cognitive Impairment in Chinese with Type 2 Diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been shown to increase the risks of cognitive decline and dementia. Paired box gene 4 (PAX4), a transcription factor for beta cell development and function, has recently been implicated in pathways intersecting Alzheimer's disease and T2DM. OBJECTIVE: In this report, we evaluated the association of the ethnic-specific PAX4 R192H variant, a T2DM risk factor for East Asians which contributes to earlier diabetes onset, and cognitive function of Chinese T2DM patients. METHODS: 590 Chinese patients aged 45-86 from the SMART2D study were genotyped for PAX4 R192H variation using Illumina OmniExpress-24 Array. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) which had been validated in the Singapore population was administered to assess five cognitive domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Multiple linear regression was used to assess the association of the R192H risk allele and cognitive domains. RESULTS: Patients with two PAX4 R192H risk alleles showed significantly lower attention index score (ß= -8.46, 95% CI [-13.71, -3.21], p = 0.002) than patients with wild-type alleles after adjusting for age, gender, diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, systolic blood pressure, metformin usage, smoking history, education level, Geriatric Depression Scale score, and presence of APOEɛ4 allele. CONCLUSION: Ethnic-specific R192H variation in PAX4 is associated with attention-specific cognitive impairment in Chinese with T2DM. Pending further validation studies, determining PAX4 R192H genotype may be helpful for early risk assessment of early-onset T2DM and cognitive impairment to improve diabetes care.

Comment on Surendran et al. The Missed Opportunity of Patient-Centered Medical Homes to Thrive in an Asian Context. Int. J. Environ. Res. Public Health 2021, 18, 1817.

We have noted the views expressed by the authors of the article "The Missed Opportunity of Patient-Centered Medical Homes (PCMH) to Thrive in an Asian Context" by Surendran et al. [...].