INTRODUCTION:Healthcare policymakers are focusing increasingly on value-driven care (VDC) models that aim to improve the quality of care and outcomes. We aimed to study the impact of community-acquired pneumonia (CAP) VDC initiatives on the trends in clinical quality indicators over a 7-year period (2018-2024). METHODS:Children admitted with CAP from January 2018 to December 2024 to KK Women's and Children's Hospital, Singapore, were included. We adopted a multifaceted approach to improving clinical quality indicators (length of stay [LOS] ≤5 days, no 30-day complications, no 30-day readmissions and no inpatient mortality) and the Clinical Quality Index (CQI)-the proportion of patients who meet all four clinical quality indicators. RESULTS:The total number of CAP admissions varied across the years (P < 0.05), with the highest number recorded in 2024 (n = 3197). The vast majority (68.7%) were of preschool age (<5 years). Viral CAP was the most common category, except in 2024 when a surge in CAP due to Mycoplasma pneumoniae was observed. The baseline CQI of 84% in 2018 (pre-VDC) increased to 90.3% in 2024 (P < 0.001). This was primarily driven by the improvement in LOS. The LOS (mean ± standard deviation) decreased from 3.65 ± 3.83 days in 2018 to 2.94 ± 2.00 days in 2024 (P < 0.001). CONCLUSION:This study highlights the positive impact of CAP VDC initiatives on key clinical quality indicators in children admitted with CAP over a 7-year period. The VDC model is scalable, and a similar multifaceted approach may be applied to VDC models for other acute and chronic conditions.
INTRODUCTION:The burden of autoimmune liver disease (AILD) is rising globally, yet data on its epidemiology and outcomes in Singapore remain limited. We aimed to characterise disease phenotype, treatment response and clinical outcomes among patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS:We retrospectively analysed patients diagnosed with AILD between 1995 and 2025 at a tertiary centre. Diagnoses and treatment responses for AILD were defined according to international guidelines. Clinical outcomes between AIH and PBC were compared using logistic regression, adjusted for baseline Model for End-stage Liver Disease score. RESULTS:Among 260 patients included, 71.2% had PBC, 22.0% had AIH, 3.8% had AIH/PBC overlap syndrome and 3.1% had PSC. The prevalence of AIH and PBC was 8.0 and 26.1 per 100,000 persons, respectively. Autoimmune hepatitis was independently associated with a higher risk of de novo steatotic liver disease (SLD) (adjusted odds ratio [OR] 5.90, 95% confidence interval [CI] 2.39-14.58). Compared with PBC, patients with AIH had a higher treatment response rate at 1 year (57.4% vs. 34.6%, P < 0.01) and a lower risk of overall mortality (OR 0.28, 95% CI 0.11-0.69). In patients with PBC, achieving a treatment response by the Toronto criteria was associated with improved transplant-free survival. CONCLUSION:The prevalence of AIH and PBC in our cohort mirrors that of East Asian populations. Despite a superior biochemical response, AIH was associated with a higher risk of hepatic steatosis. Underutilisation of second-line treatment in PBC represents an important gap for future improvement.
INTRODUCTION:No published studies have evaluated the application of Generative Pre-trained Transformer-5 (GPT-5) in the analysis of memory clinic patient clinical notes or the interpretation of plasma phosphorylated tau (P-tau) 217 values. We compared Alzheimer's disease (AD) probability estimates generated by GPT-5 before and after incorporating plasma P-tau 217 with pre- and posttest probabilities. METHODS:This was a retrospective study comprising 74 patients from a memory clinic in Queen Mary Hospital, Hong Kong. Final diagnoses were made by physicians, supported by medical history, physical examination, neuroimaging and amyloid positron emission tomography. Extracted clinical data included cognitive, functional and neuropsychiatric assessments. Pretest AD probabilities were derived from a published meta-analysis, while posttest probabilities were calculated using a Bayesian approach. These values were compared with those estimated by GPT-5. The diagnostic performance of GPT-5 and physicians was assessed using accuracy and Kappa coefficient, with final diagnosis as reference. RESULTS:There were 40 amyloid-positive (A+) and 34 amyloid-negative (A-) patients. In A+ patients, Bayesian posttest probabilities were higher than GPT-5 estimates (median 97.0% vs. 80.0%, P = 0.003), while those of A- patients were lower than GPT-5 estimates (median 3.0% vs. 27.5%, P < 0.001). With application of plasma P-tau 217, physicians achieved higher diagnostic accuracy than GPT-5 (81.1% vs. 45.9%, P < 0.001), while GPT-5 suggested mixed aetiologies more frequently (23.0% vs. 8.1%, P = 0.04) and inappropriate anti-amyloid therapy in 31% (11/36) of scenarios. CONCLUSION:Our findings show that GPT-5 has limitations in analysing clinical information of real-life memory clinic patients.
INTRODUCTION:Medial opening wedge high tibial osteotomy (MOWHTO) and unicompartmental knee arthroplasty (UKA) are established treatments for knee osteoarthritis (KOA). This study compared their effects on mental health outcomes. METHODS:A retrospective cohort study was conducted on patients who underwent MOWHTO or UKA between 2019 and 2023 at a single tertiary institution. The primary outcome measure, the Short Form-36 mental component score (SF-36 MCS), was recorded at baseline, six months and two years post-procedure. Secondary outcomes included the SF-36 physical component score (PCS) and the Oxford knee score (OKS). A total of 105 MOWHTO and 89 UKA procedures were performed. Propensity score matching accounted for preoperative scores, age, gender and body mass index, yielding 51 patients per group. Multivariable regression was used to examine associations between preoperative MCS and postoperative outcomes. Baseline predictors of postoperative MCS were analysed. The level of significance was set at P < 0.05. RESULTS:At six months postoperatively, the UKA group demonstrated better PCS (MOWHTO 42.0 vs UKA 49.6, P < 0.001) and OKS (MOWHTO 23.0 vs UKA 18.8, P = 0.002). At two years, both groups achieved similar improvements in SF-36 MCS, SF-36 PCS and OKS. Preoperative MCS showed a moderate association with postoperative MCS and weak associations with postoperative PCS and OKS. Preoperative MCS was the only baseline factor independently associated with postoperative MCS. CONCLUSION:In patients with KOA, MOWHTO and UKA achieved similar improvements in mental health scores at two years. Preoperative mental health is an important determinant of postoperative mental health, highlighting its importance in preoperative assessment and counselling.
INTRODUCTION:Resistant hypertension poses significant management challenges in primary care, with varying practices influencing patient outcomes. We evaluated current practices of primary care physicians in Singapore in managing resistant hypertension and examined their concordance with local and international guidelines. METHODS:An anonymised cross-sectional survey was conducted from July 2021 to October 2023, using a 26-item questionnaire distributed to primary care physicians across Singapore. The survey included physicians from both the public and private healthcare sectors, while specialists were excluded. The survey assessed their knowledge of the definitions, diagnostic criteria, treatment preferences and referral patterns for resistant hypertension. RESULTS:A total of 85 respondents participated in the survey. Only 74% (n = 63) of respondents correctly defined resistant hypertension as uncontrolled blood pressure (BP) (above 140/90 mmHg) despite concurrent use of three or more antihypertensives, including a diuretic. In addition, 53% (n = 45) correctly defined uncontrolled hypertension as home BP exceeding 135/85 mmHg. The majority (69%, n = 59) of primary care physicians would consider referral to a specialist after a trial of three antihypertensives, whereas 13% (n = 14) chose to continue management in primary care. Referrals were made mainly to Endocrinology (43%, n = 47) and Cardiology (35%, n = 39). Notably, few primary care physicians (27%, n = 23) considered the necessary work-up for secondary causes such as primary aldosteronism. CONCLUSION:This study identifies discrepancies between clinical practice and guidelines. The findings highlight a need to improve education on accurate definitions and guideline-based diagnosis of resistant hypertension, and develop clear national referral pathways for suspected secondary hypertension in primary care.
INTRODUCTION:Knee osteoarthritis is a common and debilitating problem. Safe and effective nonoperative treatments with sustained outcomes are needed, especially for patients unsuitable for knee replacement. Cooled radiofrequency ablation (CRFA) and hyaluronic acid (HA) injection have demonstrated efficacy, but CRFA is less well studied in Asian populations. METHODS:In this prospective, open-label, randomised controlled pilot study, patients with chronic knee osteoarthritis seen at a single tertiary centre in Singapore, who had at least 50% pain reduction after a genicular nerve block, were allocated to undergo CRFA or receive a single 6 mL injection of HA. Visual Analogue Scale (VAS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee scores, Knee Injury and Osteoarthritis Outcome Score (KOOS), EuroQol-5 Dimensions-5 Level and Global Perceived Effect were compared at 2 weeks, 1 month, 3 months and 6 months after treatment. RESULTS:Twelve participants underwent intervention (7 CRFA and 5 HA), and 11 completed follow-up to 6 months (7 CRFA and 4 HA). Responder rates at 6 months were 40.0% (95% confidence interval [CI] 11.8%-76.9%) for HA and 28.6% (95% CI 8.2%-64.1%) for CRFA. Over time, VAS, KOOS and WOMAC pain scores and GPE improved in both groups, with peak improvement at 1 month. Adverse events were generally minor and self-limiting. Intergroup differences were not statistically significant. CONCLUSION:Both interventions were safe and efficacious for knee osteoarthritis. Owing to the small sample size, the findings were preliminary and hypothesis-generating. Larger studies comparing CRFA with other interventions for knee osteoarthritis in the Singapore population are warranted.
ABSTRACT:Diabetic kidney disease (DKD) management has advanced rapidly in recent years, with new therapies supplementing established treatments. The cardiorenal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) in patients with DKD have been proven in several large randomised controlled trials. Recent studies show that combining SGLT2i, ns-MRA and renin-angiotensin-aldosterone system (RAAS) blockade significantly slows DKD progression compared with using single agents. The concurrent use of four agents, including GLP-1RA, SGLT2i, ns-MRA and RAAS blockade, may confer additional benefits, and a four-pillar approach to managing DKD could become standard therapy in the future. Additional investigational agents, including endothelin receptor antagonists, aldosterone synthesis inhibitors, and Janus kinase 1 and Janus kinase 2 inhibitors, have demonstrated encouraging results in Phase 2 trials. These therapies may offer further treatment options for patients who are unable to use other agents.
ABSTRACT:Alcohol-related liver disease remains a major and growing global health concern, with limited diagnostic and therapeutic options, particularly in advanced stages. Conventional diagnostic methods, including serum biomarkers, imaging and biopsy, often lack the sensitivity, specificity or practicality required for early detection and monitoring. Nanotheranostic platforms offer both targeted drug delivery and real-time assessment of disease activity. Organic, inorganic, polymeric and hybrid nanoparticles are being developed to improve the bioavailability and hepatic targeting of antioxidant, antifibrotic and RNA-based therapies. The use of novel nanodiagnostic probes and exosome-based assays enables the detection of early molecular alterations. However, delivery barriers and potential hepatotoxicity remain key translational challenges.
INTRODUCTION:Ursodeoxycholic acid (UDCA) is the first-line treatment for primary biliary cholangitis. We aimed to determine the prevalence of suboptimal response to UDCA and to examine the use of fenofibrate as an add-on therapy. METHODS:This was a retrospective study on all patients with primary biliary cholangitis seen at Gastroenterology and Hepatology Clinic between January 2019 and December 2024. RESULTS:Data for 59 patients were analysed (median age 62.5 [range 51.0-72.3] years, 78.0% female). More than half (54.2%) of the patients had suboptimal response (i.e. failure to achieve alkaline phosphatase [ALP] ≤1.67 times the upper limit of normal [ULN], total bilirubin less than ULN and ALP decreased by ≥15%) after 1 year of UDCA. Among them, 73.1% continued UDCA monotherapy, whereas the remaining 26.9% received fenofibrate add-on therapy. A significantly greater proportion of patients who received fenofibrate add-on therapy achieved biochemical response (83.3% vs. 14.3%, P = 0.003), ALP normalisation (66.7% vs. 14.3%, P = 0.019) and deep response (i.e. ALP normalisation and total bilirubin ≤0.6 ULN) (33.3% vs. 0%, P = 0.023) compared with patients who continued UDCA monotherapy. After a median follow-up of 56 (19-122) months, seven patients developed cirrhosis, eight patients developed decompensated cirrhosis and three patients had liver-related mortality. There were no liver-related events among patients who achieved a biochemical response after 1 year of UDCA therapy and among patients who were on fenofibrate add-on therapy. CONCLUSION:Suboptimal response to UDCA is common among patients with primary biliary cholangitis, and fenofibrate add-on therapy can improve biochemical response in these patients.
INTRODUCTION:Sarcopenia and cardiovascular-kidney-metabolic (CKM) syndrome are common comorbidities. We evaluated their cumulative impact on all-cause and cardiovascular mortality, and the modifying effect of a Composite Dietary Antioxidant Index (CDAI). METHODS:This prospective study used data from the National Health and Nutrition Examination Survey linked to the National Death Index. Sarcopenia (Foundation for the National Institutes of Health criteria) and CKM syndrome (American Heart Association stages, dichotomised into advanced/non-advanced) defined the primary exposure. Outcomes were all-cause and cardiovascular mortality. Cox models estimated hazard ratios (HRs). Maximally selected rank statistics determined optimal outcome-specific CDAI thresholds. RESULTS:Among 8782 participants (median follow-up 131 months), advanced CKM syndrome was associated with sarcopenia (odds ratio 2.29, 95% confidence interval [CI] 1.48-3.53). This study demonstrated a cumulative risk of comorbid advanced CKM syndrome and sarcopenia on mortality, with this group exhibiting the highest risk for all-cause (HR 3.11, 95% CI 1.72-5.61) and cardiovascular (HR 1.80, 95% CI 1.04-3.12) mortality. Furthermore, we identified an inverse relationship between disease burden and protective CDAI thresholds for all-cause mortality, whereas cardiovascular mortality exhibited a distinctly higher threshold. Specifically, the comorbidity group required lower antioxidant intake (CDAI >-3.80) than the non-comorbidity group (CDAI >-1.19) for all-cause mortality. Conversely, cardiovascular mortality required a substantially higher threshold (CDAI >3.04). CONCLUSION:Coexisting advanced CKM syndrome and sarcopenia present a significant cumulative mortality risk. Exploratory analyses suggest that this risk may be mitigated by dietary antioxidants, but the protective threshold is context-dependent. Modest dietary improvement was associated with improved all-cause survival in high-risk patients, whereas higher antioxidant intake correlated with better cardiovascular outcomes. These results suggest that precision nutrition strategies may vary depending on the specific health outcome.
INTRODUCTION:Patients with chronic hepatitis C remain at risk of hepatocellular carcinoma (HCC) even after attaining sustained virological response at 12 weeks (SVR12). The optimal strategy to stratify HCC risk, particularly in non-cirrhotic patients, remains unclear. This study compared the predictive performance of baseline and post-SVR12 fibrosis-4 index (FIB-4 index) for incident HCC. METHODS:We conducted a post hoc analysis of consecutive patients with chronic hepatitis C treated with direct-acting antivirals between 2018 and 2019, with follow-up for de novo HCC occurrence. Primary predictors were FIB-4 at baseline, post-SVR12 and their dynamic change. The primary outcome was the development of post-SVR12 HCC. RESULTS:Among 762 patients, 2.4% developed HCC over a median follow-up of 53 months. Patients who developed HCC were older (58 years vs. 52 years; P = 0.003), exclusively male, and had a higher baseline FIB-4. The FIB-4 values declined after SVR12 (2.9 ± 3.6 vs. 2.1 ± 2.6, P = 0.043), resulting in a different optimal threshold for HCC prediction (baseline 2.9; post-SVR 2.4). Both baseline and post-SVR12 FIB-4 showed strong and comparable predictive performance (area under the receiver operating characteristic curves 0.91 vs. 0.88, P = 0.279). By contrast, changes in FIB-4 were not predictive of HCC risk. CONCLUSION:Both baseline and post-SVR12 FIB-4 reliably predict HCC after direct-acting antiviral-induced SVR, although the optimal threshold differs due to post-SVR improvements. A post-SVR12 FIB-4 of less than 1.3 identifies a very low-risk group who may be safely discharged from long-term HCC surveillance.
Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism, characterised by highly elevated low-density lipoprotein cholesterol (LDL-C) from birth, leading to adverse cardiovascular effects at an early age. The prevalence of heterozygous FH is 1:200–250, while that of homozygous FH is 1:100,000–160,000 individuals. Patients with homozygous FH may have cholesterol levels of 25 mmol/L and develop cardiovascular diseases (CVDs) in their early twenties. In contrast, patients with heterozygous FH may have cholesterol levels of 5.2–10.4 mmol/L, with CVD manifesting around the age of 40 to 50 years. Familial hypercholesterolaemia is usually caused by inherited mutations in the APOB , LDLR and PCSK9 genes, and can be detected by routine lipid testing. Early recognition and aggressive management to lower the LDL-C level help to delay or prevent coronary atherosclerosis. This review summarises the epidemiology, genetic basis, screening and treatment options available for the management of FH.
INTRODUCTION:The study aimed to determine the outcome of children with transfusion-dependent thalassaemia (TDT) who underwent haematopoietic stem cell transplantation (HSCT) at Universiti Malaya Medical Centre, Malaysia. METHODS:This was a retrospective analysis of 115 children (aged <18 years) who underwent 128 transplant procedures between 1 June 1987 and 30 December 2023. RESULTS:The study included 53 boys, and the median age at time of HSCT was 5 years. One-third of patients were in Pesaro class 3. The 15-year overall survival and thalassaemia-free survival (TFS) were 83% and 71%, respectively. Transplant-related mortality (TRM) was 16%. Multivariate analysis revealed that patients who were aged >7 years and did not receive pre-HSCT anti-thymocyte globulin (ATG) had the worst outcomes (TFS 52%). In 62 patients who received busulfan-cyclophosphamide conditioning, 32 had addition of ATG that improved TFS (78% vs. 64%, P = 0.02). Graft failure, seen in 26% of patients, was the main contributing factor to TRM. Omission of ATG in the conditioning regimen was the main cause of graft failure (relative risk [RR] 8.26, 95% confidence interval [CI] 1.68-40.51; P = 0.009). The incidence of Grade II-IV graft-versus-host disease (GVHD) was 26%. Non-inclusion of ATG also significantly increased the risk of GVHD (RR 8.52, 95% CI 1.95-37.25; P = 0.04). CONCLUSION:Haematopoietic stem cell transplantation is a feasible curative option for children with TDT in Malaysia, with the best outcomes observed in patients undergoing transplantation before the age of 7 years. Our study also highlights the role of ATG in improving HSCT outcomes in this population.
