1.Development and validation of odour identification tests for olfactory assessment in Singapore.
Xinni XU ; Margaret Ru Xiang ZHANG ; Terese Huiying LOW ; Yew Kwang ONG
Annals of the Academy of Medicine, Singapore 2025;54(6):329-339
INTRODUCTION:
Odour recognition is influenced by culture. Odour identification tests need to be adapted to a population to accurately assess olfactory function. This study's objectives were to validate the Singapore version of the Sniffin' Sticks (SS-Sg) and a locally-developed odour recognition test (Scentsor) for Singapore.
METHOD:
This prospective study was performed in 3 otolaryngology outpatient clinics in 3 phases (1 May to 15 November 2024). Phase 1 was a survey evaluation of 93 odour descriptors to identify familiar odour descriptors to be used in the tests (n=414); Phase 2 evaluated and finalised SS-Sg and Scentsor to ensure test odours were recognised by ≥75% of healthy controls (n=130); and Phase 3 validated both tests on healthy controls (n=473) to obtain normative data, to determine test-retest reliability (n=50), and to assess the ability to distinguish patients with olfactory loss (n=67).
RESULTS:
In Phase 1, the unmodified SS blue and purple sets had 15/32 (46.9%) unfamiliar test odours and 25 unfamiliar distractors combined. In Phase 2, after modification, all odours in SS-Sg and Scentsor were correctly identified by ≥75% of controls. In Phase 3, normative data (age 21-83 years) was obtained. Both tests had good test-retest reliability (Pearson's correlation coefficient of 0.88 with<0.001 for SS-Sg; and at 0.90 with<0.001 for Scentsor). Both tests differentiated among normosmia, hyposmia and anosmia (SS-Sg scores: 12.6 [±2.4] versus [vs] 9.8 (±3.2) vs 6.0 [±2.3] respectively,<0.001; Scentsor scores: 14.3 [±1.8] vs 11.3 [±2.8] vs 5.8 [±3.4] respectively,<0.001).
CONCLUSION
SS-Sg and Scentsor have been validated to assess olfaction in Singapore.
Humans
;
Singapore
;
Male
;
Female
;
Odorants/analysis*
;
Middle Aged
;
Prospective Studies
;
Olfaction Disorders/diagnosis*
;
Adult
;
Reproducibility of Results
;
Aged
;
Smell/physiology*
;
Young Adult
2.Diagnostic patterns and predictors of cognitive outcomes in autistic children in Singapore.
Chui Mae WONG ; Hwan Cui KOH ; Pratibha AGARWAL ; Lourdes Mary DANIEL
Annals of the Academy of Medicine, Singapore 2025;54(7):396-409
INTRODUCTION:
This study aimed to examine patterns of diagnosis, cognitive and adaptive functioning, and school placement outcomes in autistic children in Singapore, and to assess earlier predictive factors of cognitive outcomes.
METHOD:
Retrospective data were extracted from medical records of a specialist developmental paediatrics service for children born in 2008-2011 and referred to the autism clinic or were given a diagnosis of autism. Data items included demographic data, diagnostic methods, psychological assessment results, early intervention attendance and school placement outcomes.
RESULTS:
A total of 2124 children (82.6% male; 66.4% Chinese, 13.4% Malay, 9.8% Indian and 10.5% Others) were diagnosed with autism from the 4 birth-year cohorts. The mean (SD) age of the first clinical diagnosis of autism was 3.56 (1.14) years, with 81.0% of children receiving a concordant initial clinical diagnosis. A total of 1811 (85.2%) had a formal diagnostic assessment using the Autism Diagnostic Observation Schedule (ADOS) at a mean (SD) age of 4.16 (1.11) years. Of 1326 with cognitive and adaptive assessment results, 16.6% had mild and 19.8% had moderate-severe cognitive impairment. Of 1483 with school placement outcomes, 45.9% went to mainstream schools, 21.8% entered SPED schools offering the national curriculum and 32.3% required customised curriculum SPED schools. Logistic regression showed that factors predicting intellectual impairment included higher ADOS scores (aOR 95% CI 1.13 [1.08-1.19] for Comm+SI total and 1.53 [1.33-1.75] for SBRI total), higher social communication level of support (based on the DSM-5 criteria) (aOR [95% CI] 2.14 [1.10-4.16] for level 2 and 14.94 [5.77-38.64] for level 3), and minority race (aOR [95% CI] 2.82 [1.52-5.20] for Malay, 5.19 [2.36-11.44] for Indian, and 4.54 [1.91-10.79] for Others).
CONCLUSION
These findings could guide policymakers and practitioners worldwide to strategically allocate diagnostic, intervention and educational resources, maximising developmental outcomes for autistic children across diverse settings.
Humans
;
Singapore/epidemiology*
;
Male
;
Female
;
Retrospective Studies
;
Child, Preschool
;
Autistic Disorder/complications*
;
Child
;
Early Intervention, Educational
;
Cognitive Dysfunction/diagnosis*
;
Cognition
3.Childhood-onset Takayasu arteritis: Unique characteristics and outcomes from a Singapore cohort.
Amanda Xin Yi YAP ; Junjie HUANG ; Kai Liang TEH ; Lena DAS ; Yun Xin BOOK ; Sook Fun HOH ; Xiaocong GAO ; Thaschawee ARKACHAISRI
Annals of the Academy of Medicine, Singapore 2025;54(9):531-541
INTRODUCTION:
Takayasu arteritis is the most common large-vessel vasculitis in childhood, but there is a lack of literature regarding childhood-onset Takayasu arteritis (c-TAK) in Southeast Asia. We aim to describe a c-TAK cohort in Singapore and highlight a unique subset that first presents with Kawasaki-like disease (KD).
METHOD:
A single-centre cohort study in Singapore of consecutive children diagnosed with c-TAK between 2002 and 2023 was performed. Demographic and clinical features, laboratory and angiographic findings, treatment, and outcomes were summarised. Disease activity was evaluated using the Paediatric Vasculitis Disease Activity Score and inflammatory markers.
RESULTS:
Twenty-three patients, fulfilling both the EULAR/ PRINTO/PReS and ACR/EULAR 2022 criteria, were recruited. The most common clinical features at diagnosis were fever (15, 65%) and neurological symptoms (11, 48%, half of which presented with stroke), while the most prevalent angiographic pattern by Hata's classification was Type V (21, 91%). Eight children (35%) initially presented with refractory KD, and these patients were significantly younger, more male-predominant, and had higher inflammatory markers at diagnosis; all of them had coronary artery involvement, but none had intracranial vascular findings. Of the entire cohort, 16 (70%) achieved inactive disease on medications with a median duration of 6 months (interquartile range [IQR]: 4-11), and 8 (35%) achieved remission off medications with a median duration of 43 months (IQR 35-60).
CONCLUSION
Our c-TAK cohort has high proportions of neurological involvement and stroke. This is also the first cohort study to describe a distinct group of patients who first presented with refractory KD.
Humans
;
Takayasu Arteritis/complications*
;
Singapore/epidemiology*
;
Male
;
Female
;
Child
;
Adolescent
;
Age of Onset
;
Mucocutaneous Lymph Node Syndrome/diagnosis*
;
Cohort Studies
;
Child, Preschool
;
Fever/etiology*
;
Stroke/epidemiology*
;
Retrospective Studies
4.Singapore consensus statements on the management of obstructive sleep apnoea.
Leong Chai LEOW ; Chuen Peng LEE ; Sridhar VENKATESWARAN ; Michael Teik Chung LIM ; Oon Hoe TEOH ; Ruth CHANG ; Yam Cheng CHEE ; Khai Beng CHONG ; Ai Ping CHUA ; Joshua GOOLEY ; Hong Juan HAN ; Nur Izzianie KAMARUDDIN ; See Meng KHOO ; Lynn Huiting KOH ; Shaun Ray Han LOH ; Kok Weng LYE ; Mark IGNATIUS ; Yingjuan MOK ; Jing Hao NG ; Thun How ONG ; Chu Qin PHUA ; Rui Ya SOH ; Pei Rong SONG ; Adeline TAN ; Alvin TAN ; Terry TAN ; Jenny TANG ; David TAY ; Jade TAY ; Song Tar TOH ; Serene WONG ; Chiang Yin WONG ; Mimi YOW
Annals of the Academy of Medicine, Singapore 2025;54(10):627-643
INTRODUCTION:
Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration.
METHOD:
An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded.
RESULTS:
The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations.
CONCLUSION
The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans
;
Sleep Apnea, Obstructive/diagnosis*
;
Singapore
;
Consensus
;
Adult
5.Risk-based screening programmes for cancer diagnosis: A systematic review with narrative synthesis.
Yong Yi TAN ; Sara TASNIM ; Mohammad Fahmy Bin FADZIL ; Xin Rong NG ; Sabrina Kw WONG ; Jo-Anne Elizabeth MANSKI-NANKERVIS ; Joseph Jao-Yiu SUNG ; Joanne NGEOW
Annals of the Academy of Medicine, Singapore 2025;54(10):644-663
INTRODUCTION:
Risk-based screening (RBS) has emerged as a promising alternative to age-based cancer screening. However, evidence regarding real-world implementation outcomes remains fragmented. Thus, a systematic review was conducted to evaluate the implementation metho-dologies and outcomes of RBS programmes across different cancer types.
METHODS:
MEDLINE, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials and Scopus were systematically searched from their respective dates of inception up to 8 July 2024. Prospective and rando-mised controlled trials (RCTs), which implement the RBS of cancer in an asymptomatic population, or studies retrospectively evaluating the outcomes of the same were included. Geographic distribution, population characteristics, RBS methodology, diagnostic accuracy and clinical outcomes were narratively synthesised.
RESULTS:
Among the 33 included studies (i.e. 21 prospective cohort, 8 RCTs, 3 retrospective and 1 non-RCT), sample sizes ranged from 102 to 1,429,890 participants. Most RBS trials were conducted in China (n=7, 21.2%), followed by the Netherlands (n=4, 12.1%) then the US, Australia and Sweden (n=3, 9.8%). Studies predominantly examined colorectal (27.3%), breast (21.2%) and prostate cancer (18.2%). Three main stratification approaches emerged: algorithmic (48.5%), validated risk models (39.4%) and physician assessment (9.1%). Implementation outcomes showed higher uptake in moderate-risk (75.4%) compared to high-risk (71.3%) and low-risk groups (67.9%). Five studies demonstrated cost-effectiveness with increased quality-adjusted life years, while 12 studies showed superior or non-inferior cancer detection rates compared to traditional screening.
CONCLUSION
The RBS of cancer has the potential to optimise healthcare resource allocation while minimising harm and increasing receptiveness for patients. More work is needed to evaluate long-term outcomes prior to the scaling of RBS programmes.
Humans
;
Early Detection of Cancer/methods*
;
Neoplasms/diagnosis*
;
Risk Assessment
;
Mass Screening/methods*
6.Brain injury biomarkers and applications in neurological diseases.
Han ZHANG ; Jing WANG ; Yang QU ; Yi YANG ; Zhen-Ni GUO
Chinese Medical Journal 2025;138(1):5-14
Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans
;
Biomarkers/cerebrospinal fluid*
;
Nervous System Diseases/diagnosis*
;
Brain Injuries/metabolism*
;
Phosphopyruvate Hydratase/cerebrospinal fluid*
;
Glial Fibrillary Acidic Protein/blood*
;
S100 Calcium Binding Protein beta Subunit/blood*
;
tau Proteins/cerebrospinal fluid*
;
Ubiquitin Thiolesterase/blood*
;
Myelin Basic Protein/cerebrospinal fluid*
;
Neurofilament Proteins/blood*
;
MicroRNAs/blood*
;
Brain Injuries, Traumatic/metabolism*
7.Preliminary clinical practice of radical prostatectomy without preoperative biopsy.
Ranlu LIU ; Lu YIN ; Shenfei MA ; Feiya YANG ; Zhenpeng LIAN ; Mingshuai WANG ; Ye LEI ; Xiying DONG ; Chen LIU ; Dong CHEN ; Sujun HAN ; Yong XU ; Nianzeng XING
Chinese Medical Journal 2025;138(6):721-728
BACKGROUND:
At present, biopsy is essential for the diagnosis of prostate cancer (PCa) before radical prostatectomy (RP). However, with the development of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and multiparametric magnetic resonance imaging (mpMRI), it might be feasible to avoid biopsy before RP. Herein, we aimed to explore the feasibility of avoiding biopsy before RP in patients highly suspected of having PCa after assessment of PSMA PET/CT and mpMRI.
METHODS:
Between December 2017 and April 2022, 56 patients with maximum standardized uptake value (SUVmax) of ≥4 and Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions who received RP without preoperative biopsy were enrolled from two tertiary hospitals. The consistency between clinical and pathological diagnoses was evaluated. Preoperative characteristics were compared among patients with different pathological types, T stages, International Society of Urological Pathology (ISUP) grades, and European Association of Urology (EAU) risk groups.
RESULTS:
Fifty-five (98%) patients were confirmed with PCa by pathology, including 49 (89%) with clinically significant prostate cancer (csPCa, defined as ISUP grade ≥2 malignancy). One patient was diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN). CsPCa patients, compared with clinically insignificant prostate cancer (cisPCa) and HGPIN patients, were associated with a higher level of prostate-specific antigen (22.9 ng/mL vs . 10.0 ng/mL, P = 0.032), a lower median prostate volume (32.2 mL vs . 65.0 mL, P = 0.001), and a higher median SUVmax (13.3 vs . 5.6, P <0.001).
CONCLUSIONS
It might be feasible to avoid biopsy before RP for patients with a high probability of PCa based on PSMA PET/CT and mpMRI. However, the diagnostic efficacy of csPCa with PI-RADS ≥4 and SUVmax of ≥4 is inadequate for performing a procedure such as RP. Further prospective multicenter studies with larger sample sizes are necessary to confirm our perspectives and establish predictive models with PSMA PET/CT and mpMRI.
Humans
;
Male
;
Prostatectomy/methods*
;
Prostatic Neoplasms/diagnosis*
;
Middle Aged
;
Aged
;
Positron Emission Tomography Computed Tomography/methods*
;
Biopsy
;
Multiparametric Magnetic Resonance Imaging
;
Prostate-Specific Antigen/metabolism*
8.Cancer therapy-related interstitial lung disease.
Chengzhi ZHOU ; Haiyi DENG ; Yilin YANG ; Fei WANG ; Xinqing LIN ; Ming LIU ; Xiaohong XIE ; Tao LUAN ; Nanshan ZHONG
Chinese Medical Journal 2025;138(3):264-277
With the increasing utilization of cancer therapy, the incidence of lung injury associated with these treatments continues to rise. The recognition of pulmonary toxicity related to cancer therapy has become increasingly critical, for which interstitial lung disease (ILD) is a common cause of mortality. Cancer therapy-related ILD (CT-ILD) can result from a variety of treatments including chemotherapy, targeted therapy, immune checkpoint inhibitors, antibody-drug conjugates, and radiotherapy. CT-ILD may progress rapidly and even be life-threatening; therefore, prompt diagnosis and timely treatment are crucial for effective management. This review aims to provide valuable information on the risk factors associated with CT-ILD; elucidate its underlying mechanisms; discuss its clinical features, imaging, and histological manifestations; and emphasize the clinical-related views of its diagnosis. In addition, this review provides an overview of grading, typing, and staging treatment strategies used for the management of CT-ILD.
Humans
;
Lung Diseases, Interstitial/diagnosis*
;
Neoplasms/therapy*
;
Risk Factors
;
Immune Checkpoint Inhibitors/adverse effects*
;
Antineoplastic Agents/therapeutic use*
9.Chest computed tomography-based artificial intelligence-aided latent class analysis for diagnosis of severe pneumonia.
Caiting CHU ; Yiran GUO ; Zhenghai LU ; Ting GUI ; Shuhui ZHAO ; Xuee CUI ; Siwei LU ; Meijiao JIANG ; Wenhua LI ; Chengjin GAO
Chinese Medical Journal 2025;138(18):2316-2323
BACKGROUND:
There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA).
METHODS:
This retrospective study included 413 patients hospitalized at Xinhua Hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods.
RESULTS:
The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections ( P <0.001) than patients with subphenotype-2 and had lower 30-day ( P <0.001) and 90-day ( P <0.001) mortality, and lower in-hospital ( P = 0.001) and 2-year ( P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes ( P <0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment.
CONCLUSIONS
A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.
Humans
;
Tomography, X-Ray Computed/methods*
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Artificial Intelligence
;
Aged
;
Pneumonia/diagnosis*
;
Latent Class Analysis
;
Adult
10.Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
Ming XU ; Wenhao ZHU ; Siyu HOU ; Hongzhi XU ; Jingwen XIA ; Liyu LIN ; Hao FU ; Mingyu YOU ; Jiafeng WANG ; Zhi XIE ; Xiaohong WEN ; Yingwei WANG
Chinese Medical Journal 2025;138(17):2170-2179
BACKGROUND:
Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.
METHODS:
PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.
RESULTS:
PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.
CONCLUSIONS:
The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.
TRIAL REGISTRATION
ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Algorithms
;
Lung Diseases/etiology*
;
Machine Learning
;
Neurosurgical Procedures/adverse effects*
;
Postoperative Complications/diagnosis*
;
Risk Factors
;
ROC Curve

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