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*

Background: Consumption and abuse of alcohol remains a significant cause of concern worldwide. Furthermore, there is evidence of the association between chronic alcohol use and reduced life expectancy. Objectives: To study the effects of Garcinia binucao extract (GBE) supplementation on lifespan of Drosophila melanogaster, in the presence or absence of chronic alcohol exposure. Methods: D. melanogaster was mass cultured and given GBE supplementation in high (1 mg/mL) and low (200 µg/mL) sublethal doses. D. melanogaster flies were divided into groups - with and without chronic alcohol exposure, and their respective lifespans were monitored. Results: In D. melanogaster without alcohol exposure, mean lifespan was highest in the control flies (38.15 days), followed by high-dose GBE (34.42 days), low-dose GBE (33.24 days), and DMSO (22.29 days). In D. melanogaster chronically exposed to alcohol, the longest mean lifespan was observed in flies treated with high-dose GBE (33.80 days), followed by low-dose GBE (33.63 days), the DMSO group (30.30), and the control group (29.65 days), but the differences were not statistically significant. Comparing groups with and without chronic alcohol exposure, the mean lifespan of the control group chronically exposed to alcohol significantly decreased by 9.51 days (p < 0.05). In GBE treatment groups, mean lifespan significantly decreased by 0.82 days in high-dose set-up (p < 0.05), and significantly increased by 0.39 days in the low-dose set-up (p < 0.05) upon chronic alcohol exposure. Conclusion Garcinia binucao extract supplementation ameliorated the observed reduction in lifespan of Drosophila melanogaster chronically exposed to alcohol.
Drosophila melanogaster ; Longevity

INTRODUCTION: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative option for relapse/refractory (R/R) lymphomas that have failed autologous transplantation or for high-risk lymphomas in the upfront setting. We conducted a retrospective analysis on consecutive lymphoma patients who underwent allo-HSCT over a 20-year period (2003- 2022) at Singapore General Hospital and National University Hospital Singapore. METHOD: A total of 121 patients were included in the study. Median age was 41 years. Diagnoses include Hodgkin lymphoma (HL, 15%), B-cell non- Hodgkin lymphoma (B-NHL, 34%), T-cell non-Hodgkin lymphoma (T-NHL, 31%) and natural killer T-cell lymphoma (NKTL, 20%). Moreover, 27% of patients had prior auto-haematopoietic stem cell transplanta-tion (auto-HSCT), and 84% received reduced intensity conditioning (RIC). Donor types were matched sibling donor (45%), matched unrelated donor (29%), haploidentical donor (19%) and cord blood (CB, 7%). RESULTS: After median follow-up of 56 months, estimated 4-year progression-free survival (PFS) and overall survival (OS) for all patients were 38% and 45%, respectively. Non-relapse mortality (NRM) was 15% at day 100 and 24% at 1 year. On univariate analysis, complete remission status at transplant and RIC confers superior OS. On multivariate analysis, HL was associated with superior OS compared to NHL, whereas matched unrelated donor transplant was associated with significantly inferior OS compared to matched sibling donor. CONCLUSION Long-term curative durability was observed with allo-HSCT for patients with relapsed/ refractory lymphomas. This real-world data serves as a valuable historical benchmark for future studies on lymphomas in Singapore and the Asia Pacific region.
Humans ; Singapore/epidemiology* ; Adult ; Male ; Retrospective Studies ; Female ; Hematopoietic Stem Cell Transplantation/methods* ; Middle Aged ; Transplantation, Homologous ; Young Adult ; Transplantation Conditioning/methods* ; Lymphoma/mortality* ; Adolescent ; Hodgkin Disease/mortality* ; Aged ; Lymphoma, B-Cell/mortality*

Knowledge of an underlying genetic predisposition to cancer allows the use of personalised prognostic, preventive and therapeutic strategies for the patient and carries clinical implications for family members. Despite great progress, we identified six challenging areas in the management of patients with hereditary cancer predisposition syndromes and suggest recommendations to aid in their resolution. These include the potential for finding unexpected germline variants through somatic tumour testing, optimal risk management of patients with hereditary conditions involving moderate-penetrance genes, role of polygenic risk score in an under-represented Asian population, management of variants of uncertain significance, clinical trials in patients with germline pathogenic variants and technology in genetic counselling. Addressing these barriers will aid the next step forward in precision medicine in Singapore. All stakeholders in healthcare should be empowered with genetic knowledge to fully leverage the potential of novel genomic insights and implement them to provide better care for our patients.
Humans ; Singapore ; Genotype ; Neoplasms/therapy* ; Risk Factors ; Family

Genetic testing has the power to identify individuals with increased predisposition to disease, allowing individuals the opportunity to make informed management, treatment and reproductive decisions. As genomic medicine continues to be integrated into aspects of everyday patient care and the indications for genetic testing continue to expand, genetic services are increasingly being offered by non-genetic clinicians. The current complexities of genetic testing highlight the need to support and ensure non-genetic professionals are adequately equipped with the knowledge and skills to provide services. We describe a series of misdiagnosed/mismanaged cases, highlighting the common pitfalls in genetic testing to identify the knowledge gaps and where education and support is needed. We highlight that education focusing on differential diagnoses, test selection and result interpretation is needed. Collaboration and communication between genetic and non-genetic clinicians and integration of genetic counsellors into different medical settings are important. This will minimise the risks and maximise the benefits of genetic testing, ensuring adverse outcomes are mitigated.
Humans ; Missed Diagnosis ; Genetic Testing ; Educational Status ; Diagnosis, Differential ; Genotype

INTRODUCTION: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. METHODS: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. RESULTS: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. CONCLUSION Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.
Humans ; Asian People ; COVID-19/complications* ; Inflammation/complications* ; SARS-CoV-2 ; Thrombosis

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients. Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography. Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037). Conclusion Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Background: Vision impairment impacts children’s physical well-being, psychological state, and productivity. The Impact of Vision Impairment for Children (IVI_C) is a vision-specific pediatric instrument designed to assess the effects of visual impairment on the quality of life (QoL) in children aged 8 to 18 years who have no additional disabilities. It measures quality of life to assess the needs of children with low vision and outcomes of interventions by deriving answers from both children and their caregivers. Objectives: The primary objective of the study was to determine the effect of visual impairment on the quality of life of children aged 8 to 18 years. Methods: This was an observational, analytical, cross-sectional study conducted at the Outpatient Department of the University of the Philippines-Philippine General Hospital, Sentro Oftalmologico Jose Rizal (SOJR), General and Pediatric Ophthalmology Clinics. We included children 8 to 18 years of age with best corrected visual acuity of less than or equal to 20/40 in the better-seeing eye for the visually impaired (VI) group. The control group included children aged 8 to 18 years with best corrected visual acuity of 20/20 to 20/30 in both eyes. Participants underwent a complete ophthalmologic examination, including the determination of visual acuity using the Early Treatment Diabetic Retinopathy Study( ETDRS ) chart prior to administration of the Filipino version of IVI_C questionnaire. After the ophthalmologic examination and prior to end of the medical consultation, the investigator administered the questionnaire to the children and their parents. Results: A total of 133 participants were included in the study, 67 in the visually impaired group and 66 in the control group. Participants had a median age of 10 years (range, 8 to 18), and 54% were female. Overall QoL scores and sub-scores across domains were significantly lower in the visually impaired group compared to the control group. The mean total and domain IVI_C scores progressively declined with increasing severity of visual impairment. The mean (±SD) total score ranged from 56 ± 6 in the mildly impaired to 42 ± 8 in the severe bilateral impairment group. On multivariate analysis, the significant predictors of quality of life were visual impairment and age. Quality of life of children with visual impairment is lower by 33.59 points (95% CI -35.82 to -31.36) than those in the control group. The QoL score increased by 0.579 per one unit increase in age. This model explained 87.05% of the variance in the IVI_C scores (p < 0.01). Conclusion Children with visual impairment have significantly decreased IVI_C and quality of life scores, overall and across domains. Lower scores are associated with increased severity of visual impairment.
Vision Disorders ; Quality of Life ; Child

PURPOSE: BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. MATERIALS AND METHODS: Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored. RESULTS: p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib. CONCLUSION: The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.
Asian Continental Ancestry Group ; Biomarkers ; Biopsy ; Breast Neoplasms ; Breast ; Diagnosis ; Disease-Free Survival ; Female ; Humans ; Neoplasm Metastasis ; Prevalence ; RNA, Messenger ; Trastuzumab

With the exception of shellfish, the overall food allergy rates in Singapore have not reached the epidemic proportions of the West. The rates of egg, milk and fish allergies remain low. However, the patterns of some food allergies in Singapore have changed over the last decade. For example, peanut allergy, once rare in Singapore, is now the most common cause of anaphylaxis in children. Studies analysing lifestyle practices, particularly with respect to prevention of food allergy, are necessary in order for practitioners to understand global differences and maintain this low prevalence.
Anaphylaxis ; diagnosis ; Child ; Child, Preschool ; Egg Hypersensitivity ; Fish Products ; Food Hypersensitivity ; diagnosis ; epidemiology ; prevention & control ; Humans ; Infant ; Infant, Newborn ; Milk Hypersensitivity ; Peanut Hypersensitivity ; Singapore ; epidemiology ; Surveys and Questionnaires