The Singapore National Precision Medicine Strategy.

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic-phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world's population, many Asian ancestries are under-represented in existing databases, leading to missed opportunities for new discoveries, particularly for diseases most relevant for these populations. The Singapore National Precision Medicine initiative is a whole-of-government 10-year initiative aiming to generate precision medicine data of up to one million individuals, integrating genomic, lifestyle, health, social and environmental data. Beyond technologies, routine adoption of precision medicine in clinical practice requires social, ethical, legal and regulatory barriers to be addressed. Identifying driver use cases in which precision medicine results in standardized changes to clinical workflows or improvements in population health, coupled with health economic analysis to demonstrate value-based healthcare, is a vital prerequisite for responsible health system adoption.

Singapore's experience in managing the COVID-19 pandemic: Key lessons from the ground.

Singapore managed the COVID-19 pandemic in the past three years and gleaned valuable lessons on patient management when the public healthcare system was inundated with COVID-19 patients. There were several initiatives, which included setting up of community treatment facilities to help hospitals manage in-patient loads that did not require acute monitoring, leveraging telemedicine, and developing heuristics to sort patients based on their clinical disposition to various care pathways and to effectively manage patients of different medical needs. These initiatives were implemented in the second year of the epidemic in 2021 and did not include the dormitory-based migrant workers and migrant workers in the construction, maritime and production sectors who were under the care of the Assurance, Care and Engagement Group (ACE) in the Ministry of Manpower that had its own set of treatment management measures. The different care pathways ensured that patients received appropriate levels of care and allowed healthcare facilities to focus on more acute cases. In 2022 alone, 23,159 patients were discharged from community treatment facilities against the background of 1.9 million COVID-19 patients. These initiatives would not be possible without the oversight of an advisory board comprising senior leadership from the healthcare clusters and the Ministry of Health to align clinical governance with medical policies, and prompt and immense support from medical specialist panels. The strong public-private partnership forged in the process was instrumental in the successful operation of community facilities and implementation of patient care protocols, coupled with harnessing information technology and leveraging on emerging data to refine care protocols.

SARS-CoV-2 in migrant worker dormitories: Geospatial epidemiology supporting outbreak management.

BACKGROUND: Migrant worker dormitories-residential complexes where 10-24 workers share living spaces-account for the majority of cases of SARS-CoV-2 infection in Singapore. To prevent overspill of transmission to the wider population, starting in early April 2020, residents were confined to their dormitories while measures were put in place to arrest the spread of infection. This descriptive study presents epidemiological data for a population of more than 60 000 migrant workers living in two barracks-style and four apartment-style dormitories located in western Singapore from April 3 to June 10, 2020. METHODS: Our report draws from data obtained over the first 50 days of outbreak management in order to describe SARS-CoV-2 transmission in high-density housing environments. Cumulative counts of SARS-CoV-2 cases and numbers of housing units affected were analyzed to report the harmonic means of harmonic means of doubling times and their 95% confidence intervals (CI). RESULTS: Multiple transmission peaks were identified involving at least 5467 cases of SARS-CoV-2 infection across six dormitories. Our geospatial heat maps gave an early indication of outbreak severity in affected buildings. We found that the number of cases of SARS-CoV-2 infection doubled every 1.56 days (95% CI 1.29-1.96) in barracks-style buildings. The corresponding doubling time for apartment-style buildings was 2.65 days (95% CI 2.01-3.87). CONCLUSIONS: Geospatial epidemiology was useful in shaping outbreak management strategies in dormitories. Our results indicate that building design plays an integral role in transmission and should be considered in the prevention of future outbreaks.

Effectiveness of Containment Measures Against COVID-19 in Singapore: Implications for Other National Containment Efforts.

BACKGROUND: We hypothesize that comprehensive surveillance of COVID-19 in Singapore has facilitated early case detection and prompt contact tracing and, with community-based measures, contained spread. We assessed the effectiveness of containment measures by estimating transmissibility (effective reproduction number, (Equation is included in full-text article.)) over the course of the outbreak. METHODS: We used a Bayesian data augmentation framework to allocate infectors to infectees with no known infectors and determine serial interval distribution parameters via Markov chain Monte Carlo sampling. We fitted a smoothing spline to the number of secondary cases generated by each infector by respective onset dates to estimate (Equation is included in full-text article.)and evaluated increase in mean number of secondary cases per individual for each day's delay in starting isolation or quarantine. RESULTS: As of April 1, 2020, 1000 COVID-19 cases were reported in Singapore. We estimated a mean serial interval of 4.6 days [95% credible interval (CI) = 4.2, 5.1] with a SD of 3.5 days (95% CI = 3.1, 4.0). The posterior mean (Equation is included in full-text article.)was below one for most of the time, peaking at 1.1 (95% CI = 1.0, 1.3) on week 9 of 2020 due to a spreading event in one of the clusters. Eight hundred twenty-seven (82.7%) of cases infected less than one person on average. Over an interval of 7 days, the incremental mean number of cases generated per individual for each day's delay in starting isolation or quarantine was 0.03 cases (95% CI = 0.02, 0.05). CONCLUSIONS: We estimate that robust surveillance, active case detection, prompt contact tracing, and quarantine of close contacts kept (Equation is included in full-text article.)below one.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma.

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Changing models of care for emergency surgical and trauma patients in Singapore.

The last 15 years have seen changing patterns of injury in emergency surgery and trauma patients. The ability to diagnose, treat and manage these patients nonoperatively has led to a decline in interest in trauma surgery as a career. In addition, healthcare systems face multiple challenges, including limited resources, an ageing population and increasing subspecialisation of medical care, while maintaining government-directed standards and managing public expectations. In the West, these challenges have led to the emergence of a new subspecialty, 'acute care surgery', with some models of care providing dedicated acute surgical units or separating acute and elective streams with the existing manpower resources. The outcomes for emergency surgery patients and efficiency gains are promising. In Singapore, Khoo Teck Puat Hospital has implemented its first dedicated acute surgical unit. This article outlines the evolution of acute care surgery and its relevance to Asia.

Successful nutritional therapy for superior mesenteric artery syndrome.

Superior mesenteric artery (SMA) syndrome is an uncommon cause of duodenal outlet obstruction. Symptoms and signs suggestive of this condition are nonspecific, and a high index of suspicion coupled with appropriate imaging studies are necessary for diagnosis. We present the case of a 70-year-old man who developed SMA syndrome following prolonged hospitalisation for a surgically treated bleeding duodenal ulcer. His SMA syndrome resolved after successful nonoperative management based on accepted guidelines for nutritional therapy, thus avoiding the need for reoperation and its attendant risks in a malnourished patient.

Expanding the donor pool for liver transplantation in the setting of an "opt-out" scheme: 3 years after new legislation.

INTRODUCTION: The revised Human Organ Transplant Act (HOTA) was implemented in Singapore in July 2004. We aim to evaluate expanding the potential donor pool for liver transplant in Singapore with the inclusion of marginal donors. MATERIALS AND METHODS: All donor referrals between July 2004 and June 2007 were studied. All potential deceased liver donors were heart-beating. After being reviewed by the transplant coordinator, potential donors were assessed by a transplant hepatologist and a transplant surgeon for suitability of organ donation strictly based on the programme's donor assessment protocol. Reasons for rejection as potential donors were documented. The clinical characteristics of all donor referrals were retrospectively reviewed, and an independent decision was made as to whether liver retrieval in each rejected case might have been possible. RESULTS: Among the 128 potential donor referrals, 20 donors (15.6%) underwent liver retrieval. Of the 20 livers retrieved, 16 were implanted and 4 were not implanted (3 unfit recipients, and 1 donor liver with 40% steatosis). Another 10 donor livers were assessed intraoperatively and were rejected because of varying levels of steatosis. Of these livers assessed, 5 donor livers had steatosis <40% and 5 had steatosis >40%. Of the remaining potential donors, 45 were deemed not possible because of prolonged hypotension (9), on-going or unresolved sepsis (13), high-risk behaviour (4), non-actualisation (8), or pre-existing medical conditions (11). Another 53 donors may potentially have been suitable donors but were rejected because of possible sepsis (13), no suitable recipients (12), transient hypotension (10), transient abnormal liver function test (6), history of alcohol ingestion (5), non-actualisation because of consent (4) and other reasons (3). Overall, it was deemed that 61 donors (47.7%) might potentially have been suitable liver donors. CONCLUSIONS: Despite new legislation (HOTA) in Singapore, the utilisation of cadaveric donor livers showed no increase in the last 3 years. By expanding our donor criteria to include marginal donors, we could potentially increase the availability of deceased donor livers to meet our waiting list demands.

Laparoscopic cholecystectomy for acute cholecystitis: safe implementation of successful strategies to reduce conversion rates.

INTRODUCTION: A higher rate of conversion to open surgery is a well-known problem in patients with acute cholecystitis undergoing laparoscopic cholecystectomy. The aim of this study is to analyze factors which may impact on conversion rates, and to analyze our outcomes following implementation of a departmental strategy in reducing conversion rates. MATERIALS AND METHODS: 122 patients with acute cholecystitis were considered for laparoscopic cholecystectomy from July 2003 to July 2007. An audit of the results of laparoscopic cholecystectomy was done in July 2005 and a departmental strategy aimed at reducing the conversion rates was introduced. The strategies included early laparoscopic cholecystectomy (within 72 hours of admission), performed or supervised by specialist hepatobiliary surgeons, and modifications of operative techniques. This study compares the conversion rates before and after that audit. Forty-eight patients (group A) were from the preaudit period and the remaining 74 (group B) were from the postaudit period. A multivariate analysis was performed to identify risk factors for conversion to open surgery and whether the strategies implemented resulted in decrease in conversion rates. RESULTS: In the group A patients, there was a conversion rate of 29.2%. Gallbladder wall thickness of greater than 5 mm was found to be a statistically significant (p = 0.028) risk factor for conversion to open surgery. In group B patients, the conversion rates were significantly lower at 6.75% (p = 0.001). Analyzing both groups of patients, using multivariate analysis, gallbladder wall thickness, increasing age, and preaudit operative period were found to be independently associated with conversion to open surgery. CONCLUSIONS: This study demonstrated that, with specific strategies to decrease conversion and with technical improvements, the conversion rates can be decreased with no demonstrable difference in postoperative complications. Gallbladder wall thickness and increasing age are risk factors for conversion to open surgery.

How to appraise a prognostic study.

Prognostic studies are studies that examine selected predictive variables or risk factors and assess their influence on the outcome of a disease. They allow clinicians to understand better the natural history of a disease, guide clinical decision-making by facilitating the selection of appropriate treatment options, and allow more accurate prediction of disease outcomes. Appraising prognostic studies involves determining the internal validity of the study design and evaluating the influence of systemic errors or bias. In studies examining multiple prognostic variables, care must be taken to minimize the confounding influence each variable would have on the other parameters. Evaluating the results of appropriate statistical analysis enables conclusions to be made that may influence clinical practice. Care must be taken to ensure that the conditions under which the prognostic study were conducted resemble circumstances in the local institution so as to allow the conclusions to be applied to local practices.

Close temporal association of bronchial asthma and ischemic colitis--case report and review of the literature.

We report a case of ischemic colitis in an elderly male who had initially presented with acute asthma exacerbation. The clinical course of hospitalization, surgical and pathological findings were described. We review three previously reported cases of ischemic colitis and bronchial asthma and explore possible mechanisms to explain this association. The complex interaction of smooth muscle tone and autonomic nervous system in the etiopathogenesis of bronchial asthma and ischemic colitis is discussed. Further studies should be undertaken to clarify this association.

Liver transplantation for hepatocellular carcinoma: an Asian perspective.

Liver transplantation is an established treatment modality for patients with hepatocellular carcinoma (HCC), creating a potential for disease-free, long-term survival. In Asia, due to a severe shortage of donors, resection remains the treatment of choice for patients with HCC and good liver functional reserve. The use of marginal donors, split liver grafts and grafts from living donors are potential solutions that are best performed in experienced liver transplant centres to ensure an optimal outcome. Ethical issues relating to living donor liver transplantation have yet to be fully addressed. The roles of therapies to limit tumour progression during the waiting period, such as transarterial chemoembolization, need to be further investigated in the setting of a prospective trial and their benefits better defined.