Artificial intelligence innovation in healthcare: Relevance of reporting guidelines for clinical translation from bench to bedside.

Artificial intelligence (AI) and digital innovation are transforming healthcare. Technologies such as machine learning in image analysis, natural language processing in medical chatbots and electronic medical record extraction have the potential to improve screening, diagnostics and prognostication, leading to precision medicine and preventive health. However, it is crucial to ensure that AI research is conducted with scientific rigour to facilitate clinical implementation. Therefore, reporting guidelines have been developed to standardise and streamline the development and validation of AI technologies in health. This commentary proposes a structured approach to utilise these reporting guidelines for the translation of promising AI techniques from research and development into clinical translation, and eventual widespread implementation from bench to bedside.

Analysis of COVID-19 Incidence and Severity Among Adults Vaccinated With 2-Dose mRNA COVID-19 or Inactivated SARS-CoV-2 Vaccines With and Without Boosters in Singapore.

Importance: Assessing booster effectiveness of COVID-19 mRNA vaccine and inactivated SARS-CoV-2 vaccine over longer time intervals and in response to any further SARS-CoV-2 variants is crucial in determining optimal COVID-19 vaccination strategies. Objective: To determine levels of protection against severe COVID-19 and confirmed SARS-CoV-2 infection by types and combinations of vaccine boosters in Singapore during the Omicron wave. Design, Setting, and Participants: This cohort study included Singapore residents aged 30 years or more vaccinated with either at least 2 doses of mRNA COVID-19 vaccines (ie, Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) or inactivated SARS-CoV-2 vaccines (Sinovac CoronaVac or Sinopharm BBIBP-CorV) as of March 10, 2022. Individuals with a known SARS-CoV-2 infection prior to December 27, 2021, an infection on or before the date of their second vaccine dose, or with reinfection cases were excluded. Exposures: Two or 3 doses of Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, Sinovac CoronaVac, or Sinopharm BBIBP-CorV. Main Outcomes and Measures: Notified infections from December 27, 2021, to March 10, 2022, adjusted for age, sex, race, housing status, and calendar days. Estimated booster effectiveness, defined as the relative incidence-rate reduction of severe disease (supplemental oxygen, intensive care, or death) or confirmed infection following 3-dose vaccination compared with 5 months after second mRNA dose, was determined using binomial regression. Results: Among 2 441 581 eligible individuals (1 279 047 [52.4%] women, 846 110 (34.7%) aged 60 years and older), there were 319 943 (13.1%) confirmed SARS-CoV-2 infections, of which 1513 (0.4%) were severe COVID-19 cases. mRNA booster effectiveness against confirmed infection 15 to 60 days after boosting was estimated to range from 31.7% to 41.3% for the 4 boosting combinations (homologous BNT162b2, homologous mRNA-1273, 2-dose BNT162b2/mRNA-1273 booster, and 2-dose mRNA-1273/BNT162b2 booster). Five months and more after boosting, estimated booster effectiveness against confirmed infection waned, ranging from -2.8% to 14.6%. Against severe COVID-19, estimated mRNA booster effectiveness was 87.4% (95% CI, 83.3%-90.5%) 15 to 60 days after boosting and 87.2% (95% CI, 84.2%-89.7%) 5 to 6 months after boosting, with no significant difference comparing vaccine combinations. Booster effectiveness against severe COVID-19 15 days to 330 days after 3-dose inactivated COVID-19 vaccination, regardless of combination, was estimated to be 69.6% (95% CI, 48.7%-81.9%). Conclusions and Relevance: Booster mRNA vaccine protection against severe COVID-19 was estimated to be durable over 6 months. Three-dose inactivated SARS-CoV-2 vaccination provided greater protection than 2-dose but weaker protection compared with 3-dose mRNA.

Global human security in the post-COVID-19 era: The rising role of East Asia.

Kenji Shibuya and coauthors discuss the potential contribution of East Asian countries to global health in the light of COVID-19.

Singapore's health-care system: key features, challenges, and shifts.

Since Singapore became an independent nation in 1965, the development of its health-care system has been underpinned by an emphasis on personal responsibility for health, and active government intervention to ensure access and affordability through targeted subsidies and to reduce unnecessary costs. Singapore is achieving good health outcomes, with a total health expenditure of 4·47% of gross domestic product in 2016. However, the health-care system is contending with increased stress, as reflected in so-called pain points that have led to public concern, including shortages in acute hospital beds and intermediate and long-term care (ILTC) services, and high out-of-pocket payments. The main drivers of these challenges are the rising prevalence of non-communicable diseases and rapid population ageing, limitations in the delivery and organisation of primary care and ILTC, and financial incentives that might inadvertently impede care integration. To address these challenges, Singapore's Ministry of Health implemented a comprehensive set of reforms in 2012 under its Healthcare 2020 Masterplan. These reforms substantially increased the capacity of public hospital beds and ILTC services in the community, expanded subsidies for primary care and long-term care, and introduced a series of financing health-care reforms to strengthen financial protection and coverage. However, it became clear that these measures alone would not address the underlying drivers of system stress in the long term. Instead, the system requires, and is making, much more fundamental changes to its approach. In 2016, the Ministry of Health encapsulated the required shifts in terms of the so-called Three Beyonds-namely, beyond health care to health, beyond hospital to community, and beyond quality to value.

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.

Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review.

Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.

National Health Survey on the prevalence of urinary abnormalities in the population: then and now (1975 to 2012).

INTRODUCTION: This paper presents the results of a community survey on urinary abnormalities which covered 1/80th of the population of Singapore in 1975. These findings were compared with the data from the Singapore National Service Registrants in 1974 as well as data from a recent survey in Singapore and that of other Asian and Western countries. MATERIALS AND METHODS: The study covered 18,000 persons aged 15 years and above, representing a sampling fraction of 1/80th of the population. A total of 16,808 respondents attended the field examination centres, of whom 16,497 had their urine sample tested representing 92.7% of the sample population. RESULTS: In the dipstick urine testing at the field examination centres, 769 subjects (4.6%) were found to have urinary abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were found to have urinary abnormalities based on urine microscopy constituting a prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43% and renal insufficiency was 0.1%. DISCUSSION: The consensus is that routine screening for chronic kidney disease (CKD) in the general population is not cost effective as the yield is too low. Whilst, most studies showed that screening of the general population was not cost effective, it has been suggested that screening for targeted groups of subjects could help to identify certain risk groups who may benefit from early intervention to prevent or retard the progression of CKD. CONCLUSION: The prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.

Global evolutionary trend of the prevalence of primary glomerulonephritis over the past three decades.

OBJECTIVE: The prevalence of primary glomerulonephritis in Singapore is compared with that of 28 other countries to review changing trends in the evolution of primary glomerulonephritis in Asia and other countries. METHOD: 2,586 renal biopsies in Singapore over the past 3 decades were reviewed and compared with data from 28 other countries. RESULTS: In the 1st decade most Asian countries have mesangial proliferative glomerulonephritis as the most common form of primary glomerulonephritis, and in the 3rd decade there has been a dramatic increase in focal and segmental glomerulosclerosis reflecting aging and obesity in keeping with more developed countries. IgA nephritis remains the commonest glomerulonephritis in many countries. Membranous glomerulonephritis continues to be more prevalent in Western countries while mesangial proliferative glomerulonephritis remains prevalent in many Asian countries. CONCLUSION: Apart from geographical and genetic influences, socioeconomic factors may play a role in the evolution of the biopsy pattern in some countries. Worldwide, the prevalence of focal segmental glomerulosclerosis continues to increase. In third world countries some of the commoner forms of glomerulonephritis are related to infections, in contrast to developed countries where the antigenic exposure may be related to diet, allergens and other industrial agents.

High dose Losartan and ACE gene polymorphism in IgA nephritis.

Background/aims Several studies have reported varying results of the influence of ACE gene on ACEI/ARB therapy. The efficacy of high dose ARB and its influence on ACE gene have not been explored. This is a 6 year randomised trial in IgA nephritis comparing high dose ARB (Losartan 200 mg/day) with normal dose ARB (Losartan 100 mg/day), normal dose ACEI (20 mg/day) and low dose ACEI (10 mg/day). Results Patients on high dose ARB had significantly lower proteinuria, 1.0 +/- 0.8 gm/day compared to 1.7 +/- 1.0 g/day in the other groups (P = 0.0005). The loss in eGFR was 0.7 ml min(-1)year(-1) for high dose ARB compared to 3.2-3.5 ml min(-1)year(-1) for the other three groups (P = 0.0005). There were more patients on high dose ARB with improvement in eGFR compared to other three groups (P < 0.001). Comparing patients with the three ACE genotypes DD, ID and II, all three groups responded well to therapy with decrease in proteinuria (P < 0.002). Only those on low dose ACEI (10 mg/day) with the I allele had increased in ESRF (P = 0.037). Conclusion High dose ARB is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI, and also obviates the genomic influence of ACE gene polymorphism on renal survival.

SARS in Singapore--key lessons from an epidemic.

The rapid containment of the Singapore severe acute respiratory syndrome (SARS) outbreak in 2003 involved the introduction of several stringent control measures. These measures had a profound impact on the healthcare system and community, and were associated with significant disruptions to normal life, business and social intercourse. An assessment of the relative effectiveness of the various control measures is critical in preparing for future outbreaks of a similar nature. The very "wide-net" surveillance, isolation and quarantine policy adopted was effective in ensuring progressively earlier isolation of probable SARS cases. However, it resulted in nearly 8000 contacts being put on home quarantine and 4300 on telephone surveillance, with 58 individuals eventually being diagnosed with probable SARS. A key challenge is to develop very rapid and highly sensitive tests for SARS infection, which would substantially reduce the numbers of individuals that need to be quarantined without decreasing the effectiveness of the measure. Daily temperature monitoring of all healthcare workers (HCWs) in hospitals was useful for early identification of HCWs with SARS. However, daily temperature screening of children in schools failed to pick up any SARS cases. Similarly, temperature screening at the airport and other points of entry did not yield any SARS cases. Nevertheless, the latter 2 measures probably helped to reassure the public that schools and the community were safe during the SARS outbreak. Strong political leadership and effective command, control and coordination of responses were critical factors for the containment of the outbreak.

Health economics of renal replacement therapy: perspectives from Singapore.

The prevalence of end-stage renal disease (ESRD) in Singapore is high and projected to increase sharply due to the aging population and the high prevalence of diabetes. The number of patients treated with dialysis was projected to rise from 2633 in 1999 to nearly 6000 in the year 2010. The cost of dialysis provision was estimated to increase 2.5-fold from US dollar 90 million in 1999 to US dollar 241 million in 2010. To address this, the Singapore Ministry of Health launched three initiatives in the year 2000: First, to reduce the incidence of ESRD through (1) primary prevention of diabetes, (2) community-based screening to facilitate early detection of patients with diabetes, (3) improving glycemic and blood pressure (BP) control of diabetics in the primary care setting, and (4) the establishment of dedicated Renal Retardation clinics to optimize BP control (and glycemic control for diabetics), and reduce the level of proteinuria in patients at high risk of ESRD development. Second, to increase the percentage of ESRD patients treated with continuous ambulatory peritoneal dialysis (CAPD), which is a lower-cost modality compared with hemodialysis; and third, amendments to the existing opt-out legislation for organ procurement for transplantation to increase the supply of kidneys for cadaveric renal transplant.

SARS transmission and hospital containment.

An outbreak of severe acute respiratory syndrome (SARS) was detected in Singapore at the beginning of March 2003. The outbreak, initiated by a traveler to Hong Kong in late February 2003, led to sequential spread of SARS to three major acute care hospitals in Singapore. The critical factor in containing this outbreak was early detection and complete assessment of movements and follow-up of patients, healthcare workers, and visitors who were contacts. Visitor records were important in helping identify exposed persons who could carry the infection into the community. In the three hospital outbreaks, three different containment strategies were used to contain spread of infection: closing an entire hospital, removing all potentially infected persons to a dedicated SARS hospital, and managing exposed persons in place. On the basis of this experience, if a nosocomial outbreak is detected late, a hospital may need to be closed in order to contain spread of the disease. Outbreaks detected early can be managed by either removing all exposed persons to a designated location or isolating and managing them in place.

Secondary household transmission of SARS, Singapore.

Secondary household transmission of severe acute respiratory syndrome (SARS) was studied in 114 households involving 417 contacts. The attack rate was low (6.2%). Occupation of the index case was the factor that most influenced household transmission (adjusted hazard ratio for healthcare workers 0.157; 95% confidence interval 0.042 to 0.588).

Transmission dynamics and control of severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic.