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.

Inclination towards research and the pursuit of a research career among medical students: an international cohort study.

BACKGROUND: Involvement of clinicians in biomedical research is imperative for the future of healthcare. Several factors influence clinicians' inclination towards research: the medical school experience, exposure to research article reading and writing, and knowledge of research. This cohort study follows up medical students at time of graduation to explore changes in their inclination towards research and pursuing a research career compared to their inclination at time of entry into medical school. METHODS: Students from medical schools in six different countries were enrolled in their first year of school and followed-up upon graduation in their final year. Students answered the same self-administered questionnaire at both time points. Changes in inclination towards research and pursuing a research career were assessed. Factors correlated with these changes were analysed. RESULTS: Of the 777 medical students who responded to the study questionnaire at entry into medical school, 332 (42.7%) completed the follow-up survey. Among these 332 students, there was no significant increase in inclination towards research or pursuing a research career over the course of their medical schooling. Students from a United States based school, in contrast to those from schools other countries, were more likely to report having research role models to guide them (51.5% vs. 0%-26.4%) and to have published in a peer-reviewed journal (75.7% vs. 8.9%-45%). Absence of a role model was significantly associated with a decrease in inclination towards research, while an increased desire to learn more about statistics was significantly associated with an increase in inclination towards pursuing a research career. CONCLUSION: Most medical students did not experience changes in their inclination towards research or pursuing a research career over the course of their medical schooling. Factors that increased their inclination to undertaking research or pursuing a research career were availability of a good role model, and a good knowledge of both the research process and the analytical tools required.

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.

Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial.

BACKGROUND: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. METHODS: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. DISCUSSION: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.

On developing a pragmatic strategy for clinical trials: A case study of hepatocellular carcinoma.

Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness. In this article, we aim to present a Bayesian approach for synthesizing the cumulative evidence of the use of adjuvant hepatic intra-arterial iodine-131-lipiodol (I131L) following curative resection in hepatocellular carcinoma (HCC) patients. We constructed a posterior distribution using the information from two small RCTs, three non-randomised comparative studies, three single arm studies and the views of investigators on the use of I131L. This distribution enables calculation of the probability that the Test therapy is more effective than the Standard by a pre-stipulated amount. If this is very high, then for example, one may conclude the Test may replace the Standard therapy. If it is not, then the Standard would be retained for clinical use. Despite a strong early indication of the effectiveness of I131L, the evolving evidence over a 10-year period became more sceptical of its value. Although highly recommended, difficulties of implementing a Bayesian approach in this context are highlighted.

Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria.

UNLABELLED: Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations. CONCLUSION: In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.

BACKGROUND: The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. METHODS: Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). RESULTS: Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. CONCLUSIONS: This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712790.

Stress myocardial perfusion imaging for the evaluation and triage of chest pain in the emergency department: a randomized controlled trial.

BACKGROUND: Patients with acute coronary syndrome (ACS) often present atypically. In a randomized controlled trial, we studied whether adding stress myocardial perfusion imaging (SMPI) to an evaluation strategy for emergency department (ED) patients presenting with chest pain more effectively identifies patients with ACS. METHODS: Participants were randomized to standard ED chest pain protocol (clinical assessment) or standard protocol supplemented with SMPI results. During 6 hours of electrocardiogram (ECG) monitoring and serial cardiac markers (creatine kinase-MB isoenzyme, troponin), participants developing ST segment changes or elevated cardiac markers were admitted. Those with a negative observation period underwent SMPI (N = 1,004) or clinical assessment (N = 504) based on randomization, and admitted if their SMPI scan was abnormal or senior clinicians found a high or intermediate risk for ACS. RESULTS: SMPI participants had a significantly lower admission rate than clinical assessment participants (10.16% vs 18.45%), with no significant between-group differences in risk of cardiac events (CEs) after 30 days (0.40% vs 0.79%) or 1 year (0.70% vs 0.99%). CONCLUSIONS: When added to a standard triage strategy incorporating clinical evaluation, serial ECGs, and cardiac markers, SMPI improved clinical decision making for chest pain patients, significantly reducing the need for hospitalization without an increase in adverse CE rates at 30 days or 1 year.

Chinese medicine NeuroAiD efficacy stroke recovery-extension study (CHIMES-E study): an observational multicenter study to investigate the longer-term efficacy of NeuroAiD in stroke recovery.

BACKGROUND: Stroke carries a poor long-term prognosis for death and disability. There are few acute treatments that reduce death and disability after stroke. The ongoing international, multicenter, randomized, placebo-controlled, double-blind CHIMES trial is currently testing the hypothesis that a 3-month course of the traditional Chinese medicine MLC601 (NeuroAiD) is superior to placebo in reducing neurological deficit and improving functional outcome after acute ischemic stroke in patients receiving standard stroke care. This extension study tests the hypothesis that at 2 years, an initial 3-month administration of NeuroAiD is superior to placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction of an intermediate range of severity. METHODS: Study subjects will be those who are already participants in CHIMES - aged above 21 years, had signs and symptoms of acute stroke, 6 ≤ NIHSS ≤ 14, neuroimaging consistent with ischemic stroke, and received study medication within 72 h of stroke onset. A subject will not be eligible for inclusion in CHIMES-E if they have withdrawn consent from all participation and follow-up for CHIMES. Subjects will be contacted at 6, 12, 18 and 24 months after CHIMES enrollment. After verbal consent is obtained, subjects will be assessed for functional state by the modified Rankin scale (mRS) and Barthel Index (BI), and a history of recurrent vascular events as well as medical events. The primary outcome measure will be the mRS at month 24. Secondary outcome measures will be mRS and BI at 6, 12 and 18 months, and BI at 24 months. Analysis will be based on the intention-to-treat principle. If the number of patients lost to follow-up is substantial, a sensitivity analysis based on the last observation carried forward method will be carried out, to compare the results with those from the main analysis without imputation. Based on a cumulative odds ratio of 1.5 for the NeuroAiD group, a two-sided test of 5% type I error and an expected 30% dropout rate after 2 years of follow-up for the 1,100 patients recruited into CHIMES, the 770 subjects with mRS data expected to be available at year 2 yields an 89% power to detect a difference in efficacy between NeuroAiD and placebo. CONCLUSIONS: This study will provide evidence for the longer-term efficacy of an initial course of a neurorestorative therapy after acute ischemic stroke of intermediate severity.

An exploratory study of ageing women's perception on access to health informatics via a mobile phone-based intervention.

OBJECTIVE: This is an exploratory study examining the perceived attitudes and readiness of women aged 50 years or older on adopting a mobile phone-based intervention named as Infohealth in Singapore. METHOD: Infohealth is designed as a health informatics to tailor personalized healthcare advice for the well-being for women - very little is known about the acceptability level of self-care technology, especially the older among the female population. To explore participants' perceptions and acceptance, a telephone survey was developed from concepts identified from various user acceptance theories and models. Correlation was used to identify significant dependent variables while partial least square and boot-strapping procedures were used to estimate the significance of the path coefficients. RESULTS: Analysis supports the validity and reliability of the 27-item research model consisting of 8 constructs. 700 women aged 50years and older responded to the survey. Findings show the extent of ageing women's existing dependency on others for help, regard for close ones whom they care for, opinion from family and friends, and guarding the health of people who are important for them do not directly affect the intention of using Infohealth, but are rather mediated by perceived usefulness. This study validated some ageing-specific and female-posited variables to suggest as main constructs in future innovation adoption studies about older women. Technological anxiety and perceived physical condition both have no direct relationship with perceived ease of use and usefulness, lifestyle and intention to use. CONCLUSION: Findings reinforced the significant roles of perceived usefulness and perceived ease of use, compatibility, and subjective norm in predicting the adoption intention of Infohealth among ageing women. More extensive statistical analysis is needed to discover more interesting findings while qualitative analysis can help to detect humanistic design opportunities.

Comparing statistical models to predict dengue fever notifications.

Dengue fever (DF) is a serious public health problem in many parts of the world, and, in the absence of a vaccine, disease surveillance and mosquito vector eradication are important in controlling the spread of the disease. DF is primarily transmitted by the female Aedes aegypti mosquito. We compared two statistical models that can be used in the surveillance and forecast of notifiable infectious diseases, namely, the Autoregressive Integrated Moving Average (ARIMA) model and the Knorr-Held two-component (K-H) model. The Mean Absolute Percentage Error (MAPE) was used to compare models. We developed the models using used data on DF notifications in Singapore from January 2001 till December 2006 and then validated the models with data from January 2007 till June 2008. The K-H model resulted in a slightly lower MAPE value of 17.21 as compared to the ARIMA model. We conclude that the models' performances are similar, but we found that the K-H model was relatively more difficult to fit in terms of the specification of the prior parameters and the relatively longer time taken to run the models.

Geographical variation in ambulance calls is associated with socioeconomic status.

OBJECTIVES: The main objective was to explore the relationship between socioeconomic status and the spatial distribution of ambulance calls, as modeled in the island nation of Singapore, at the Development Guide Plan (DGP) level (equivalent to census tracts in the United States). METHODS: Ambulance call data came from a nationwide registry from January to May 2006. We used a conditional autoregressive (CAR) model to create smoothed maps of ambulance calls at the DGP level, as well as spatial regression models to evaluate the relationship between the risk of calls with regional measures of socioeconomic status, such as household type and both personal and household income. RESULTS: There was geographical correlation in the ambulance calls, as well as a socioeconomic gradient in the relationship with ambulance calls of medical-related (but not trauma-related) reasons. For instance, the relative risk (RR) of medical ambulance calls decreased by a factor of 0.66 (95% credible interval [CrI] = 0.56 to 0.79) for every 10% increase in the proportion of those with monthly household income S$5000 and above. The top three DGPs with the highest risk of medical-related ambulance calls were Changi (RR = 29, 95% CrI = 24 to 35), downtown core (RR = 8, 95% CrI = 6 to 9), and Orchard (RR = 5, 95% CrI = 4 to 6). CONCLUSIONS: This study demonstrates the utility of geospatial analysis to relate population socioeconomic factors with ambulance call volumes. This can serve as a model for analysis of other public health systems.

The burden of diabetes mellitus in elderly patients from an Asian tertiary hospital.

SUMMARY: Diabetes mellitus (DM) has been declared as a global public health threat to society. However, the burden of the disease in elderly Asian patients has not been described. The aim of the study is to assess the disease burden of DM and its associated adverse outcomes in elderly patients from an Asian hospital using the hospital inpatient database. METHODS: Retrospective study of hospital discharge database from 2004 to 2008 to identify patients aged 65 years and above with DM and its associated 'adverse outcomes' using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. RESULTS: Of 89,875 hospitalized patients aged 65 years and above over the 5 years, 31,124 (34.6%) patients had DM, and the percentage of DM cases increased steadily from 34.3% to 35.6%. Prevalence of DM-associated adverse outcomes was higher in DM patients than in non-DM patients (53.8% vs. 31.5%, p<0.001). For trends over time, the adverse outcomes decreased in both DM patients (58.1% to 53.6%) and non-DM patients (34.3% to 31.4%, all p<0.001). All disease-specific adverse outcomes except renal disease decreased over time both in DM and non-DM patients (all p<0.05). There were increased trends over time for renal disease in both DM patients (16.1% to 23.2%, p<0.001) and non-DM patients (6.7% to 10.4%, p<0.001). CONCLUSION: The burden of DM in this group of elderly patients is high. Elderly patients with DM experienced much higher rates of the adverse outcomes.

Sample sizes for estimating differences in proportions--can we keep things simple?

Sample sizes for studies that aim to estimate differences in proportions are often calculated using a confidence interval approach. In particular, the methods advocated by Day ( 1988 ) and Bristol ( 1989 ), based on asymptotic normal approximations, are commonly used. We compare these to the Wilson score approach discussed by Newcombe ( 1998 ) and show, except for extreme values, that the Day method gives results close to those of Wilson score method, while that of Bristol is consistently higher. We argue that the asymptotic normal approximation approach of Day serves as a better guide for quick calculations of sample sizes.

Risk factors for lower extremity amputation among patients with diabetes in Singapore.

BACKGROUND: Among other risk factors, renal disease and ethnicity have been associated with diabetic lower extremity amputation (LEA) in Western populations. However, little is known about risk factors for LEA among Asian patients. OBJECTIVE: The objective was to assess the proportion of hospitalized patients with diabetes who have a LEA among all hospital patients with diabetes mellitus (DM) and to investigate risk factors for diabetic LEA (especially renal disease and ethnicity) using hospital discharge database. METHOD: A retrospective study of hospital discharge database (2004-2009) was performed to identify patients with DM, LEA and renal disease using the International Statistical Classification of Diseases and Related Health Problems, Ninth Revision, Australian Modification codes. RESULTS: Of 44 917 hospitalized patients with DM during the 6 years, 7312 (16.3%) patients had renal disease, and 1457 (3.2%) patients had LEA. DM patients with renal disease had significant higher rates of LEA (7.1%) compared to DM patients without renal disease (2.5%, P < .001). The differences were present for foot (2.7% vs. 1.2%), ankle or leg (2.8% vs. 0.9%), and knee or above amputation (1.6% vs. 0.4%, all P<.001). Malays had the highest rate of diabetic LEA (5.1%), followed by Indians (3.0%), Chinese (3.0%), and others (2.3%, P < .001). In logistic regression analyses, renal disease and ethnicity were significant predictors of diabetic LEA (renal disease: odds ratio 3.2, 95% confidence interval 2.8-3.6; ethnicity: odds ratio, 1.6, Malays vs. Chinese, P < .001; 1.0, Indians vs. Chinese, P = .784) after adjustment for age, gender, and year of discharge. CONCLUSION: DM patients with renal disease and Malay ethnicity had higher rates of LEA in this Asian patient population. Malay patients with DM and diabetic patients with renal disease should be considered as high-risk groups for LEA and therefore screened and monitored systematically.

Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria.

OBJECTIVE: To compare microvascular invasion (McVI) with parameters defined by the Milan criteria in predicting tumor recurrence and overall survival (OS) in patients with surgical resection (SR) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Although the Milan criteria is discriminatory for selecting patients with good outcomes in liver transplantation and SR for HCC, it neither adequately predict tumor recurrence nor explain differences in survival for patients with good liver function. McVI is a strong indicator of intrahepatic metastasis in HCC, but its relative significance for predicting clinical outcomes compared to the Milan criteria is unclear. METHODS: Patients undergoing SR with curative intent from January 2000 to March 2009 at the Singapore General Hospital were followed up for long-term outcomes till January 1, 2010. They were stratified first by the Milan criteria and then by the presence of McVI and compared relative to OS. RESULTS: Altogether, 454 of the 515 patients received curative SR. There were stratified into 4 groups (Milan+, McVI-), (Milan+, McVI+), (Milan-, McVI-), and (Milan-, McVI+). All pair-wise comparisons between groups relative to OS were significant except (Milan+, McVI-) (OS, 90%, 73%, and 60% at 1, 3, and 5 years) with (Milan-, McVI-) (OS, 86%, 71%, and 61% at 1, 3, 5 years) and (Milan+, McVI+) with (Milan-, McVI+). Multivariate Cox regression analysis showed that McVI was predictive of OS, after which Milan status did not add additional discriminative information. CONCLUSIONS: McVI is a better predictor of tumor recurrence and OS than the Milan criteria after SR for HCC. Assessment of McVI should aid in patient selection for adjuvant treatments to improve outcomes after SR.

Risk communication in clinical trials: a cognitive experiment and a survey.

BACKGROUND: A Royal Statistical Society Working Party recently recommended that "Greater use should be made of numerical, as opposed to verbal, descriptions of risk" in first-in-man clinical trials. This echoed the view of many clinicians and psychologists about risk communication. As the clinical trial industry expands rapidly across the globe, it is important to understand risk communication in Asian countries. METHODS: We conducted a cognitive experiment about participation in a hypothetical clinical trial of a pain relief medication and a survey in cancer and arthritis patients in Singapore. In part 1 of the experiment, the patients received information about the risk of side effects in one of three formats (frequency, percentage and verbal descriptor) and in one of two sequences (from least to most severe and from most to least severe), and were asked about their willingness to participate. In part 2, the patients received information about the risk in all three formats, in the same sequence, and were again asked about their willingness to participate. A survey of preference for risk presentation methods and usage of verbal descriptors immediately followed. RESULTS: Willingness to participate and the likelihood of changing one's decision were not affected by the risk presentation methods. Most patients indicated a preference for the frequency format, but patients with primary school or no formal education were indifferent. While the patients used the verbal descriptors "very common", "common" and "very rare" in ways similar to the European Commission's Guidelines, their usage of the descriptors "uncommon" and "rare" was substantially different from the EU's. CONCLUSION: In this sample of Asian cancer and arthritis patients, risk presentation format had no impact on willingness to participate in a clinical trial. However, there is a clear preference for the frequency format. The lay use of verbal descriptors was substantially different from the EU's.

Phase II clinical trials in oncology: are we hitting the target?

The number of novel and molecularly targeted agents in the last decade that need screening for preliminary efficacy in Phase II trials has increased. Many of these agents have a cytostatic mode of action that is difficult to assess using traditional Phase II designs. These new agents require detailed evaluation to optimize their dosing, to evaluate their effects on their target and to define early markers that predict for a definitive benefit. This review focuses on the options for Phase II trial designs. The different end points, single versus multiarm and randomized designs, the use of biomarkers and Bayesian approaches are also reviewed. The final design chosen will depend on the characteristics and circumstances of each individual study.

The effect of body mass on health-related quality of life among Singaporean adolescents: results from the SCORM study.

PURPOSE: To investigate the relationship between body mass and health-related quality of life (HRQOL) among Singaporean adolescents. Variation in this relationship by age, gender and ethnicity, and association of HRQOL with change in body mass over time and with demographic, socioeconomic and health variables were also assessed. METHODS: HRQOL was assessed for Singaporean adolescents aged 11-18 from their own (N=1,249) and their parent's (N=948) perspective using PedsQLTM 4.0 generic core scales. Body mass, measured as body mass index z-score based on the WHO Reference 2007, was categorized as thin, healthy weight, overweight and obese. Multiple linear regression models assessed the relationship between current body mass and HRQOL, adjusting for demographic, socioeconomic and health variables. Differences between adolescent and parent-proxy reported HRQOL were also investigated. RESULTS: Obese adolescents (and their parents) reported significantly lower HRQOL, overall and in most domains, compared to healthy weight adolescents. Parents tended to report lower HRQOL for their adolescents than the adolescents did themselves; however, this difference was much larger and statistically significant for obese adolescents. CONCLUSIONS: Obesity is associated with reduced HRQOL among adolescents. The effect in these Singaporean adolescents is similar to that in populations with higher rates of obesity. Awareness of this relationship can make it easier for health professionals, teachers, parents and peers to be supportive of obese adolescents.