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 (Y) 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.

Surgical resection offers good overall survival for patients with HCC within the Milan criteria and with good liver function, although recurrence rates remain high. Outcomes have tended to improve in more recent years.

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Our objective was to determine the association between temperature, humidity, rainfall and dengue activity in Singapore, after taking into account lag periods as well as long-term climate variability such as the El Niño Southern Oscillation Index (SOI). We used a Poisson model which allowed for autocorrelation and overdispersion in the data. We found weekly mean temperature and mean relative humidity as well as SOI to be significantly and independently associated with dengue notifications. There was an interaction effect by periods of dengue outbreaks, but periods where El Niño was present did not moderate the relationship between humidity and temperature with dengue notifications. Our results help to understand the temporal trends of dengue in Singapore, and further reinforce the findings that meteorological factors are important in the epidemiology of dengue.

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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 CLTrelated 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. (HEPATOLOGY 2015;61:227-237) H epatocellular carcinoma (HCC) is a common cancer with a higher disease burden in East Asia due to the prevalence of chronic viral hepatitis in the region. 8 Emerging data show improving trends in LR outcomes, possibly due to better patient selection, postoperative management, and multimodality treatment for recurrences.9 While recurrence rates in LT are often lower than LR, LT faces considerable resource challenges in many countries, such as the limited supply of cadaveric transplant organs, leading to cancer progression during long waiting times that limit intention-to-treat survival for LT.10 LT patients also require long-term immune suppression, with attendant risks and significant lifetime costs.Randomized trials comparing the two treatments are neither ethical nor practical. Due to the large financial outlay and recurrent costs needed to run a liver transplant program for a large number of HCC patients, 11 the decision to adopt either therapy as a first-line option carries major implications with respect to costs, utility of scarce re...

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Confidence intervals (CI) are a key output of many statistical analyses, and have a critical role to play in the interpretation of estimates of parameters. Although they are commonly used, CIs are often misunderstood and incorrectly interpreted. In this article, we discuss how CIs should correctly be interpreted and also highlight some common misunderstandings associated with them. RelaTIonshIp beTween ConfIdenCe InTeRvals and p-valuesCIs and p-values are closely related although they provide different information. While p-values are the outcome of hypothesis tests and indicate whether or not the sample data provide sufficient evidence to reject the null hypothesis (e.g. whether an observed difference between 2 treatments is because the 2 treatments really have different levels of efficacy, or whether it is due to random chance), CIs describe how uncertain our estimated difference is. Simply, CI indicates whether the estimate is a precise one or only a very "rough" estimate. For example, if the objective of a study is to test whether there is a difference in systolic blood pressure between 2 groups of people, the p-value only tells if there is a statistically "significant" or statistically "non-significant" difference in the systolic blood pressure between the 2 groups. It does not provide an estimate of what this difference is. To get such an estimate, we need to compute the mean difference in the systolic blood pressure, along with the associated CI, which tells us how precise (i.e. how "good") this estimate is in predicting the population level. A narrower CI will indicate a more precise estimate, while a wider CI indicates a less precise estimate.If the 95% CI for the DIFFERENCE between the 2 groups contains the value 0, this means that the p-value will be greater than 0.05. Conversely, if the 95% CI does not contain the value 0, then the p-value will be strictly less than 0.05. The same applies when comparing groups using a ratio, such as an odds ratio or risk ratio. When using a RATIO instead of a DIFFERENCE, the situation of no difference between the 2 groups will be indicated by a value of 1 instead of 0. If the ratio equals to 1, the 2 groups are equal. Hence, if the 95% CI of the ratio contains the value 1, the p-value will be greater than 0.05. Alternatively, if the 95% CI does not contain the value 1, the p-value is strictly less than 0.05. Many values of ConfIdenCe InTeRvals and how To CalCulaTe ConfIdenCe InTeRvalsCIs can be presented as 90% CI, 95% CI, 99% CI or any percentage (between 0% and 100%) CI of interest. Although 95% CI are commonly used in many applications, the choice of whether to use a 90% or 95% CI is somewhat arbitrary, and depends on the level of "confidence" that the investigator wishes to convey in his or her estimate. The calculation method of the CI depends on the estimate of interest (mean, median, proportion, odds ratio, etc). Typically, the expression of a CI for a mean will be: [(sample mean) -(constant) x (SEM)] to [(sample mean) + (constant) x (SEM)] )where "constant" tak...