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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The singapore 5-Fluorouracil trabeculectomy study: effects on intraocular pressure control and disease progression at 3 years.

PURPOSE: To report 3-year results of a randomized, controlled trial comparing the use of a single application of 5-fluorouracil (5-FU) with placebo in trabeculectomy surgery. DESIGN: Prospective, randomized, double-blinded treatment trial. PARTICIPANTS: Two hundred forty-three Asian patients with primary open-angle or primary angle-closure glaucoma undergoing primary trabeculectomy. METHODS: One eye of each patient was randomized to receive either intraoperative 5-FU or normal saline (placebo) during trabeculectomy. MAIN OUTCOME MEASURES: Primary outcome measure was the level of intraocular pressure (IOP). Secondary outcomes were progression of visual field loss, rates of adverse events, and interventions after surgery. RESULTS: Of the 288 eligible patients, 243 were enrolled and 228 completed 3 years follow-up; 120 patients received 5-FU and 123 received placebo. Trial failure, according to predefined IOP criteria, was lower in the 5-FU group compared with the placebo group, although the difference was only significant with a failure criterion of IOP >17 mmHg (P = 0.0154). There was no significant difference in progression of optic disc and/or visual field loss over 36 months between 5-FU and placebo (relative risk [RR], 0.67; 95% confidence interval [CI], 0.34-1.31; P = 0.239). Uveitis occurred more often in the 5-FU-treated group (14/115 [12%] vs 5/120 [4%]; P = 0.032). CONCLUSIONS: This is the first masked, prospective, randomized trial reporting the effect of adjunctive 5-FU in trabeculectomy surgery in an East Asian population. The trial shows that an increased success rate can be achieved for several years after a single intraoperative treatment with 5-FU. We conclude that 5-FU is relatively safe and can be routinely used in low-risk East Asian patients. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Can external and subjective information ever be used to reduce the size of randomised controlled trials?

In the design of randomised trials in rare cancers, a Bayesian approach has been advocated, which allows for external and subjective information to be formally incorporated. We explore whether this can be extended more generally to allow for smaller trials to be conducted using a case study involving a trial of nasopharyngeal carcinoma. The external information available at various points during the trial is first summarised in the form of 'prior distributions'. Each of these is then combined with the accumulated data from the trial at that point in time to form 'posterior distributions', from which conclusions are drawn. We have argued that such a framework for the design, analysis and interpretation of a randomised trial in the light of external evidence is particularly useful in situations such as trials in rare cancers. But more generally, it may potentially also allow for smaller trials to be conducted. Although, at this point in time, we are hesitant to recommend the full implementation of the Bayesian methodology to modify the (conventionally) planned trial size we submit that a formal synthesis of the external evidence bearing on the question of concern is a valuable exercise in itself.

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.

Confirmation of double-peaked time distribution of mortality among Asian breast cancer patients in a population-based study.

INTRODUCTION: Double-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone. These are thought to reflect accelerated tumour growth at micrometastatic sites mediated by angiogenesis after primary tumour removal as well as tumor dormancy. Similar data are not available for Asian populations. We sought to investigate whether differences exist in the pattern of mortality hazard function between Western breast cancer patients and their Asian counterparts in Singapore, which may suggest underlying differences in tumor biology between the two populations. METHODS: We performed a retrospective cohort study of female unilateral breast cancer patients diagnosed in Singapore between October 1994 and June 1999. Data regarding patient demographics, tumour characteristics and death were available. Overall survival curves were calculated using the Kaplan-Meier method. The hazard rate was calculated as the conditional probability of dying in a time interval, given that the patient was alive at the beginning of the interval. The life table method was used to calculate the yearly hazard rates. RESULTS: In the 2,105 women identified, 956 patients (45.4%) had mastectomy alone. Demographic characteristics were as follows: 86.5% were Chinese, 45.2% were postmenopausal, 38.9% were hormone receptor positive, 54.6% were node negative and 44.1% had high histological grade. We observed a double-peaked mortality hazard pattern, with a first peak in mortality achieving its maximum between years 2 and 4 after mastectomy, and a second large peak in mortality during year 9. Analyses by subgroups revealed a similar pattern regardless of T stage, or node or menopausal status. This pattern was also noted in high-grade tumors but not in those that were well to moderately differentiated. The double-peaked pattern observed in Singaporean women was quantitatively and qualitatively similar to those reported in Western series. CONCLUSION: Our study confirms the existence of a double-peaked process in Asian patients, and it gives further support to the tumour dormancy hypothesis after mastectomy.

A cohort study of incident myopia in Singaporean children.

PURPOSE: To determine the risk factors of incident myopia in a school-based cohort study in Singaporean children. METHODS: A 3-year prospective cohort study was conducted in Singaporean school children aged 7 to 9 years in three schools at entry. Chinese children without myopia at baseline (n = 994) were included in the analysis. The main outcome was incident myopia, defined as spherical equivalent (SE) at least -0.75 D based on cycloplegic autorefraction. Other definitions of incident myopia, at least -0.5 D and at least -1.0 D, were also assessed. RESULTS: After controlling for school, age, gender, income, reading in books per week and intelligence quotient (IQ) test scores, we found the relative risk (RR) of incident myopia defined as -0.75 D to be 1.55 (95% confidence interval [CI] 1.18-2.04) for two versus no myopic parents. The multivariate RR of myopia for IQ in the third versus first tertile was 1.50 (95% CI, 1.19-1.89). However, the RR of incident myopia was 1.01 (95% CI, 0.97-1.05) for every unit increase in books read per week. Similar results were obtained with definitions of -0.5 and -1.0 D for incident myopia. CONCLUSIONS: These data provide new prospective evidence of essential links between parental myopia, IQ scores and subsequent myopia development. However, reading in books per week was not associated with incident myopia.

The journal impact factor: too much of an impact?

INTRODUCTION: The journal impact factor is often used to judge the scientific quality of individual research articles and individual journals. Despite numerous reviews in the literature criticising such use, in some countries the impact factor has become an outcome measure for grant applications, job applications, promotions and bonuses. The aim of this review is to highlight the major issues involved with using the journal impact factor as a measure of research quality. METHODS: A literature review of articles on journal impact factors, science citation index, and bibliometric methods was undertaken to identify relevant articles. RESULTS: The journal impact factor is a quantitative measure based on the ratio between yearly citations in a particular journal to total citations in that journal in the previous 2 years. Its use as a criterion for measuring the quality of research is biased. The major sources of bias include database problems from the Institute for Scientific Information and research field effects. The journal impact factor, originally designed for purposes other than the individual evaluation of research quality, is a useful tool provided its interpretation is not extrapolated beyond its limits of validity. CONCLUSION: Research quality cannot be measured solely using the journal impact factor. The journal impact factor should be used with caution, and should not be the dominant or only factor determining research quality.

Bayesian designs with frequentist and Bayesian error rate considerations.

So far, most Phase II trials have been designed and analysed under a frequentist framework. Under this framework, a trial is designed so that the overall Type I and Type II errors of the trial are controlled at some desired levels. Recently, a number of articles have advocated the use of Bayesian designs in practice. Under a Bayesian framework, a trial is designed so that the trial stops when the posterior probability of treatment is within certain prespecified thresholds. In this article, we argue that trials under a Bayesian framework can also be designed to control frequentist error rates. We introduce a Bayesian version of Simon's well-known two-stage design to achieve this goal. We also consider two other errors, which are called Bayesian errors in this article because of their similarities to posterior probabilities. We show that our method can also control these Bayesian-type errors. We compare our method with other recent Bayesian designs in a numerical study and discuss implications of different designs on error rates. An example of a clinical trial for patients with nasopharyngeal carcinoma is used to illustrate differences of the different designs.

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.

IQ and the association with myopia in children.

PURPOSE: To evaluate the association between intelligence and myopia in children. METHODS: Cycloplegic refraction and ocular biometry parameters, including axial length, vitreous chamber depth, lens thickness, anterior chamber depth, and corneal curvature were obtained in 1204 Chinese school children aged 10 to 12 years from three schools who were participants in the Singapore Cohort Study Of the Risk Factors for Myopia (SCORM). Intelligence quotient (IQ) was assessed using the nonverbal Raven Standard Progressive Matrix test. RESULTS: After controlling for age, gender, school, parental myopia, father's education, and books read per week, myopia (spherical equivalent [SE]) of at least -0.5 D was associated with high nonverbal IQ (highest quartile) versus low IQ (lowest quartile) (odds ratio = 2.4; 95% confidence interval, 1.7-3.4). Controlling for the same factors, children with higher nonverbal IQ scores had significantly more myopic refractions (-1.86 D for children with nonverbal IQ in the highest quartile compared with -1.24 D for children with nonverbal IQ in the lowest quartile; P = 0.002) and longer axial lengths (24.06 mm versus 23.80 mm; P = 0.022). Nonverbal IQ accounted for a greater proportion of the variance in refraction compared with books read per week. CONCLUSIONS: Nonverbal IQ may be an independent risk factor of myopia, and this relationship may not be explained merely by increased reading (books per week) among myopes. An interesting observation is that nonverbal IQ may be a stronger risk factor for myopia compared with books read per week. The complexity of the relationships between nonverbal IQ, reading, and myopia warrant additional studies to clarify any cause-effect relationship.