Estimating the False Discovery Rate Using Mixed Normal Distribution for Identifying Differentially Expressed Genes in Microarray Data Analysis

The recent development of DNA microarray technology allows us to measure simultaneously the expression levels of thousands of genes and to identify truly correlated genes with anticancer drug response (differentially expressed genes) from many candidate genes. Significance Analysis of Microarray (SAM) is often used to estimate the false discovery rate (FDR), which is an index for optimizing the identifiability of differentially expressed genes, while the accuracy of the estimated FDR by SAM is not necessarily confirmed. We propose a new method for estimating the FDR assuming a mixed normal distribution on the test statistic and examine the performance of the proposed method and SAM using simulated data. The simulation results indicate that the accuracy of the estimated FDR by the proposed method and SAM, varied depending on the experimental conditions. We applied both methods to actual data comprised of expression levels of 12,625 genes of 10 responders and 14 non-responders to docetaxel for breast cancer. The proposed method identified 280 differentially expressed genes correlated with docetaxel response using a cut-off value for achieving FDR <0.01 to prevent false-positive genes, although 92 genes were previously thought to be correlated with docetaxel response ones

Effects of a self-management program on antiemetic-induced constipation during chemotherapy among breast cancer patients: a randomized controlled clinical trial.

Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, -3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy

Railway suicide attempts are associated with amount of sunlight in recent days.

Background:To assess the relationship between hours of sunlight and railway suicide attempts, 3-7 days before these attempts.Methods:All railway suicide attempts causing railway suspensions or delays of 30 min or more between 2002 and 2006. We used a linear probability model to assess this relationship. This study was conducted at Tokyo, Kanagawa, and Osaka prefectures in Japan. Data were collected from the railway delay incident database of the Japanese Railway Technical Research Institute and public weather database of the Japan Meteorological Agency.Results:About 971 railway suicides attempts occurred between 2002 and 2006 in Tokyo, Kanagawa, and Osaka. Less sunlight in the 7 days leading up to the railway suicide attempts was associated with a higher proportion of attempts (p=0.0243). Sunlight over the 3 days before an attempt had a similar trend (p=0.0888). No difference was found in sunlight hours between the days with (median: 5.6 [IQR: 1.1-8.8]) and without (median: 5.7 [IQR: 1.0-8.9]) railway suicide attempts in the evening. Finally, there was no apparent correlation between the railway suicide attempts and the monthly average sunlight hours of the attempted month or those of a month before.Limitations:Railway suicides were not the main suicidal methods in Japan,Conclusions:We observed an increased proportion of railway suicide attempts after several days without sunlight. Light exposure (blue light or bright white light) in trains may be useful in reducing railway suicides, especially when consecutive days without sunshine are forecasted

Group cognitive behavioural therapy (GCBT) versus treatment as usual (TAU) in the treatment of irritable bowel syndrome (IBS): A study protocol for a randomized controlled trial

Background: Irritable bowel syndrome (IBS) is a common disease that affects the quality of life (QOL) and social functioning of sufferers. Visceral anxiety is currently considered a key factor in the onset and exacerbation of IBS, and cognitive-behavioural therapy (CBT) targeting visceral anxiety is thought to be effective. However, access to CBT is limited due to the lack of trained therapists, the substantial time required for therapy and the associated costs. Group CBT (GCBT) may solve some of these problems. We have therefore planned this trial to examine the efficacy of GCBT for IBS. Methods: The trial is a two-armed, parallel group, open label, stratified block randomized superiority trial. The study group will consist of 112 participants (aged 18–75 years) with IBS (Rome-III or IV criteria). Participants will be randomly allocated 1:1 to (i) the intervention group: ten-week GCBT plus treatment as usual (TAU) or (ii) the control group: waiting list (WL) plus TAU. The co-primary outcomes are the change in IBS severity or disease-specific quality of life from baseline to week 13 which is 1 month after the end of treatment. The efficacy of GCBT for IBS will be examined through mixed-effects repeated-measures analysis. Discussion: GCBT, if found effective, can address the issues of the shortage of therapists as well as the time required and the costs associated with individual CBT. Clinically, the findings will help make effective CBT programmes accessible to a large number of distressed IBS patients at lower costs. Theoretically, the results will clarify the relationship between IBS and psychological stress and will help elucidate the underlying mechanisms of IBS. Trial registration: UMIN, CTR-UMIN000031710. Registered on March 13, 2018

Group-Sequential Strategies in Clinical Trials with Multiple Co-Primary Outcomes.

We discuss the decision-making frameworks for clinical trials with multiple co-primary endpoints in a group-sequential setting. The decision-making frameworks can account for flexibilities such as a varying number of analyses, equally or unequally spaced increments of information and fixed or adaptive Type I error allocation among endpoints. The frameworks can provide efficiency, i.e., potentially fewer trial participants, than the fixed sample size designs. We investigate the operating characteristics of the decision-making frameworks and provide guidance on constructing efficient group-sequential strategies in clinical trials with multiple co-primary endpoints

Which is more generalizable, powerful and interpretable in meta-analyses, mean difference or standardized mean difference?

Background: To examine empirically whether the mean difference (MD) or the standardised mean difference (SMD) is more generalizable and statistically powerful in meta-analyses of continuous outcomes when the same unit is used. Methods: From all the Cochrane Database (March 2013), we identified systematic reviews that combined 3 or more randomised controlled trials (RCT) using the same continuous outcome. Generalizability was assessed using the I-squared (I2) and the percentage agreement. The percentage agreement was calculated by comparing the MD or SMD of each RCT with the corresponding MD or SMD from the meta-analysis of all the other RCTs. The statistical power was estimated using Z-scores. Meta-analyses were conducted using both random-effects and fixed-effect models. Results: 1068 meta-analyses were included. The I2 index was significantly smaller for the SMD than for the MD (P < 0.0001, sign test). For continuous outcomes, the current Cochrane reviews pooled some extremely heterogeneous results. When all these or less heterogeneous subsets of the reviews were examined, the SMD always showed a greater percentage agreement than the MD. When the I2 index was less than 30%, the percentage agreement was 55.3% for MD and 59.8% for SMD in the random-effects model and 53.0% and 59.8%, respectively, in the fixed effect model (both P < 0.0001, sign test). Although the Z-scores were larger for MD than for SMD, there were no differences in the percentage of statistical significance between MD and SMD in either model. Inclusions: The SMD was more generalizable than the MD. The MD had a greater statistical power than the SMD but did not result in material differences