Intervention Effects in the Case of Heterogeneity between Three Subgroups

Saddlepoint methods provide quick and easy approximations to significance levels for conditional tests of logistic regression parameters. We evaluate the accuracies of saddlepoint approximations for three well-known conditional tests: Bartlett's test for no three-factor interaction in a 2 x 2 x 2 table, the test for trend in a series of probabilities, and the exact test of no association in stratified 2 x 2 tables with a common odds ratio. General recommendations are suggested regarding the use of saddlepoint approximations for exact conditional significance levels.

7501 Background: The proven efficacy of E in advanced NSCLC warranted its evaluation in the adjuvant setting. BR.21 data suggested pts with EGFR positive tumors (IHC/FISH) were more likely to benefit from E. Methods: Completely resected IB-IIIA NSCLC pts were randomized 2:1 to receive E 150 mg qd or P for 2 years. Pts were stratified according to stage, histology, prior adjuvant chemotherapy, smoking status, EGFR FISH status, and country. The primary endpoint was disease free survival (DFS) in the full analysis set (FAS). Secondary endpoints included overall survival (OS) in the FAS and DFS and OS in the EGFR mutation (EGFR M+) subset (del19/L858R). Hierarchical testing procedure was used. Results: Between NOV 2007 and JUL 2010, 973 pts were randomized. Baseline characteristics were balanced between arms (age > 65 41%; female 41%; stage IB 51%, II 33%, IIIA 16% [AJCC 6th ed]; adenocarcinoma 59%; prior adjuvant chemotherapy 53%; never smoker 20%; Asian 17%; EGFR FISH+ 72% and EGFR M+ 16.5%). The planned number of events (410) for the final DFS analysis was reached in APR 2013; 277 (28%) pts had died. Median follow-up was 47 months (m). No statistically significant difference in DFS was observed in FAS; hierarchical testing rendered all secondary endpoints non-significant. The median treatment duration was 12 m for E and 22 m for P in FAS. Rash and diarrhea occurred in 58% and 52% pts for E vs 17% and 16% for P. Grade ≥3 rash and diarrhea occurred in 12.6% and 6.2% pts for E vs 0.3% and 0.3% for P. No drug-related adverse events led to death. Conclusions: Adjuvant E did not prolong DFS in the overall population. Further investigation in EGFR M+ pts is warranted. The safety profile of E was consistent with that in advanced disease. Clinical trial information: NCT00373425. Full analysis set. Median (m) HR (95% CI) P value E (N=623) P (N=350) DFS 50.5 48.2 0.90 (0.741-1.104) 0.3235 OS NR NR 1.13 (0.881-1.448) 0.3350 EGFR M+ subset Median (m) HR (95% CI) P value E (N=102) P (N=59) DFS 46.4 28.5 0.61 (0.384-0.981) 0.0391* OS NR NR 1.09 (0.545-2.161) 0.8153 Abbreviations: HR, hazard ratio; NR, not reached. *Not significant due to hierarchical testing.

In patients with venous thromboembolism at high risk of recurrence for whom extended treatment with direct oral anticoagulants has been indicated, the optimal dose is unknown. We aimed to assess efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants in patients in whom extended anticoagulation has been indicated. RENOVE was a non-inferiority, investigator-initiated, multicentre, randomised, open-label, blinded endpoint trial done in 47 hospitals in France. Ambulatory patients aged 18 years or older with acute symptomatic venous thromboembolism (pulmonary embolism or proximal deep vein thrombosis) who had received 6-24 uninterrupted months of full-dose anticoagulation and for whom extended anticoagulation has been indicated were eligible. Eligible participants were categorised as having either a first unprovoked venous thromboembolism, recurrent venous thromboembolism, presence of persistent risk factors, or other clinical situations considered to be a high risk of recurrence. Participants were randomly assigned (1:1) to receive oral treatment with either a reduced dose of apixaban (2·5 mg twice daily) or rivaroxaban (10 mg once daily) or a full dose of apixaban (5 mg twice daily) or rivaroxaban (20 mg once daily) using a centralised randomisation procedure with an interactive web response system. The sequence generation method was a computerised random number generator and was balanced by blocks of different sizes. Randomisation was stratified by centre, type of direct oral anticoagulant, and antiplatelet drug. Physicians and participants were unmasked to treatment allocation; recurrent venous thromboembolism, clinically relevant bleeding, and all-cause death were adjudicated by an independent committee blinded to treatment allocation. The primary outcome was symptomatic recurrent venous thromboembolism, including recurrent fatal or non-fatal pulmonary embolism or isolated proximal deep vein thrombosis (non-inferiority hypothesis 90% power to exclude a hazard ratio [HR] of 1·7). The primary outcome and first two secondary outcomes were included in a hierarchical testing procedure. This trial is registered with ClinicalTrials.gov, NCT03285438. From Nov 2, 2017, to July 6, 2022, 2768 patients were enrolled and randomly assigned to the reduced-dose group (n=1383) or the full-dose group (n=1385). 970 (35·0%) participants were female, 1797 (65·0%) were male, and one (<0·1%) had sex not reported. Median follow-up was 37·1 months (IQR 24·0-48·3). Recurrent venous thromboembolism occurred in 19 of 1383 patients in the reduced-dose group (5-year cumulative incidence 2·2% [95% CI 1·1-3·3]) versus 15 of 1385 patients in the full-dose group (5-year cumulative incidence 1·8% [0·8-2·7]; adjusted HR 1·32 [95% CI 0·67-2·60]; absolute difference 0·40% [95% CI -1·05 to 1·85]; p=0·23 for non-inferiority). Major or clinically relevant bleeding occurred in 96 patients in the reduced-dose group (5-year cumulative incidence 9·9% [95% CI 7·7-12·1]) and 154 patients in the full-dose group (5-year cumulative incidence 15·2% [12·8-17·6]; adjusted HR 0·61 [95% CI 0·48-0·79]). 1136 (82·1%) of 1383 patients in the reduced-dose group and 1150 (83·0%) of 1385 in the full-dose group had an adverse event; 374 (27·0%) patients in the reduced-dose group and 420 (30·3%) in the full-dose group has a serious adverse event. 35 (5-year cumulative incidence 4·3% [95% CI 2·6-6·0]) patients in the reduced-dose group and 54 (5-year cumulative incidence 6·1% [4·3-8·0]) patients in the full-dose group died during the study period. In patients with venous thromboembolism requiring extended anticoagulation, reduction of the direct oral anticoagulant dose did not meet the non-inferiority criteria. However, the low recurrence rates in both groups and substantial reduction of clinically relevant bleeding with the reduced dose could support this regimen as an option. Further research will be needed to identify subgroups for whom the anticoagulation dose should not be reduced. French Ministry of Health.

BackgroundAtopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates.MethodsThis is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter.DiscussionThis study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health.Trial registrationClinicalTrials.gov Identifier: NCT02537509, first received: 1 September 2015.

Meta-analysis plays an important role in the analysis and interpretation of clinical trials in medicine and of trials in the social sciences but is of importance in other fields (e.g., particle physics 1) as well. In 2001, Hartung and Knapp 2, 3 introduced a new approach to test for a nonzero treatment effect in a meta-analysis of k studies. Hartung and Knapp 2, 3 suggest to use the random effects estimate according to DerSimonian and Laird 4 and propose a variance estimator q so that the test statistics for the treatment effect is t distributed with k − 1 degrees of freedom. In their paper on dichotomous endpoints, results of a simulation study with 6 and 12 studies illustrate for risk differences, log relative risks and log odds ratios, the excellent properties regarding control of the type I error, and the achieved power 2. They investigate different sample sizes in each study, and different amounts of heterogeneity between studies and compare their new approach (Hartung and Knapp approach (HK)) with the fixed effects approach (FE) and the classical random effects approach by DerSimonian and Laird (DL). It can be clearly seen that, with increasing heterogeneity, the FE as well as the DL does not control the type I error rate, while the HK keeps the type I error rate in nearly every situation and in every scale. Advantages and disadvantages of the two standard approaches and respective test statistics have been extensively discussed (e.g., 5-7). While it is well known that the FE is too liberal in the presence of heterogeneity, the DL is often thought to be rather conservative because heterogeneity is incorporated into the standard error of the estimate for the treatment effect and this should lead to larger confidence intervals and smaller test statistics for the treatment effect (8 chapter 9.4.4.3). This was disproved among others by Ziegler and Victor 7, who observed in situations with increasing heterogeneity severe inflation of the type I error for the DerSimonian and Laird test statistic. Notably, the asymptotic properties of this approach will be valid, if both the number of studies and the number of patients per study are large enough (8 chapter 9.54, 9, 10). Although power issues of meta-analysis tests have received some interest, comparisons between the approaches and the situation with two studies were not the main interest 11, 12. Borenstein et al. (10, pp. 363/364) recommend the random effects approach in general for meta-analysis and do not recommend meta-analyses of small numbers of studies. However, meta-analyses of few and of even only two trials are of importance. In drug licensing in many instances, two successful phase III clinical trials have to be submitted as pivotal evidence for drug licensing 13, and summarizing the findings of these studies is required according to the International Conference on Harmonisation guidelines E9 and M4E (14, 15). It is stated that ‘An overall summary and synthesis of the evidence on safety and efficacy from all the reported clinical trials is required for a marketing application [...]. This may be accompanied, when appropriate, by a statistical combination of results’ (14, p. 31). For the summary, ‘The use of meta-analytic techniques to combine these estimates is often a useful addition, because it allows a more precise overall estimate of the size of the treatment effects to be generated, and provides a complete and concise summary of the results of the trials’ (14, p. 32). While in standard drug development, this summary will include usually more than two studies; in rare diseases for the same intervention, barely ever more than two studies are available because of the limited number of patients. Likewise, decision making in the context of health technology assessment is based on systematic reviews and meta-analyses. Often in practice, only two studies are considered homogeneous enough from clinical grounds to be included into a meta-analysis and then form the basis for decision making about reimbursement 16. Despite the fact that meta-analysis is non-experimental observational (secondary) research 17 and p-values should be interpreted with caution, meta-analyses of randomized clinical trials are termed highest-level information in evidence-based medicine and are the recommended basis for decision making 18. As statistical significance plays an important role in the assessment of the meta-analysis, it is mandatory to understand the statistical properties of the relevant methodology also in a situation, where only two clinical trials are included into a meta-analysis. We found Cochrane reviews including meta-analyses with two studies only, which are considered for evidence-based decision making even in the presence of a large amount of heterogeneity (I2≈75%) 19-21 We repeated the simulation study for dichotomous endpoints of Hartung and Knapp 2 with programs written in R 3.1.0 22 to compare the statistical properties of the FE, the DL, and the HK for testing the overall treatment effect θ (H0: θ = 0) in a situation with two to six clinical trials. We considered scenarios under the null and alternative hypothesis for the treatment effect with and without underlying heterogeneity. We present the findings for the odds ratio with pC=0.2 and did vary probability of success in the treatment group pT to investigate the type I error and the power characteristics. The total sample size per meta-analysis was kept constant in the different scenarios (n = 480) and n/k number of patients per study to clearly demonstrate the effect of the number of included studies on power and type I error of the various approaches. Likewise, we attempted to avoid problems with zero cell counts or extremely low event rates that may impact on type I error and power as well. I2 was used to describe heterogeneity because thresholds have been published (low: I2=25%, moderate: I2=50%, and high: I2=75%) 23 for the quantification of the degree of heterogeneity with this measure. We termed I2≤15% negligible, and this refers to simulations assuming no heterogeneity (i.e., the fixed effects model). Table 1 summarizes the results of our simulation study. The well-known anticonservative behavior of the FE and the DL in the presence of even low heterogeneity is visible for small numbers of studies in the meta-analysis. Particularly for the FE, the increase in the type I error is pronounced. With more than four studies even in situations with substantial heterogeneity, the HK perfectly controls the type I error. There is almost no impact on the power of the test in situations with no or low heterogeneity, and overall, it seems as if the only price to be paid for an increased heterogeneity is a reduced power of the test. This is in strong contrast to the situation with only two studies. Again, the HK perfectly controls the prespecified type I error. However, even in a homogeneous situation, the power of the meta-analysis test was lower than 15% in situations where the power of the FE and the DL approximates 70% and 60%, respectively. In the presence of even low heterogeneity with the HK, there is not much chance to arrive at a positive conclusion even with substantial treatment effects. Figure 1 summarizes the main finding of our simulation study with k = 2 and 6 studies impressively. In the homogeneous situation with two studies, the DL and even better the FE can be used to efficiently base conclusions on a meta-analysis. In contrast, already with mild to moderate heterogeneity, both standard tests severely violate the prespecified type I error, and there is a high risk of false positive conclusion with the classical approaches. This has major implications for decision making in drug licensing as well. We have noted previously that a meta-analysis can be confirmatory if a drug development program was designed to include a preplanned meta-analysis of the two pivotal trials 24. As an example, thrombosis prophylaxis was discussed in the paper by Koch and Röhmel 24, where venous thromboembolism is accepted as primary endpoint in the pivotal trials. In case when both pivotal trials are successful, they can be combined to demonstrate a positive impact on, for example, mortality. This can be preplanned as a hierarchical testing procedure: first, both pivotal trials will be assessed individually before confirmatory conclusions will be based on the meta-analysis. As explained, neither the FE, nor the DL, nor the HK can be the methodology to be recommended for a priori planning in this sensitive area unless any indication for heterogeneity is taken as a trigger not to combine studies in a meta-analysis at all. It is our belief that not enough emphasis has been given to this finding in the original paper and the important role of heterogeneity is not acknowledged enough in the discussion of findings from meta-analyses, in general. This work has been funded partly by the FP7-HEALTH-2013-INNOVATION-1 project Advances in Small Trials Design for Regulatory Innovation and Excellence (ASTERIX) Grant Agreement No. 603160. We thank the editors and reviewers for useful comments to tailor the main messages.

The "Paracetamol and Ibuprofen in Combination" (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events. In these pre-planned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between (a) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists (ASA) score, and type of anesthesia) and morphine consumption, and (b) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs (NSAIDs), and ASA score) and seriousadverse events. Test of interaction between age and the pairwise comparison between paracetamol 1g vs paracetamol 0.5g+ibuprofen 200mg (P=.009) suggested lower morphine consumption in patients >65years. However, post hoc analyses of related outcomes showed no interaction for this pairwise comparison. All other tests of interaction regarding both benefit and harm were not statistically significant. These pre-planned subgroup analyses did not suggest that patients in the investigated subgroups benefitted differently from a basic non-opioid analgesic regimen consisting of paracetamol and ibuprofen. Further, there was no evidence of subgroup heterogeneity regarding harm and use of ibuprofen. Because of reduced statistical power in subgroup analyses, we cannot exclude clinically relevant subgroup heterogeneity.

Aim and Objective:The objective of this study was to optimize the threshold for discrete cosine transform (DCT) coefficients for near-lossless compression of Tc-99 m Dimercaptosuccinic acid (DMSA) scan images using discrete cosine transformation.Materials and Methods:Two nuclear medicine (NM) Physicians after reviewing several Tc-99 m DMSA scan images provided 242 Tc-99 m DMSA scan images that had scar. These Digital imaging and communication in medicine (DICOM) images were converted in the Portable Network Graphics (PNG) format. DCT was applied on these PNG images, which resulted in DCT coefficients corresponding to each pixel of the image. Four different thresholds equal to 5, 10, 15, and 20 were applied and then inverse discrete cosine transformation was applied to get the compressed Tc-99 m DMSA scan images. Compression factor was calculated as the ratio of the number of nonzero elements after thresholding DCT coefficients to the number of nonzero elements before thresholding DCT coefficients. Two NM physicians who had provided the input images visually compared the compressed images with its input image, and categorized the compressed images as either acceptable or unacceptable. The quality of compressed images was also assessed objectively using the following eight image quality metrics: perception-based image quality evaluator, structural similarity index measure (SSIM), multiSSIM, feature similarity indexing method, blur, global contrast factor, contrast per pixel, and brightness. Pairwise Wilcoxon signed-rank sum tests were applied to find the statistically significant difference between the value of image quality metrics of the compressed images obtained at different thresholds and the value of the image quality metrics of its input images at the level of significance = 0.05.Results:At threshold 5, (1) all compressed images (242 out of 242 Tc-99 m DMSA scan images) were acceptable to both the NM Physicians, (2) Compressed image looks identical to its original image and no loss of clinical details was noticed in compressed images, (3) Up to 96.65% compression (average compression: 82.92%) was observed, and (4) Result of objective assessment supported the visual assessment. The quality of compressed images at thresholds 10, 15, and 20 was significantly better than that of input images at P < 0.0001. However, the number of unacceptable compressed images at thresholds 10, 15, and 20 was 6, 38, and 70, respectively.Conclusions:Up to 96.65%, near-losses compression of Tc-99 m DMSA images was found using DCT by thresholding DCT coefficients at a threshold value equal to 5.

This paper is divided into two parts. The significance tests investigated in Part I concern the population mean and are based on the quantity [(sample midrange)-(hypothetical mean)]/(sample range). The case in which the observations are a sample from a normal population is considered in detail. The tests investigated are summarized in Table 1. These tests are found to be very efficient for small samples (see Table 4, power efficiency is defined in section 3). An investigation of several extremely non-normal populations using the values of $D\alpha$ obtained for normality indicates that the significance level of the range-midrange test is not very sensitive to the requirement of normality for small samples (see Table 6). Also the tests of Table 1 can be applied without computation through the use of an easily constructed graph (see section 4). These properties suggest that the range-midrange test is preferable to the Student $t$-test and the analogue of the Student $t$-test using the sample range (see [1] and [2]) whenever the sample size is sufficiently small. Use of the range-midrange test for the case of normality was proposed by E. S. Pearson in [3], where properties of the test were experimentally investigated for the normal and certain non-normal populations. In Part II several significance tests for the mean are developed which have a specified significance level for the case of a sample from a normal population but whose significance level is bounded near the specified value under very general conditions, one of which is that the observations are from continuous symmetrical populations. Some of these tests are range-midrange tests. Table 2 contains a summary of the tests and their properties ($x_i = i$th largest observation, $i = 1, \cdots, n$; conditions $(D)$ are given in section 7).

Interactions between treatments and covariates in RCTs are a key topic. Standard methods for modelling treatment-covariate interactions with continuous covariates are categorisation or linear functions. Both approaches are easily criticised, but for different reasons. Multivariable fractional polynomial interactions, an approach based on fractional polynomials with the linear interaction model as the simplest special case, was proposed. Four variants of multivariable fractional polynomial interaction (FLEX1-FLEX4), allowing varying flexibility in functional form, were suggested. However, their properties are unknown, and comparisons with other procedures are unavailable. Additionally, we consider various methods based on categorisation and on cubic regression splines. We present the results of a simulation study to determine the significance level (probability of a type 1 error) of various tests for interaction between a binary covariate ('treatment effect') and a continuous covariate in univariate analysis. We consider a simplified setting in which the response variable is conditionally normally distributed, given the continuous covariate. We consider two main cases with the covariate distribution well behaved (approximately symmetric) or badly behaved (positively skewed). We construct nine scenarios with different functional forms for the main effect. In the well-behaved case, significance levels are in general acceptably close to nominal and are slightly better for the larger sample size (n = 250 and 500 were investigated). In the badly behaved case, departures from nominal are more pronounced for several approaches. For a final assessment of these results and recommendations for practice, a study of power is needed.

The study assessed agricultural land use change and food security linkage in Nigeria from 1981 to 2023. The study adopted a historical survey design using time series data spanning the period of 43 years from 1981 to 2023.Data on the variables were collected from the archives of World Bank and Food and Agriculture Organization database and analyzed using descriptive statistics such as mean, maximum and minimum with trend graphs, Autoregressive distributed lag model (ARDL) after testing for unit root, granger causality test and Autoregressive Moving Average (ARIMA) model. The Augmented Dickey-Fuller (ADF) test for unit roots indicated that agricultural land use change is integrated of order one, I(1), while food security is integrated of order two, I(2). This suggests that both variables follow a random walk, meaning their future values do not revert to their past values. The results from the Bound test for a long-run relationship between agricultural land use change and food security showed that the F-statistic value of 4.676068 exceeds the upper critical bound of 4.35 at the 5% significance level, confirming a long-run relationship between the two variables. Additionally, the pairwise Granger causality test revealed a significant causal link between agricultural land use change and food security. The trend forecast indicated that over the next decade, agricultural land use change is expected to follow a downward trend, while food security is projected to increase, assuming other factors remain constant. Based on these findings, the study suggests that the government should implement comprehensive food security monitoring systems to track changes in land use and food security indicators. Early warning systems could prove valuable in predicting and addressing potential food security challenges, particularly in light of declining agricultural productivity.

Push-out bond strength of CAD/CAM-ceramic luted to dentin with self-adhesive resin cements

PERFORMANCE OF HIGH-SPEED DENTAL HANDPIECES SUBJECTED TO SIMULATED CLINICAL USE AND STERILIZATION

A dataset is presented of an experiment that was conducted to compare the proportions of males obtained from hormonal sex reversed pure strain of Oreochromis shiranus and from interspecific hybridization of O.karongae male x O. shiranus female. Part of the data in the dataset were published in a journal article https://doi.org/10.1016/j.aqrep.2020.100274. The data were generated from four SETs of treatments of an experiment that was conducted at the National Aquaculture Center, in Malawi. The first SET of treatment comprised hybrids from interspecific crossing of O.karongae male and O. shiranus female in a pond based breeding hapa 1. SETs 2 and 4 were for fry from hapa spawned pure cross of O.shiranus males and females in a pond based breeding hapa 2. SET 3 comprised fry from pure cross of O. shiranus males and females under controlled temperature (27°C) in an indoor re-circulatory hatchery (Tables 1 to 4). During the first part of the experiment, the fry was raised for 28 days in tanks at three replicates and was fed a fry formulated feed containing 38% crude protein, three times a day. However, for SETs 2 and 3, the feed contained 17α-methyl testosterone at 60mg/kg of feed. The second part of the experiment involved growth performance testing of fry in each SET. The growth experiment was conducted in rearing hapas that were inserted in a common pond for a period of 70 days. The body weight data were collected every 14 days (Tables 1 to 4). On the 70th day, the proportions of males and females in the four SETs was determined using Aceto-carmine staining method (Table 5). The pictures of the stained male and female gonads under compound microscope are presented in the published journal article at https://doi.org/10.1016/j.aqrep.2020.100274. Dataset presented in this paper is for body weights of fish from day 0 to day 70 and proportion of males and females in each SET on the 70th day of the experiment (Tables 1, 2, 3, 4 and 5). The data were analyzed using SPSS version 20.0. Chi-square goodness of fit test was used to investigate if the observed sex ratios significantly deviated from the expected sex ratios at 5% level of significance. The differences among fish body weights were determined using Analysis of Variance and significantly different means were separated using Duncan's multiple range test at the 5% test level of significance. These data are useful for various stakeholders that are interested in sexing juvenile tilapia and for scientists that conduct tilapia sex reversal experiments. This data can also guide hatchery managers during commercial production of all male tilapias which grow faster than those in the mixed sex tilapia culture.

Clinical trial investigators often record a great deal of baseline data on each patient at randomization. When reporting the trial's findings such baseline data can be used for (i) subgroup analyses which explore whether there is evidence that the treatment difference depends on certain patient characteristics, (ii) covariate-adjusted analyses which aim to refine the analysis of the overall treatment difference by taking account of the fact that some baseline characteristics are related to outcome and may be unbalanced between treatment groups, and (iii) baseline comparisons which compare the baseline characteristics of patients in each treatment group for any possible (unlucky) differences. This paper examines how these issues are currently tackled in the medical journals, based on a recent survey of 50 trial reports in four major journals. The statistical ramifications are explored, major problems are highlighted and recommendations for future practice are proposed. Key issues include: the overuse and overinterpretation of subgroup analyses; the underuse of appropriate statistical tests for interaction; inconsistencies in the use of covariate-adjustment; the lack of clear guidelines on covariate selection; the overuse of baseline comparisons in some studies; the misuses of significance tests for baseline comparability, and the need for trials to have a predefined statistical analysis plan for all these uses of baseline data.

BackgroundEvidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects.MethodsWe aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26).ResultsWomen with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% lower myocardial MRGlu value (P = 0.04) and women with T2DM a 74% lower value (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% lower myocardial MRGlu value (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association.ConclusionsOur data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.