Research progress of mechanism of acupuncture for migraine. / é’ˆåˆºæ²»ç–—åå¤´ç—›çš„æœºåˆ¶ç ”ç©¶è¿›å±•.

The literature regarding the action mechanism of acupuncture for migraine published from 2013 to 2023 was searched in China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese Science and Technology Periodical Database, PubMed, Medline, and Cochrane Library. The pathogenesis of migraine and potential mechanisms of acupuncture treatment were summarized from the aspects of trigeminovascular system (TGVS), metabolic-related mechanisms, genetic factors, and alterations in brain structure and function. The results revealed that current research on the mechanisms of acupuncture for migraine predominantly centered around the TGVS, with studies confirming the specific regulatory effects of acupuncture on trigeminal system-related components, such as cortical spreading depression (CSD), astrocytes, and neurogenic kinin. While metabolic-related mechanisms and genetic factors are gaining attention, further in-depth exploration is needed to fully understand their roles in the mechanism of acupuncture for migraine. The study of brain structure and function in migraine has advanced, albeit with some controversies. Future research should prioritize larger sample sizes and standardized study designs to delve deeper into the mechanisms of acupuncture in treating migraine.

A framework for sample size calculations in longitudinal surveys to measure net and gross changes.

In longitudinal surveys, repeated measurements are collected from the same sample units over time to measure gross change (i.e., change at the level of individual sample members). Longitudinal samples are sometimes supplemented by fresh sample to measure net change (i.e., change at the aggregate level). That is, in each measurement wave, while one part of the sample is newly recruited (fresh), another part overlaps with previously interviewed sample (repeated interviews). Many aspects of survey design of longitudinal surveys have been studied extensively, such as definition of target population, sample design, survey weighting, intervals between interviews, nonresponse, and panel attrition. Although the impact of the overlap between samples on the statistical power has been studied, sample size determination lacks a formulation that takes account of these factors in longitudinal surveys that aim to measure net and gross changes simultaneously. In this study, we propose a framework for sample size calculation to measure net and gross changes in estimated means or proportions concurrently in longitudinal surveys. We present a framework to compute panel and fresh sample sizes for varying levels of net and gross change. Finally, we illustrate the framework using nchange, an R package we developed to execute the algorithm of the proposed framework. The framework and the R package will support researchers to determine sample sizes targeting specific power of analysis with respect to measuring net and gross changes in rotating- or split-panel surveys.

Comparison of Effectiveness of Moringa Oleifera Leaves Extract Gel (2%) with Retino A (0.1%) Cream for Treatment of Oral Leukoplakia: Double Blinded Randomized Control Trial.

AIM: The study aims to evaluate and compare the efficacy of Moringa oleifera leaf extract gel (2%) & Retino A cream (0.1%) in reducing the size of lesions in oral leukoplakia. OBJECTIVES: The present study aimed to evaluate the efficacy of two interventions, Moringa oleifera mucoadhesive gel and Retino-A cream, in reducing the size of lesions in patients with oral leukoplakia. Specifically, the objectives were: (1) to assess the efficacy of Moringa oleifera mucoadhesive gel in determining the reduction in lesion size, (2) to assess the efficacy of Retino-A cream in determining the reduction in lesion size, and (3) to compare the efficacy of Moringa oleifera mucoadhesive gel (2%) in determining the change in lesion size in oral leukoplakia patients. METHODS: Clinically diagnosed cases of oral Leukoplakia were included in this study. The sample size is 72. Thirty-six patients had lesion sizes ranging from 2- 4 cm, and 36 patients had lesion sizes ranging from 4.1 - 6 cm that were equally distributed in the case and control groups using the chit system. The case and control groups had 36 patients with an equal size range of lesions. The case and control group participants will be advised topical application of the intervention and Retino-A thrice daily using a sterile cotton bud. RESULTS: M. oleifera gel (2%) was found to be more effective in the reduction in the size of the lesion as compared to Retino-A in the treatment of oral leukoplakia patients. CONCLUSION: This study showed that M. oleifera mucoadhesive gel (2%) is an effective and safe treatment option for oral leukoplakia patients. It demonstrated a significant reduction in lesion size compared to Retino-A cream (0.1%) after 3 months of therapy, without any reported adverse effects. However, long-term follow-up studies are needed to evaluate its long-term effectiveness. The potent antioxidant property of M. oleifera makes it a promising candidate for further studies with concentration variations and in other potentially malignant oral disorders, such as lichen planus and OSMF. The development of chemotherapeutic drugs from M. oleifera for cancer treatment should also be considered. Overall, M. oleifera appears to be a promising natural alternative to synthetic drugs for the treatment of oral leukoplakia. KEY WORDS: Leukoplakia, Oral leukoplakia, premalignant lesion, precancer, potentially malignant disorders.

An enhanced three-stage design with trend analysis for allergen immunotherapy trials.

We previously introduced a three-stage design and associated end-of-stage analyses for allergen immunotherapy (AIT) trials. End-of-stage differences alone may not provide a fuller picture of Stages 2 and 3 effects because they may depend upon stage-specific durations. Therefore, we introduce an additional trend analysis to evaluate the difference in progression curves of two groups over the entire stage. Results from such analysis are used to inform persistence of end-of-stage benefit and thus provide evidence for stagewise effects beyond the study periods. We jointly apply end-of-stage and trend analyses to support the enhanced three-stage design to determine treatment response over time and sustained response to AIT. A simulation study was performed to illustrate the statistical properties (bias and power) of trend analyses under varying statistical missing mechanisms and effect sizes. The extent of bias depended on the missing mechanism and magnitude. Powers were largely driven by effect and sample sizes as well as pre-specified success margins, particularly of relative trend. As an illustration, assuming relative treatment differences of 25-30%, stagewise dropout rate of 15%, and parallel outcome progressions, a sample size of 200 per group may achieve 97% power to demonstrate a treatment effect and 53% power to demonstrate a sustained effect post-treatment. Trend analysis supplements the end-of-stage analysis to enhance the statistical claims of stagewise effects. Inferential statistics support our proposed trend analysis for evaluating benefits of AIT over time and inform clinical understanding and decisions.

The relationship of publication language, study population, risk of bias, and treatment effects in acupuncture related systematic reviews: a meta-epidemiologic study.

BACKGROUND: There are debates in acupuncture related systematic reviews and meta-analyses on whether searching Chinese databases to get more Chinese-language studies may increase the risk of bias and overestimate the effect size, and whether the treatment effects of acupuncture differ between Chinese and non-Chinese populations. METHODS: In this meta-epidemiological study, we searched the Cochrane library from its inception until December 2021, and identified systematic reviews and meta-analyses with acupuncture as one of the interventions. Paired reviewers independently screened the reviews and extracted the information. We repeated the meta-analysis of the selected outcomes to separately pool the results of Chinese- and non-Chinese-language acupuncture studies and presented the pooled estimates as odds ratios (OR) with 95% confidence interval (CI). We calculated the Ratio of ORs (ROR) by dividing the OR of the Chinese-language trials by the OR of the non-Chinese-language trials, and the ROR by dividing the OR of trials addressing Chinese population by the OR of trials addressing non-Chinese population. We explored whether the impact of a high risk of bias on the effect size differed between studies published in Chinese- and in non-Chinese-language, and whether the treatment effects of acupuncture differed between Chinese and non-Chinese population. RESULTS: We identified 84 Cochrane acupuncture reviews involving 33 Cochrane groups, of which 31 reviews (37%) searched Chinese databases. Searching versus not searching Chinese databases significantly increased the contribution of Chinese-language literature both to the total number of included trials (54% vs. 15%) and the sample size (40% vs. 15%). When compared with non-Chinese-language trials, Chinese-language trials were associated with a larger effect size (pooled ROR 0.51, 95% CI 0.29 to 0.91). We also observed a higher risk of bias in Chinese-language trials in blinding of participants and personnel (97% vs. 51%) and blinding of outcome assessment (93% vs. 47%). The higher risk of bias was associated with a larger effect estimate in both Chinese-language (allocation concealment: high/unclear risk vs. low risk, ROR 0.43, 95% CI 0.21 to 0.87) and non-Chinese-language studies (blinding of participants and personnel: high/unclear risk vs. low risk, ROR 0.41, 95% CI 0.23 to 0.74). However, we found no evidence that the higher risk of bias would increase the effect size of acupuncture in Chinese-language studies more often than in non-Chinese-language studies (the confidence intervals of all ROR in the high-risk group included 1, Table 3). We further found acupuncture appeared to be more effective in Chinese than in non-Chinese population (Table 4). CONCLUSIONS: The findings of this study suggest the higher risk of bias may lead to an overestimation of the treatment effects of acupuncture but would not increase the treatment effects in Chinese-language studies more often than in other language studies. The difference in treatment effects of acupuncture was probably associated with differences in population characteristics. TRIAL REGISTRATION: We registered our protocol on the Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/PZ6XR ).

A Scoping Review of Personal, Financial, and Environmental Determinants of Mobility Among Older Adults.

OBJECTIVE: To synthesize available evidence of factors comprising the personal, financial, and environmental mobility determinants and their association with older adults' self-reported and performance-based mobility outcomes. DATA SOURCES: PubMed, EMBASE, PsychINFO, Web of Science, AgeLine, Sociological Abstract, Allied and Complementary Medicine Database, and Cumulative Index to Nursing and Allied Health Literature databases search for articles published from January 2000 to December 2021. STUDY SECTION: Using predefined inclusion and exclusion criteria, multiple reviewers independently screened 27,293 retrieved citations from databases, of which 422 articles underwent full-text screening, and 300 articles were extracted. DATA EXTRACTION: The 300 articles' information, including study design, sample characteristics including sample size, mean age and sex, factors within each determinant, and their associations with mobility outcomes, were extracted. DATA SYNTHESIS: Because of the heterogeneity of the reported associations, we followed Barnett et al's study protocol and reported associations between factors and mobility outcomes by analyses rather than by article to account for multiple associations generated in 1 article. Qualitative data were synthesized using content analysis. A total of 300 articles were included with 269 quantitative, 22 qualitative, and 9 mixed-method articles representing personal (n=80), and financial (n=1), environmental (n=98), more than 1 factor (n=121). The 278 quantitative and mixed-method articles reported 1270 analyses; 596 (46.9%) were positively and 220 (17.3%) were negatively associated with mobility outcomes among older adults. Personal (65.2%), financial (64.6%), and environmental factors (62.9%) were associated with mobility outcomes, mainly in the expected direction with few exceptions in environmental factors. CONCLUSIONS: Gaps exist in understanding the effect of some environmental factors (eg, number and type of street connections) and the role of gender on older adults' walking outcomes. We have provided a comprehensive list of factors with each determinant, allowing the creation of core outcome set for a specific context, population, or other forms of mobility, for example, driving.

Effectiveness of non-pharmacological treatments for postpartum depression: an umbrella review protocol.

INTRODUCTION: Non-pharmacological treatments for postpartum depression have been investigated in various systematic reviews, and their efficacy has been evaluated. However, the quality of the evidence as a whole has not been quantified. The quality of this evidence may influence the choice of interventions and even cause misleading clinical decisions. This study aims to provide an objective presentation of the methodological bias and identify treatments supported by solid evidence. METHODS AND ANALYSIS: For the purpose of conducting systematic reviews and meta-analyses, a comprehensive search of the relevant published literature will be conducted in English databases such as PubMed, Embase, Cochrane Library, PsycINFO and Scopus, as well as in four Chinese databases: the Chinese Biomedical Databases (CBM), Wan fang database, China National Knowledge Infrastructure and VIP Database (VIP). The time of publication will be limited from their inception to 31 May 2022. We will extract the following data from the included literature: title, first author, journal type of included literature, number and sample size, intervention/control measures, outcome indicators and main study outcomes. The Assessment of Multiple Systematic Reviews-2 will be used to measure the quality of the methods. In addition, we will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to evaluate the quality of the reporting, as well as the Grading of Recommendations Assessment, Development and Evaluation to evaluate the quality of the evidence. PROSPERO REGISTRATION NUMBER: CRD42021285470.

Introduction to the Meta-analysis method of functional magnetic resonance imaging research and the exploration of its application in the field of acupuncture. / åŠŸèƒ½ç£å ±æŒ¯ç ”ç©¶å ƒåˆ†æžæ–¹æ³•ä»‹ç»åŠå ¶åœ¨é’ˆåˆºé¢†åŸŸçš„åº”ç”¨æŽ¢æž.

In recent years, the number of functional magnetic resonance imaging (fMRI) research in acupuncture grows increasingly. However, due to the differences in acupoint selection, acupuncture technique and sample size, the problems get more prominent in terms of the diverse results and the lack of common rules of acupuncture among researches. By taking the fMRI research for post-stroke motor dysfunction (PSMD) treated with acupuncture as the example, this paper introduces the fMRI Meta-analysis technology for integrating the relevant research results and extracting the common rules, namely image-based Meta-analysis (IBMA) and coordinate-based Meta-analysis (CBMA). Considering the higher feasibility of CBMA, three available CBMA methods are explained specially, including activation likelihood estimation (ALE), kernel density analysis (KDA), and seed-based d mapping (SDM). Focusing on the precautions and operation procedure of CBMA, the review is conducted systematically on the type of fMRI research, task design, analytical method, and the thinking integrity of fMRI Meta-analysis, and the review findings are collated in charts. It aims to assist readers to understand the abstract and complex theories and practical information of this technology efficiently, conveniently and systematically, and hopes to provide the references for the future learning and the application.

Sample size estimation in acupuncture imaging research. / æ ·æœ¬é‡ä¼°ç®—åœ¨é’ˆç¸å½±åƒå­¦ç ”ç©¶ä¸­çš„åº”ç”¨ä¸Žæ€è€ƒ.

The size of the sample significantly impacts the accuracy of research outcomes. While preliminary results have been achieved in acupuncture imaging research, sample size estimation is often subjective and arbitrary, leading to insufficient reliability of study results. This article reviews the current application of sample size estimation in acupuncture imaging research, and provides recommendations to address existing issues. It is suggested that future researches should include the sample sizes that meet statistical power based on the characteristics of functional magnetic resonance imaging (fMRI) protocols, with group sizes of 12 and 20-30 cases having become the "minimum requirement" for confirmatory studies and a common choice. Additionally, the adoption of adaptive design approaches, which dynamically adjust sample sizes based on accumulated data, can be considered. Furthermore, efforts should be made to establish an open platform for sharing acupuncture imaging data to enhance data accessibility, and consequently, improve the quality and overall impact of acupuncture imaging research.

Actionable absolute risk prediction of atherosclerotic cardiovascular disease based on the UK Biobank.

Cardiovascular diseases (CVDs) are the primary cause of all death globally. Timely and accurate identification of people at risk of developing an atherosclerotic CVD and its sequelae is a central pillar of preventive cardiology. One widely used approach is risk prediction models; however, currently available models consider only a limited set of risk factors and outcomes, yield no actionable advice to individuals based on their holistic medical state and lifestyle, are often not interpretable, were built with small cohort sizes or are based on lifestyle data from the 1960s, e.g. the Framingham model. The risk of developing atherosclerotic CVDs is heavily lifestyle dependent, potentially making many occurrences preventable. Providing actionable and accurate risk prediction tools to the public could assist in atherosclerotic CVD prevention. Accordingly, we developed a benchmarking pipeline to find the best set of data preprocessing and algorithms to predict absolute 10-year atherosclerotic CVD risk. Based on the data of 464,547 UK Biobank participants without atherosclerotic CVD at baseline, we used a comprehensive set of 203 consolidated risk factors associated with atherosclerosis and its sequelae (e.g. heart failure). Our two best performing absolute atherosclerotic risk prediction models provided higher performance, (AUROC: 0.7573, 95% CI: 0.755-0.7595) and (AUROC: 0.7544, 95% CI: 0.7522-0.7567), than Framingham (AUROC: 0.680, 95% CI: 0.6775-0.6824) and QRisk3 (AUROC: 0.725, 95% CI: 0.7226-0.7273). Using a subset of 25 risk factors identified with feature selection, our reduced model achieves similar performance (AUROC 0.7415, 95% CI: 0.7392-0.7438) while being less complex. Further, it is interpretable, actionable and highly generalizable. The model could be incorporated into clinical practice and might allow continuous personalized predictions with automated intervention suggestions.

Effects of Nutrition on Cognitive Function in Adults with or without Cognitive Impairment: A Systematic Review of Randomized Controlled Clinical Trials.

New dietary approaches for the prevention of cognitive impairment are being investigated. However, evidence from dietary interventions is mainly from food and nutrient supplement interventions, with inconsistent results and high heterogeneity between trials. We conducted a comprehensive systematic search of randomized controlled trials (RCTs) published in MEDLINE-PubMed, from January 2018 to July 2021, investigating the impact of dietary counseling, as well as food-based and dietary supplement interventions on cognitive function in adults with or without cognitive impairment. Based on the search strategy, 197 eligible publications were used for data abstraction. Finally, 61 articles were included in the analysis. There was reasonable evidence that dietary patterns, as well as food and dietary supplements improved cognitive domains or measures of brain integrity. The Mediterranean diet showed promising results, whereas the role of the DASH diet was not clear. Healthy food consumption improved cognitive function, although the quality of these studies was relatively low. The role of dietary supplements was mixed, with strong evidence of the benefits of polyphenols and combinations of nutrients, but with low evidence for PUFAs, vitamin D, specific protein, amino acids, and other types of supplements. Further well-designed RCTs are needed to guide the development of dietary approaches for the prevention of cognitive impairment.

[Sample size estimation in acupuncture and moxibustion clinical trials].

The appropriate sample size estimation is very important in the design of clinical trials. However, insufficient or inappropriate sample size estimation is still a prominent problem in the currently published acupuncture and moxibustion clinical trials. At present, the superiority test, non-inferiority test and equivalence test have been widely used in acupuncture and moxibustion clinical trials. This article focuses on the application, calculation methods and PASS11 software using of these three hypothesis test types. In view of the problems in the estimation of sample size in acupuncture and moxibustion clinical trials, the particularity of sample size estimation in acupuncture and moxibustion is summarized from the aspects of parameter setting, ratio of intervention group and control group, and multi-group comparison, in order to guide acupuncture clinical researchers to correctly estimate sample size when conducting clinical trials.

The Effects of Lavender and Citrus aurantium on Anxiety and Agitation of the Conscious Patients in Intensive Care Units: A Parallel Randomized Placebo-Controlled Trial.

BACKGROUND: Conscious patients admitted to intensive care units (ICU) suffer from anxiety and agitation for various reasons, which can affect their recovery processes. AIMS: To compare the effects of lavender and Citrus aurantium essential oils on anxiety and agitation of conscious patients admitted to ICUs. DESIGN: A randomized parallel placebo-controlled trial. METHODS: One hundred and fifty conscious patients admitted to ICUs were selected by convenience sampling and were randomly divided into three groups, groups of lavender aromatherapy and Citrus aurantium aromatherapy, in addition to the routine care and inhalation of five drops of lavender or Citrus aurantium essential oils for 30 minutes. The placebo group, in addition to routine care, was provided with 5 drops of normal saline for 30 minutes. Anxiety was assessed with the state subscale of State-Trait Anxiety Inventory, and agitation was examined with Richmond Agitation-Sedation Scale before, immediately, one hour, and three hours after the intervention. RESULTS: All three groups suffered from relatively severe state anxiety before the intervention. The level of anxiety in the lavender and Citrus aurantium groups was significantly lower than that of the placebo group immediately and three hours after the intervention (P < 0.05). No significant difference was observed between the two groups of lavender and Citrus aurantium. The majority of the samples in all three groups were agitated before the intervention, but agitation of all three groups decreased after the intervention. Restless/agitation reduced significantly in all three groups. Although restless/agitation of the lavender and Citrus aurantium groups reduced more than that of the placebo, no significant difference was found between the three groups. CONCLUSION: The results of the present study showed the positive effects of lavender aromatherapy and Citrus aurantium aromatherapy on reducing the anxiety of patients admitted to ICUs. Relevance to Clinical Practice. Aromatherapy can be used as an effective and safe intervention to reduce anxiety in ICUs.

Right ventricular endomyocardial biopsy in patients with cardiac magnetic resonance showing left ventricular myocarditis.

AIMS: The aim of this study was to evaluate the sensitivity of right ventricular endomyocardial biopsy (EMB) in myocarditis patients with cardiac magnetic resonance (CMR) and electroanatomical mapping (EAM) showing left ventricular abnormalities. METHODS: We performed right ventricular EMB in 144 consecutive patients (66% men, age 43 ±â€Š15 years) with acute symptoms and CMR-proved diagnosis of left ventricular myocarditis. Right ventricular EMB sensitivity has been evaluated in patients with different localization and extension of abnormal substrate at both CMR and -- when performed -- EAM. Abnormal substrate was defined, respectively, by late gadolinium enhancement (LGE) and low-voltage areas (LVAs). RESULTS: Globally, right ventricular EMB sensitivity was 87.5%. EMB-negative cases had significantly smaller fragment sizes (cumulative area 2.8 ±â€Š1.7 vs. 3.8 ±â€Š1.8 mm2, P = 0.023), and lower LGE surface extension (24.7 ±â€Š14.2 vs. 38.5 ±â€Š20.2%, P = 0.006) and transmurality (32.0 ±â€Š26.1 vs. 49.3 ±â€Š22.6, P = 0.003). Right ventricular EMB sensitivity in patients with LGE involving both right ventricular and interventricular septum (IVS), isolated right ventricular or IVS, and remote left ventricular areas (n = 10, 49 and 67 cases) was 83.3, 84.4 and 90.5%, respectively (P = 0.522). Overall, 34 patients (23.6%) underwent EAM. On the basis of EAM, right ventricular EMB sensitivity was 85.3%: in detail, it was 50.0, 88.2 and 86.7% in patients with both right ventricular and IVS, isolated right ventricular/IVS and distant left ventricular involvement (n = 2, 17 and 15, respectively, P > 0.05). Sample size area was the only factor associated with right ventricular EMB sensitivity (hazard ratio = 1.6/mm2, 95% confidence interval 1.1-2.4, P = 0.013). CONCLUSION: Right ventricular EMB is still an accurate technique to confirm diagnosis in patients with CMR-proved left ventricular myocarditis. In particular, provided there is an adequate sample size, its sensitivity is comparable among patients with heterogeneous LGE or LVA localization.

The Antibacterial and Antioxidant Roles of Buckwheat Honey (BH) in Liquid Preservation of Boar Semen.

In the present study, we hypothesized that buckwheat honey (BH) should be regarded as a potential alternative to antibacterial and antioxidant agent in liquid storage of boar semen. To this end, boar semen was firstly studied for in vitro dose tolerability to BH by measuring sperm progressive motility. The optimum progressive motility of boar spermatozoa was observed in extender with 0.5% and 0.6% BH addition. Afterward, sperm quality parameters, bacterial profile and composition, total antioxidant (T-AOC), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels of control, BH supplementation, antibiotics supplementation, and incorporated supplementation were compared during liquid storage period, to further investigate antibacterial and antioxidant properties of BH. The results showed that BH supplementation significantly improved sperm motility, acrosome integrity, plasma membrane integrity, inhibited opportunistic bacterial growth, and altered microbial compositions at the end of preservation. Additionally, T-AOC, SOD, and CAT levels were significantly higher in the BH supplementation group than those in the control and antibiotic supplementation group, whereas MDA level exhibited opposite change pattern. Importantly, BH addition to the extender was able to exert a synergistic effect in combination of antibiotic use. Our findings suggested that the appropriate concentrations (0.5% and 0.6%) of BH were added to the extender could act antibacterial and antioxidant roles in liquid preservation of boar semen.

Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility.

A recent flood of publications has documented serious problems in scientific reproducibility, power, and reporting of biomedical articles, yet scientists persist in their usual practices. Why? We examined a popular and important preclinical assay, the Forced Swim Test (FST) in mice used to test putative antidepressants. Whether the mice were assayed in a naïve state vs. in a model of depression or stress, and whether the mice were given test agents vs. known antidepressants regarded as positive controls, the mean effect sizes seen in the experiments were indeed extremely large (1.5-2.5 in Cohen's d units); most of the experiments utilized 7-10 animals per group which did have adequate power to reliably detect effects of this magnitude. We propose that this may at least partially explain why investigators using the FST do not perceive intuitively that their experimental designs fall short-even though proper prospective design would require ~21-26 animals per group to detect, at a minimum, large effects (0.8 in Cohen's d units) when the true effect of a test agent is unknown. Our data provide explicit parameters and guidance for investigators seeking to carry out prospective power estimation for the FST. More generally, altering the real-life behavior of scientists in planning their experiments may require developing educational tools that allow them to actively visualize the inter-relationships among effect size, sample size, statistical power, and replicability in a direct and intuitive manner.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Unpaired data empowers association tests.

MOTIVATION: There is growing interest in the biomedical research community to incorporate retrospective data, available in healthcare systems, to shed light on associations between different biomarkers. Understanding the association between various types of biomedical data, such as genetic, blood biomarkers, imaging, etc. can provide a holistic understanding of human diseases. To formally test a hypothesized association between two types of data in Electronic Health Records (EHRs), one requires a substantial sample size with both data modalities to achieve a reasonable power. Current association test methods only allow using data from individuals who have both data modalities. Hence, researchers cannot take advantage of much larger EHR samples that includes individuals with at least one of the data types, which limits the power of the association test. RESULTS: We present a new method called the Semi-paired Association Test (SAT) that makes use of both paired and unpaired data. In contrast to classical approaches, incorporating unpaired data allows SAT to produce better control of false discovery and to improve the power of the association test. We study the properties of the new test theoretically and empirically, through a series of simulations and by applying our method on real studies in the context of Chronic Obstructive Pulmonary Disease. We are able to identify an association between the high-dimensional characterization of Computed Tomography chest images and several blood biomarkers as well as the expression of dozens of genes involved in the immune system. AVAILABILITY AND IMPLEMENTATION: Code is available on https://github.com/batmanlab/Semi-paired-Association-Test. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.