Erianin serves as an NFATc1 inhibitor to prevent breast cancer-induced osteoclastogenesis and bone destruction.

Introduction: Breast cancer-related bone metastasis can lead to skeletal-related events (SREs), which decrease patient quality of life. Inhibition of osteoclastogenesis is a key treatment for SREs; however, the availability of clinical drugs remains limited, and all existing ones disrupt physiological bone formation, while exhibiting no effect on patient survival time.

Objectives: This study aimed to identify a novel osteoclast inhibitor for the treatment of breast cancer-induced SREs.

A retrospective cohort study of tamoxifen versus surgical treatment for ER-positive gynecomastia.

Background: Gynecomastia is a common condition in clinical practice. The present study aimed to review the clinical data of ER-positive gynecomastia patients treated by tamoxifen (TAM) versus surgery and discussed the clinical effects of the two treatment strategies.

Method: We retrospectively collected the clinical indicators of patients with unilateral or bilateral gynecomastia who received treatment at our hospital between April 2018 and December 2021.

A Flexible Ensemble Learning Method for Survival Extrapolation.

Objectives: Survival extrapolation is an important statistical concept for estimating long-term survival from short-term clinical trial data. It is widely used in health technology assessment (HTA). Survival extrapolation is often performed by fitting one or two parametric models selected based on experience or selecting a model based on some goodness of fit statistics from a predefined collection of models.

A comparative study of the efficacy of tamoxifen and Chinese patented medicine (Pingxiao capsules) in gynecomastia: A retrospective cohort study.

To compare the clinical efficacy of tamoxifen and Chinese patented medicine (Pingxiao capsules) in patients with gynecomastia and discuss the safety of the two treatments. We retrospectively analysed the clinical data of 388 male patients with gynecomastia who were treated in the Outpatient Clinic of our hospital between January 2010 and December 2020. There were 103 patients in the tamoxifen (TAM) group and 103 patients in the Chinese patented medicine group.

Smartphone-Based and Data-Driven Superstructure State Prediction Method for Highway Bridges in Service.

Survival analysis is a data-driven approach that is widely used in various fields of biomedical prognostic research, and it is highly reliable in the processing of time-event data. This study developed a method for evaluating the service performance of bridge superstructures using the built-in acceleration sensor of smartphones and the prediction of survival analysis theory. It will be used to assist in the daily maintenance and repair of small and medium bridges.

Differential expression profile of mRNAs, lncRNAs, and circRNAs reveals potential molecular mechanism in breast cancer.

In recent years, breast cancer attracts more and more attention because of its high incidence. To explore the molecular functions and mechanisms, we performed RNA sequencing on the tumor tissues and their paired normal tissues from three breast cancer patients. By differential expression analysis, we found 3764 differentially expressed (DE) mRNAs, 5416 DE lncRNAs, and 148 DE circRNAs.

Practical considerations in utilizing cluster randomized controlled trials conducted in biopharmaceutical industry.

Cluster randomized controlled trials (cluster RCTs), also known as parallel-arm group-randomized trials, are trials in which the randomized units are groups of participants, as opposed to individual participants. These trials have largely been implemented to address broad public health issues, but with the growing interest in use of real-world data in the regulatory setting, this design may be increasingly considered for industry trials. The key difference between cluster RCTs and traditional RCTs is the intraclass correlation coefficient (ICC) that needs to be considered in cluster RCTs.

Tirofiban combined with heparin's effect and safety in the treatment of mild to moderate acute ischemic stroke.

Tirofiban can be used to treat patients with acute ischemic stroke (AIS), this study was to evaluate the efficacy and safety of tirofiban combined with heparin in the treatment of mild to moderate AIS. A total of 98 patients with mild to moderate AIS randomly were divided into 2 groups within 48 h: the treatment group treated with tirofiban and, and the control group treated with aspirin + clopidogrel. The treatment group was given the same scheme as the control group after the treatment of tirofiban combined with heparin for 48 h.

The Vacuum-Assisted Breast Biopsy System is an Effective Strategy for the Treatment of Gynecomastia.

Background: Gynecomastia is the most common benign disease in males with an increasing prevalence in recent years. It may cause local pain and psychological disorders. The vacuum-assisted breast biopsy system has been reported to be a novel surgical approach for the treatment of gynecomastia.

A method for sample size calculation via E-value in the planning of observational studies.

Confounding adjustment plays a key role in designing observational studies such as cross-sectional studies, case-control studies, and cohort studies. In this article, we propose a simple method for sample size calculation in observational research in the presence of confounding. The method is motivated by the notion of E-value, using some bounding factor to quantify the impact of confounders on the effect size.

Key considerations in the design of real-world studies.

Randomized controlled clinical trials (RCTs) are the gold standard for evaluating the safety and efficacy of pharmaceutical drugs, but in many cases their costs, duration, limited generalizability, and ethical or technical feasibility have caused some to look for real-world studies as alternatives. However, real-world studies may be less convincing due to the lack of randomization and blinding. In this article, we discuss some key considerations in the design of real-world studies, which include experimental studies (e.

A new framework to address challenges in quantitative benefit-risk assessment for medical products.

In recent years, there has been a proliferation of regulatory and industry-wide initiatives on structured benefit-risk (BR) assessment. Examples of structured BR frameworks include the PrOACT-URL (Problem formulation, Objectives, Alternatives, Consequences, Trade-Offs, Uncertainties, Risk Attitude and Linked Decisions) from European Medicines Agency Work Package 3, multiple U.S.

A Statistical Roadmap for Journey from Real-World Data to Real-World Evidence.

Randomized controlled clinical trials are the gold standard for evaluating the safety and efficacy of pharmaceutical drugs, but in many cases their costs, duration, limited generalizability, and ethical or technical feasibility have caused some to look for real-world studies as alternatives. On the other hand, real-world data may be much less convincing due to the lack of randomization and the presence of confounding bias. In this article, we propose a statistical roadmap to translate real-world data (RWD) to robust real-world evidence (RWE).

Presenting Risks and Benefits: Helping the Data Monitoring Committee Do Its Job.

Data monitoring committees (DMCs), or data and safety monitoring boards, protect clinical trial participants by conducting benefit-risk assessments during the course of a clinical trial. These evaluations may be improved by broader access to data and more effective analyses and presentation. Data monitoring committees should have access to all data, including efficacy data, at each interim review.

Intraspinal administration of interleukin-7 promotes neuronal apoptosis and limits functional recovery through JAK/STAT5 pathway following spinal cord injury.

It has been previously reported that the blockade of interleukin-7 receptor (IL-7R) promotes functional recovery following spinal cord injury (SCI), however, the direct function and molecular mechanism of IL-7 involved in this pathogenic process are unclear. Here, we report that, contrary to IL-7R blockade, the intraspinal administration of IL-7 limits functional recovery following SCI. In addition, IL-7 treatment promotes neuronal apoptosis in spinal cord lesions, which may be attributed to exacerbated focal inflammatory response, as shown by increased accumulation of activated microglia/macrophage and production of proinflammatory mediators.

On a Stepwise Quantitative Approach for Benefit-Risk Assessment.

The field of structured benefit-risk assessment has evolved rapidly in the last few years with a great deal of regulatory and industry-wide initiatives. The available structured approaches to benefit-risk assessments exhibit and share many common elements in terms of defining the decision problem and therapeutic context, identifying key benefit and risk factors, and interpreting and communicating benefit-risk findings. However, there is limited guidance with these initiatives that is specific to metrics and methods to conduct benefit-risk assessment.

The Case for a Bayesian Approach to Benefit-Risk Assessment:: Overview and Future Directions.

The benefit-risk assessment of a new medicinal product or intervention is one of the most complex tasks that sponsors, regulators, payers, physicians, and patients face. Therefore, communicating the trade-off of benefits and risks in a clear and transparent manner, using all available evidence, is critical to ensure that the best decisions are made. Several quantitative methods have been proposed in recent years that try to provide insight into this challenging problem.

DIA's Adaptive Design Scientific Working Group (ADSWG): Best Practices Case Studies for "Less Well-understood" Adaptive Designs.

Adaptive design (AD) clinical trials use accumulating subject data to modify the parameters of the design of an ongoing study, without compromising the validity and integrity of the study. The 2010 US Food and Drug Administration (FDA) Draft Guidance on Adaptive Design Clinical Trials described a subset of 7 primary design types as "less well-understood." FDA defined these designs as those with limited regulatory experience.

Addressing Challenges and Opportunities of "Less Well-Understood" Adaptive Designs.

The draft adaptive design guidance released by FDA in 2010 included references to adaptive study designs that were described as "less well-understood." At that time, there was relatively little regulatory experience with such designs, and their properties were felt to be insufficiently understood. In order to promote greater use of adaptive designs, especially those categorized as less well-understood, the Best Practice Subteam of the DIA Adaptive Designs Scientific Working Group (ADSWG) has worked on describing and characterizing these designs, identifying challenges associated with them and suggesting improvements to design or study conduct aspects that might make them more acceptable.

Benefit-Risk Evaluation and Decision Making: Some Practical Insights.

Pharmaceutical drugs and devices are increasingly evaluated by quantitative tools that combine benefit and risk. These tools vary by their limitations and desirable properties, which may confuse the decision-making process. Experts from the Food and Drug Administration (FDA) and industry shared their perspectives at the 2012 American Statistical Association (ASA) Biopharmaceutical Section FDA-Industry Statistics Workshop, and these insights are presented here.

Effective Drug Supply for Adaptive Clinical Trials: Recommendations by the DIA Adaptive Design Scientific Working Group Drug Supply Subteam.

During the past decade, there has been increasing interest in adaptive clinical trials in pharmaceutical drug development as a means to improved decision making, better dose selection, and reduction in cost and time to market. Nevertheless, the operational challenge of drug supply continues to be a barrier preventing greater uptake of adaptive designs. Such studies require the ability to quickly accommodate changes in treatment allocation while maintaining the integrity of the blind.

Diary of hot flashes reported upon occurrence: results of a randomized double-blind study of raloxifene, placebo, and paroxetine.

Objective: This trial examined diaries of hot flash events reported upon occurrence to assess the test/retest reliability of the diaries and their ability to measure treatment effects on hot flash frequency and severity.

Methods: Forty-two postmenopausal women (aged ≥40 y; 5-50 hot flashes/wk) were randomized (3:3:1) to placebo, raloxifene 60 mg, or paroxetine 20 mg daily for 12 weeks. Diaries of hot flash frequency and severity were evaluated at 1-week intervals (twice before study treatment and thrice during study treatment).

A framework for joint modeling and joint assessment of efficacy and safety endpoints for probability of success evaluation and optimal dose selection.

The evaluation of clinical proof of concept, optimal dose selection, and phase III probability of success has traditionally been conducted by a subjective and qualitative assessment of the efficacy and safety data. This, in part, was responsible for the numerous failed phase III programs in the past. The need to utilize more quantitative approaches to assess efficacy and safety profiles has never been greater.

The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: results of a 4-week, double-blind, randomized, controlled trial.

Background: Metastatic bone disease (MBD) is a frequent complication in patients with breast cancer and is associated with significant morbidity. This study assessed the pharmacokinetics, efficacy, and safety of odanacatib, a selective Cat K inhibitor, in reducing markers of bone resorption in women with breast cancer and MBD.

Patients And Methods: Women with breast cancer and MBD were randomized 2:1 (double-blind) to oral odanacatib 5 mg daily for 4 weeks or intravenous (I.

Evaluation of the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases.

Aim: This study aimed to evaluate the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer (HRPC) and bone metastases.

Methods: A total of 21 patients with bone metastases and HRPC were randomized to receive MK-0429 200 mg b.i.