Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for : A Phase 2, Open-Label Clinical Trial.

Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age. To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2-5 years. This phase 2 trial had two parts: part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2-5 years (previously reported) was followed by a 48-week open-label treatment period in which all children received LUM/IVA (part 2; reported here).

Marginal versus conditional rate estimation for count and recurrent event data with an estimand framework.

Count and recurrent event endpoints are common key efficacy endpoints in clinical research. For example, in clinical research of pulmonary diseases such as chronic obstructive pulmonary disease (COPD) or asthma, the reduction of the occurrence of a recurrent event, pulmonary exacerbation (PEx) caused by acute respiratory symptoms, is often used to measure the treatment effect. The occurrence of PEx is often analyzed with nonlinear models, such as Poisson regression or Negative Binomial regression.

Conduction and validation of a novel prognostic signature in cervical cancer based on the necroptosis characteristic genes via integrating of multiomics data.

The significance of necroptosis in recurrent or metastatic cervical cancer remains unclear. In this study, we utilized various bioinformatics methods to analyze the cancer genome atlas (TCGA) data, gene chip and the single-cell RNA-sequencing (scRNA seq) data. And a necroptosis-related genes signature for prognostic assessment of patients with cervical cancer was constructed successfully.

Effects of Lumacaftor/Ivacaftor on Cystic Fibrosis Disease Progression in Children 2 through 5 Years of Age Homozygous for : A Phase 2 Placebo-controlled Clinical Trial.

Lumacaftor/ivacaftor (LUM/IVA) was shown to be safe and well tolerated in children 2 through 5 years of age with cystic fibrosis (CF) homozygous for in a Phase 3 open-label study. Improvements in sweat chloride concentration, markers of pancreatic function, and lung clearance index (LCI), along with increases in growth parameters, suggested the potential for early disease modification with LUM/IVA treatment. To further assess the effects of LUM/IVA on CF disease progression in children 2 through 5 years of age using chest magnetic resonance imaging (MRI).

Wetting Behavior of LBE on Corroded Candidate LFR Structural Materials of 316L, T91 and CLAM.

In this work, the wetting behaviors of lead-bismuth eutectic (LBE) on corroded 316L, T91, and CLAM surfaces were studied. The wettability of LBE on virgin and corroded surfaces were tested at 450 °C by using the sessile-drop (SD) method after immersing the samples in LBE with saturated oxygen concentration for 400, 800, and 1200 h at 450 °C. Additionally, the morphology, as well as element distribution of the corrosion structure, were characterized by scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS).

Statistical considerations in clinical trial design with event-free survival as the primary efficacy endpoint.

In late-phase confirmatory clinical trials in the oncology field, time-to-event (TTE) endpoints are commonly used as primary endpoints for establishing the efficacy of investigational therapies. Among these TTE endpoints, overall survival (OS) is always considered as the gold standard. However, OS data can take years to mature, and its use for measurement of efficacy can be confounded by the use of post-treatment rescue therapies or supportive care.

Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study.

Purpose: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML.

Patients And Methods: Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled.

An efficient sample size adaptation strategy with adjustment of randomization ratio.

In clinical trials, sample size reestimation is a useful strategy for mitigating the risk of uncertainty in design assumptions and ensuring sufficient power for the final analysis. In particular, sample size reestimation based on unblinded interim effect size can often lead to sample size increase, and statistical adjustment is usually needed for the final analysis to ensure that type I error rate is appropriately controlled. In current literature, sample size reestimation and corresponding type I error control are discussed in the context of maintaining the original randomization ratio across treatment groups, which we refer to as "proportional increase.

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia.

Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. B-cell lymphoma 2 (BCL-2) overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study.

Statins enhance efficacy of venetoclax in blood cancers.

Statins have shown promise as anticancer agents in experimental and epidemiologic research. However, any benefit that they provide is likely context-dependent, for example, applicable only to certain cancers or in combination with specific anticancer drugs. We report that inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) using statins enhances the proapoptotic activity of the B cell lymphoma-2 (BCL2) inhibitor venetoclax (ABT-199) in primary leukemia and lymphoma cells but not in normal human peripheral blood mononuclear cells.

Defining information fractions in group sequential clinical trials with multiple endpoints.

The group sequential design has been well understood and widely applied in designs of late phase clinical trial to enable potentially early stopping for efficacy or futility. The information fraction (IF) is one of the key elements to determine the decision boundary at the interim analyses. The family-wise error rate (FWER) control is highly critical for clinical trials with multiple endpoints to be tested.

Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study.

Background: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study.

Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma.

Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in multiple myeloma (MM) cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-X and MCL-1. In this phase 1 study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion.

Flexible combination of multiple diagnostic biomarkers to improve diagnostic accuracy.

Background: In medical research, it is common to collect information of multiple continuous biomarkers to improve the accuracy of diagnostic tests. Combining the measurements of these biomarkers into one single score is a popular practice to integrate the collected information, where the accuracy of the resultant diagnostic test is usually improved. To measure the accuracy of a diagnostic test, the Youden index has been widely used in literature.

Comparing logistic regression, support vector machines, and permanental classification methods in predicting hypertension.

In this paper, we compare logistic regression and 2 other classification methods in predicting hypertension given the genotype information. We use logistic regression analysis in the first step to detect significant single-nucleotide polymorphisms (SNPs). In the second step, we use the significant SNPs with logistic regression, support vector machines (SVMs), and a newly developed permanental classification method for prediction purposes.

Minimum clinically important difference in medical studies.

In clinical trials, minimum clinically important difference (MCID) has attracted increasing interest as an important supportive clinical and statistical inference tool. Many estimation methods have been developed based on various intuitions, while little theoretical justification has been established. This article proposes a new estimation framework of the MCID using both diagnostic measurements and patient-reported outcomes (PROs).

A model-free estimation for the covariate-adjusted Youden index and its associated cut-point.

In medical research, continuous markers are widely employed in diagnostic tests to distinguish diseased and non-diseased subjects. The accuracy of such diagnostic tests is commonly assessed using the receiver operating characteristic (ROC) curve. To summarize an ROC curve and determine its optimal cut-point, the Youden index is popularly used.

catena-Poly[[tetraaquairon(II)]-mu-succinato-kappa2O:O'].

The title complex, ([Fe(C(4)H(4)O(4))(H(2)O)(4)])(n), is an infinite polymeric compound bridged by the succinate dianion. Two carboxylate groups coordinate in a monodentate manner to the Fe(II) atom, in a trans fashion, with an O-Fe-O bond angle of 175.72 (6) degrees and Fe-O distances of 2.