Demonstrating efficacy and effectiveness in clinical studies with recurrent event as primary end point: a chronic obstructive pulmonary disease example.

Pivotal clinical trials of persistent disorders such as chronic obstructive pulmonary disease and severe asthma often utilize recurrent event (e.g., exacerbations) as primary study end point.

Precision medicine in clinical practice.

In reports of clinical efficacies of new therapies in prospective randomized controlled trials, evidence showing proportion of respondents who meet the minimum clinically important difference in prespecified clinical end points are often not presented. Such reporting deficiency negatively impacts precision medicine practice in clinics. As all patient-centric decisions are binary, patients must be understood as individuals and not group averages.

Relationship of Blood Eosinophil Count to Exacerbations in Chronic Obstructive Pulmonary Disease.

Background: Eosinophilic airway inflammation characterizes a chronic obstructive pulmonary disease (COPD) phenotype that requires more study.

Objective: To investigate the relationship of blood eosinophil count to exacerbations in COPD.

Methods: Using administrative pharmacy and health care utilization data from 2009 to 2012, we retrospectively identified patients 40 years or older with a COPD diagnosis, postbronchodilator FEV/forced vital capacity ratio of less than 0.

Burden of Chronic Oral Corticosteroid Use by Adults with Persistent Asthma.

Background: Chronic oral corticosteroid (C-OCS) use in asthma is an indicator of disease severity, but its risk factors are largely unknown.

Objective: To describe patient characteristics and disease burden associated with C-OCS use by adults with persistent asthma.

Methods: We identified 9546 patients aged 18 to 64 years in a large managed care organization who met the Healthcare Effectiveness Data and Information Set 2-year criteria (2009-2010) for persistent asthma.

Characteristics and Outcomes of HEDIS-Defined Asthma Patients with COPD Diagnostic Coding.

Background: Little is known of the disease burden of patients with persistent asthma (PA) who also have a chronic obstructive pulmonary disease (COPD) diagnosis code (AS-COPD).

Objective: The objective of this study was to characterize and compare patients with AS-COPD with those with PA without COPD diagnosis, and determine in AS-COPD the relationship between blood eosinophil count and future asthma exacerbations.

Methods: This retrospective cohort study used administrative pharmacy and health care utilization data to identify, characterize, and compare the burden and asthma exacerbations in adults with AS-COPD (N = 901) with those with PA (N = 2392).

High blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma.

Background: Exacerbation-associated uncontrolled asthma represents a major public health problem. The relationship of elevated blood eosinophils to this process needs study.

Objective: To determine whether a high blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma.

Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study.

Background: Persistent eosinophilic airway inflammation in asthma increases the risk of exacerbations. In a phase 2b dose-ranging study, we aimed to assess the efficacy and safety of benralizumab, an anti-interleukin 5 receptor α monoclonal antibody that depletes blood and airway eosinophils, in adults with uncontrolled eosinophilic asthma.

Methods: We did a randomised, controlled, double-blind, dose-ranging phase 2b study.

High blood eosinophil count is associated with more frequent asthma attacks in asthma patients.

Background: The clinical importance of eosinophils in asthma has been shown by the observation of frequent exacerbation in patients with high sputum eosinophil counts and a corresponding decrease in exacerbations when anti-inflammatory therapy was adjusted to maintain low sputum eosinophil percentages. However, less is known of the relation between blood eosinophilia and asthma exacerbation.

Objective: To examine whether patients with asthma and a higher blood eosinophil count have more asthma attacks than those with a lower count.

Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities.

Glioblastoma is classified into two subtypes on the basis of clinical history: "primary glioblastoma" arising de novo without detectable antecedent disease and "secondary glioblastoma" evolving from a low-grade astrocytoma. Despite their distinctive clinical courses, they arrive at an indistinguishable clinical and pathologic end point highlighted by widespread invasion and resistance to therapy and, as such, are managed clinically as if they are one disease entity. Because the life history of a cancer cell is often reflected in the pattern of genomic alterations, we sought to determine whether primary and secondary glioblastomas evolve through similar or different molecular pathogenetic routes.

High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients.

To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using nonnegative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs.

High-resolution genomic profiles of human lung cancer.

Lung cancer is the leading cause of cancer mortality worldwide, yet there exists a limited view of the genetic lesions driving this disease. In this study, an integrated high-resolution survey of regional amplifications and deletions, coupled with gene-expression profiling of non-small-cell lung cancer subtypes, adenocarcinoma and squamous-cell carcinoma (SCC), identified 93 focal copy-number alterations, of which 21 span <0.5 megabases and contain a median of five genes.

Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification.

Background: Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges.

The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion.

HGK (hepatocyte progenitor kinase-like/germinal center kinase-like kinase) is a member of the human STE20/mitogen-activated protein kinase kinase kinase kinase family of serine/threonine kinases and is the ortholog of mouse NIK (Nck-interacting kinase). We have cloned a novel splice variant of HGK from a human tumor line and have further identified a complex family of HGK splice variants. We showed HGK to be highly expressed in most tumor cell lines relative to normal tissue.