A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer.

Purpose: Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride (radium-223) in men with mCRPC.

Patients And Methods: This phase Ib study evaluated atezolizumab + radium-223 in men with mCRPC and bone and lymph node and/or visceral metastases that progressed after androgen pathway inhibitor treatment.

Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade.

Integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients identifies molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis reveals seven molecular subsets with distinct angiogenesis, immune, cell-cycle, metabolism, and stromal programs. While sunitinib and atezolizumab + bevacizumab are effective in subsets with high angiogenesis, atezolizumab + bevacizumab improves clinical benefit in tumors with high T-effector and/or cell-cycle transcription.

Five-Factor Prognostic Model for Survival of Post-Platinum Patients with Metastatic Urothelial Carcinoma Receiving PD-L1 Inhibitors.

Purpose: A prognostic model for overall survival of post-platinum patients with metastatic urothelial carcinoma receiving PD-1/PD-L1 inhibitors is necessary as existing models were constructed in the chemotherapy setting.

Materials And Methods: Patient level data were used from phase I/II trials evaluating PD-L1 inhibitors following platinum based chemotherapy for metastatic urothelial carcinoma. The derivation data set consisted of 2 phase I/II trials evaluating atezolizumab (405).

Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial.

Background: Atezolizumab can induce sustained responses in metastatic urothelial carcinoma. We report the results of IMvigor130, a phase 3 trial that compared atezolizumab with or without platinum-based chemotherapy versus placebo plus platinum-based chemotherapy in first-line metastatic urothelial carcinoma.

Methods: In this multicentre, phase 3, randomised trial, untreated patients aged 18 years or older with locally advanced or metastatic urothelial carcinoma, from 221 sites in 35 countries, were randomly assigned to receive atezolizumab plus platinum-based chemotherapy (group A), atezolizumab monotherapy (group B), or placebo plus platinum-based chemotherapy (group C).

Cost of cystectomy-related complications in patients with bladder cancer in the United States.

To describe healthcare utilization and cost associated with the short-term and long-term complications of cystectomy among commercially insured bladder cancer patients in the United States. This retrospective, observational cohort study evaluated adults with bladder cancer receiving a transurethral resection of bladder tumor followed by a partial or radical cystectomy procedure using U.S.

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Clinical Experience from an Expanded Access Study in the United States.

Background: Atezolizumab (anti-programmed death-ligand 1) was approved in the USA, Europe, and elsewhere for treatment-naive and platinum-treated locally advanced/metastatic urothelial carcinoma (mUC).

Objective: To report efficacy and safety from an atezolizumab expanded access study.

Design, Setting, And Participants: This single-arm, open-label study enrolled 218 patients at 36 US sites.

Regional disparities in the quality of stroke care.

Background And Purpose: There is widespread geographic variation in healthcare quality, but we often lack clear strategies for improving quality in underserved areas. This study characterized geographic disparities in stroke care quality to assess whether improved access to neurological services has the potential to bridge the care quality gap, particularly in terms of alteplase (rt-PA) administration.

Methods: This was a retrospective study using quality performance data from the 2015 Hospital Compare database linked to information on certification status from the Joint Commission and information on local access to neurological services from the Area Health Resources File.

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke).

Quality adjusted life year gains associated with administration of recombinant tissue-type plasminogen activator for treatment of acute ischemic stroke: 1998-2011.

Background: Intravenous recombinant tissue-type plasminogen activator (r-tPA) is an approved treatment for select patients with acute ischemic stroke (AIS). Data indicate r-tPA improves functional outcome three months after AIS compared with placebo. This study models the increase in quality adjusted life years (QALYs) associated with r-tPA compared with similar patients not treated with r-tPA.

Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3: Post Hoc Analysis.

Background And Purpose: Randomized trial evidence on the risk/benefit ratio of thrombolysis for mild stroke is limited. We sought to determine the efficacy of intravenous recombinant tissue-type plasminogen activator (IV r-tPA) in a subset of patients with mild deficit in the third International Stroke Trial (IST-3).

Methods: IST-3 compared IV r-tPA with control within 6 hours of onset in patients for whom IV r-tPA was considered promising but unproven.

Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies.

Large multicenter acute stroke trials demand a randomization procedure with a high level of treatment allocation randomness, an effective control on overall and within-site imbalances, and a minimized time delay of study treatment caused by the randomization procedure. Driven by the randomization algorithm design of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients with Mild Stroke (PRISMS) (NCT02072226), this paper compares operational and statistical properties of different randomization algorithms in local, central, and step-forward randomization settings. Results show that the step-forward randomization with block urn design provides better performances over others.

Cost-effectiveness of recombinant tissue-type plasminogen activator within 3 hours of acute ischemic stroke: current evidence.

Background And Purpose: Despite the availability of results from multiple newer clinical trials and changing healthcare costs, the cost-effectiveness of recombinant tissue-type plasminogen activator (r-tPA) for treatment of acute ischemic stroke within 0 to 3 hours of symptom onset was last evaluated in 1998 for the United States Using current evidence, we evaluate the long-term cost-effectiveness of r-tPA administered 0 to 3 hours after acute ischemic stroke onset versus no r-tPA.

Methods: A disease-based decision model to project lifetime outcomes of patients after acute ischemic stroke by r-tPA treatment status from the US payer perspective was developed. Model inputs were derived from a recent meta-analysis of r-tPA trials, cohort studies, and health state preference studies.

Comparison of hospital length of stay, costs, and readmissions of alteplase versus catheter replacement among patients with occluded central venous catheters.

Background: Central venous catheter (CVC) occlusion is common, affecting 30% of all CVCs.

Objective: To compare length of stay (LOS), costs, and readmissions associated with the use of alteplase to clear catheter blockage to outcomes associated with catheter replacement.

Design: Retrospective observational study utilizing a large hospital database.

Gene expression profiles and B-type natriuretic peptide elevation in heart transplantation: more than a hemodynamic marker.

Background: B-type natriuretic peptide (BNP) is chronically elevated in heart transplantation and reflects diastolic dysfunction, cardiac allograft vasculopathy, and poor late outcome. This investigation studied peripheral gene expression signatures of elevated BNP concentrations in clinically quiescent heart transplant recipients in an effort to elucidate molecular correlates beyond hemodynamic perturbations.

Methods And Results: We performed gene microarray analysis in peripheral blood mononuclear cells of 28 heart transplant recipients with clinical quiescence (absence of dyspnea or fatigue; normal left ventricular ejection fraction [EF >55%]; ISHLT biopsy score 0 or 1A; and normal hemodynamics [RAP <7 mm Hg, PCWP < or = 15 mm Hg, and CI > or = 2.