An audit strategy for time-to-event outcomes measured with error: application to five randomized controlled trials in oncology.

Background: Measurement error in time-to-event end points complicates interpretation of treatment effects in clinical trials. Non-differential measurement error is unlikely to produce large bias [1]. When error depends on treatment arm, bias is of greater concern.

Research outcomes and recommendations for the assessment of progression in cancer clinical trials from a PhRMA working group.

Purpose: Progression free survival (PFS) is increasingly used as a primary end-point in oncology clinical trials. This paper provides recommendations for optimal trial design, conduct and analysis in situations where PFS has the potential to be an acceptable end-point for regulatory approval.

Patients And Methods: These recommendations are based on research performed by the Pharmaceutical Research and Manufacturers Association (PhRMA) sponsored PFS Working Group, including the re-analysis of 28 randomised Phase III trials from 12 companies/institutions.

Blinded independent central review of progression in cancer clinical trials: results from a meta-analysis.

Purpose: Progression free survival (PFS) is increasingly used as a primary end-point in oncology clinical trials. This paper provides observations and recommendations on the use of a blinded independent central review (BICR) for progression.

Patients And Methods: The findings and recommendations are based on extensive simulations and a meta-analysis based on 27 previously conducted randomised phase III trials with BICR performed by the Pharmaceutical Research and Manufacturers Association (PhRMA) sponsored PFS Independent Review Working Group.

Optimizing collection of adverse event data in cancer clinical trials supporting supplemental indications.

Purpose: Although much is known about the safety of an anticancer agent at the time of initial marketing approval, sponsors customarily collect comprehensive safety data for studies that support supplemental indications. This adds significant cost and complexity to the study but may not provide useful new information. The main purpose of this analysis was to assess the amount of safety and concomitant medication data collected to determine a more optimal approach in the collection of these data when used in support of supplemental applications.

Blinded independent central review of the progression-free survival endpoint.

Presented are the efforts of the Pharmaceutical Research and Manufacturing Association PFS Working Group to address concerns related to blinded independent central review of locally evaluated progression times and the proposed audit methodology to minimize potential biases, along with the U.S. Food and Drug Administration's comments on this work.

Effects of deoxynivalenol on content of chloroplast pigments in barley leaf tissues.

To understand further the role of deoxynivalenol (DON) in development of Fusarium head blight (FHB), we investigated effects of the toxin on uninfected barley tissues. Leaf segments, 1 to 1.2 cm long, partially stripped of epidermis were floated with exposed mesophyll in contact with DON solutions.

Morphology, life cycle biology, and DNA sequence analysis of rust fungi on garlic and chives from california.

ABSTRACT In the late 1990s, commercial garlic fields in California (CA) were devastated by an outbreak of rust caused by Puccinia allii. We compared collections of the pathogen from garlic (Allium sativum) and chives (A. schoenoprasum) in central CA and Oregon (OR) to collections from garlic and leek (A.

Distribution of Mycelial Colonies and Lesions in Field-Grown Barley Inoculated with Fusarium graminearum.

ABSTRACT External surfaces of barley florets have thick-walled epidermal cells resistant to direct penetration by the head blight pathogen, Fusarium graminearum. Surfaces within the floral cavity have thin-walled, susceptible cells. How the fungus gains access to the floral cavity, causing head blight, has not been determined.

Spore dimensions of Puccinia species of cereal hosts as determined by image analysis.

Digital image analysis was used to measure dimensions of spores produced by Puccinia coronata, P. graminis, P. hordei, P.

A comparison of the efficacy and safety of mupirocin cream and cephalexin in the treatment of secondarily infected eczema.

The efficacy and safety of mupirocin calcium cream were compared with those of oral cephalexin in the treatment of secondarily infected eczema. In this multicentre, double-blind, double-dummy study, 159 patients with secondarily infected eczema (suitable for treatment with topical antimicrobials) and a total skin infection rating scale score of 8 or more were randomized to receive either topical mupirocin cream three times daily or oral cephalexin, 250 mg four times daily, for 10 days (intent-to-treat group). Clinical success (per-protocol group), defined in part as a patient with a response of improvement in the skin infection rating scale, was similar in the two groups: 89% for mupirocin (n = 44) and 82% for cephalexin (n = 38) [P = 0.

Double-blind, randomized, parallel-group study on the efficacy and safety of oral granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in patients receiving hyperfractionated total body irradiation.

The efficacy and safety of granisetron and ondansetron for the prophylaxis of nausea and vomiting resulting from hyperfractionated total body irradiation (TBI) were assessed. Thirty-four patients randomly received double-blind, oral granisetron (2 mg, 1 h before first daily fraction of radiation) or ondansetron (8 mg, 1.5 h prior to each fraction of TBI).

Fungal development and induction of defense response genes during early infection of wheat spikes by Fusarium graminearum.

Fusarium head blight (FHB) of wheat is a crippling disease that causes severe economic losses in many of the wheat-growing regions of the world. Temporal patterns of fungus development and transcript accumulation of defense response genes were studied in Fusarium graminearum-inoculated wheat spikes within the first 48 to 76 h after inoculation (hai). Microscopy of inoculated glumes revealed that the fungus appeared to penetrate through stomata, exhibited subcuticular growth along stomatal rows, colonized glume parenchyma cells, and sporulated within 48 to 76 hai.

Mupirocin cream is as effective as oral cephalexin in the treatment of secondarily infected wounds.

Background: Topical antimicrobials have been considered for treatment of secondarily infected wounds because of the potential for reduced risk of adverse effects and greater patient convenience. We compared mupirocin cream with oral cephalexin in the treatment of wounds such as small lacerations, abrasions, or sutured wounds.

Methods: In 2 identical randomized double-blind studies, 706 patients with secondarily infected wounds (small lacerations, abrasions, or sutured wounds) received either mupirocin cream topically 3 times daily or cephalexin orally 4 times daily for 10 days.

Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial.

Context: The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use.

Objective: To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia.

Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy.

Purpose: To compare the antiemetic efficacy of a single dose of an oral antiemetic (granisetron 2 mg) with a single dose of an intravenous (i.v.) antiemetic (ondansetron 32 mg) given before cisplatin-based chemotherapy.

Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study.

Purpose: The antiemetic effectiveness and safety of single-dose oral granisetron were compared with intravenous (I.V.) ondansetron in chemotherapy-naive patients who received moderately emetogenic chemotherapy.

Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder.

Objective: This study was designed to determine the minimum paroxetine dose effective for treating panic disorder.

Method: Of 425 patients with DSM-III-R panic disorder with or without agoraphobia who underwent a 2-week drug-free screening period, 278 patients were randomly assigned to double-blind treatment with a 10-week course of placebo or paroxetine at a dose of 10, 20, or 40 mg/day.

Results: At 40 mg/day, paroxetine was superior to placebo across the majority of outcome measures.

Isolation and expression of a host response gene family encoding thaumatin-like proteins in incompatible oat-stem rust fungus interactions.

Four cDNA clones (corresponding to tlp-1, -2, -3, and -4 genes) encoding thaumatin-like (TL), pathogenesis-related proteins were isolated from oat (Avena sativa) infected by an incompatible isolate Pga-1H of the oat stem rust fungus (Puccinia graminis f. sp. avenae).

A double-blind, randomized study to provide safety information on switching fluoxetine-treated patients to paroxetine without an intervening washout period.

Background: The long elimination half-lives of fluoxetine and norfluoxetine, the active metabolite of fluoxetine, are of potential consequence when alternative antidepressant agents are introduced after the termination of fluoxetine therapy. It is not known whether paroxetine, an antidepressant agent in the same pharmacologic class as fluoxetine, can be substituted for fluoxetine without the need for an intervening washout period. The objective of this trial was to assess the tolerability of an immediate switch from fluoxetine to paroxetine therapy.

Molecular cloning and analysis of abundant and stage-specific mRNAs from Puccinia graminis.

To characterize highly expressed mRNAs from germinated urediniospores of Puccinia graminis f. sp. tritici, we isolated 68 cDNA clones of abundant mRNA species belonging to at least six homology groups.

Callus formation and plant regeneration from somatic embryos of oat (Avena sativa L.).

Globular-stage somatic embryos were isolated by vortexing friable, embryogenic callus of oat (Avena sativa L.) followed by fractionation based on size. Somatic embryos were most frequently found in the 300-380 μm size fraction.

Pontentiometric cyanine dyes are sensitive probes for mitochondria in intact plant cells : kinetin enhances mitochondrial fluorescence.

Selected fluorescent dyes were tested for uptake by mitochrondria in intact cells of barley, maize, and onion. The cationic cyanine dye 3,3'-diheptyloxacarbocyanine iodide [DiOC(7)(3)] accumulated in mitochondria within 15 to 30 minutes without appreciable staining of other protoplasmic constituents. The number, shape, and movement of the fluorescent mitochondria could be seen readily, and the fluorescence intensity of the mitochondria could be monitored with a microscope photometer.