Frequency of safety net errors in the emergency department: Effect of patient handoffs.

Objectives: The objective of this study was to determine physician awareness of abnormal vital signs and key clinical interventions (oxygen provision, intravenous access) in the emergency department, and to measure the effect of patient handoffs on this awareness.

Methods: This was a prospective observational study at two large, urban, academic emergency departments. Emergency department physicians were asked the following about each of the physician's patients: 1) the number of IV lines, 2) whether the patient was on supplemental oxygen, and 3) whether the patient had any abnormal vital signs.

Evaluation of Commercial Milk-Specific Lateral Flow Devices.

The requirement for validation of allergen cleaning processes is increasing. The use of lateral flow devices (LFDs) to identify allergens has rapidly expanded, but the best practices for use of these devices are still developing. The goal of this study was to compare commercially available milk-specific LFDs and a general protein identification method.

Novel homozygous likely-pathogenic intronic variant in INS causing permanent neonatal diabetes in siblings.

Permanent neonatal diabetes (PNDM) is a rare genetic condition characterized by hyperglycemia, insulinopenia, and failure to thrive beginning in the first 6 months of life. Recessive mutations in INS lead to decreased production of insulin via a variety of mechanisms. We present a case of two brothers, born to consanguineous parents, with a novel homozygous intronic variant in the INS gene.

Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study.

Background: Activation of the Hedgehog signalling pathway contributes to cancer progression and the development of myeloid leukaemia stem cell therapeutic resistance. We aimed to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose of the selective Hedgehog antagonist PF-04449913 in myeloid malignancies.

Methods: We undertook an open-label, dose-finding, standard 3+3 design phase 1 study of PF-04449913 in adult patients with acute myeloid leukaemia, chronic myeloid leukaemia, chronic myelomonocytic leukaemia, myelodysplastic syndrome, or myelofibrosis who were refractory, resistant, or intolerant to previous treatments, at three centres in the USA and one in Italy.

A phase I study of PF-04449913, an oral hedgehog inhibitor, in patients with advanced solid tumors.

Purpose: To estimate the maximum tolerated dose (MTD) of single-agent PF-04449913, and to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in patients with advanced tumors.

Experimental Design: A 3+3 design was used in this open-label, multicenter, phase I study and dose escalation/de-escalation applied until identification of the MTD. PF-04449913 was orally administered once daily in continuous 28-day treatment cycles.

Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.

Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis.

Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer.

Purpose: To identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the first-in-class, oral CDK4/6 inhibitor PD 0332991 administered once daily for 21 of 28 days (3/1 schedule) in patients with retinoblastoma protein (Rb)-positive advanced solid tumors and to describe pharmacokinetic-pharmacodynamic relationships relative to drug effects.

Experimental Design: This open-label phase I study (NCT00141297) enrolled patients who received PD 0332991 orally in six dose-escalation cohorts in a standard 3 + 3 design.

Results: Forty-one patients were enrolled.

A phase 2, randomized, dose-response trial of taprenepag isopropyl (PF-04217329) versus latanoprost 0.005% in open-angle glaucoma and ocular hypertension.

Purpose: To evaluate the safety of escalating doses of taprenepag isopropyl (PF-04217329), a selective EP(2) receptor agonist administered as a topical ophthalmic solution, versus its vehicle (Stage I), and dose-response of taprenepag isopropyl alone and in unfixed combination with latanoprost ophthalmic solution 0.005% versus latanoprost alone (Stage II).

Subjects And Methods: Randomized, vehicle- and active-controlled, double-masked, two-stage, dose-finding trial in primary open-angle glaucoma (POAG) or ocular hypertension; first taprenepag isopropyl study in patients (NCT00572455).

Latanoprost systemic exposure in pediatric and adult patients with glaucoma: a phase 1, open-label study.

Objective: To evaluate short-term safety and steady-state systemic pharmacokinetics (PK) of latanoprost acid in pediatric subjects with glaucoma or ocular hypertension who received the adult latanoprost dose.

Design: Phase 1, open-label, multicenter study.

Participants: Pediatric patients of 3 age groups (<3, 3-<12, and 12-<18 years) and adults (≥18 years) receiving latanoprost ophthalmic solution 0.

Modulation of 11beta-hydroxysteroid dehydrogenase (11betaHSD) activity biomarkers and pharmacokinetics of PF-00915275, a selective 11betaHSD1 inhibitor.

Context: 11beta-Hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a promising target for the treatment of type 2 diabetes mellitus. 11betaHSD1 catalyzes the intracrine conversion of inactive cortisone to the active glucocorticoid cortisol.

Objective: Demonstrating inhibition of 11betaHSD1 is challenging because there is no accessible way to directly assess the enzyme activity in vivo.

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 activity in vivo limits glucocorticoid exposure to human adipose tissue and decreases lipolysis.

Context: The pathophysiological importance of glucocorticoids (GCs) is exemplified by patients with Cushing's syndrome who develop hypertension, obesity, and insulin resistance. At a cellular level, availability of GCs to the glucocorticoid and mineralocorticoid receptors is controlled by the isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). In liver and adipose tissue, 11beta-HSD1 converts endogenous, inactive cortisone to active cortisol but also catalyzes the bioactivation of the synthetic prednisone to prednisolone.

Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations.

Background And Objective: Posaconazole is a potent, extended-spectrum triazole antifungal agent currently in clinical development for the treatment of invasive fungal infections. This study was conducted to compare the bioavailability and resulting serum concentrations of posaconazole 800 mg following administration of three different dose regimens to fasting adults.

Study Design: This was a randomised, open-label, three-way crossover study.

Disposition of posaconazole following single-dose oral administration in healthy subjects.

Posaconazole is a potent, broad-spectrum triazole antifungal agent currently in clinical development for the treatment of refractory invasive fungal infections. Eight healthy male subjects received a single 399-mg (81.7 microCi) oral dose of [(14)C]posaconazole after consuming a high-fat breakfast.

Pharmacokinetics of posaconazole coadministered with antacid in fasting or nonfasting healthy men.

Posaconazole is a potent broad-spectrum azole antifungal agent in clinical development for the treatment of invasive fungal infections. This study evaluated the potential for a pH-dependent pharmacokinetic interaction between posaconazole and an antacid (Mylanta), under fasting and nonfasting conditions. Twelve men completed this randomized, four-period crossover, single-dose study.

Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults.

Aims: This randomized, crossover, single-dose study evaluated the relative oral bioavailability of posaconazole suspension and coprecipitate tablet formulations. Additionally, the study determined whether systemic exposure to posaconazole was affected by prandial status or by the fat content of a meal.

Methods: This was a randomized, open-label, four-way crossover, single-dose study in 20 healthy men.

A practical model for preventing type 2 diabetes in minority youth.

Purpose: This article proposes a model grounded in behavioral theory and empirical evidence for use when developing a program to prevent type 2 diabetes in high-risk minority youth.

Methods: The model is based on key concepts of 4 behavioral theories: the Health Belief Model, Social Learning Theory, the Theory of Planned Behavior, and the Ecological Model. Determinants of behavior to target for change are selected based on their theoretical link to behavior change, their success in changing behavior in past programs, and through thorough formative research in the target community.

Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults.

The pharmacokinetics, safety, and tolerability of posaconazole, an investigational triazole antifungal, were evaluated following the administration of rising single and multiple oral doses. A total of 103 healthy adults were enrolled in two phase I trials. Each study had a double-blind, placebo-controlled, parallel-group design with a rising single-dose (RSD) or rising multiple-dose (RMD) scheme.