Effects of duloxetine on norepinephrine and serotonin transporter activity in healthy subjects.

Duloxetine selectively inhibits the serotonin (5-HT) and norepinephrine (NE) transporters (5-HTT and NET, respectively), as demonstrated in vitro and in preclinical studies; however, transporter inhibition has not been fully assessed in vivo at the approved dose of 60 mg/d. Here, the in vivo effects of dosing with duloxetine 60 mg once daily for 11 days in healthy subjects were assessed in 2 studies: (1) centrally (n = 11), by measuring concentrations of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylglycol (DHPG), and NE in cerebrospinal fluid, and (2) versus escitalopram 20 mg/d (n = 32) in a 2-period crossover study by assessing the ΔDHPG/ΔNE ratio in plasma during orthostatic testing and by pharmacokinetic/pharmacodynamic modeling of reuptake inhibition using subjects' serum in cell lines expressing cloned human 5-HTT or NET. At steady state, duloxetine significantly reduced concentrations of DHPG and 5-hydroxyindoleacetic acid (P < 0.

A phase II study with cetuximab and radiation therapy for patients with surgically resectable esophageal and GE junction carcinomas: Hoosier Oncology Group G05-92.

Introduction: On the basis of the promising activity of cetuximab and radiation therapy for head and neck cancers, we evaluated the efficacy of this regimen followed by surgery in patients with resectable esophageal cancer. This was a phase II, open-label, single-arm, multicenter study of patients with potentially resectable esophageal cancer.

Methods: Patients received two weekly doses of cetuximab followed by weekly cetuximab combined with radiation therapy for 6 weeks.

Capturing incentives and avoiding penalties: The carrot and the stick.

Over the past decade, health care in the United States has been a topic of intense political debate, resulting in dramatic legislative, regulatory, and economic changes. These changes have occurred due to the unsustainable rise of health care costs without accompanying improvement in measured health outcomes when compared to other economically developed countries. In an attempt to contain costs and improve the quality of health care provided, the Center for Medicare and Medicaid Services has implemented 4 distinct incentive-based programs.

Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia.

Background: Familial hypocalciuric hypercalcemia is a genetically heterogeneous disorder with three variants: types 1, 2, and 3. Type 1 is due to loss-of-function mutations of the calcium-sensing receptor, a guanine nucleotide-binding protein (G-protein)-coupled receptor that signals through the G-protein subunit α11 (Gα11). Type 3 is associated with adaptor-related protein complex 2, sigma 1 subunit (AP2S1) mutations, which result in altered calcium-sensing receptor endocytosis.

Methods for the design of vasomotor symptom trials: the menopausal strategies: finding lasting answers to symptoms and health network.

Objective: This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials.

Methods: Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control.

Proceedings of the 46th annual Pancreas Club meeting.

The 46th annual Pancreas Club meeting was held on May 18 and 19 at the Hyatt Regency Mission Bay in San Diego, California. A brief summary of the meeting including an overview in table form is presented below.

Epigenetic regulation of NANOG by miR-302 cluster-MBD2 completes induced pluripotent stem cell reprogramming.

While most somatic cells undergoing induced pluripotent stem (iPS) cell reprogramming with Yamanaka factors accumulate at stable partially reprogrammed stages, the molecular mechanisms required to achieve full reprogramming are unknown. MicroRNAs (miRNAs) fine-tune mRNA translation and are implicated in reprogramming, but miRNA functional targets critical for complete iPS cell reprogramming remain elusive. We identified methyl-DNA binding domain protein 2 (MBD2) as an epigenetic suppressor, blocking full reprogramming of somatic to iPS cells through direct binding to NANOG promoter elements preventing transcriptional activation.

Navigating ethics of physician-patient confidentiality: a communication privacy management analysis.

The ethics of physician-patient confidentiality is often fraught with contradictions. Privacy boundaries are not always clear, and patients can leave an interaction with their physicians feeling uncomfortable about the security of their private medical information. The best way to meet confidentiality and privacy management expectations that patients have may not be readily apparent.

Preemptive use of high-frequency oscillatory ventilation in pediatric burn patients.

There is a high incidence of developing acute respiratory distress syndrome (ARDS) in pediatric patients with major burns, and this development leads to higher mortality. High-frequency oscillatory ventilation (HFOV) has been used to treat pediatric patients with severe ARDS. The decision of when to start HFOV in the pediatric burn victim with ARDS is debatable.

The effect of reference panels and software tools on genotype imputation.

Genotype imputation is increasingly employed in genome-wide association studies, particularly for integrative and cross-platform analysis. Several imputation algorithms use reference panels with a larger set of genotyped markers to infer genotypes at ungenotyped marker locations. Our objective was to assess which method and reference panel was more accurate when carrying out imputation.

All health care is not local: an evaluation of the distribution of Emergency Department care delivered in Indiana.

The Emergency Department (ED) delivers a major portion of health care - often with incomplete knowledge about the patient. As such, EDs are particularly likely to benefit from a health information exchange (HIE). The Indiana Public Health Emergency Surveillance System (PHESS) sends real-time registration information for emergency department encounters.

Practical challenges in the secondary use of real-world data: the notifiable condition detector.

The interoperability specifications for electronic laboratory reporting specify the use of HL7, LOINC, SNOMED CT and UCUM. We explored the degree to which health care transactions comply with these standards by evaluating laboratory data captured in a health information exchange to support automated detection of public health notifiable diseases. We studied the NCD's ability to detect and report Lead, Influenza and MRSA.

Implementation of a stroke self-management program: A randomized controlled pilot study of veterans with stroke.

Secondary stroke prevention is championed as guideline care; yet there are no systematic programs offered. We developed a stroke self-management program to address this gap and pilot test the program. We conducted a randomized controlled trial at two Veterans Administration (VA) hospital sites where we recruited patients with an acute stroke to receive either the stroke program or an attention-control protocol over a 12-week period following hospital discharge.

Initial findings: primary diabetes care responsibility among emerging adults with type 1 diabetes post high school and move out of parental home.

Background: Emerging adults with diabetes are assuming diabetes care responsibility, graduating from high school and leaving their parental homes. We examined: (1) how diabetes care responsibility changed in relation to time (high school to post high school) and living situation (living independently or not of parents) and (2) the association of diabetes self-efficacy, worry about hypoglycaemia, gender and glycaemic control with these changes in responsibility among emerging adults with type 1 diabetes.

Methods:   During the last 6 months in high school (T1), 113 participants completed diabetes care responsibility (total, daily and non-daily), diabetes self-efficacy and worry about hypoglycaemia scales.

Understanding Values in a Large Health Care Organization through Work-Life Narratives of High-Performing Employees.

OBJECTIVE—: To understand high-performing frontline employees' values as reflected in their narratives of day-to-day interactions in a large health care organization. METHODS—: A total of 150 employees representing various roles within the organization were interviewed and asked to share work-life narratives (WLNs) about value-affirming situations (i.e.

Autopsy diagnosis of fat embolism syndrome.

The fat embolism syndrome (FES) is considered a clinical diagnosis. It typically occurs within several days following major traumatic injury, usually involving fractures of the pelvis and/or lower extremities. Fat embolism syndrome is characterized by the onset of respiratory, neurological, cutaneous, and hematologic manifestations and is thought to be related to intravascular embolization of fat, presumably arising from within the fractured bone marrow space.

Facility and market factors affecting transitions from nursing home to community.

Background: Research into nursing home transitions has given limited attention to the facility or community contexts.

Objective: To identify facility and market factors affecting transitions of nursing home residents back to the community.

Research Design: Multilevel models were used to estimate effects of facility and market factors on facility-level community discharge rates after controlling for resident demographic, health, and functional conditions.

Ectopic expression of cadherin 8 is sufficient to cause cyst formation in a novel 3D collagen matrix renal tubule culture.

While a variety of genetic mutations have been shown to be associated with renal cyst formation, mechanisms of renal cyst formation are largely unknown. In prior communications we described alterations in E-cadherin assembly in cultured cystic epithelial cells (Charron AJ, Nakamura S, Bacallao R, Wandinger-Ness A. J Cell Biol 149: 111-124, 2000).

Efficacy and onset of action of hydrocortisone acetate 2.5% and pramoxine hydrochloride 1% lotion for the management of pruritus: results of a pilot study.

Itch is the most common symptom among patients presenting to the dermatology clinic. Scratching can cause mechanical trauma to the skin, further damaging the epidermal barrier and its function. This damage can facilitate the introduction of microbes that complicate the presenting disease and its management.

Disclosure predicaments arising during the course of patient care: nurses' privacy management.

At times, nurses receive patient disclosures that have the potential to create challenges resulting in needs for strategies to manage patient information and expectations. This study examines disclosure predicaments nurses experience in critical care and emergency units at a large urban hospital. Utilizing the constant comparative method to identify disclosure themes guided by the principles of communication privacy management (CPM), the findings show that nurses regulate patient privacy in the role of stakeholder confidants.

Representing Patient Assessments in LOINC®.

Without being included in accepted vocabulary standards, the results of completed patient assessment instruments cannot be easily shared in health information exchanges. To address this important barrier, we have developed a robust model to represent assessments in LOINC through iterative refinement and collaborative development. To capture the essential aspects of the assessment, the LOINC model represents the hierarchical panel structure, global item attributes, panel-specific item attributes, and structured answer lists.

Automatic Prediction of Conversion from Mild Cognitive Impairment to Probable Alzheimer's Disease using Structural Magnetic Resonance Imaging.

Mild Cognitive Impairment (MCI) is thought to be a precursor to the development of early Alzheimer's disease (AD). For early diagnosis of AD, the development of a model that is able to predict the conversion of amnestic MCI to AD is challenging. Using automatic whole-brain MRI analysis techniques and pattern classification methods, we developed a model to differentiate AD from healthy controls (HC), and then applied it to the prediction of MCI conversion to AD.