Performance of Multiple-Batch Approaches to Pharmacokinetic Bioequivalence Testing for Orally Inhaled Drug Products with Batch-to-Batch Variability.

Batch-to-batch pharmacokinetic (PK) variability of orally inhaled drug products has been documented and can render single-batch PK bioequivalence (BE) studies unreliable; results from one batch may not be consistent with a repeated study using a different batch, yet the goal of PK BE is to deliver a product comparison that is interpretable beyond the specific batches used in the study. We characterized four multiple-batch PK BE approaches to improve outcome reliability without increasing the number of clinical study participants. Three approaches include multiple batches directly in the PK BE study with batch identity either excluded from the statistical model ("Superbatch") or included as a fixed or random effect ("Fixed Batch Effect," "Random Batch Effect").

Performance of the Population Bioequivalence (PBE) Statistical Test with Impactor Sized Mass Data.

This article extends previous work studying performance characteristics of the population bioequivalence (PBE) statistical test recommended by the US Food and Drug Administration (FDA) for orally inhaled and nasal drug products. Based on analysis of a metered dose inhaler database for impactor sized mass, a simulation study was designed to compare performance of the recommended PBE approach with several modified or alternative approaches. These included an extended PBE that separately modeled within-batch (can) and between-batch (batch) variability and average bioequivalence (ABE) tests that modeled with or without between-batch variability and with or without log-transformation.

Performance of the Population Bioequivalence (PBE) Statistical Test Using an IPAC-RS Database of Delivered Dose from Metered Dose Inhalers.

This article reports performance characteristics of the population bioequivalence (PBE) statistical test recommended by the US Food and Drug Administration (FDA) for orally inhaled products. A PBE Working Group of the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) assembled and considered a database comprising delivered dose measurements from 856 individual batches across 20 metered dose inhaler products submitted by industry. A review of the industry dataset identified variability between batches and a systematic lifestage effect that was not included in the FDA-prescribed model for PBE.

Randomized Trial of Telegenetics vs. In-Person Cancer Genetic Counseling: Cost, Patient Satisfaction and Attendance.

Telegenetics-genetic counseling via live videoconferencing-can improve access to cancer genetic counseling (CGC) in underserved areas, but studies on cancer telegenetics have not applied randomized methodology or assessed cost. We report cost, patient satisfaction and CGC attendance from a randomized trial comparing telegenetics with in-person CGC among individuals referred to CGC in four rural oncology clinics. Participants (n = 162) were randomized to receive CGC at their local oncology clinic in-person or via telegenetics.

Feasibility and preliminary effects of a virtual environment for adults with type 2 diabetes: pilot study.

Background: Innovative interventions that empower patients in diabetes self-management (DSM) are needed to provide accessible, sustainable, cost-effective patient education and support that surpass current noninteractive interventions. Skills acquired in digital virtual environments (VEs) affect behaviors in the physical world. Some VEs are programmed as real-time three-dimensional representations of various settings via the Internet.

Care of an undocumented immigrant: Case and comment.

This commentary addresses the care of an undocumented immigrant with neuromyelitis optica in the context of a state law designed to deny state-funded medical services to individuals whose presence in the United States is unlawful. It considers specific circumstances in which the law would permit or require medical care for undocumented persons in state medical facilities, including a duty to "stabilize" an "emergency medical condition" and the provision of care necessary to "protect life or safety." It also addresses dilemmas clinicians may experience when faced with an apparent tension between their professional ethical obligations and legal rules aimed at enforcing immigration policies.

Legal process, litigation, and judicial decisions.

Ethically salient issues in neurologic care may have important legal overtones. This chapter considers some of these, emphasizing how law may influence the outcome of controversies over how best to promote autonomy, beneficence, and justice in the care of individuals with neurologic disorders. Constitutional, statutory, and judicial dimensions are addressed.

Building a Virtual Environment for Diabetes Self-Management Education and Support.

The authors developed an immersive diabetes community to provide diabetes self-management education and support for adults with type 2 diabetes. In this article the authors describe the procedures used to develop this virtual environment (VE). Second Life Impacts Diabetes Education & Self-Management (SLIDES), the VE for our diabetes community was built in Second Life.

Research management team (RMT): a model for research support services at Duke University.

Collecting and managing data for clinical and translational research presents significant challenges for clinical and translational researchers, many of whom lack needed access to data management expertise, methods, and tools. At many institutions, funding constraints result in differential levels of research informatics support among investigators. In addition, the lack of widely shared models and ontologies for clinical research informatics and health information technology hampers the accurate assessment of investigators' needs and complicates the efficient allocation of crucial resources for research projects, ultimately affecting the quality and reliability of research.

Evaluation of the effectiveness of a phonoaudiology program for the rehabilitation of dysphagia in the elderly.

The object of this study was to evaluate the effectiveness of a phonoaudiology rehabilitation program directed towards the degenerative changes of the neurophysiological mechanisms responsible for the upper digestive system compromised by the age between 80 and 90 years, in a regime of internment in a long permanence institution in the city of Rio de Janeiro, which express, bodily, their difficulty in swallowing food of liquid or pasty consistency. To achieve such an object, the current study was developed in an experimental format or design, comprised of a sample group of 23 elderly subjects, of both genders, undergoing evaluation by the phonoaudiology protocol for evaluating the risk of dysphagia (abbreviated from the Portuguese name: Protocolo de Avaliação do Risco para Disfagia=PARD), pre- and post-intervention procedure. The developed program used the indirect therapy approach based on the adaptive myotherapeutic and myofunctional stimulation, contemplating two isometric and isokinetic orofacial active myotherapeutic exercises, two passive myotherapeutic manipulations for the supra-hyoidal musculature, as well as adaptive cephalic postural maneuvres, associated to the intra-oral olfactive and gustative sensory stimulation.

Quality of life (QOL) axiological profile of the elderly population served by the Family Health Program (FHP) in Brazil.

With the purpose of optimizing the satisfaction of the elderly subjects, either existential or not, presenting their unique preference, this research aimed to evaluate the effects of aging on QOL of the aged persons, served by the FHP. The basic intention was to establish parameters of QOL-impact on aging. Our sample was a non-selected population of aged volunteers from Perequê-Mirim-I Family Health Unity, in Caraguatatuba, São Paulo, Brazil.

Invited article: professionalism in neurology: the role of law.

Professionalism may be defined as the obligation of the physician to uphold the primacy of patients' interests, to achieve and maintain medical competency, and to abide by high ethical standards. Recent commentary has suggested that medical professionalism is being threatened by commercialism and the legal system. Consideration of judicial rulings centered on primacy of patients' interests (informed consent, end-of-life care, and conflicts of interest), medical competence (standard of care in medical malpractice cases, medical futility cases, and confidentiality of peer review), and enforcement of ethical standards (peer review by professional organizations) demonstrates that the law generally defers to standards set by the medical profession, but competing views over what health care model is operative may generate non-deferential outcomes.

Formulation development and manufacturing of a gastrin/CCK-2 receptor targeting peptide as an intermediate drug product for a clinical imaging study.

A DOTA-gastrin analogue (APH070) which, when labelled with (111)In, has high affinity for the gastrin/CCK-2 receptor (3nM) and low tumour to kidney ratio in animal models, has been formulated and manufactured for a clinical study. Oxidation of the peptide methionine residue greatly reduces receptor affinity, therefore development work focused on producing a stable intermediate drug product (iDP) whilst ensuring that the formulation, container, closure and manufacturing process did not inhibit the extremely sensitive radiolabelling reaction (itself a source of oxidation). Stress testing revealed that APH070 was stable at 2-8 degrees C at pH 6-9.

Hypercortisolism in alcohol dependence and its relation to hippocampal volume loss.

Objective: The effects of hypercortisolism on hippocampal volume have not been studied in heavy drinkers. Prior work suggested increased hypothalamic-pituitary-adrenal activity in relation to lowered total hippocampus volume (THV) in heavy-drinking alcohol-dependent (AD) subjects. The present study hypothesized the following: (1) that chronic heavy-drinking subjects would demonstrate significantly higher salivary cortisol concentrations than light-drinking control subjects and (2) that data from the whole sample group would present an inverse relationship between cortisol concentration and THV.

Cyclosporine-A discourages ethanol intake in C57bl/6j mice: a preliminary study.

Objective: Remarkably high rates of abstinence occur among alcohol-dependent persons after a liver transplant. This was thought to be solely due to selection or other nonbiological factors. Observing sustained abstinence for many months to years after a liver transplant, however, we asked whether immunosuppressants might exert a biological effect that supported abstinence from ethanol.

Aripiprazole in schizophrenia with cocaine dependence: a pilot study.

The debilitation of schizophrenia (SCHZ) worsens markedly with comorbid cocaine dependence (CD) and alcohol abuse. To date, no medications have conclusively demonstrated effects against both SCHZ and CD (SCHZ + CD) simultaneously. Because of its dopamine-modulating properties, we hypothesized that aripiprazole would alleviate cocaine craving in patients with SCHZ + CD.

Brain death.

Current law in the United States authorizes physicians to diagnose brain death by applying generally accepted neurologic criteria for determining loss of function of the entire brain. This article offers a medical-legal perspective on problems that may arise with respect to the determination of brain death. These include the possibility of diagnostic error, conceptual disagreements that may constrain the use of neurologic criteria to diagnose death, and the conflation of brain death and loss of consciousness.