IDEAL-D Framework for Device Innovation: A Consensus Statement on the Preclinical Stage.

OBJECTIVE: To extend the IDEAL framework for device innovation, IDEAL-D, to include the preclinical stage of development (stage 0). BACKGROUND: In previous work, the IDEAL collaboration has proposed frameworks for new surgical techniques and complex therapeutic technologies, the central tenet being that development and evaluation can and should proceed together in an ordered and logical manner that balances innovation and safety. METHODS: Following agreement at the IDEAL Collaboration Council, a multidisciplinary working group was formed comprising 12 representatives from healthcare, academia, industry, and a patient advocate. The group conducted a series of discussions following the principles used in the development of the original IDEAL framework. Importantly, IDEAL aims for maximal transparency, optimal validity in the evaluation of primary effects, and minimization of potential risk to patients or others. The proposals were subjected to further review and editing by members of the IDEAL Council before a final consensus version was adopted. RESULTS: In considering which studies are required before a first-in-human study, we have: (1) classified devices according to what they do and the risks they carry, (2) classified studies according to what they show about the device, and (3) made recommendations based on the principle that the more invasive and high risk a device is, the greater proof required of their safety and effectiveness before progression to clinical studies (stage 1). CONCLUSIONS: The proposed recommendations for preclinical evaluation of medical devices represent a proportionate and pragmatic approach that balances the de-risking of first-in-human translational studies against the benefits of rapid translation of new devices into clinical practice.

Research for practice: a new in vitro test for identification of tuberculosis infection.

Tuberculosis is one of the biggest global health problems. One-third of the world's population (2 billion) is latently infected with tuberculosis. The tuberculin skin test is commonly used to diagnose tuberculosis infection. This test has poor specificity and sensitivity, cross-reactivity with bacille Calmette-Guérin vaccination and many environmental mycobacteria, and poor sensitivity (only 75-90% in active tuberculosis). Mycobacterium tuberculosis activates a strong T cell-mediated immune response. That is why, a better marker for tuberculosis infection could be the presence of mycobacteria specific interferon-gamma-secreting T cells. These cells can be identified in blood or any other sample, which contains T cells. The test specificity is 99.9% (in low-risk control groups), and the sensitivity is 97.2% (in subjects with culture-confirmed active disease). New in vitro diagnostic test of tuberculosis, based on tuberculosis-induced immunological mechanisms, seems to be more specific and useful as previous methods.

Making interprofessional education real: a university clinic model.

Interprofessional education (IPE) is an emerging focus in the professional training of allied health students. To date, IPE has occurred in classroom teaching or case simulations, rather than in the provision of client services. At the University of Queensland, students in occupational therapy, speech pathology and music therapy participate in both on-campus and community-based IPE clinics conducted by university staff. These clinics are planned and implemented to promote interprofessional learning for students, and to provide integrated service provision for children and young people in the community. An adapted version of Bronstein's model of interdisciplinary collaboration is used to guide IPE processes, including team orientation, joint goal-setting and intervention planning, and integrated delivery of therapy sessions. The development and implementation of these IPE clinics is described, together with challenges to clinical IPE in the university context.

A novel peptide modulates alpha7 nicotinic receptor responses: implications for a possible trophic-toxic mechanism within the brain.

The alpha7 nicotinic acetylcholine receptor (nAChR) plays a key role in neural development and neurodegeneration. Here, we identify a novel, modulatory receptor ligand, a 14-amino acid peptide (AEFHRWSSYMVHWK) derived from the C-terminus of acetylcholinesterase (AChE). In three different in vitro preparations, this 'AChE-peptide' is bioactive in a ligand-specific and concentration-dependent manner. First, it modulates acutely the effect of acetylcholine (ACh) on Xenopus oocytes transfected with human alpha7, but not alpha4/beta2, nAChR. The action persists when intracellular calcium is chelated with BAPTA or when calcium is substituted with barium ions. This observation suggests that intracellular Ca(2+) signals do not mediate the interaction between the peptide and nAChR, but rather that the interaction is direct: however, the intervention of other mediators cannot be excluded. Secondly, in recordings from the CA1 region in guinea-pig hippocampal slices, AChE-peptide modulates synaptic plasticity in a alpha-bungarotoxin (alpha-BgTx)-sensitive manner. Thirdly, in organotypic cultures of rat hippocampus, long-term exposure to peptide attenuates neurite outgrowth: this chronic, functional effect is selectively blocked by the alpha7 nAChR antagonists, alpha-BgTx and methyllycaconitine, but not by the alpha4/beta2-preferring blocker dihydro-beta-ethroidine. A scrambled peptide variant, and the analogous peptide from butyrylcholinesterase, are ineffective in all three paradigms. The consequences of this novel modulation of the alpha7 nAChR may be activation of a trophic-toxic axis, of relevance to neurodegeneration.