Telerehabilitation versus traditional centre-based pulmonary rehabilitation for people with chronic respiratory disease: protocol for a randomised controlled trial

Background: Pulmonary rehabilitation is an effective therapeutic intervention for people with chronic respiratory disease. However, fewer than 5% of eligible individuals receive pulmonary rehabilitation on an annual basis, largely due to limited availability of services and difficulties associated with travel and transport. The Rehabilitation Exercise At Home (REAcH) study is an assessor-blinded, multi-centre, randomised controlled equivalence trial designed to compare the efficacy of home-based telerehabilitation and traditional centre-based pulmonary rehabilitation in people with chronic respiratory disease. Methods: Participants will undertake an 8-week group-based pulmonary rehabilitation program of twice-weekly supervised exercise training, either in-person at a centre-based pulmonary rehabilitation program or remotely from their home via the Internet. Supervised exercise training sessions will include 30 min of aerobic exercise (cycle and/ or walking training). Individualised education and self-management training will be delivered. All participants will be prescribed a home exercise program of walking and strengthening activities. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and 12-months post intervention. The primary outcome is change in dyspnea score as measured by the Chronic Respiratory Questionnaire – dyspnea domain (CRQ-D). Secondary outcomes will evaluate the efficacy of telerehabilitation on 6- min walk distance, endurance cycle time during a constant work rate test, physical activity and quality of life. Adherence to pulmonary rehabilitation between the two models will be compared. A full economic analysis from a societal perspective will be undertaken to determine the cost-effectiveness of telerehabilitation compared to centre-based pulmonary rehabilitation. Discussion: Alternative models of pulmonary rehabilitation are required to improve both equity of access and patient-related outcomes. This trial will establish whether telerehabilitation can achieve equivalent improvement in outcomes compared to traditional centre-based pulmonary rehabilitation. If efficacious and cost-effective, the proposed telerehabilitation model is designed to be rapidly deployed into clinical practice.Narelle S. Cox, Christine F. McDonald, Jennifer A. Alison, Ajay Mahal, Richard Wootton, Catherine J. Hill, Janet Bondarenko, Heather Macdonald, Paul O’Halloran, Paolo Zanaboni, Ken Clarke, Deidre Rennick, Kaye Borgelt, Angela T. Burge, Aroub Lahham, Bruna Wageck, Hayley Crute, Pawel Czupryn, Amanda Nichols and Anne E. Hollan

A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11Rα is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs

Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice

Evolutionarily old and conserved homeostatic systems in the brain, including hypothalamus, are organized into nuclear structures of heterogeneous and diverse neuron populations. To investigate whether such circuits can be functionally reconstituted by synaptic integration of similarly diverse populations of neurons, we generated physically chimeric hypothalami by micro-transplanting small numbers of embryonic enhanced green fluorescent protein-expressing, leptin-responsive hypothalamic cells into hypothalami of postnatal leptin receptor-deficient (db/db) mice that develop morbid obesity. Donor neurons differentiated and integrated as four distinct hypothalamic neuron subtypes, formed functional excitatory and inhibitory synapses, partially restored leptin responsiveness, and ameliorated hyperglycemia and obesity in db/db mice. These experiments serve as proof of concept that transplanted neurons can functionally reconstitute complex neuronal circuitry in the mammalian brain.Other Research Uni

Perceived autonomy support in telerehabilitation by people with chronic respiratory disease: a mixed methods study

Background - Autonomy-supportive health environments can assist patients in achieving behavior change and can influence adherence positively. Telerehabilitation may increase access to rehabilitation services, but creating an autonomy-supportive environment may be challenging. Research Question - To what degree does telerehabilitation provide an autonomy-supportive environment? What is the patient experience of an 8-week telerehabilitation program? Study Design and Methods - Individuals undertaking telerehabilitation or center-based pulmonary rehabilitation within a larger randomized controlled equivalence trial completed the Health Care Climate Questionnaire (HCCQ; short form) to assess perceived autonomy support. Telerehabilitation participants were invited 1:1 to undertake semistructured interviews. Interviews were transcribed verbatim and coded thematically to identify major themes and subthemes. Results - One hundred thirty-six participants (n = 69 telerehabilitation) completed the HCCQ and 30 telerehabilitation participants (42%) undertook interviews. HCCQ summary scores indicated that participants strongly agreed that the telerehabilitation environment was autonomy supportive, which was similar to center-based participants (HCCQ summary score, P = .6; individual HCCQ items, P ≥ .3). Telerehabilitation interview data supported quantitative findings identifying five major themes, with subthemes, as follows: (1) making it easier to participate in pulmonary rehabilitation, because telerehabilitation was convenient, saved time and money, and offered flexibility; (2) receiving support in a variety of ways, including opportunities for peer support and receiving an individualized program guided by expert staff; (3) internal and external motivation to exercise as a consequence of being in a supervised group, seeing results for effort, and being inspired by others; (4) achieving success through provision of equipment and processes to prepare and support operation of equipment and technology; and (5) after the rehabilitation program, continuing to exercise, but dealing with feelings of loss. Interpretation - Telerehabilitation was perceived as an autonomy-supportive environment, in part by making it easier to undertake pulmonary rehabilitation. Support for behavior change, understanding, and motivation were derived from clinicians and patient-peers. The extent to which autonomy support translates into ongoing self-management and behavior change is not clear