A Scoping Review Investigating the “Gene-Dosage Theory” of Mitochondrial DNA in the Healthy Skeletal Muscle

This review provides an overview of the evidence regarding mtDNA and valid biomarkers for assessing mitochondrial adaptions. Mitochondria are small organelles that exist in almost all cells throughout the human body. As the only organelle, mitochondria contain their own DNA, mitochondrial DNA (mtDNA). mtDNA-encoded polypeptides are subunits of the enzyme complexes in the electron transport chain (ETC) that are responsible for production of ATP to the cells. mtDNA is frequently used as a biomarker for mitochondrial content, since changes in mitochondrial volume are thought to induce similar changes in mtDNA. However, some exercise studies have challenged this “gene-dosage theory”, and have indicated that changes in mitochondrial content can adapt without changes in mtDNA. Thus, the aim of this scoping review was to summarize the studies that used mtDNA as a biomarker for mitochondrial adaptions and address the question as to whether changes in mitochondrial content, induce changes in mtDNA in response to aerobic exercise in the healthy skeletal muscle. The literature was searched in PubMed and Embase. Eligibility criteria included: interventional study design, aerobic exercise, mtDNA measurements reported pre- and postintervention for the healthy skeletal muscle and English language. Overall, 1585 studies were identified. Nine studies were included for analysis. Eight out of the nine studies showed proof of increased oxidative capacity, six found improvements in mitochondrial volume, content and/or improved mitochondrial enzyme activity and seven studies did not find evidence of change in mtDNA copy number. In conclusion, the findings imply that mitochondrial adaptions, as a response to aerobic exercise, can occur without a change in mtDNA copy number

Adaptations and modifications to a co-designed intervention and its clinical implementation : a qualitative study in Denmark

Background There is a long-standing debate in implementation research on whether adaptations to evidence-based interventions (EBIs) are desirable in health care. If an intervention is adapted and not delivered as conceived and planned, it is said to have low fidelity. The WALK-Cph project was developed based on the assumption that involving stakeholders in co-design processes would facilitate the fidelity of an intervention to increase the mobility of acutely admitted older medical patients and its implementation in two hospitals in Denmark. The purpose of this study is to describe and analyse adaptations and modifications that were made to the co-designed WALK-Cph intervention and its implementation. Methods This study used a qualitative design. An ethnographic field study was performed using participant observations, workshops and semi-structured interviews. Data were analysed twice using the Framework Method. The first analysis was based on the frameworks from Stirman, Moore and Proctor. The second analysis, a retrospective modifications analysis, was based on the Adaptation-Impact Framework. Results Many different types of adaptations and modifications were made to the WALK-Cph intervention and its implementation plan. Most of the modifications were made on the contents of the intervention. In total, 44 adaptations and modifications were made, of which 21 were planned (adaptations) and 23 were made haphazardly (modifications). Most of the content and context adaptations and modifications made on the intervention had a mixed result regarding enhanced fidelity. The retrospective modifications analysis showed that modifications were ongoing and both situationally and contextually shaped. Conclusions Although an extensive co-design process was carried out to facilitate the fidelity of the WALK-Cph intervention, this study showed that many adaptations and modifications were still made to both the intervention and its implementation plan. It could indicate that the co-design process had a small effect or that adaptations and modifications are ongoing and both situationally and contextually shaped, which challenge the assumption and the desire to be able to plan and control changes.Funding Agencies|Velux Foundations [F-21835-0104-03]; Association of Danish Physiotherapists [PD-2018-30-10]; Capital Region of Denmark [P-2018-2-11]</p

Feasibility and implementation fidelity of a co-designed intervention to promote in-hospital mobility among older medical patients - the WALK-Copenhagen project (WALK-Cph)

Background: Mobility interventions can prevent functional decline among older patients, but implementation of such interventions may be complicated by barriers in the clinical setting. The WALK-Copenhagen project (WALK-Cph) is aimed at promoting a 24-h mobility among older medical patients during hospitalization. The WALK-Cph intervention was co-designed by researchers and stakeholders to tailor the intervention to the clinical context. The aim of this study was to investigate the feasibility and implementation fidelity of the WALK-Cph intervention before evaluating clinical effectiveness in a randomized controlled trial (ClinicalTrials.gov NCT03825497). Methods: The WALK-Cph intervention consisted of six components: a welcome folder explaining the importance of in-hospital activity, a WALK-plan prescribing up to three daily walking sessions during and after hospitalization, a WALK-path in the hallway that patients were motivated to use daily, exercise posters in the hallways and bedrooms, self-service on beverages and clothes, and discharge with a WALK-plan. The present study reports on phase 2 of WALK-Cph and consists of a feasibility and a fidelity component. The study was conducted at the two WALK-Cph intervention departments after the initiation of the WALK-Cph intervention. A cohort of older medical patients (+65) was recruited for the feasibility study to assess recruitment and data collection procedures and the method for assessment of activity. Simultaneously, implementation fidelity was assessed by observing clinical practice and intervention delivery at the intervention departments. Results: A feasibility cohort of 48 patients was included. Inclusion was considered feasible with recruitment rates between 62% and 70% of all eligible patients. Also, data collection was conducted without obstacles, and all patients accepted to wear activity monitors. The fidelity observations showed that three of the six intervention components were partially implemented as planned whereas three components were not implemented as planned. Conclusion: The WALK-Cph intervention was found feasible, and although the intervention was not implemented with fidelity, the level of fidelity was considered sufficient to continue with further testing of the WALK-Cph intervention in a large-scale trial.Funding Agencies|Velux FoundationsVelux Fonden [F-21835-0104-03]; Association of Danish Physiotherapists [PD-2018-30-10]; Capital Region of Denmark [P-2018-2-11]</p