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The aim of this study is to explore participants' views and experiences of an eHealth phase 3 cardiac rehabilitation (CR) intervention: Physical Activity Towards Health (PATHway). Sixty participants took part in the PATHway intervention. Debriefs were conducted after the six-month intervention. All interviews were audio recorded and transcribed verbatim. Transcripts were analysed with Braun and Clarke's thematic analysis. Forty-four (71%) debriefs were conducted (n = 34 male, mean (SD) age 61 (10) years). Five key themes were identified: (1) Feedback on the components of the PATHway system, (2) Motivation, (3) Barriers to using PATHway, (4) Enablers to using PATHway, and (5) Post programme reflection. There were a number of subthemes within each theme, for example motivation explores participants motivation to take part in PATHway and participants motivation to sustain engagement with PATHway throughout the intervention period. Participant engagement with the components of the PATHway system was variable. Future research should focus on optimising participant familiarisation with eHealth systems and employ an iterative approach to development and evaluation.

Cardiac rehabilitation (CR) is highly effective as secondary prevention for cardiovascular diseases (CVDs). Uptake of CR remains suboptimal (30% of eligible patients), and long-term adherence to a physically active lifestyle is even lower. Innovative strategies are needed to counteract this phenomenon. The Physical Activity Toward Health (PATHway) system was developed to provide a comprehensive, remotely monitored, home-based CR program for CVD patients. The PATHway-I study aimed to investigate its feasibility and clinical efficacy during phase III CR. Participants were randomized on a 1:1 basis to the PATHway (PW) intervention group or usual care (UC) control group in a single-blind, multicenter, randomized controlled pilot trial. Outcomes were assessed at completion of phase II CR and 6-month follow-up. The primary outcome was physical activity (PA; Actigraph GT9X link). Secondary outcomes included measures of physical fitness, modifiable cardiovascular risk factors, endothelial function, intima-media thickness of the common carotid artery, and quality of life. System usability and patients' experiences were evaluated only in PW. A mixed-model analysis of variance with Bonferroni adjustment was used to analyze between-group effects over time. Missing values were handled by means of an intention-to-treat analysis. Statistical significance was set at a 2-sided alpha level of .05. Data are reported as mean (SD). A convenience sample of 120 CVD patients (mean 61.4 years, SD 13.5 years; 22 women) was included. The PATHway system was deployed in the homes of 60 participants. System use decreased over time and system usability was average with a score of 65.7 (SD 19.7; range 5-100). Moderate-to-vigorous intensity PA increased in PW (PW: 127 [SD 58] min to 141 [SD 69] min, UC: 146 [SD 66] min to 143 [SD 71] min; P =.04; effect size of 0.42), while diastolic blood pressure (PW: 79 [SD 11] mmHg to 79 [SD 10] mmHg, UC: 78 [SD 9] mmHg to 83 [SD 10] mmHg; P =.004; effect size of -0.49) and cardiovascular risk score (PW: 15.9% [SD 10.4%] to 15.5% [SD 10.5%], UC: 14.5 [SD 9.7%] to 15.7% [SD 10.9%]; P =.004; effect size of -0.36) remained constant, but deteriorated in UC. This pilot study demonstrated the feasibility and acceptability of a technology-enabled, remotely monitored, home-based CR program. Although clinical effectiveness was demonstrated, several challenges were identified that could influence the adoption of PATHway. ClinicalTrials.gov NCT02717806; https://clinicaltrials.gov/ct2/show/NCT02717806. RR2-10.1136/bmjopen-2017-016781.

Cardiovascular diseases are a leading cause of premature death worldwide. International guidelines recommend routine delivery of all phases of cardiac rehabilitation. Uptake of traditional cardiac rehabilitation remains suboptimal, as attendance at formal hospital-based cardiac rehabilitation programs is low, with community-based cardiac rehabilitation rates and individual long-term exercise maintenance even lower. Home-based cardiac rehabilitation programs have been shown to be equally effective in clinical and health-related quality of life outcomes and yet are not readily available. Given the potential that home-based cardiac rehabilitation programs have, it is important to explore how to appropriately design any such intervention in conjunction with key stakeholders. The aim of this study was to engage with individuals with cardiovascular disease and other professionals within the health ecosystem to (1) understand the personal, social, and physical factors that inhibit or promote their capacity to engage with physical activity and (2) explore their technology competencies, needs, and wants in relation to an eHealth intervention. Fifty-four semistructured interviews were conducted across two countries. Interviews were audiotaped, transcribed verbatim, and analyzed using thematic analysis. Barriers to the implementation of PATHway were also explored specifically in relation to physical capability and safety as well as technology readiness and further mapped onto the COM-B model for future intervention design. Key recommendations included collection of patient data and use of measurements, harnessing hospital based social connections, and advice to utilize a patient-centered approach with personalization and tailoring to facilitate optimal engagement. In summary, a multifaceted, personalizable intervention with an inclusively designed interface was deemed desirable for use among cardiovascular disease patients both by end users and key stakeholders. In-depth understanding of core needs of the population can aid intervention development and acceptability.

Background Cardiac rehabilitation (CR) can slow or reverse the progression of cardiovascular disease (CVD). However, uptake of community-based CR is very low. E-cardiology, e-health and technology solutions for physical activity uptake and monitoring have evolved rapidly and have potential in CVD management. However, it is unclear what the current technology usage is of CVD patients, and their needs and interests for technology enabled CR. Methods A technology usage questionnaire was developed and completed by patients from a supervised ambulatory CR program and an adult congenital heart disease clinic and from two community-based CR programs. Results were described and related with age, gender and educational level by Spearman correlations. Results Of 310 patients, 298 patients (77 % male; mean age 61,7 ± 14,5 years) completed at least 25 questions of the survey and were included in the analysis (completion rate 96 %). Most (97 %) patients had a mobile phone and used the internet (91 %). Heart rate monitors were used by 35 % and 68 % reported to find heart rate monitoring important when exercising at home. Physical activity monitoring was reported by 12 % of the respondents. Respondents were interested in CR support through internet (77 %) and mobile phone (68 %). Many patients reported interest in game-based CR (67 %) and virtual rehabilitation (58 %). At least medium interest in technology enabled CR was reported by 75 % of the patients. Interest decreased with increasing age ( r  = −0.16; p  = 0.005). Conclusions CVD patients show interest for technology enabled home-based CR. Our results could guide the design of a technology-based, virtual CR intervention.

Current guidelines recommend supervised exercise training (SET) as a first-line treatment in patients with intermittent claudication (IC). SET has been shown to be more effective than home-based exercise therapy (HBET). However, the lack of available SET programs hampers broad SET implementation in clinical practice. The aim of this study is to assess patient satisfaction and acceptability of a structured HBET program using wearable technology and elastic band resistance exercises. A total of 20 patients with IC (Rutherford 1-3) with internet access and currently not engaged in structured exercise training were recruited in a pragmatic observational pilot study. Participants were instructed to complete 3 walking sessions and 2 elastic band resistance exercise sessions per week in their home environment during a 4-week period. Patient satisfaction and acceptability were assessed using a 5-point Likert scale questionnaire (1-2=very unsatisfied, 3=neutral, and 4-5=very satisfied) evaluating the materials and intervention content. Secondary outcomes were evaluated at baseline and at completion of the 4-week intervention and included maximal walking distance (MWD) and pain-free walking distance (PFWD), physical fitness, and patient-reported outcomes on quality of life, walking capacity, levels of kinesiophobia, and self-efficacy. Statistically significant changes were tested using paired t tests or Wilcoxon signed-rank tests. All patients (15 men, 5 women; mean age 64.6, SD 10.6 years; range 41-81 years) completed the 4-week intervention and were highly satisfied with the program (mean overall score 4.5, SD 0.5). Patients' questionnaire responses documented willingness to recommend the exercise program to other patients (mean 4.5, SD 0.5; median 4.5) and preference for continuing the intervention (mean 4.3, SD 0.5; median 4). Furthermore, participants endorsed the use of the sports watches to track walking sessions (mean 4.25, SD 0.6; median 4), felt safe (mean 4.4, SD 0.6; median 4), and appreciated personal feedback (mean 4.55, SD 0.5; median 5) and flexibility of training (mean 4.1, SD 0.7; median 4). Resistance training was not preferred over walking training (mean 2.65, SD 0.8; median 3). In addition, PFWD (+89 m; P=.001), MWD (+58 m; P=.03), Walking Impairment Questionnaire distance score (+0.18; P=.01), activity-related scores (+0.54; P<.001), and total quality of life (+0.36; P=.009) improved following the intervention. Other patient-related outcomes, physical fitness, and physical activity remained to be statistically unaltered. Patients with IC were satisfied and accepted technology to monitor and guide HBET, with observed short-term effectiveness regarding walking capacity and quality of life. However, elastic band resistance exercises as a part of HBET were not preferred over progressive walking. ClinicalTrials.gov NCT04043546; https://clinicaltrials.gov/ct2/show/NCT04043546.

Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8 + T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection. The third vaccine dose of the single T cell epitope peptide results in superior generation of effector-memory T cells and tissue-resident memory T cells, and these tertiary vaccine-specific CD8 + T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8 + effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8 + T cell response leading to protection against otherwise lethal SARS-CoV-2 infection. Vaccination regimens and the number of doses required for optimal immunity and protection are critical factors in the translation of vaccines. Here the authors show administration of a three dose protocol of a single T cell epitope to the SARS-CoV-2 spike protein induces a robust CD8 + T cell response and confers protection in a lethal murine challenge model of infection.

ObjectiveTo further explore deiodinase iodothyronine type 2 (DIO2) as a therapeutic target in osteoarthritis (OA) by studying the effects of forced mechanical loading on in vivo joint cartilage tissue homeostasis and the modulating effect herein of Dio2 deficiency.MethodsWild-type and C57BL/6-Dio2−/− -mice were subjected to a forced running regime for 1 h per day for 3 weeks. Severity of OA was assessed by histological scoring for cartilage damage and synovitis. Genome-wide gene expression was determined in knee cartilage by microarray analysis (Illumina MouseWG-6 v2). STRING-db analyses were applied to determine enrichment for specific pathways and to visualise protein–protein interactions.ResultsIn total, 158 probes representing 147 unique genes showed significantly differential expression with a fold-change ≥1.5 upon forced exercise. Among these are genes known for their association with OA (eg, Mef2c, Egfr, Ctgf, Prg4 and Ctnnb1), supporting the use of forced running as an OA model in mice. Dio2-deficient mice showed significantly less cartilage damage and signs of synovitis. Gene expression response upon exercise between wild-type and knockout mice was significantly different for 29 genes.ConclusionsMice subjected to a running regime have significant increased cartilage damage and synovitis scores. Lack of Dio2 protected against cartilage damage in this model and was reflected in a specific gene expression profile, and either mark a favourable effect in the Dio2 knockout (eg, Gnas) or an unfavourable effect in wild-type cartilage homeostasis (eg, Hmbg2 and Calr). These data further support DIO2 activity as a therapeutic target in OA.

To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis. Previously generated microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. RT-qPCR and western blot analyses of overexpression and knockdown of Calr in mouse chondro-progenitor cells (ATDC5) were applied to assess the direct effect of differential Calr expression on cartilage deposition. Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice (FC = -1.731; P = 0.044). Furthermore, overexpression of Calr during early chondrogenesis in ATDC5 cells leads to decreased proteoglycan deposition and corresponding lower Aggrecan expression, whereas knocking down Calr expression does not lead to histological differences of matrix composition. We here demonstrate that the beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction. The consistent association between Calr and Dio2 expression suggests that enhanced expression of these genes facilitate detrimental effects on cartilage integrity.

Findings from studies of muscle regeneration can significantly contribute to the treatment of age-related loss of skeletal muscle mass, which may predispose older adults to severe morbidities. We established a human experimental model using excised skeletal muscle tissues from reconstructive surgeries in eight older adults. Muscle samples from each participant were preserved immediately or maintained in agarose medium for the following 5, 9, or 11 days. Immunofluorescence analyses of the structural proteins, actin and desmin, confirmed the integrity of muscle fibers over 11 days of maintenance. Similarly, the numbers of CD80-positive M1 and CD163-positive M2 macrophages were stable over 11 days in vitro. However, the numbers of PAX7-positive satellite cells and MYOD-positive myoblasts changed in opposite ways, suggesting that satellite cells partially differentiated in vitro. Further experiments revealed that stimulation with unsaturated fatty acid C18[2]c (linoleic acid) increased resident M1 macrophages and satellite cells specifically. Thus, the use of human skeletal muscle tissue in vitro provides a direct experimental approach to study the regulation of muscle tissue regeneration by macrophages and stem cells and their responses to therapeutic compounds.