Exercise therapy for the treatment of tendinopathies: a scoping review protocol.

Objective: The aim of the review is to provide a map of exercise interventions and outcomes that have been reported for the treatment of any tendinopathy. Introduction: Tendinopathy is a common condition that affects athletic and non-athletic populations. Exercise is the mainstay of conservative management of tendinopathy, and a range of different exercise types are recommended. There is a significant body of literature on exercise for tendinopathy, but to date no scoping review has provided a clear map of interventions used and outcomes reported in the literature. Inclusion criteria: We will include people of any age or gender with a diagnosis of tendinopathy of any severity or duration at any anatomical location. We will exclude full-thickness/massive tears and plantar fasciitis. The exercise therapy may take place at any location, including hospital, community, or people's homes, and may be supervised or unsupervised. We will include systematic reviews, quantitative, qualitative, and mixed-methods studies conducted in any developed nation. Methods: We will search MEDLINE, CINAHL, AMED, Embase, SPORTDiscus, Cochrane (controlled trials; systematic reviews), JBI Evidence Synthesis, Epistemonikos, four trial registries, and six gray literature databases. We will use Scopus to search for cited/citing articles from included studies and will perform hand searching where relevant. We will include literature from 1998 to 2020 in any language for which we can access translation. Studies will be screened by two independent reviewers at title/abstract and full-text screening stages; a third reviewer will resolve conflicts. Data will be extracted into a bespoke charting form and will be presented as figure/tables with accompanying narrative

Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks

Which treatments are most effective for common tendinopathies? A systematic review and network meta-analysis protocol.

This is a preprint for a protocol. The purpose of the study described by the protocol was to compare the effectiveness of different treatment classes across a range of tendinopathies and outcomes, to better establish a treatment hierarchy. Where sufficient data were obtained, the potential for covariates - including patient demographics and condition specifics (e.g. symptom severity) - to explain statistical heterogeneity was explored

The effect of dose on resistance exercise therapies for tendinopathy: a systematic review and meta-analysis protocol.

This is a preprint for a protocol. The purpose of the study described by the protocol was to investigate the effect of resistance exercise dose across multiple common tendinopathies (rotator cuff, lateral elbow, patellar or Achilles), where the frequency, volume and intensity can be accurately quantified. By combining a large data set with contemporary meta-analysis and meta-regression approaches (including relevant covariates within models), the systematic review attempted to explore statistical heterogeneity and better assess potential dose-response relationships that may exist. Where placebo and no-treatment arms were included, these studies were used to reduce heterogeneity and provide sensitivity analyses to support or refute analyses with larger, but more complex data

Comparison of exercise therapies across multiple tendinopathies: a systematic review and network meta-analysis protocol.

This is a preprint for a protocol. The study described by the protocol aimed to use network structures to compare exercise treatments and treatment classes in attempts to identify a treatment hierarchy. Additionally, the large amount of data synthesised was used to explore relevant factors that may explain statistical heterogeneity

The effect of dose components on resistance exercise therapies for tendinopathy management: a systematic review and meta-analysis.

The purpose of this study was to investigate potential moderating effects of resistance exercise dose components including intensity, volume and frequency, for the management of common tendinopathies. The research was undertaken through a systematic review and meta-analysis, comprising an extensive search of databases and trial registries. Eligibility criteria for selecting studies included randomised and non-randomised controlled trials investigating resistance exercise as the dominant treatment class and reporting sufficient information regarding at least two components of exercise dose (intensity, frequency, volume). Non-controlled standardised mean difference effect sizes were calculated across a range out outcome domains and combined with Bayesian hierarchical meta-analysis models for domains generating large (disability; function; pain) and small (range of motion; physical function capacity; and quality of life) effect size values. Meta-regressions were used to estimate differences in pooled mean values across categorical variables quantifying intensity, frequency and volume. Ninety-one studies presented sufficient data to be included in meta-analyses, comprising 126 treatment arms (TAs) and 2965 participants. Studies reported on five tendinopathy locations (Achilles: 39 TAs, 31.0%; rotator cuff: 39 TAs, 31.0%; lateral elbow: 25 TAs, 19.8%; patellar: 19 TAs, 15.1%; and gluteal: 4 TAs, 3.2%). Meta-regressions provided consistent evidence of greater pooled mean effect sizes for higher intensity therapies comprising additional external resistance compared to body mass only (large effect size domains: 0.39 [95% CrI: 0.00 to 0.82; p = 0.976]; small effect size domains (0.09 [95% CrI: -0.20 to 0.37; p = 0.723]) when data were combined across tendinopathy locations or analysed separately. Consistent evidence of greater pooled mean effect sizes was also identified for the lowest frequency (less than daily) compared with mid (daily) and high frequencies (more than daily) for both large effect size domain ( -0.66 [95% CrI: -1.2 to -0.19; p >0.999]; -0.54 [95% CrI:-0.99 to -0.10; p >0.999]) and small effect size domains ( -0.51 [95% CrI: -0.78 to -0.24; p >0.999]; -0.34 [95% CrI: -0.60 to -0.06; p = 0.992]) when data were combined across tendinopathy locations or analysed separately. Minimal and inconsistent evidence was obtained for differences for a moderating effect of training volume. The study concluded that resistance exercise dose is poorly reported within the tendinopathy management literature. However, this large meta-analysis identified some consistent patterns indicating greater efficacy on average with therapies prescribing higher intensities (through the inclusion of additional external loads) and lower frequencies, potentially creating stronger stimuli and facilitating adequate recovery

Empirically derived guidelines for interpreting the effectiveness of exercise therapy for tendinopathies: a protocol.

This is a preprint for a protocol. The aim of the study described by the protocol was to perform a large synthesis of the available research investigating exercise therapy for tendinopathies, creating empirically derived thresholds to benchmark interventions and explore potential differences across tendinopathy types and outcome domains

Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks

Are patients satisfied? A systematic review and meta-analysis of patient ratings in exercise therapy for the management of tendinopathy.

Outcomes measuring patient rating of overall condition, including patient satisfaction, are associated with improved general health and higher quality of life. However, this outcome domain is under-explored in the management of tendinopathy. The purpose of this systematic review and meta-analysis was to synthesise intervention data investigating patient satisfaction and perceived improvement or deterioration following engagement in exercise therapy for the management of tendinopathy. A search of randomised controlled trials investigating exercise therapy interventions across all tendinopathies was conducted, extracting data assessing patient rating of overall condition. Outcomes were split into those measuring satisfaction (binary) and those measuring global rating of change (GROC). Bayesian hierarchical models were used to meta-analyse proportions and mean effect size (percentage of maximum) for the two outcome categories. From a total of 124 exercise therapy studies, 34 (Achilles: 41%, rotator cuff: 32%, patellar: 15%, elbow: 9% and gluteal: 3%) provided sufficient information to be meta-analysed. The data were obtained across 48 treatment arms and 1246 participants. The pooled estimate for proportion of satisfaction was 0.63 [95% CrI: 0.53 to 0.73], and the pooled estimate for percentage of maximum GROC was 53 [95% CrI: 38 to 69%]. Evidence was also obtained that the proportion of patients reporting positive satisfaction and perception of change increased with longer durations relative to treatment onset. The study concluded that patient satisfaction is not commonly reported in tendinopathy research and, in those studies where it is reported, satisfaction and GROC appear similar and are ranked moderately high, demonstrating that patients generally perceive exercise therapy for tendinopathy management positively. Further research including greater consistency in measurement tools is required to explore, and where possible identify patient and exercise moderating factors that can be used to improve person-centred care