Process evaluation of complex interventions tested in randomised controlled trials in musculoskeletal disorders: A systematic review protocol

Introduction The effectiveness of complex interventions for the management of musculoskeletal disorders has been estimated in many randomised clinical trials (RCTs). These trials inform which interventions are the most effective, however they do not always inform how an intervention achieved its clinical outcomes, nor how and what elements of an intervention were delivered to patients. Such information is useful for translating findings into clinical practice. A few process evaluation studies have been conducted alongside RCTs and a variety of methods have been used. To gain a better understanding of current practices of process evaluation in RCTs in musculoskeletal disorders, this systematic review is designed to answer the following research question: How are process evaluation of complex interventions tested in RCTs in musculoskeletal disorders being conducted? Methods and analysis We will systematically search seven electronic databases (MEDLINE, SCOPUS, CINAHL, PsycINFO, EMBASE, Web of Science and Cochrane database) from the date of inception to August 2018 for studies on process evaluation of RCTs on non-surgical and non-pharmacological management of musculoskeletal disorders. We will include qualitative and quantitative studies conducted alongside RCTs, reported with the RCTs or separate studies that assessed interventions for musculoskeletal disorders. Two reviewers will screen abstracts and apply prespecified inclusion criteria to identify relevant studies, extract the data and assess the risk of bias within included studies. We will follow recommendations from the Cochrane Qualitative and Implementation Methods Group Guidance Series' when assessing methodological strengths and limitations of included studies. We will use a narrative synthesis to describe findings. Ethics and dissemination Ethical approval is not required as this review will not collect original data. Findings from this systematic review will be presented at a scientific conference and published in a peer reviewed journal. PROSPERO registration number CRD4201810960

Initial effect of high-volume mobilisation with movement on shoulder range of motion and pain in patients with rotator cuff-related shoulder pain: Protocol for a randomised controlled trial (Evolution Trial)

Copyright © Author(s) (or their employer(s)) 2023. Introduction Mobilisation with movement (MWM) is commonly used for treating patients with rotator cuff-related shoulder pain (RCRSP). However, the evidence supporting MWM efficacy for improving shoulder range of motion (ROM) and pain in patients with RCRSP is limited. It is also unclear whether higher volume MWM leads to better clinical outcomes compared with lower volume MWM in patients with RCRSP. The primary aim of this study is to assess the effect of MWM on the angular onset of pain during shoulder abduction in patients with RCRSP. Methods and analysis Sixty participants with RCRSP will be randomised to receive either MWM or sham MWM intervention. The primary outcome is the angular onset of pain during shoulder abduction, and secondary outcomes are pain intensity at the angular onset of pain during shoulder abduction, maximum shoulder ROM, pain intensity during maximum shoulder abduction, pressure pain threshold, mechanical temporal summation, global rating of change scale (GROC) and Brief Pain Inventory-Short Form (BPI-SF). The angular onset of pain and the pain intensity at that range will be assessed at baseline, after 1 set and 3 sets of 10 repetitions of MWM or sham MWM. The GROC will be measured immediately after receiving 3 sets of interventions and on day 3 after interventions. The BPI-SF will be measured on days 1, 3, 5 and 7 after interventions. Other secondary outcomes will be assessed at baseline and after 3 sets of interventions. A linear mixed effects model with a random intercept will be used to compare changes in the outcome measures between MWM and sham MWM interventions. Ethics and dissemination This study has been approved by the University of Otago Ethics Committee (Ref. H21/117). Findings from this study will be disseminated through presentations at international and national conferences and will be submitted for publication in a peer-reviewed journal. Trial registration number ACTRN 12621001723875.This project is partially supported by the School of Physiotherapy Fund (N/A), the Dunedin School of Medicine Research Student Support Committee of University of Otago (GL.10.NB.M01) and New Zealand Manipulative Physiotherapists Association Educational Trust Fund (N/A). Part of this work was conducted during the Sir Charles Hercus Health Research Fellowship (18/111). SW was supported by the University of Otago Doctoral Scholarship (N/A)

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

Mediators of the effects of exercise and manual therapy for people with knee and hip osteoarthritis: A secondary, exploratory analysis of the MOA trial

This is the final version. Available on open access from Elsevier via the DOI in this recordOBJECTIVE: To explore whether pain beliefs and functional strength mediate the treatment effect of manual therapy (MT) and exercise therapy (ET) on the Western Ontario and McMaster Osteoarthritis Index (WOMAC) composite scores and its subscales in individuals with hip and/or knee osteoarthritis in the MOA trial. DESIGN: Secondary analysis of a randomised controlled trial that compared the incremental effects of supervised MT and ET in addition to usual care in patients with osteoarthritis of the hip or knee. 206 participants enrolled in the MOA trial were analysed. The primary outcome measure was the WOMAC composite score after 1 year. RESULTS: Pain belief mediated the effect of MT (b: -10.7, 95 ​% CI: -22.3, -0.9), ET (b: -14.5 95%CI: -26.0, -4.4). Functional strength did not mediate the effect of MT, ET, or MT ​+ ​ET. Mediation sensitivity analyses suggest findings are likely to change if small confounding between those mediators and WOMAC composite score is present. CONCLUSIONS: We identified possible mediators of MT and ET. Future confirmatory studies could be designed to assess the mechanisms through which manual therapy and exercise cause improvements in pain and function scores in patients with hip or knee osteoarthritis.Health Research Council of New ZealandNational Institute for Health and Care Research (NIHR

Explicit kinetic heterogeneity: mechanistic models for interpretation of labeling data of heterogeneous cell populations

Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system. Deuterium, in the form of deuterated glucose or heavy water, can be used to measure rates of proliferation and death of lymphocytes in vivo. Inferring these rates from labeling and delabeling curves has been subject to considerable debate with different groups suggesting different mathematical models for that purpose. We show that the three models that are most commonly used are in fact mathematically identical and differ only in their interpretation of the estimated parameters. By extending these previous models, we here propose a more mechanistic approach for the analysis of data from deuterium labeling experiments. We construct a model of "kinetic heterogeneity" in which the total cell population consists of many sub-populations with different rates of cell turnover. In this model, for a given distribution of the rates of turnover, the predicted fraction of labeled DNA accumulated and lost can be calculated. Our model reproduces several previously made experimental observations, such as a negative correlation between the length of the labeling period and the rate at which labeled DNA is lost after label cessation. We demonstrate the reliability of the new explicit kinetic heterogeneity model by applying it to artificially generated datasets, and illustrate its usefulness by fitting experimental data. In contrast to previous models, the explicit kinetic heterogeneity model 1) provides a mechanistic way of interpreting labeling data; 2) allows for a non-exponential loss of labeled cells during delabeling, and 3) can be used to describe data with variable labeling length

Association Between Alcohol Intake and Cardiac Remodeling

Background: Alcohol-induced cardiotoxicity is incompletely understood. Specifically, the long-term impact of alcohol use on ventricular remodeling or dysfunction, its modulators, and effect thresholds among young adults remain controversial. Objectives: The authors sought to evaluate a potential relationship between alcohol intake and cardiac remodeling, assessed by echocardiography, over 20 years of follow-up. Methods: Among the CARDIA (Coronary Artery Risk Development in Young Adults) study cohort, the authors studied all subjects without baseline heart disorders who provided adequate information on their drinking habits and underwent echocardiographic evaluation at years 5 and 25 of the study. The echocardiographic outcomes were left ventricular (LV) ejection fraction, indexed LV end-diastolic volume and LV mass, and left atrial diameter. Participants were grouped according to their weighted-average weekly drinking habits. An additional analysis used the estimated cumulative alcohol consumption. Regression models and multivariable fractional polynomials were used to evaluate the association between alcohol consumption and the outcomes. Results: Among the 2,368 participants, alcohol consumption was an independent predictor of higher indexed LV mass (p = 0.014) and indexed LV end-diastolic volume (p = 0.037), regardless of sex. No significant relationship between alcohol intake and LV ejection fraction was found. Drinking predominantly wine was associated with less cardiac remodeling and there was a nonsignificant trend for a harmful effect of binge drinking. Conclusions: After 20 years of follow-up, alcohol intake was associated with adverse cardiac remodeling, although it was not related with LV systolic dysfunction in this initially healthy young cohort. Our results also suggest that drinking predominantly wine associates with less deleterious findings in cardiac structure.info:eu-repo/semantics/publishedVersio

Test-retest reliability of movement-evoked pain and sensitivity to movement-evoked pain in patients with rotator cuff-related shoulder pain

Supplementary materials are available online at: https://www.sciencedirect.com/science/article/pii/S1413355523000564?via%3Dihub#sec0021 .Copyright © 2023 The Authors. Background: The number of researchers and clinicians using movement-evoked pain and sensitivity to movement-evoked pain to assess shoulder pain has increased. However, the intrarater test-retest reliability of movement-evoked pain and sensitivity to movement-evoked pain in people with rotator cuff-related shoulder pain (RCRSP) is still unknown. Objective: We examined the intrarater test-retest reliability of movement-evoked pain and sensitivity to movement-evoked pain in participants with RCRSP. Methods: Seventy-four participants with RCRSP performed five trials of active shoulder abduction to elicit pain under two experimental conditions: active shoulder abduction to the onset of pain and maximum range of motion (ROM). The primary outcome measures were pain intensity and ROM. Test-retest reliability of movement-evoked pain and sensitivity to movement-evoked pain was examined using intraclass correlation coefficient (ICC3,1) and minimal detectable change (MDC90). Results: The reliability of movement-evoked pain under both experimental conditions was good to excellent (ICC: 0.81 to 0.95), while the reliability of sensitivity to movement-evoked pain was poor in both conditions (ICC≤0.45). The MDC90 for pain intensity was 1.6 and 1.8 during shoulder abduction to the onset of pain and maximum ROM, respectively. The MDC90 for ROM was 17.5° and 11.2° during shoulder abduction to the onset of pain and maximum ROM condition, respectively. Conclusion: This study confirms movement-evoked pain testing during active shoulder abduction to the onset of pain or maximum ROM condition is reliable to assess pain associated with movement in patients with RCRSP. The minimal detectable change score of movement-evoked pain can guide clinicians and researchers on how to interpret changes in these outcomes.This project was partially supported by the School of Physiotherapy Fund (N/A), the Dunedin School of Medicine Research Student Support Committee of University of Otago (GL.10.NB.M01), and New Zealand Manipulative Physiotherapists Association Educational Trust Fund (N/A)

Dosage of joint mobilisation for the management of rotator cuff-related shoulder pain: protocol for a scoping review

Supplementary Data: This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content. It is available online at: https://bmjopen.bmj.com/highwire/filestream/251724/field_highwire_adjunct_files/0/bmjopen-2021-056771supp001_data_supplement.pdf .Copyright © Author(s) (or their employer(s)) 2022. Introduction Rotator cuff-related shoulder pain is the most common diagnosis of shoulder pain, which ranks as the third most common musculoskeletal disorder. The first-line treatment for patients with rotator cuff-related shoulder pain is physiotherapy, and joint mobilisation is widely used in conjunction with other modalities. The type and dosage of joint mobilisations could influence treatment outcomes for patients with rotator cuff-related shoulder pain, although research evidence is inconclusive. Objectives To (1) systematically search, identify and map the reported type and dosage of joint mobilisations used in previous studies for the management of patients with rotator cuff-related shoulder pain; and (2) summarise the rationale for adopting a specific joint mobilisation dosage. Methods and analysis We will follow the methodological framework outlined by Arksey and O'Malley and report the results as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guideline. Two authors will independently screen and extract data from the six databases: PubMed, Scopus, Web of Science, CINAHL, Cochrane Library and SPORTDiscus, with publication date from their inceptions to 25 August 2021. A third author will be consulted if the two authors disagree about the inclusion of any study in the review. We will summarise the results using descriptive statistics and qualitative thematic analysis. Ethics and dissemination Ethical approval is not required for this protocol. Mapping and summarising the reported type and dosage of joint mobilisations for patients with rotator cuff-related shoulder pain from previous studies will provide a foundation for further optimal selection of type and dosage of joint mobilisations for treating patients with rotator cuff-related shoulder pain. The review is part of an ongoing research that focuses on joint mobilisation for patients with rotator cuff-related shoulder pain. The results will be disseminated through presentations at academic conferences and a peer-reviewed publication.Sir Charles Hercus Health Research Fellowship (18/111) awarded to DCR. SW was supported by the University of Otago Doctoral Scholarship. CC and DCR are supported by the Stanley Paris Research Fellowship