Early and Intensive Motor Training for people with spinal cord injuries (the SCI-MT Trial): protocol of the process evaluation.

INTRODUCTION: People with spinal cord injury receive physical rehabilitation to promote neurological recovery. Physical rehabilitation commences as soon as possible when a person is medically stable. One key component of physical rehabilitation is motor training. There is initial evidence to suggest that motor training can enhance neurological recovery if it is provided soon after injury and in a high dosage. The Early and Intensive Motor Training Trial is a pragmatic randomised controlled trial to determine whether 10 weeks of intensive motor training enhances neurological recovery for people with spinal cord injury. This pragmatic randomised controlled trial will recruit 220 participants from 15 spinal injury units in Australia, Scotland, Italy, Norway, England, Belgium and the Netherlands. This protocol paper describes the process evaluation that will run alongside the Early and Intensive Motor Training Trial. This process evaluation will help to explain the trial results and explore the potential facilitators and barriers to the possible future rollout of the trial intervention. METHODS AND ANALYSIS: The UK Medical Research Council process evaluation framework and the Implementation Research Logic Model will be used to explain the trial outcomes and inform future implementation. Key components of the context, implementation and mechanism of impact, as well as the essential elements of the intervention and outcomes, will be identified and analysed. Qualitative and quantitative data will be collected and triangulated with the results of the Early and Intensive Motor Training Trial to strengthen the findings of this process evaluation. ETHICS AND DISSEMINATION: Ethical approval for the Early and Intensive Motor Training Trial and process evaluation has been obtained from the Human Research Ethics Committee at the Northern Sydney Local Health District (New South Wales) in Australia (project identifier: 2020/ETH02540). All participants are required to provide written consent after being informed about the trial and the process evaluation. The results of this process evaluation will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ACTRN12621000091808); Universal Trial Number (U1111-1264-1689).

Early and intensive motor training to enhance neurological recovery in people with spinal cord injury: trial protocol.

STUDY DESIGN: Protocol for a multi-centre randomised controlled trial (the SCI-MT trial). OBJECTIVES: To determine whether 10 weeks of intensive motor training enhances neurological recovery in people with recent spinal cord injury (SCI). SETTING: Fifteen spinal injury units in Australia, Scotland, England, Italy, Netherlands, Norway, and Belgium. METHODS: A pragmatic randomised controlled trial will be undertaken. Two hundred and twenty people with recent SCI (onset in the preceding 10 weeks, American Spinal Injuries Association Impairment Scale (AIS) A lesion with motor function more than three levels below the motor level on one or both sides, or an AIS C or D lesion) will be randomised to receive either usual care plus intensive motor training (12 h of motor training per week for 10 weeks) or usual care alone. The primary outcome is neurological recovery at 10 weeks, measured with the Total Motor Score from the International Standards for Neurological Classification of SCI. Secondary outcomes include global measures of motor function, ability to walk, quality of life, participants' perceptions about ability to perform self-selected goals, length of hospital stay and participants' impressions of therapeutic benefit at 10 weeks and 6 months. A cost-effectiveness study and process evaluation will be run alongside the trial. The first participant was randomised in June 2021 and the trial is due for completion in 2025. CONCLUSIONS: The findings of the SCI-MT Trial will guide recommendations about the type and dose of inpatient therapy that optimises neurological recovery in people with SCI. TRIAL REGISTRATION: ACTRN12621000091808 (1.2.2021).

Developing spinal cord injury physiotherapy clinical practice guidelines: a qualitative study to determine how physiotherapists and people living with spinal cord injury use evidence.

STUDY DESIGN: Generic qualitative design. OBJECTIVES: Australian and New Zealand SCI physiotherapists are developing clinical practice guidelines for the physiotherapy management of people living with spinal cord injury. To guide the development of the guidelines it was important to understand how physiotherapists and people living with spinal cord injury use evidence to choose interventions and the potential barriers and facilitators to the uptake of the clinical practice guidelines. SETTING: Spinal Cord Injury Centres in Sydney, Australia and New Zealand. METHODS: Focus groups and interviews with physiotherapists and people living with spinal cord injury were recorded, transcribed, and subjected to thematic analysis. RESULTS: A total of 75 participants took part in the study, 45 physiotherapists and 30 people living with spinal cord injury. Three main themes were identified from the data: (1) Types and sources of evidence that influence treatment choices, (2) the many factors determining treatment choices, and (3) ways in which clinical practice guidelines could influence treatment. CONCLUSIONS: Clinical practice guidelines have the potential to reduce the barriers identified by physiotherapists in accessing and interpreting research evidence on interventions for people living with spinal cord injury. Supported implementation of guidelines is required to demonstrate their benefit and encourage physiotherapists to factor in evidence when balancing the multiple factors influencing choice of physiotherapy intervention.

The effects of 10,000 voluntary contractions over 8 weeks on the strength of very weak muscles in people with spinal cord injury: a randomised controlled trial.

STUDY DESIGN: A multi-centred, single-blinded randomised controlled trial. OBJECTIVES: To determine the effect of 10,000 voluntary contractions over 8 weeks on the strength of very weak muscles in people with spinal cord injury (SCI). SETTINGS: Seven hospitals in Australia and Asia. METHODS: One hundred and twenty people with recent SCI undergoing inpatient rehabilitation were randomised to either a Treatment or Control Group. One major muscle group from an upper or lower limb was selected if the muscle had grade 1 or grade 2 strength on a standard six-point manual muscle test. Participants allocated to the Treatment Group performed 10,000 isolated contractions of the selected muscle group, as well as usual care in 48 sessions over 8 weeks. Participants allocated to the Control Group received usual care alone. Participants were assessed at baseline and 8 weeks by a blinded assessor. The primary outcome was voluntary muscle strength on a 13-point manual muscle test. There were three secondary outcomes capturing therapists' and participants' perceptions of strength and function. RESULTS: The mean between-group difference of voluntary strength at 8 weeks was 0.4/13 points (95% confidence interval -0.5 to 1.4) in favour of the Treatment Group. There were no notable between-group differences on any secondary outcome. CONCLUSION: Ten thousand isolated contractions of very weak muscles in people with SCI over 8 weeks has either no or a very small effect on voluntary strength.

An app with remote support achieves better adherence to home exercise programs than paper handouts in people with musculoskeletal conditions: a randomised trial.

QUESTION: Do people with musculoskeletal conditions better adhere to their home exercise programs when these are provided to them on an app with remote support compared to paper handouts? DESIGN: Randomised, parallel-group trial with intention-to-treat analysis. PARTICIPANTS: Eighty participants with upper or lower limb musculoskeletal conditions were recruited to the trial. Each participant was prescribed a 4-week home exercise program by a physiotherapist at a tertiary teaching hospital in Australia. Participants were randomly assigned via a computer-generated concealed block randomisation procedure to either intervention (n=40) or control (n=40) groups. INTERVENTION: Participants in the intervention group received their home exercise programs on an app linked to the freely available website www.physiotherapyexercises.com. They also received supplementary phone calls and motivational text messages. Participants in the control group received their home exercise programs as a paper handout. OUTCOME MEASURES: Blinded assessors collected outcome measures at baseline and 4 weeks. The primary outcome was self-reported exercise adherence. There were five secondary outcomes, which captured functional performance, disability, patient satisfaction, perceptions of treatment effectiveness, and different aspects of adherence. RESULTS: Outcomes were available on 77 participants. The mean between-group difference for self-reported exercise adherence at 4 weeks was 1.3/11 points (95% CI 0.2 to 2.3), favouring the intervention group. The mean between-group difference for function was 0.9/11 points (95% CI 0.1 to 1.7) on the Patient-Specific Functional Scale, also favouring the intervention group. There were no significant between-group differences for the remaining outcomes. CONCLUSION: People with musculoskeletal conditions adhere better to their home exercise programs when the programs are provided on an app with remote support compared to paper handouts; however, the clinical importance of this added adherence is unclear. TRIAL REGISTRATION: ACTRN12616000066482. [Lambert TE, Harvey LA, Avdalis C, Chen LW, Jeyalingam S, Pratt CA, Tatum HJ, Bowden JL, Lucas BR (2017) An app with remote support achieves better adherence to home exercise programs than paper handouts in people with musculoskeletal conditions: a randomised trial. Journal of Physiotherapy 63: 161-167].

Comparative cytotoxicity of fourteen trivalent and pentavalent arsenic species determined using real-time cell sensing.

The occurrence of a large number of diverse arsenic species in the environment and in biological systems makes it important to compare their relative toxicity. The toxicity of arsenic species has been examined in various cell lines using different assays, making comparison difficult. We report real-time cell sensing of two human cell lines to examine the cytotoxicity of fourteen arsenic species: arsenite (AsIII), monomethylarsonous acid (MMAIII) originating from the oxide and iodide forms, dimethylarsinous acid (DMAIII), dimethylarsinic glutathione (DMAGIII), phenylarsine oxide (PAOIII), arsenate (AsV), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), monomethyltrithioarsonate (MMTTAV), dimethylmonothioarsinate (DMMTAV), dimethyldithioarsinate (DMDTAV), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox), and 4-aminobenzenearsenic acid (p-arsanilic acid, p-ASA). Cellular responses were measured in real time for 72hr in human lung (A549) and bladder (T24) cells. IC50 values for the arsenicals were determined continuously over the exposure time, giving rise to IC50 histograms and unique cell response profiles. Arsenic accumulation and speciation were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). On the basis of the 24-hr IC50 values, the relative cytotoxicity of the tested arsenicals was in the following decreasing order: PAOIII≫MMAIII≥DMAIII≥DMAGIII≈DMMTAV≥AsIII≫MMTTAV>AsV>DMDTAV>DMAV>MMAV≥Rox≥p-ASA. Stepwise shapes of cell response profiles for DMAIII, DMAGIII, and DMMTAV coincided with the conversion of these arsenicals to the less toxic pentavalent DMAV. Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.

Complementary chromatography separation combined with hydride generation-inductively coupled plasma mass spectrometry for arsenic speciation in human urine.

This study aimed to establish complementary high performance liquid chromatography (HPLC) methods including three modes of separation: ion pairing, cation exchange, and anion exchange chromatography, with detection by inductively coupled plasma mass spectrometry (ICPMS). The ion pairing mode enabled the separation of inorganic arsenate (As(V)), monomethylarsonic acid (MMA(V)), and dimethylarsinic acid (DMA(V)). However, the ion pair mode was unable to differentiate inorganic arsenite (As(III)) from arsenobetaine (AsB); instead, cation exchange chromatography was used to isolate and quantify AsB. Anion exchange chromatography was able to speciate all of the aforementioned arsenic species. Potential inaccurate quantification problem with urine sample containing elevated concentration of AsB, which eluted immediately after As(III) in anion exchange or ion pairing mode, was overcame by introducing a post-column hydride generation (HG) derivatization step. Incorporating HG between HPLC and ICPMS improved sensitivity and specificity by differentiating AsB from hydride-forming arsenic species. This paper emphasizes the usefulness of complementary chromatographic separations in combination with HG-ICPMS to quantitatively determine concentrations of As(III), DMA(V), MMA(V), As(V), and AsB in the sub-microgram per liter range in human urine.