Preventing OsteoPorosis in Spinal Cord Injury (POPSCI) Study-Early Zoledronic Acid Infusion in Patients with Acute Spinal Cord Injury.

Accelerated sub-lesional bone loss is common in the first 2-3 years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An 'acute interventional cohort' (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4 mg zoledronic acid (ZOL) at baseline. A 'chronic non-interventional cohort' (n = 9) with TSCI (duration 1-5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4 years). At baseline, the 'acute' cohort had higher serum CTx, P1NP and sclerostin concentrations, while the 'chronic' cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82%). In the acute cohort, left hip BMD fell by mean ~ 15% by 48 months. Left distal femoral and proximal tibial BMD declined by mean ~ 6-13% at 12 months and ~ 20-23% at 48 months, with a tendency towards greater BMD loss in motor-complete TSCI. A single early ZOL infusion in acute TSCI could not attenuate rapidly declining hip and knee BMD. Prospective controlled studies are required to establish the optimal strategy for preventing early bone loss after acute TSCI.

A systematic review of the effects of robotic exoskeleton training on energy expenditure and body composition in adults with spinal cord injury.

Metabolic diseases disproportionately affect people with spinal cord injury (SCI). Increasing energy expenditure and remodeling body composition may offset deleterious consequences of SCI to improve cardiometabolic health. Evidence is emerging that robotic exoskeleton use increases physical activity in SCI, but little is known about its effects on energy expenditure and body composition. This study therefore aimed to evaluate the impact of robotic exoskeleton training on body composition and energy expenditure in adults with SCI. A systematic literature review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Five databases were searched to retrieve studies meeting pre-set eligibility criteria: adults with SCI, interventions evaluating the effects of robotic exoskeleton devices on body composition or energy expenditure. The PEDro scale guided quality assessments with findings described narratively. Of 2163 records, 10 studies were included. Robotic exoskeleton training does not significantly improve energy expenditure compared to other exercise interventions. Significant changes ( P  < 0.05) in body composition, particularly reduced fat mass, however, were reported. High variability seen with the interventions was coupled with poor quality of the studies. While robotic exoskeleton interventions may propose modest cardiometabolic benefits in adults with SCI, further robust trials in larger samples are needed to strengthen these findings.

Management of Sleep-Disordered Breathing in a Spinal Cord Injury Rehabilitation Center: Model of Care Adaptation and Implementation.

Background: Obstructive sleep apnea (OSA) is highly prevalent and poorly managed in spinal cord injury (SCI). Alternative management models are urgently needed to improve access to care. We previously described the unique models of three SCI rehabilitation centers that independently manage uncomplicated OSA. Objectives: The primary objective was to adapt and implement a similar rehabilitation-led model of managing OSA in an SCI rehabilitation center in Australia. Secondary objectives were to identify the local barriers to implementation and develop and deliver tailored interventions to address them. Methods: A clinical advisory group comprised of rehabilitation clinicians, external respiratory clinicians, and researchers adapted and developed the care model. A theory-informed needs analysis was performed to identify local barriers to implementation. Tailored behavior change interventions were developed to address the barriers and prepare the center for implementation. Results: Pathways for ambulatory assessments and treatments were developed, which included referral for specialist respiratory management of complicated cases. Roles were allocated to the team of rehabilitation doctors, physiotherapists, and nurses. The team initially lacked sufficient knowledge, skills, and confidence to deliver the OSA care model. To address this, comprehensive education and training were provided. Diagnostic and treatment equipment were acquired. The OSA care model was implemented in July 2022. Conclusion: This is the first time a rehabilitation-led model of managing OSA has been implemented in an SCI rehabilitation center in Australia. We describe a theory-informed method of adapting the model of care, assessing the barriers, and delivering interventions to overcome them. Results of the mixed-methods evaluation will be reported separately.

Co-design of the Spinal Cord Injury Health Maintenance Tool to Support Self-Management: A Mixed-Methods Approach.

Background: There is a lack of consumer-friendly tools to empower and support people living with spinal cord injury (SCI) to self-manage complex health needs in community. This article describes the co-design process of the new SCI Health Maintenance Tool (SCI-HMT). Methods: Co-design of the SCI-HMT using a mixed-methods approach included a rapid review, e-Delphi surveys with range of multidisciplinary health care professionals (n = 62), interviews of participants with SCI (n = 18) and general practitioners (n = 4), focus groups (n = 3 with 7, 4, and 4 participants with SCI, respectively), design workshops with stakeholders (n = 11, 8), and end-user testing (n = 41). Results: The SCI-HMT (healthmaintenancetool.com) was developed based on participatory research with data synthesis from multiple sources. Five priority health maintenance issues for bladder, bowel, skin, pain, and autonomic dysreflexia were originally covered. Best practice recommendations, red flag conditions, referrals, and clinical pathways were agreed on through an e-Delphi technique. Qualitative analysis identified six broad key concepts for self-management, including early symptom recognition, role of SCI peers, knowledge sharing with primary care, general practitioners as gatekeepers, and shared decision-making and highlighted a need to place much stronger emphasis on mental health and well-being. Design workshops and end-user testing provided key insights about user experience, functionality, and content for the SCI-HMT. Conclusion: The co-design process engaging end users, including people with SCI and general practitioners, enabled a shared understanding of the problem and identification of important needs and how to meet them. Informed by this process, the SCI-HMT is a freely accessible resource supporting SCI self-management, shared decision-making, and early problem identification.

Differentiating essential hypertension from autonomic dysreflexia: a case report.

INTRODUCTION: Autonomic dysreflexia (AD), a condition of critically raised blood pressure, is a severe complication of spinal cord injury. Primary (essential) hypertension may present with similar blood pressure levels to AD, though the causes, pathophysiology, presentation and treatment will differ. CASE PRESENTATION: We report a case of a 74-year-old patient with a C1 spinal injury, who developed primary (essential) hypertension during her rehabilitation phase of care, requiring extensive investigations for autonomic dysreflexia. Despite this, no underlying cause was found; essential hypertension was subsequently confirmed with 24-hour ambulatory blood pressure monitoring. Treatment with an ACE inhibitor was introduced to good effect. DISCUSSION: Essential hypertension can affect patients with spinal injury, even though most patients with higher level injuries (particularly cervical spinal cord injuries) are expected to have low resting baseline hypotension. Relevant features of this are presented within this case; a set of criteria to differentiate essential hypertension from autonomic dysreflexia are also proposed.

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).

Australian arm of the International Spinal Cord Injury (Aus-InSCI) Community Survey: 3. Drivers of quality of life in people with spinal cord injury.

STUDY DESIGN: Cross-sectional population-based survey for the Australian cohort of the International Spinal Cord Injury (InSCI) Community Survey. OBJECTIVES: To differentiate subgroups of people with spinal cord injury (SCI) who self-report good and poor overall quality of life (QoL) using domains of the International Classification of Functioning (ICF), and to evaluate how these factors contribute to QoL when considered together, while controlling confounders. SETTING: Australian survey data from four state-wide SCI services, one government insurance agency, and three not-for-profit consumer organisations. METHODS: Explanatory factors for QoL were compared between participants reporting poor vs. good QoL. Path models estimated total, direct and mediated contributions from each explanatory factor to QoL ratings after accounting for confounders. RESULTS: Most participants (62%) reported good or very good QoL, 12% reported poor or very poor QoL. When explanatory factors were considered together, the strongest total effects on QoL involved social integration (+0.36 SDs), subjective social position (+0.29), secondary health condition burden (-0.28), activity/participation problem burden (-0.26), day-to-day assistance (-0.26), mental health (+0.18), pain (-0.16), self-efficacy (+0.15), vitality (+0.14) and environmental barriers (-0.11). Effects of social integration, mental health, vitality, self-efficacy, pain and activity/participation problems were partly or wholly direct. CONCLUSION: Opportunities to improve QoL in people with SCI exist at every level of the health system. Virtually all aspects of the ICF framework make a substantive difference to QoL outcomes. Social and psychological factors and ability to complete desired activities have key direct effects and influence effects of secondary health condition burden and environmental barriers.

Cognitive Impairment in Individuals With Spinal Cord Injury: Findings of a Systematic Review With Robust Variance and Network Meta-analyses.

BACKGROUND AND OBJECTIVES: Estimates of the prevalence (10-60%) of cognitive impairment in individuals with spinal cord injury (SCI) are too broad and which domains of cognition are most affected is unclear. We performed a meta-analysis to investigate impairments across domains of cognitive functioning to provide a nuanced picture of research conducted to date into cognitive impairment following SCI. METHODS: Results of peer reviewed studies published in English between 1980 and 2021 comparing ≥20 participants with SCI to able-bodied controls were synthesized using meta-analysis. The primary outcomes were neurocognitive test scores categorized into five cognitive domains as listed in the Diagnostic and Statistical Manual of Mental Disorders: Complex Attention, Executive Functioning, Learning and Memory, Language, and Perceptual Motor Function. Two researchers independently assessed and verified extracted data to comply with meta-analytic reporting guidelines. Robust variance estimation (RVE) meta-analysis was conducted to determine an overall pooled effect size across all cognitive domains using data extracted from studies. Using network meta-analysis, we synthesised eligible studies and made comparisons with the five domains of cognitive functioning serving as the outcomes and SCI as the condition. RESULTS: Of 4,783 potential studies, 13 met final inclusion criteria. Studies met 6 of 8 quality assessment criteria generally. Results suggested that adults with SCI have reduced cognitive functioning (effect size:-0.84; 95%CI: -1.24, -0.44, p < .001) compared to able-bodied individuals, with deficits mostly in attention (g= -0.64; 95%CI: -0.92, -0.38) and executive functioning (g= -0.61, 95%CI: -0.89, -0.04). Publication bias and high heterogeneity (I2:86%) qualify these findings and highlight the need to improve research methods in this area. DISCUSSION: Adults with SCI appear more likely than adults who are able-bodied to display cognitive impairments mostly in areas of attention and executive functioning. Research practices must become consistent to reduce heterogeneity so that the validity and reliability of the results of future studies into cognitive impairment following SCI improves.

The Need for a Specialized Neurocognitive Screen and Consistent Cognitive Impairment Criteria in Spinal Cord Injury: Analysis of the Suitability of the Neuropsychiatry Unit Cognitive Assessment Tool.

The assessment of mild cognitive impairment (MCI) following spinal cord injury (SCI) is vital. However, there are no neurocognitive screens which have been developed specifically to meet the unique requirements for SCI, nor are there consistent MCI criteria applied to determine the rates of MCI. The aim of this study was to determine the suitability of a neurocognitive screen for assessing MCI in adults with SCI. A total of 127 participants were recruited. Socio-demographic and injury related variables were assessed. All participants completed the screen. Descriptive statistics are provided for total/domain screen scores and all items, and the screen's ability to distinguish MCI was examined. Congeneric confirmatory factor analyses (CFA) were employed to investigate structural validity. The screen total score was sensitive to differences in neurocognitive capacity, as well as for time since the injury occurred (p < 0.01). The MCI rate ranged between 17−36%. CFA revealed attention and visuoconstruction domains had an adequate model fit and executive function had poor fit, while CFA models for memory and language did not fit the data (did not converge), hence could not be determined. While the screen differentiated between those with MCI and those without, and MCI as a function of time since injury, limitations of its suitability for assessing MCI after SCI exist, demonstrating the need for a specialized neurocognitive screen for adults with SCI.

A prospective cohort study investigating contributors to mild cognitive impairment in adults with spinal cord injury: study protocol.

BACKGROUND: Studies report rates of mild cognitive impairment (MCI) in spinal cord injury (SCI) range between 10 and 60%. This broad estimate of MCI in SCI is most likely a result of: (i) inconsistent operationalization of MCI; (ii) heterogeneity among individuals with SCI; (iii) failure to account for MCI subtypes, thereby adding to the heterogeneity of samples; and, (iv) poor control for traumatic brain injury (TBI) that obscures differentiation of MCI attributable to TBI versus other factors. There is a paucity of longitudinal studies following the course of MCI in SCI, and none that account for multiple predictors of MCI, including interactions among predictors. METHODS: An inception cohort longitudinal study will assess approximately 100 individuals aged 17-80 years with acute SCI, with measures taken at three timepoints (baseline, 3 months post-baseline, and 12 months post-injury). Data relevant to medical care received within the first 24-48 h of presentation to the emergency department will be analysed, as will measures of cognition, injury characteristics, medical history, personal factors, psychological status, psychosocial functioning, and quality of life. Latent class mixture modelling will determine trajectories for the primary outcome of interest, cognitive functioning and its subtypes, and secondary outcomes of interest such as depression. Multiple regression analyses will identify predictors of MCI and its subtypes. DISCUSSION: The prospective design will reveal change in cognitive functioning across time and unveil different outcome trajectories; thus addressing the lack of knowledge on trajectories of MCI and MCI subtypes in SCI. Through subtyping MCI, we hope to yield groups of cognitively impaired individuals with SCI that are potentially more homogenous and thereby stable and predictable. This is the first study to capture emergency department and acute care diagnostic evidence of mild TBI, which has been poorly controlled in previous studies. Our study will also be the first to distinguish the contribution of TBI from other factors to the development of MCI in individuals with SCI. TRIAL REGISTRATION: The study was prospectively registered with the Australian and New Zealand Clinical Trial Registry ( ACTRN12619001702101 ) on 3rd December 2019.

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a randomised controlled trial.

STUDY DESIGN: Randomised double-blind factorial-design placebo-controlled trial. OBJECTIVE: Urinary tract infections (UTIs) are common in people with spinal cord injury (SCI). UTIs are increasingly difficult to treat due to emergence of multi-resistant organisms. Probiotics are efficacious in preventing UTIs in post-menopausal women. We aimed to determine whether probiotic therapy with Lactobacillus reuteri RC-14+Lactobacillus GR-1 (RC14-GR1) and/or Lactobacillus rhamnosus GG+Bifidobacterium BB-12 (LGG-BB12) are effective in preventing UTI in people with SCI. SETTING: Spinal units in New South Wales, Australia with their rural affiliations. METHODS: We recruited 207 eligible participants with SCI and stable neurogenic bladder management. They were randomised to one of four arms: RC14-GR1+LGG-BB12, RC14-GR1+placebo, LGG-BB12+ placebo or double placebos for 6 months. Randomisation was stratified by bladder management type and inpatient or outpatient status. The primary outcome was time to occurrence of symptomatic UTI. RESULTS: Analysis was based on intention to treat. Participants randomised to RC14-GR1 had a similar risk of UTI as those not on RC14-GR1 (HR 0.67; 95% CI: 0.39-1.18; P = 0.17) after allowing for pre-specified covariates. Participants randomised to LGG-BB12 also had a similar risk of UTI as those not on LGG-BB12 (HR 1.29; 95% CI: 0.74-2.25; P = 0.37). Multivariable post hoc survival analysis for RC14-GR1 only vs. the other three groups showed a potential protective effect (HR 0.46; 95% CI: 0.21-0.99; P = 0.03), but this result would need to be confirmed before clinical application. CONCLUSION: In this RCT, there was no effect of RC14-GR1 or LGG-BB12 in preventing UTI in people with SCI.

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial.

BACKGROUND: Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. METHOD: This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons with SCI. The primary outcome will be analysed using survival analysis of factorial groups, with Cox regression modelling to test the effect of each treatment while allowing for the other, assuming no interaction effect. Hazard ratios and Kaplan-Meier survival curves will be used to summarise results. DISCUSSION: If these probiotics are shown to be effective in preventing UTI and MRO colonisation, they would be a very attractive alternative for UTI prophylaxis and for combating the increasing rate of antibiotic resistance after SCI. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry [ ACTRN 12610000512022 ]. Date of registration: 21 June 2010.

Effects of concomitant spinal cord injury and brain injury on medical and functional outcomes and community participation.

BACKGROUND: There are limited data on the interactions between concomitant spinal cord injury (SCI) and traumatic brain injury (TBI) in terms of medical, psychological, functional, and community outcomes. OBJECTIVE: To investigate the hypothesis that in addition to SCI-associated sensory-motor impairments, people with dual diagnosis would experience additional TBI-associated cognitive impairments that would have a negative impact on community reintegration. METHODS: Cross-sectional, case-matched study comparing a consecutive sample of participants with dual diagnosis (n = 30) to an SCI group (n = 30) and TBI group (n = 30). Participants who were on average 3.6 years postrehabilitation discharge were interviewed using a battery of standardized outcome measures. RESULTS: Length of rehabilitation stay was significantly longer in SCI and dual diagnosis participants. Fatigue, pain, sexual dysfunction, depression, and sleep disturbances were frequently reported by all groups. Similar levels of anxiety and depression were reported by participants in all groups, however TBI participants reported higher stress levels. All groups achieved mean FIM scores > 100. The dual diagnosis and SCI groups received more daily care and support than TBI participants. Similar levels of community reintegration were achieved by all groups with a high level of productive engagement in work, study, or volunteer activities. CONCLUSIONS: The findings of this study do not support the hypotheses. Postrehabilitation functioning was better than anticipated in adults with dual diagnosis. The contribution of rehabilitation factors, such as longer admission time to develop compensatory techniques and strategies for adaptation in the community, may have contributed to these positive findings.