Effectiveness of remotely delivered motivational conversations on health outcomes in patients living with musculoskeletal conditions: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of remotely delivered motivational conversations on health outcomes in musculoskeletal populations. METHODS: Four electronic databases (inception-March 2022) were searched and combined with grey literature. Randomised control trials (RCTs) evaluating the effect of remotely delivered motivational conversation-based interventions within musculoskeletal populations, using valid measures of pain, disability, quality of life (QoL), or self-efficacy were included. Overall quality was assessed using GRADE criteria. Meta-analyses were performed using random effects models with pooled effect sizes expressed as standardised mean differences ( ± 95%CIs). RESULTS: Twelve RCTs were included. Meta-analyses revealed very-low to moderate quality evidence that remote interventions have a positive effect on pain and disability both immediately post intervention and at long-term follow-up compared to control, and have a positive effect on self-efficacy immediately post intervention. There was no effect on QoL immediately post intervention or at long-term follow up. CONCLUSION: Remotely delivered motivation-based conversational interventions have a positive effect on pain, disability, and self-efficacy but not on QoL. PRACTICE IMPLICATIONS: Motivational conversations, delivered remotely, may be effective in improving some health-related outcomes in MSK populations. However, higher quality evidence is needed to determine optimal intervention durations, and dosing frequencies using sufficient sample sizes and follow-up time frames.

Lower systemic nitric oxide bioactivity, cerebral hypoperfusion and accelerated cognitive decline in formerly concussed retired rugby union players.

NEW FINDINGS: What is the central question of this study? What are the molecular, cerebrovascular and cognitive biomarkers of retired rugby union players with concussion history? What is the main finding and its importance? Retired rugby players compared with matched controls exhibited lower systemic nitric oxide bioavailability accompanied by lower middle cerebral artery velocity and mild cognitive impairment. Retired rugby players are more susceptible to accelerated cognitive decline. ABSTRACT: Following retirement from sport, the chronic consequences of prior-recurrent contact are evident and retired rugby union players may be especially prone to accelerated cognitive decline. The present study sought to integrate molecular, cerebrovascular and cognitive biomarkers in retired rugby players with concussion history. Twenty retired rugby players aged 64 ± 5 years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex-, age-, cardiorespiratory fitness- and education-matched controls with no prior concussion history. Concussion symptoms and severity were assessed using the Sport Concussion Assessment Tool. Plasma/serum nitric oxide (NO) metabolites (reductive ozone-based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light-chain (ELISA and single molecule array) were assessed. Middle cerebral artery blood velocity (MCAv, doppler ultrasound) and reactivity to hyper/hypocapnia ( CVR CO 2 hyper ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hyper}}}$ / CVR CO 2 hypo ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hypo}}}$ ) were assessed. Cognition was determined using the Grooved Pegboard Test and Montreal Cognitive Assessment. Players exhibited persistent neurological symptoms of concussion (U = 109(41) , P = 0.007), with increased severity compared to controls (U = 77(41) , P < 0.001). Lower total NO bioactivity (U = 135(41) , P = 0.049) and lower basal MCAv were apparent in players (F2,39  = 9.344, P = 0.004). This was accompanied by mild cognitive impairment (P = 0.020, 95% CI, -3.95 to -0.34), including impaired fine-motor coordination (U = 141(41) , P = 0.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non-concussed, non-contact controls.

Goal-Directed Haemodynamic Therapy Improves Patient Outcomes in Kidney Transplantation.

Introduction: Kidney transplant graft function depends on optimised haemodynamics. However, high fluid volumes risk hypervolaemic complications. The Edwards Lifesciences ClearSight™ device permits fluid titration through markers of preload and beat-to-beat blood pressure monitoring. We evaluated the implementation of a novel goal-directed haemodynamic therapy protocol to determine whether patient outcomes had improved. Design: A retrospective evaluation of standard care versus goal-directed haemodynamic therapy in adults undergoing kidney transplantation was performed in a single centre between April 2016 and October 2019. Twenty-eight standard-of-care patients received intraoperative fixed-rate infusion and 28 patients received goal-directed haemodynamic therapy. The primary outcome was volume of fluid administered intraoperatively. Secondary outcomes included blood product and vasoactive drug exposure, graft and recipient outcomes. Results: Intraoperative fluid administered was significantly reduced in the goal-directed haemodynamic therapy cohort (4325 vs 2751 ml, P < .001). Exposure to vasopressor (67.9% vs 42.9%, P = .060) and blood products (17.9% vs 3.6%, P = .101) was unchanged. Immediate graft function (82.1% vs 75.0%, P = .515), dialysis requirement (14.3% vs 21.4%, P = .729) and creatinine changes post-operatively were unchanged. In the goal-directed haemodynamic therapy cohort, 1 patient had pulmonary oedema (3.6%) versus 21.4% in the standard cohort. Patients in the goal-directed haemodynamic therapy group were more likely to mobilise within 48 hours of surgery (number needed to treat = 3.5, P = .012). Conclusions: Protocolised goal-directed haemodynamic therapy in kidney transplantation was safe and may improve patient, graft, and surgical outcomes. Clinical trials assessing goal-directed approaches are needed.

Contact events in rugby union and the link to reduced cognition: evidence for impaired redox-regulation of cerebrovascular function.

NEW FINDINGS: What is the central question of this study? How does recurrent contact incurred across a season of professional rugby union impact molecular, cerebrovascular and cognitive function? What is the main findings and its importance? A single season of professional rugby union increases systemic oxidative-nitrosative stress (OXNOS) confirmed by a free radical-mediated suppression in nitric oxide bioavailability. Forwards encountered a higher frequency of contact events compared to backs, exhibiting elevated OXNOS and lower cerebrovascular function and cognition. Collectively, these findings provide mechanistic insight into the possible cause of reduced cognition in rugby union subsequent to impairment in the redox regulation of cerebrovascular function. ABSTRACT: Contact events in rugby union remain a public health concern. We determined the molecular, cerebrovascular and cognitive consequences of contact events during a season of professional rugby. Twenty-one male players aged 25 (mean) ± 4 (SD) years were recruited from a professional rugby team comprising forwards (n = 13) and backs (n = 8). Data were collected across the season. Pre- and post-season, venous blood was assayed for the ascorbate free radical (A•- , electron paramagnetic resonance spectroscopy) and nitric oxide (NO, reductive ozone-based chemiluminescence) to quantify oxidative-nitrosative stress (OXNOS). Middle cerebral artery velocity (MCAv, Doppler ultrasound) was measured to assess cerebrovascular reactivity (CVR), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Notational analysis determined contact events over the season. Forwards incurred more collisions (Mean difference [MD ] 7.49; 95% CI, 2.58-12.40; P = 0.005), tackles (MD 3.49; 95% CI, 0.42-6.56; P = 0.028) and jackals (MD 2.21; 95% CI, 0.18-4.24; P = 0.034). Forwards suffered five concussions while backs suffered one concussion. An increase in systemic OXNOS, confirmed by elevated A•- (F2,19  = 10.589, P = 0.004) and corresponding suppression of NO bioavailability (F2,19  = 11.492, P = 0.003) was apparent in forwards and backs across the season. This was accompanied by a reduction in cerebral oxygen delivery ( cDO2 , F2,19  = 9.440, P = 0.006) and cognition (F2,19  = 4.813, P = 0.041). Forwards exhibited a greater decline in the cerebrovascular reactivity range to changes in PETCO2 ( CVRCO2RANG compared to backs (MD 1.378; 95% CI, 0.74-2.02; P < 0.001).

Identifying consistent biomechanical parameters across rising-to-walk subtasks to inform rehabilitation in practice: A systematic literature review.

BACKGROUND: The best approach to rehabilitate the control of everyday whole-body movement (e.g. rise-to-walk) after pathology remains unclear in part because the associated controlled performance variables are not known. Rise-to-walk can be performed fluidly (sit-to-walk) or non-fluidly (sit-to-stand, proceeded by gait-initiation). Biomechanical variables that remain consistent in health regardless of how rise-to walk is performed represent controlled performance variable candidates which could monitor rehabilitative change. RESEARCH QUESTION: To determine if any biomechanical parameters remain consistent across rising-to-walk (RTW) subtasks (sit-to-stand, gait-initiation, and sit-to-walk) in healthy adults for purposes of movement control assessment in clinical practice. METHODS: Data sources included Medline, Cinahl, and Scopus databases, and the grey literature. Study selection was based on eligibility criteria and must have reported spatiotemporal, kinematic and/or kinetic biomechanical parameters featuring >1 RTW subtask. Data extraction and synthesis; standardised-mean-differences (SMDs) were calculated (pooled if replicated in >1 study) for each parameter. Consistency was determined if SMD95 %CIs included the zero-effect line. RESULTS: Nine studies (n = 99) were included (40 ±â€¯7.5yrs). Seven parameters were replicated in >1 study and subjected to meta-analysis (fixed-effect model). Two were consistent between sit-to-stand and sit-to-walk: flexion-momentum time (M(95 %CI) = 0.055(-0.423 to 0.533); p = 0.823) and peak whole-body-centre-of-mass vertical velocity (M(95 %CI)= -0.415(-0.898 to 0.069); p = 0.093); and centre-of-pressure to whole-body-centre-of-mass distance at toe-off (M(95 %CI)= -0.137(-0.712 to 0.439); p = 0.642) between gait-initiation and sit-to-walk. Another 20 parameters were consistent based on single-study SMDs. SIGNIFICANCE: Consistent parameters might exist across RTW subtasks. However, the evidence is based on few studies with small samples and variable RTW protocols. Future studies designed to confirm consistency using a standardised RTW protocol are needed.

Assessment of a Dedicated Transplant Low Clearance Clinic and Patient Outcomes on Dialysis After Renal Allograft Loss at 2 UK Transplant Centers.

BACKGROUND: Low clearance transplant clinics (LCTCs) are recommended for the management of recipients with a failing kidney transplant (RFKT) but data to support their use is limited. We conducted a retrospective study to assess management of RFKT at 2 transplant centers, 1 with a LCTC (center A) and 1 without (center B). METHODS: Patients who transitioned to an alternative form of renal replacement therapy (RRT) between January 1, 2012, and November 30, 2016, were included. Patients with graft failure within a year of transplantation or due to an unpredictable acute event were excluded. Clinical data were collected after review of medical records. RESULTS: One hundred seventy-nine patients (age, 48.6 ± 13.4 years, 99 [55.3%] male, and mean transplant duration 10.3 ± 7.8 years) were included. RRT counseling occurred in 79 (91%) and 68 (74%) patients at centers A and B (P = 0.003), at median 135 (61-319) and 133 (69-260) days before dialysis after graft loss (P = 0.92). Sixty-one (34.1%) patients were waitlisted for retransplantation; 18 (32.7%) nonwaitlisted patients were still undergoing workup at center A compared with 37 (58.7%) at center B (P = 0.028). Preemptive retransplantation occurred in 4 (4.6%) and 5 (5.4%) patients at centers A and B (P = 0.35). At 1 year after initiation of dialysis after graft loss, 11 (15.3%) and 11 (17.2%) patients were retransplanted (P = 0.12), and mortality was 6.6% overall. CONCLUSIONS: A dedicated LCTC improved RRT counseling and transplant work-up but did not lead to improved rates of retransplantation. Earlier consideration of retransplantation in LCTCs is required to improve RFKT outcomes.

Development of X-ray micro-focus computed tomography to image and quantify biofilms in central venous catheter models in vitro.

Bacterial infections of central venous catheters (CVCs) cause much morbidity and mortality, and are usually diagnosed by concordant culture of blood and catheter tip. However, studies suggest that culture often fails to detect biofilm bacteria. This study optimizes X-ray micro-focus computed tomography (X-ray µCT) for the quantification and determination of distribution and heterogeneity of biofilms in in vitro CVC model systems.Bacterial culture and scanning electron microscopy (SEM) were used to detect Staphylococcus epidermidis ATCC 35984 biofilms grown on catheters in vitro in both flow and static biofilm models. Alongside this, X-ray µCT techniques were developed in order to detect biofilms inside CVCs. Various contrast agent stains were evaluated using energy-dispersive X-ray spectroscopy (EDS) to further optimize these methods. Catheter material and biofilm were segmented using a semi-automated matlab script and quantified using the Avizo Fire software package. X-ray µCT was capable of distinguishing between the degree of biofilm formation across different segments of a CVC flow model. EDS screening of single- and dual-compound contrast stains identified 10 nm gold and silver nitrate as the optimum contrast agent for X-ray µCT. This optimized method was then demonstrated to be capable of quantifying biofilms in an in vitro static biofilm formation model, with a strong correlation between biofilm detection via SEM and culture. X-ray µCT has good potential as a direct, non-invasive, non-destructive technology to image biofilms in CVCs, as well as other in vivo medical components in which biofilms accumulate in concealed areas.

Candida nivariensis isolated from a renal transplant patient with persistent candiduria-Molecular identification using ITS PCR and MALDI-TOF.

We report on the isolation of Candida nivariensis from a renal transplant patient with persistent candiduria. Biochemical profiling misidentified isolates as Candida glabrata (3/5) and Candida inconspicua (2/5). All isolates produced white colonies on CHROMagar(™) Candida medium. Internal transcribed spacer (ITS) ribosomal gene sequence analysis and MALDI-TOF-MS analysis (Bruker Biotyper(™) 2.0) identified all isolates as C. nivariensis, demonstrating the utility of MALDI-TOF as a rapid, accurate approach for the identification of cryptic Candida species.

Highly selective intraportal transplantation of pancreatic islets.

BACKGROUND: Histological assessment of intraportally transplanted islets in experimental rodent models is limited by the wide dissemination of islets throughout the liver. We describe a technique of highly selective intraportal islet transplantation, which increases the density of transplanted islets and hence facilitates their histological analysis and validate this model as a means of quantitative histological analysis of islet graft survival. We also compared the number of islets visualized histologically with that of nonabsorbable dextran beads, representing the number of transplanted islets there would have been if there had been no graft loss. MATERIALS AND METHODS: Diabetic Lewis rats or nondiabetic Sprague-Dawley rats were transplanted with 500 or 1000 syngeneic islets or an equivalent number of beads either into the main branch (MB), or selectively into the right branch (RB) of the portal vein. RESULTS: Islet transplantation led to an identical fall in blood glucose levels whichever technique was used. The graft area and number of islets recovered for histological analysis was 3- to 4-fold higher when islets were transplanted using the RB technique. Quantitative histological graft analysis demonstrated that 46% to 61% of intraportally transplanted islets were lost compared with corresponding bead graft sizes. Fewer islets were lost when a greater islet mass was transplanted. CONCLUSIONS: Selective islet transplantation increases the concentration of islets and hence facilitates islet recovery after intraportal transplantation without detrimental effects on transplantation outcome. This technique, when combined with bead transplantation and digital image analysis, provides an accurate method for estimating the number of islets surviving intra-portal transplantation.

Time course and quantification of pancreatic islet revascularization following intraportal transplantation.

A large proportion of islets are lost after transplantation partly due to a lack of functional vasculature. Islets revascularize from host tissue but the process takes up to 2 weeks and has been suggested to result in reduced vascular density in engrafted islets. We describe a method for observing and quantifying the revascularization of intraportally transplanted islets that includes number, density, and branching of islet capillaries. Syngeneic islets were transplanted selectively into the two right posterior lobes of the liver of adult Lewis rats. Sections of the livers were dual stained for insulin and Bandeiraea simplicifolia and analyzed for islet morphology, area, and vascular density from day 0 to day 14 posttransplant and compared to native islets. Vascular density was 1431 +/- 75.7 vessels/mm2 in native islets and fell to 325.3 +/- 30.8 vessels/mm2 (p < 0.001) by day 1 posttransplant and subsequently increased until day 14 when it was significantly higher than in native islets (2612.5 +/- 107.8 vessels/mm2, p < 0.001). The percentage of islet area occupied by vascular space was 9.1 +/- 0.9% in native islets. After falling to 2.3 +/- 0.3% (p < 0.001) 1 day posttransplant this rose to supranormal levels (21.5 +/- 0.8%, p < 0.001) by day 14. The index of capillary branching was 0.771 +/- 0.017 in native islets and fell to 0.465 +/- 0.02 (p = 0.001) by day 3 but returned to native values by day 7 posttransplantation (0.726 +/- 0.03). This technique provides a robust method for tracking and quantifying the revascularization of intraportally transplanted islets, which should enable the comparison of different strategies aimed at accelerating islet revascularization.

A functional analysis of mouse models of cardiac disease through metabolic profiling.

Since the completion of the human and mouse genomes, the focus in mammalian biology has been on assessing gene function. Tools are needed for assessing the phenotypes of the many mouse models that are now being generated, where genes have been "knocked out," "knocked in," or mutated, so that gene expression can be understood in its biological context. Metabolic profiling of cardiac tissue through high resolution NMR spectroscopy in conjunction with multivariate statistics has been used to classify mouse models of cardiac disease. The data sets included metabolic profiles from mouse models of Duchenne muscular dystrophy, two models of cardiac arrhythmia, and one of cardiac hypertrophy. The metabolic profiles demonstrate that the strain background is an important component of the global metabolic phenotype of a mouse, providing insight into how a given gene deletion may result in very different responses in diverse populations. Despite these differences associated with strain, multivariate statistics were capable of separating each mouse model from its control strain, demonstrating that metabolic profiles could be generated for each disease. Thus, this approach is a rapid method of phenotyping mouse models of disease.

Effect of inspired oxygen on portal and hepatic oxygenation: effective arterialization of portal blood by hyperoxia.

Because hypoxia may compromise the survival of intraportally transplanted pancreatic islets, we have measured portal blood flow and both portal and hepatic oxygenation in normal and diabetic rats breathing graded inspired oxygen concentrations. Portal blood flow and hepatic tissue oxygenation were measured using a transonic flowmeter and near infrared spectroscopy while gas analysis was carried out on portal venous blood samples. The effects of breathing 13%, 21%, 50%, or 100% oxygen were compared in animals with steptozotocin-induced diabetes and in controls. In diabetic rats breathing 21% oxygen, portal blood flow was significantly lower than in controls (7.2+/-0.7 vs. 9.1+/-0.8 ml/min, p < 0.05). In both groups, breathing 100% oxygen significantly increased portal flow (to 8.4+/-1.0 and 12.2+/-0.7 ml/min, respectively). This effect was not secondary to hepatic arterial vasoconstriction because it was not prevented by hepatic artery ligation. In controls, breathing 100% oxygen increased portal pO2 from 5.0+/-0.9 to 14.4+/-1.4 kPa (p < 0.05) and portal venous oxygen saturation (PSaO2) from 53.9+/-12.1% to 92.9+/-1.4% (p < 0.05), a value not significantly different from peripheral (arterial) saturation. Similarly, in diabetic animals pO2 rose from 5.6+/-0.3 to 11.7+/-0.4 kPa (p < 0.01) and SO2 from 55.5+/-5.2% to 88.5+/-0.6% (p < 0.05). Hepatic oxyhemoglobin rose and deoxyhemoglobin fell reciprocally as a function of the inspired oxygen concentration. Improved hepatic oxygenation observed in animals breathing oxygen-enriched gas mixtures results from an increase in splanchnic blood flow coupled with a marked increase in portal oxygen saturation. This effective arterialization of portal blood may have important consequences for the success of intraportal transplantation of pancreatic islets.