Sport Concussion Assessment Tool: baseline and clinical reference limits for concussion diagnosis and management in elite Rugby Union.

OBJECTIVES: Rugby Union has adapted the Sports Concussion Assessment Tool (SCAT) into an abridged off-field concussion screen and the complete SCAT is used during diagnostic screens performed after head impact events. No firm guidelines exist as to what should be considered "abnormal" and warrant further evaluation. This study evaluates SCAT performances in 13,479 baseline SCAT assessments, and proposes clear reference limits for each sub-component of the SCAT5. Baseline reference limits are proposed to guide management of baseline testing by identifying abnormal sub-tests, enhancing the clinical validity of baseline screens, while clinical reference limits are identified to support concussion diagnosis when no baseline is available. DESIGN: Cross sectional census sample. METHODS: 13,479 baseline SCATs from 7565 elite male rugby players were evaluated. Baseline reference limits were identified for each sub-test as the sub-test result achieved by approximately 5% of the population, while clinical references limits corresponded to the sub-test score achieved by as close as possible to 50% of the cohort. RESULTS: Players reported symptoms 35% (95% CI 1.29-1.42) more frequently during SCAT5 than SCAT3 baseline assessments (mean 1.4±2.7 vs 1.0±2.4). Ceiling effects were identified for many cognitive sub-tests within the SCAT. Baseline and Clinical reference limits corresponding to the worst performing 5th percentile and 50th percentile were described. CONCLUSIONS: Targeted baseline re-testing should be repeated when abnormal sub-tests are identified according to proposed baseline reference limits, while a more conservative clinical reference limit supports concussion diagnosis during screens in diagnostic settings.

The performance of the World Rugby Head Injury Assessment Screening Tool: a diagnostic accuracy study.

BACKGROUND: Off-field screening tools, such as the Sports Concussion Assessment Tool (SCAT), have been recommended to identify possible concussion following a head impact where the consequences are unclear. However, real-life performance, and diagnostic accuracy of constituent sub-tests, have not been well characterized. METHODS: A retrospective cohort study was performed in elite Rugby Union competitions between September 2015 and June 2018. The study population comprised consecutive players identified with a head impact event undergoing off-field assessments with the World Rugby Head Injury Assessment (HIA01) screening tool, an abridged version of the SCAT3. Off-field screening performance was investigated by evaluating real-life removal-from-play outcomes and determining the theoretical diagnostic accuracy of the HIA01 tool, and individual sub-tests, if player-specific baseline or normative sub-test thresholds were strictly applied. The reference standard was clinically diagnosed concussion determined by serial medical assessments. RESULTS: One thousand one hundred eighteen head impacts events requiring off-field assessments were identified, resulting in 448 concussions. Real-life removal-from-play decisions demonstrated a sensitivity of 76.8% (95% CI 72.6-80.6) and a specificity of 86.6% (95% CI 83.7-89.1) for concussion (AUROC 0.82, 95% CI 0.79-0.84). Theoretical HIA01 tool performance worsened if pre-season baseline values (sensitivity 89.6%, specificity 33.9%, AUROC 0.62, p < 0.01) or normative thresholds (sensitivity 80.4%, specificity 69.0%, AUROC 0.75, p < 0.01) were strictly applied. Symptoms and clinical signs were the HIA01 screening tool sub-tests most predictive for concussion; with immediate memory and tandem gait providing little additional diagnostic value. CONCLUSIONS: These findings support expert recommendations that clinical judgement should be used in the assessment of athletes following head impact events. Substitution of the tandem gait and 5-word immediate memory sub-tests with alternative modes could potentially improve screening tool performance.

Rugby World Cup 2019 injury surveillance study.

Background: Full contact team sports, such as rugby union, have high incidences of injury. Injury surveillance studies underpin player welfare programmes in rugby union. Objective: To determine the incidence, severity, nature and causes of injuries sustained during the Rugby World Cup 2019. Methods: A prospective, whole population study following the definitions and procedures recommended in the consensus statement for epidemiologic studies in rugby union. Output measures included players' age (years), stature (cm), body mass (kg), playing position, and group-level incidence (injuries/1000 player-hours), severity (days-absence), injury burden (days absence/1000 player-hours), location (%), type (%) and inciting event (%) of injuries. Results: Overall incidences of injury were 79.4 match injuries/1000 player-match-hours (95% CI: 67.4 to 93.6) and 1.5 training injuries/1000 player-training-hours (95% CI: 1.0 to 2.3). The overall mean severity of injury was 28.9 (95% CI: 20.0 to 37.8) days absence during matches and 14.8 (95% CI: 4.1 to 25.5) days absence during training. The most common locations and types of match injuries were head/face (22.4%), posterior thigh (12.6%), ligament sprain (21.7%) and muscle strain (20.3%); the ankle (24.0%), posterior thigh (16.0%), muscle strain (44.0%) and ligament sprain (16.0%) were the most common locations and types of injuries during training. Tackling (28.7%), collisions (16.9%) and running (16.9%) were responsible for most match injuries and non-contact (36.0%) and contact (32.0%) rugby skills activities for training injuries. Conclusion: The incidence, severity, nature and inciting events associated with match and training injuries at Rugby World Cup 2019 were similar to those reported for Rugby World Cups 2007, 2011 and 2015.

Sport concussion assessment tool-Third edition normative reference values for professional Rugby Union players.

OBJECTIVES: To establish normative reference data for the SCAT3 in professional Rugby Union players. DESIGN: A cross sectional study in professional Rugby Union players competing in national and international professional competitions between 2015 and 2016. METHODS: The SCAT3 was administered pre-season or prior to tournaments. Data was collected electronically using a custom tablet application. SCAT3 subcomponents distributions were described and normative ranges determined using percentile cut-offs for average, unusually low/high, and extremely low/high scores. The association between player characteristics and performance in SCAT3 subcomponents was also investigated in exploratory analyses. RESULTS: A total of 3611 professional Rugby Union players were included. The most common baseline symptom was fatigue (14%). The symptom score median (md) was 0 (interquartile range (IQR)=0-1). Symptom severity md was 0 (IQR=0-1). The md of the SAC score was 28 (IQR=26-29). The md of the MBESS was 2 (IQR=0-4). The Tandem gait md was 11.1s (IQR=10.0-12.7s). Upper limb coordination was normal in 98.4%. Younger age and lower educational level were associated with worse performance on delayed recall and reverse month sub-components of the SCAT3 (p<0.0001). No statistically significant differences in SCAT3 subcomponents were evident across gender. CONCLUSIONS: Representative normative reference values for the SCAT3 among professional Rugby Union players are provided. Baseline performance on concentration and delayed recall tests may be lower in younger athletes or in those with lower educational level.

AZA-MS: a novel multiparameter mass spectrometry method to determine the intracellular dynamics of azacitidine therapy in vivo.

The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Using AZA-MS, we have accurately quantified the abundance of the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA and the cytoplasm within the same sample using nanogram quantities of input material. We report that although AZA induces DNA demethylation in a dose-dependent manner, it has no corresponding effect on RNA methylation. By applying AZA-MS to primary bone marrow samples from patients undergoing AZA therapy, we have identified that responders accumulate more 5-AZA-CdR in their DNA compared with nonresponders. AZA resistance was not a result of impaired AZA metabolism or intracellular accumulation. Furthermore, AZA-MS has helped to uncover different modes of AZA resistance. Whereas some nonresponders fail to incorporate sufficient 5-AZA-CdR into DNA, others incorporate 5-AZA-CdR and effect DNA demethylation like AZA responders, but show no clinical benefit.

An intensive personalised support approach to treating individuals with psychosis and co-morbid mild intellectual disability.

OBJECTIVES: To evaluate the clinical benefits and associated cost effectiveness of an intensive personalised support (IPS) approach for clients suffering from psychosis and co-morbid mild intellectual disability (ID). METHOD: Four individuals with a psychotic disorder and co-morbid mild ID participated in an 18-month IPS rehabilitative intervention. Biopsychosocial measures were used to evaluate clinical effectiveness. A cost analysis was undertaken to examine the cost effectiveness of the intervention. RESULTS: Reductions in psychopathology including anxiety symptoms were noted in all individuals. In addition, increased functioning and quality of life were demonstrated in all cases. Overall cost reductions were noted in inpatient care, accommodation and legal/emergency expenses. CONCLUSION: The IPS approach was clinically effective particularly in addressing individual's psychosocial needs, psychological functioning, daily living skills and overall quality of life. Costs had decreased for three of the four individuals, ranging from a 17% to 46% savings. The findings highlight that the intervention was cost effective in most cases at this early stage. However, further research is necessary in order to ascertain if cost savings occur over time.

The accuracy and reproducibility of video assessment in the pitch-side management of concussion in elite rugby.

OBJECTIVES: To investigate the accuracy and reliability of side-line video review of head impact events to aid identification of concussion in elite sport. DESIGN: Diagnostic accuracy and inter-rater agreement study. METHODS: Immediate care, match day and team doctors involved in the 2015 Rugby Union World Cup viewed 20 video clips showing broadcaster's footage of head impact events occurring during elite Rugby matches. Subjects subsequently recorded whether any criteria warranting permanent removal from play or medical room head injury assessment were present. The accuracy of these ratings were compared to consensus expert opinion by calculating mean sensitivity and specificity across raters. The reproducibility of doctor's decisions was additionally assessed using raw agreement and Gwets AC1 chance corrected agreement coefficient. RESULTS: Forty rugby medicine doctors were included in the study. Compared to the expert reference standard overall sensitivity and specificity of doctors decisions were 77.5% (95% CI 73.1-81.5%) and 53.3% (95% CI 48.2-58.2%) respectively. Overall there was raw agreement of 67.8% (95% CI 57.9-77.7%) between doctors across all video clips. Chance corrected Gwets AC1 agreement coefficient was 0.39 (95% CI 0.17-0.62), indicating fair agreement. CONCLUSIONS: Rugby World Cup doctors' demonstrated moderate accuracy and fair reproducibility in head injury event decision making when assessing video clips of head impact events. The use of real-time video may improve the identification, decision making and management of concussion in elite sports.

Morphological and proteomic analysis of biofilms from the Antarctic archaeon, Halorubrum lacusprofundi.

Biofilms enhance rates of gene exchange, access to specific nutrients, and cell survivability. Haloarchaea in Deep Lake, Antarctica, are characterized by high rates of intergenera gene exchange, metabolic specialization that promotes niche adaptation, and are exposed to high levels of UV-irradiation in summer. Halorubrum lacusprofundi from Deep Lake has previously been reported to form biofilms. Here we defined growth conditions that promoted the formation of biofilms and used microscopy and enzymatic digestion of extracellular material to characterize biofilm structures. Extracellular DNA was found to be critical to biofilms, with cell surface proteins and quorum sensing also implicated in biofilm formation. Quantitative proteomics was used to define pathways and cellular processes involved in forming biofilms; these included enhanced purine synthesis and specific cell surface proteins involved in DNA metabolism; post-translational modification of cell surface proteins; specific pathways of carbon metabolism involving acetyl-CoA; and specific responses to oxidative stress. The study provides a new level of understanding about the molecular mechanisms involved in biofilm formation of this important member of the Deep Lake community.

Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System.

Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

Aptamer based peptide enrichment for quantitative analysis of gonadotropin-releasing hormone by LC-MS/MS.

Over recent years threats to racing have expanded to include naturally occurring biological molecules, such as peptides and proteins, and their synthetic analogues. Traditionally, antibodies have been used to enable detection of these compounds as they allow purification and concentration of the analyte of interest. The rapid expansion of peptide-based therapeutics necessitates a similarly rapid development of suitable antibodies or other means of enrichment. Potential alternative enrichment strategies include the use of aptamers, which offer the significant advantage of chemical synthesis once the nucleic acid sequence is known. A method was developed for the enrichment, detection and quantitation of gonadotropin-releasing hormone (GnRH) in equine urine using aptamer-based enrichment and LC-MS/MS. The method achieved comparable limits of detection (1 pg/mL) and quantification (2.5 pg/mL) to previously published antibody-based enrichment methods. The intra- and inter-assay precision achieved was less than 10% at both 5 and 20 pg/mL, and displayed a working dynamic range of 2.5-100 pg/mL. Significant matrix enhancement (170 ± 8%) and low analytical recovery (29 ± 15%) was observed, although the use of an isotopically heavy labelled GnRH peptide, GnRH (Pro(13)C5,(15)N), as the internal standard provides compensation for these parameters. Within the current limits of detection GnRH was detectable up to 1h post administration in urine and identification of a urinary catabolite extended this detection window to 4h. Based on the results of this preliminary investigation we propose the use of aptamers as a viable alternative to antibodies in the enrichment of peptide targets from equine urine.

Quantitative proteomics of delirium cerebrospinal fluid.

Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis.

A surveillance model for skin cancer in organ transplant recipients: a 22-year prospective study in an ethnically diverse population.

Skin cancer is a frequent complication of organ transplantation. Current guidelines advise specialist skin surveillance but there are limited data on how these should be implemented. This study determines overall burden of cancer and relevant intervals for strategic surveillance in an ethnically diverse transplant population. Prospective data on time to first and subsequent cancers and cumulative burden with respect to defined risk factors were analyzed in a cohort of 1010 patients in a UK center over 22 years. Among 931 individuals transplanted >6 months (mean 10.3 years), 1820 skin cancers occurred in 267 (29%) individuals and were multiple in 66%. Cumulative incidence at 5, 10, 20 and 30 years was 11%, 25%, 54% and 74%, with median time to second, third and fourth cancers of 24, 14.7 and 8.4 months, respectively. Tumors were overwhelmingly squamous and basal cell carcinomas (73% and 24%, respectively). Skin phototype, ultraviolet radiation exposure, age at transplant and duration of transplant were significant risk predictors and were used to construct clinically relevant surveillance intervals. This study provides a comprehensive, prospective analysis of skin cancer morbidity and risk in an ethnically diverse transplant population from which we derive an evidence-based skin cancer surveillance program.

Time-dependent effects of Prkce deletion on glucose homeostasis and hepatic lipid metabolism on dietary lipid oversupply in mice.

AIMS/HYPOTHESIS: We examined the time-dependent effects of deletion of the gene encoding protein kinase C epsilon (Prkce) on glucose homeostasis, insulin secretion and hepatic lipid metabolism in fat-fed mice. METHODS: Prkce(-/-) and wild-type (WT) mice were fed a high-fat diet for 1 to 16 weeks and subjected to i.p. glucose tolerance tests (ipGTT) and indirect calorimetry. We also investigated gene expression and protein levels by RT-PCR, quantitative protein profiling (isobaric tag for relative and absolute quantification; iTRAQ) and immunoblotting. Lipid levels, mitochondrial oxidative capacity and lipid metabolism were assessed in liver and primary hepatocytes. RESULTS: While fat-fed WT mice became glucose intolerant after 1 week, Prkce(-/-) mice exhibited normal glucose and insulin levels. iTRAQ suggested differences in lipid metabolism and oxidative phosphorylation between fat-fed WT and Prkce(-/-) animals. Liver triacylglycerols were increased in fat-fed Prkce(-/-) mice, resulting from altered lipid partitioning which promoted esterification of fatty acids in hepatocytes. In WT mice, fat feeding elevated oxygen consumption in vivo and in isolated liver mitochondria, but these increases were not seen in Prkce(-/-) mice. Prkce(-/-) hepatocytes also exhibited reduced production of reactive oxygen species (ROS) in the presence of palmitate. After 16 weeks of fat feeding, however, the improved glucose tolerance in fat-fed Prkce(-/-) mice was instead associated with increased insulin secretion during ipGTT, as we have previously reported. CONCLUSIONS/INTERPRETATION: Prkce deletion ameliorates diet-induced glucose intolerance via two temporally distinct phenotypes. Protection against insulin resistance is associated with changes in hepatic lipid partitioning, which may reduce the acute inhibitory effects of fatty acid catabolism, such as ROS generation. In the longer term, enhancement of glucose-stimulated insulin secretion prevails.

Proteomic assessment of host-associated microevolution in the fungus Thielaviopsis basicola.

Thielaviopsis basicola, a soil-borne pathogen with a broad host range and a cosmopolitan distribution, is emerging as a major risk to sustainable cotton production in Australia. Previous studies suggested that host specialization has occurred making T. basicola an ideal model for a comparative proteomic analysis of strains isolated from different hosts. Elucidation of the genomic diversity and investigation of the functional differences in the Australian population could provide valuable information towards disease control. In this study, isolates of T. basicola were investigated for genomic (internal transcribed spacers region), proteomic and cotton virulence level variations. Internal transcribed spacers sequence analysis revealed that isolates are grouped based on host of origin irrespective of geographical origin. At the proteome level a degree of diversity was apparent and hierarchical clustering analysis of the data also demonstrated a close correlation between the proteome and the host of origin. LC-MS/MS analysis and identification using cross-species similarity searching and de novo sequencing of host-specific differentially expressed proteins and the virulence-correlated proteome allowed successful identification of 43 spots. The majority were found to be involved in metabolism. Spots that were correlated with host and virulence differences included a hypothetical protein with a Rossman-fold NAD(P)(+)-binding protein domain, glyceraldehyde-3-phosphate dehydrogenase, arginase and tetrahydroxynaphthalene reductase.

Redox control of ß2-glycoprotein I-von Willebrand factor interaction by thioredoxin-1.

BACKGROUND: ß(2) -Glycoprotein I (ß(2) GPI) is an abundant plasma protein that is closely linked to blood clotting, as it interacts with various protein and cellular components of the coagulation system. However, the role of ß(2) GPI in thrombus formation is unknown. We have recently shown that ß(2) GPI is susceptible to reduction by the thiol oxidoreductases thioredoxin-1 and protein disulfide isomerase, and that reduction of ß(2) GPI can take place on the platelet surface. METHODS: ß(2) GPI, reduced by thioredoxin-1, was labeled with the selective sulfhydryl probe N(a)-(3-maleimidylpropionyl)biocytin and subjected to mass spectrometry to identify the specific cysteines involved in the thiol exchange reaction. Binding assays were used to examine the affinity of reduced ß(2) GPI for von Willebrand factor (VWF) and the effect of reduced ß2GPI on glycoprotein (GP)Ibα binding to VWF. Platelet adhesion to ristocetin-activated VWF was studied in the presence of reduced ß(2) GPI. RESULTS: We demonstrate that the Cys288-Cys326 disulfide in domain V of ß(2) GPI is the predominant disulfide reduced by thioredoxin-1. Reduced ß(2) GPI in vitro displays increased binding to VWF that is dependent on disulfide bond formation. ß(2) GPI reduced by thioredoxin-1, in comparison with non-reduced ß(2) GPI, leads to increased binding of GPIbα to VWF and increased platelet adhesion to activated VWF. CONCLUSIONS: Given the importance of thiol oxidoreductases in thrombus formation, we provide preliminary evidence that the thiol-dependent interaction of ß(2) GPI with VWF may contribute to the redox regulation of platelet adhesion.

The response of the marine bacterium Sphingopyxis alaskensis to solar radiation assessed by quantitative proteomics.

The adaptive response of the marine bacterium Sphingopyxis alaskensis RB2256 to solar radiation (both visible and ultraviolet) was assessed by a quantitative proteomic approach using iTRAQ (isobaric tags for relative and absolute quantification). Both growth phase (mid-log and stationary phase) and duration (80 min or 8 h) of different light treatments (combinations of visible light, UV-A and UV-B) were assessed relative to cultures maintained in the dark. Rates of total protein synthesis and viability were also assessed. Integrating knowledge from the physiological experiments with quantitative proteomics of the 12 conditions tested provided unique insight into the adaptation biology of UV and visible light responses of S. alaskensis. High confidence identifications were obtained for 811 proteins (27% of the genome), 119 of which displayed significant quantitative differences. Mid-log-phase cultures produced twice as many proteomic changes as stationary-phase cultures, while extending the duration of irradiation exposure of stationary-phase cultures did not increase the total number of quantitative changes. Proteins with significant quantitative differences were identified that were characteristic of growth phase and light treatment, and cellular processes, pathways and interaction networks were determined. Key factors of the solar radiation adaptive response included DNA-binding proteins implicated in reducing DNA damage, detoxification of toxic compounds such as glyoxal and reactive oxygen species, iron sequestration to minimize oxidative stress, chaperones to control protein re/folding, alterations to nitrogen metabolism, and specific changes to transcriptional and translational processes.

Belatacept as maintenance immunosuppression for postrenal transplant de novo drug-induced thrombotic microangiopathy.

De novo posttransplant thrombotic microangiopathy (TMA) is a complication of solid organ transplantation, which remains difficult to treat. In many cases, immunosuppressants and particularly calcineurin inhibitors, trigger TMA. Although withdrawing the offending drug may lead to resolution of TMA, graft and patient outcomes are poor. Specific treatments, including plasma exchange, have not gained widespread acceptance in those with fulminant disease and new approaches to the condition are urgently needed. We report a case of posttransplant de novo TMA presenting serially in association with ciclosporin, tacrolimus and sirolimus in a young recipient of a living donor kidney transplant. We describe a patient treated with belatacept, a novel CTLA4 Ig fusion protein, as ongoing maintenance immunosuppression to allow avoidance of conventional agents once associated with TMA. We report excellent early graft outcome, with no adverse events using this strategy. We suggest that belatacept may have a role in this traditionally difficult-to-treat group of patients.

Interpreting regulatory authority guidance on immunosuppressive therapy for renal transplantation: a response to the UK's National Institute for Clinical Excellence (NICE).

AIMS: A group of UK consultant transplant physicians and surgeons (the Consensus Group) met to consider the implications and interpretation of the National Institute for Clinical Excellence's (NICE) Technology Appraisal No. 85 on the use of immunosuppressive therapy for renal transplantation in adults. METHODS: This group considered what the implications of these guidelines might be for clinical practice and consensus was developed on those areas which were potentially open to different interpretations. A wider survey of nephrologists and transplant surgeons throughout the UK was also performed to gauge the impact of the NICE recommendations. RESULTS AND CONCLUSIONS: The outcome of the discussions of the Consensus Group are presented with particular reference to the recommendations of how to respond to calcineurin inhibitor (CNI) intolerance. The survey suggested that the publication of this NICE guidance has resulted in relatively few changes in prescribing practice: UK transplant centers continue to use a wide range of locally developed protocols for immunosuppressive therapy. These include the use of agents such as mycophenolate mofetil (MMF) and sirolimus, despite the fact that both drugs appeared to receive only conditional acceptance in the NICE Guidelines.

Randomized controlled study of biocompatible peritoneal dialysis solutions: effect on residual renal function.

Residual kidney function is important for patient and technique survival in peritoneal dialysis (PD). Biocompatible dialysis solutions are thought to improve function and viability of peritoneal mesothelial cells and to preserve residual renal function (RRF). We conducted a randomized controlled study comparing use of biocompatible (B) with standard (S) solutions in 93 incident PD patients during a 1-year period. The demographics, comorbidities, and RRF of both groups were similar. At 3 and 12 months, 24-h urine samples were collected to measure volume and the mean of urea and creatinine clearance normalized to body surface area. Surrogate markers of fluid status, diuretic usage, C-reactive protein concentration, peritonitis episodes, survival data, and peritoneal equilibrium tests were also collected. Changes in the normalized mean urea and creatinine clearance were the same for both groups, with no significant differences in secondary end points. Despite non-randomized studies suggesting benefits of these newer biocompatible solutions, we could not detect any clinically significant advantages. Additional studies are needed to determine if advantages are seen with longer term use.

Consensus statement on injury definitions and data collection procedures for studies of injuries in rugby union.

Wide variations in the definitions and methodologies used for studies of injuries in rugby union have created inconsistencies in reported data and made interstudy comparisons of results difficult. The International Rugby Board established a Rugby Injury Consensus Group (RICG) to agree on appropriate definitions and methodologies to standardize the recording of injuries and reporting of studies in rugby union. The RICG reviewed the consensus definitions and methodologies previously published for football (soccer) at a meeting in Dublin to assess their suitability for and application to rugby union. Following this meeting, iterative draft statements were prepared and circulated to members of the RICG for comment; a follow-up meeting was arranged in Dublin at which time all definitions and procedures were finalized. At this stage, all authors confirmed their agreement with the consensus statement. The agreed-on document was presented to and approved by the International Rugby Board Council. Agreement was reached on definitions for injury, recurrent injury, nonfatal catastrophic injury, and training and match exposures together with criteria for classifying injuries in terms of severity, location, type, diagnosis, and causation. The definitions and methodology presented in this consensus statement for rugby union are similar to those proposed for football. Adoption of the proposals presented in this consensus statement should ensure that more consistent and comparable results will be obtained from studies of injuries within rugby union.