Characterization of interactions within the Igα/Igß transmembrane domains of the human B-cell receptor provides insights into receptor assembly.

The B-cell receptor (BCR), a complex comprised of a membrane-associated immunoglobulin and the Igα/ß heterodimer, is one of the most important immune receptors in humans and controls B-cell development, activity, selection, and death. BCR signaling plays key roles in autoimmune diseases and lymphoproliferative disorders, yet, despite the clinical significance of this protein complex, key regions (i.e., the transmembrane domains) have yet to be structurally characterized. The mechanism for BCR signaling also remains unclear and has been variously described by the mutually exclusive cross-linking and dissociation activation models. Common to these models is the significance of local plasma membrane composition, which implies that interactions between BCR transmembrane domains (TMDs) play a role in receptor functionality. Here we used an in vivo assay of TMD oligomerization called GALLEX alongside spectroscopic and computational methods to characterize the structures and interactions of human Igα and Igß TMDs in detergent micelles and natural membranes. We observed weak self-association of the Igß TMD and strong self-association of the Igα TMD, which scanning mutagenesis revealed was entirely stabilized by an E-X10-P motif. We also demonstrated strong heterotypic interactions between the Igα and Igß TMDs both in vitro and in vivo, which scanning mutagenesis and computational models suggest is multiconfigurational but can accommodate distinct interaction sites for self-interactions and heterotypic interactions of the Igα TMD. Taken together, these results demonstrate that the TMDs of the human BCR are sites of strong protein-protein interactions that may direct BCR assembly, endoplasmic reticulum retention, and immune signaling.

The Womb Cancer Awareness Measure (WCAM): development of an instrument to assess public awareness of endometrial cancer.

OBJECTIVE: To develop and test a novel instrument to assess public awareness of endometrial cancer symptoms and risk factors in a UK population. METHODS: A 36-item questionnaire was developed through literature review and extraction from cancer awareness materials. The Womb Cancer Awareness Measure (WCAM) was tested for content validity in 65 self-identified female research participants and 10 endometrial cancer experts prior to UK-wide field testing using social media. Test-retest reliability was assessed over 2 weeks, construct validity was assessed by comparing womb cancer experts and non-medical academics, and sensitivity to change was assessed by comparing scores of participants who read an endometrial cancer leaflet with those given a control leaflet. RESULTS: Fifty-two percent of the items in the test-retest reliability showed >80% agreement. Construct validity was demonstrated; endometrial cancer experts achieved higher scores (median 79 (IQR 18)) than non-medical academics (median 50 (IQR 18)) (p<0.001). The WCAM was sensitive to change; volunteers who read an endometrial cancer leaflet showed greater awareness (median 73 (IQR 9)) than those who read the control leaflet (median 59 (IQR 9)) (p<0.001). Knowledge of endometrial cancer red flag symptoms and risk factors was poor in the 847 UK-based participants. CONCLUSIONS: Our findings support the validity and reliability of the Womb Cancer Awareness Measure in assessing public awareness of endometrial cancer. In a UK population sample, knowledge of warning symptoms and risk factors was low, highlighting the need for public awareness campaigns.

The effect of a novel, digital physical activity and emotional well-being intervention on health-related quality of life in people with chronic kidney disease: trial design and baseline data from a multicentre prospective, wait-list randomised controlled trial (kidney BEAM).

BACKGROUND: Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. METHODS: This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. RESULTS: 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. CONCLUSION: Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. TRIAL REGISTRATION: NCT04872933. Registered 5th May 2021.

Measuring quality of life in trials including patients on haemodialysis: methodological issues surrounding the use of the Kidney Disease Quality of Life Questionnaire.

BACKGROUND: Haemodialysis (HD) treatment causes a significant decrease in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up because they die or they receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed. METHODS: A systematic search of electronic databases for trials measuring QoL in HD patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire was conducted. The review was conducted in Covidence version 2. Quantitative analysis was conducted in Stata version 16. RESULTS: We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted a sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used, but are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many articles (70%) amending the validated questionnaires or reporting only statistically significant results. CONCLUSIONS: Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient-reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group. PROSPERO REGISTRATION: CRD42020223869.

Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.

BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes. METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months. RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio. CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.

Outcomes and care priorities for older people living with frailty and advanced chronic kidney disease: a multi-professional scoping review.

The growing older population with advanced chronic kidney disease (ACKD stages 4-5) poses a challenge for healthcare worldwide. The high prevalence of frailty and associated adverse health outcomes highlights concerns for management and interventions specific to this population. The aim was to objectively review the evidence relating to older people (≥65 years) living with frailty and ACKD. More specifically how frailty is identified, what interventions have been studied and what outcomes have been reported including outcomes important to patients, families and carers. A scoping review was undertaken following the PRISMA-Scr guidelines. Nine databases were searched and a review team of five people followed a process using defined inclusion and exclusion criteria. Data were then analysed to answer the specific questions of the review. The World Health Organization's International Classification of Functioning Disability and Health was used to map outcomes across the domains. A total of 90 studies were included. The most reported frailty measure was the frailty phenotype. The most reported outcomes were mortality, hospitalisation and healthcare utilisation. Health-related quality of life was the most common patient-reported outcome measure. There were few intervention studies and limited evidence of patient and carer perspectives. This scoping review highlights important areas for further research in older people living with frailty and ACKD. This includes a 'gold standard' measure for identifying frailty, interventions and improvements in outcome measures that matter to patients (including studies that focus on carers and carer burden) and priority setting for future research.

Living with frailty and haemodialysis: a qualitative study.

BACKGROUND: Frailty is highly prevalent in people receiving haemodialysis (HD) and is associated with poor outcomes. Understanding the lived experiences of this group is essential to inform holistic care delivery. METHODS: Semi-structured interviews with N = 25 prevalent adults receiving HD from 3 HD units in the UK. Eligibility criteria included a Clinical Frailty Scale (CFS) score of 4-7 and a history of at least one fall in the last 6 months. Sampling began guided by maximum variation sampling to ensure diversity in frailty status; subsequently theoretical sampling enabled exploration of preliminary themes. Analysis was informed by constructivist grounded theory; later we drew upon the socioecological model. RESULTS: Participants had a mean age of 69 ± 10 years, 13 were female, and 13 were White British. 14 participants were vulnerable or mildly frail (CFS 4-5), and 11 moderately or severely frail (CFS 6-7). Participants characterised frailty as weight loss, weakness, exhaustion, pain and sleep disturbance arising from multiple long-term conditions. Participants' accounts revealed: the consequences of frailty (variable function and psychological ill-health at the individual level; increasing reliance upon family at the interpersonal level; burdensome health and social care interactions at the organisational level; reduced participation at the community level; challenges with financial support at the societal level); coping strategies (avoidance, vigilance, and resignation); and unmet needs (overprotection from family and healthcare professionals, transactional health and social care exchanges). CONCLUSIONS: The implementation of a holistic needs assessment, person-centred health and social care systems, greater family support and enhancing opportunities for community participation may all improve outcomes and experience. An approach which encompasses all these strategies, together with wider public health interventions, may have a greater sustained impact. TRIAL REGISTRATION: ISRCTN12840463 .

Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients.

PURPOSE: Patients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients. METHODS: Patients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12-14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays. RESULTS: Despite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ2 ≤ 0.399) other than TNF-α (p = 0.001, ηρ2 = 0.186), though no significance was revealed upon post hoc analysis. CONCLUSION: Six months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this. TRIAL REGISTRATION: ISRCTN1129707, prospectively registered on 05/03/2015.

The Codevelopment of "My Kidneys & Me": A Digital Self-management Program for People With Chronic Kidney Disease.

BACKGROUND: Health care self-management is important for people living with nondialysis chronic kidney disease (CKD). However, the few available resources are of variable quality. OBJECTIVE: This work describes the systematic codevelopment of "My Kidneys & Me" (MK&M), a theory-driven and evidence-based digital self-management resource for people with nondialysis CKD, guided by an established process used for the successful development of the diabetes education program MyDESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed, DESMOND). METHODS: A multidisciplinary steering group comprising kidney health care professionals and researchers and specialists in the development of complex interventions and digital health provided expertise in the clinical and psychosocial aspects of CKD, self-management, digital health, and behavior change. A patient and public involvement group helped identify the needs and priorities of MK&M and co-design the resource. MK&M was developed in 2 sequential phases. Phase 1 involved the codevelopment process of the MK&M resource (content and materials), using Intervention Mapping (IM) as a framework. The first 4 IM steps guided the development process: needs assessment was conducted to describe the context of the intervention; intervention outcomes, performance objectives, and behavioral determinants were identified; theory- and evidence-based change methods and practical strategies to deliver change methods were selected; and program components were developed and refined. Phase 2 involved the adoption and adaptation of the existing MyDESMOND digital platform to suit the MK&M resource. RESULTS: The needs assessment identified that individuals with CKD have multiple differing needs and that delivering a self-management program digitally would enable accessible, tailored, and interactive information and support. The intended outcomes of MK&M were to improve and maintain effective self-management behaviors, including physical activity and lifestyle, improve knowledge, promote self-care skills, increase self-efficacy, and enhance well-being. This was achieved through the provision of content and materials designed to increase CKD knowledge and patient activation, reduce health risks, manage symptoms, and improve physical function. Theories and behavior change techniques selected include Self-Management Framework, Capability, Opportunity, Motivation Behavior model components of Behaviour Change Wheel and taxonomy of behavior change techniques, Health Action Process Approach Model, Common Sense Model, and Social Cognitive Theory. The program components developed comprised educational and behavior change sessions, health trackers (eg, monitoring blood pressure, symptoms, and exercise), goal-setting features, and forums for social support. The MyDESMOND digital platform represented an ideal existing platform to host MK&M; thus, the MyDESMOND interface and features were adopted and adapted for MK&M. CONCLUSIONS: Applying the IM framework enabled the systematic application of theory, empirical evidence, and practical perspectives in the codevelopment of MK&M content and materials. Adopting and adapting a preexisting platform provided a cost- and time-efficient approach for developing our digital intervention. In the next stage of work, the efficacy of MK&M in increasing patient activation will be tested in a randomized controlled trial.

A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass.

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated.

Standardising the measurement of physical activity in people receiving haemodialysis: considerations for research and practice.

BACKGROUND: Physical activity (PA) is exceptionally low amongst the haemodialysis (HD) population, and physical inactivity is a powerful predictor of mortality, making it a prime focus for intervention. Objective measurement of PA using accelerometers is increasing, but standard reporting guidelines essential to effectively evaluate, compare and synthesise the effects of PA interventions are lacking. This study aims to (i) determine the measurement and processing guidance required to ensure representative PA data amongst a diverse HD population, and; (ii) to assess adherence to PA monitor wear amongst HD patients. METHODS: Clinically stable HD patients from the UK and China wore a SenseWear Armband accelerometer for 7 days. Step count between days (HD, Weekday, Weekend) were compared using repeated measures ANCOVA. Intraclass correlation coefficients (ICCs) determined reliability (≥0.80 acceptable). Spearman-Brown prophecy formula, in conjunction with a priori ≥  80% sample size retention, identified the minimum number of days required for representative PA data. RESULTS: Seventy-seven patients (64% men, mean ± SD age 56 ± 14 years, median (interquartile range) time on HD 40 (19-72) months, 40% Chinese, 60% British) participated. Participants took fewer steps on HD days compared with non-HD weekdays and weekend days (3402 [95% CI 2665-4140], 4914 [95% CI 3940-5887], 4633 [95% CI 3558-5707] steps/day, respectively, p < 0.001). PA on HD days were less variable than non-HD days, (ICC 0.723-0.839 versus 0.559-0.611) with ≥ 1 HD day and ≥  3 non-HD days required to provide representative data. Using these criteria, the most stringent wear-time retaining ≥ 80% of the sample was ≥7 h. CONCLUSIONS: At group level, a wear-time of ≥7 h on ≥1HD day and ≥ 3 non-HD days is required to provide reliable PA data whilst retaining an acceptable sample size. PA is low across both HD and non- HD days and future research should focus on interventions designed to increase physical activity in both the intra and interdialytic period.

Predictors of Overnight Admission after Minimally Invasive Hysterectomy in the Expert Setting.

STUDY OBJECTIVE: To identify predictors of overnight admission after laparoscopic and robot-assisted hysterectomy to improve preoperative counseling and patient optimization. DESIGN: A single-center retrospective cohort study (Canadian Task Force classification III). SETTING: Academic university hospital. PATIENTS: Patients undergoing straight-stick laparoscopic and robot-assisted hysterectomy by fellowship-trained minimally invasive gynecologic surgeons for benign indications INTERVENTIONS: Straight-stick laparoscopic and robot-assisted hysterectomy. MEASUREMENTS AND MAIN RESULTS: Data from 396 consecutive minimally invasive hysterectomy procedures were collected for analysis. Three hundred twelve patients (79%) were discharged the same day, and 84 (21%) were admitted for at least 1 night. Data from the 2 groups were compared. Overnight stay compared with same-day discharge was associated with older age (47.3 vs 43.4 years, p < .001), lower preoperation hematocrit (35.8% vs 37.3%, p = .035), history of prior laparotomy (31% vs 14.1%, p = .003), prolonged operative time (190.5 vs 115.2 minutes, p < .001), estimated blood loss (244.6 vs 104.1 mL, p < .001), lysis of adhesion (27.4% vs 13.5%), and intraoperative organ injury (17% vs 3%, p = .005). Logistic regression analysis, adjusting for all included variables as confounders, showed that hematocrit increments of 5% were protective against any overnight stay (odds ratio, .622; p = .015), and a 30-minute increase in operative time increased the odds of an overnight stay by 1.6 (p < .001). History of a laparotomy remained a significant predictive factor for an overnight stay (odds ratio, 3.2; p = .006). Later surgery end time, in 60-minute increments, increased the odds of an overnight stay by 1.2 (p < .01). CONCLUSION: Perioperative factors such as age, hematocrit, surgery time, and surgical history as well as intraoperative factors such as prolonged operative time are predictive of overnight hospital stay.

Exploration of the Relationship between Severe and Complex Disabilities and Child Sexual Abuse: A Call for Relevant Research.

Despite the awareness that children with severe and complex difficulties experience child sexual abuse (CSA), the development of research in this area is still in its infancy. This call for relevant research seeks to identify the main gaps in knowledge in order to inform future debate, potential research questions, and raise issues for practice. Themes are identified relevant to researchers and practitioners globally. These include the complexity and duality of definition: recognition of CSA; barriers to communication with children and between services; diversity of segregated and inclusive settings; interaction of age and gender; adult and peer abuse in institutions; sexuality and disability; and intrusive care and medical practices. Recommendations for future research and practice in creating safe environments are provided.

Effects of intradialytic cycling exercise on exercise capacity, quality of life, physical function and cardiovascular measures in adult haemodialysis patients: a systematic review and meta-analysis.

Background: Intradialytic cycling (IDC), delivered during haemodialysis (HD), has the potential to improve many health issues. This systematic review and meta-analysis examine the evidence on the effects of IDC on exercise capacity, quality of life (QoL), physical function and cardiovascular health. Methods: Twenty-four databases were searched alongside Internet and hand searching, and consultation with experts. Eligibility criteria were cluster randomized, randomized and quasi-randomized controlled trials (RCTs) of IDC versus usual care in prevalent adult HD patients. Primary outcome measures were exercise capacity (VO2 peak and field tests) and QoL. Secondary measures were cardiac and physical function. Results: Thirteen RCTs were eligible. Eight provided data for use in meta-analyses, which indicated no significant change in VO2 peak (mean difference, MD 1.19 mL/kg/min, 95% confidence interval -1.15 to 3.52, P = 0.3), physical (mean change, MC 1.97, -8.27 to 12.22, P = 0.7) or mental component (MC 3.37, -7.94 to 14.68, P = 0.6) summary scores of the Medical Outcomes Short Form 36, pulse wave velocity (MD -0.57 m/s, -1.55 to 0.41, P = 0.4), systolic (MD -2.28 mmHg, -14.46 to 9.90, P = 0.7) or diastolic blood pressure (MD 2.25 mmHg, -3.01 to 7.50, P = 0.4) following IDC. IDC, however, leads to an improvement in performance on the 6-min walk test (MD 87.84 m, 39.60-136.09, P = 0.0004). All included studies were considered to have high risk of bias. Conclusions: There is insufficient evidence demonstrating whether cycling exercise during HD improves patient outcomes. High-quality, adequately powered RCTs of IDC are required.

Making Sense of Bereavement in People with Profound Intellectual and Multiple Disabilities: Carer Perspectives.

BACKGROUND: People with intellectual disabilities are thought to have a reduced capacity for understanding death. Drawing on cognitive theory, researchers have suggested that those with profound intellectual and multiple disabilities mainly perceive loss as a mismatch between past and present experiences. However, very little research has considered how carers conceptualize bereavement in relation to this group. METHOD: Semi-structured interviews obtained responses from seven carers. Transcripts were examined using interpretative phenomenological analysis. RESULTS: Two superordinate themes emerged: 'difficulty articulating the experience of loss' and 'making sense of bereavement through familiar patterns'. CONCLUSIONS: Carers conceptualize bereavement primarily in cognitive terms, but also take account of relational factors mediating loss. Implications for training and further research are outlined.

Timing of death after traumatic injury--a contemporary assessment of the temporal distribution of death.

BACKGROUND: The trimodal distribution of traumatic death was first described by Trunkey in 1983, which demonstrated that most deaths occur in the first 24 h. We postulate that since 1983, the time-to-death histogram described has shifted. METHODS: A retrospective analysis identifying timing of death was conducted on the National Trauma Data Bank (version 7.2) from 2002 to 2006. Early death was defined as death within 24 h of admission. International Classification of Diseases ninth edition codes with greater than 20% early deaths were called "high-risk codes". Bivariate analyses were conducted to assess the association between demographics, injury factors, and death. Pearson's χ(2) test was used to compare timing of death by region of injury. Multivariate logistic regression was conducted to show the effect of region of injury on death while controlling for demographic factors and injury type. RESULTS: The cohort includes 898,982 patients. The study population was predominantly male (66%) and Caucasian (62%). Mean age and injury severity score were 45 ± 20.3 and 11 ± 10, respectively. Overall mortality rate was 5% with 56% dying early. Head/neck, thorax, and abdomen/pelvis injuries were more prevalent in overall deaths (35%, 22%, and 11%, respectively). Thorax and abdomen/pelvis injuries predicted early death (odds ratio 2.03 and 1.39, respectively). CONCLUSIONS: The prevalence of early death has decreased since 1983, but the majority of deaths still occur within 24 h of injury. Ample opportunity remains to impact mortality in the first 24 h after injury.

Motivations and barriers to exercise in chronic kidney disease: a qualitative study.

BACKGROUND: Exercise has the potential to modulate a number of complications associated with chronic kidney disease (CKD). However, typically, CKD patients lead very sedentary lifestyles, the reasons for which are not fully known. The aim of this qualitative study was to gain an understanding of the motivators, barriers and beliefs held by CKD patients regarding exercise. METHODS: We conducted 3 focus groups and 22 semi-structured interviews. Data were collected from nephrology outpatient clinics in the United Kingdom. A total of 36 individuals with CKD stages 1-5 not requiring renal replacement therapy, aged 26-83 years participated in this study. This manuscript outlines the findings from patients with CKD stages 3-5. Focus groups and interviews were transcribed verbatim and analysed thematically. RESULTS: Positive attitudes to exercise reflected autonomous motivations including: exercising for health; enjoyment and social interaction. Family support and goal setting were seen as motivators for exercise and the accessibility of local facilities influenced activity levels. Barriers to exercise were poor health, fear of injury or aggravating their condition, a lack of guidance from healthcare professionals and a lack of facilities. CONCLUSIONS: These findings are an important first stage in the development of a CKD-specific exercise behaviour change intervention. Interventions should operate at multiple levels, with a focus on improving patient autonomy and exercise self-efficacy, support networks and the physical environment (e.g. the accessibility of local facilities). In addition, strategies are required to ensure that the healthcare system is actively promoting and routinely supporting exercise for all patients with CKD.

The Impact of Exercising During Haemodialysis on Blood Pressure, Markers of Cardiac Injury and Systemic Inflammation--Preliminary Results of a Pilot Study.

BACKGROUND/AIMS: Patients requiring haemodialysis have cardiovascular and immune dysfunction. Little is known about the acute effects of exercise during haemodialysis. Exercise has numerous health benefits but in other populations has a profound impact upon blood pressure, inflammation and immune function; therefore having the potential to exacerbate cardiovascular and immune dysfunction in this vulnerable population. METHODS: Fifteen patients took part in a randomised-crossover study investigating the effect of a 30-min bout of exercise during haemodialysis compared to resting haemodialysis. We assessed blood pressure, plasma markers of cardiac injury and systemic inflammation and neutrophil degranulation. RESULTS: Exercise increased blood pressure immediately post-exercise; however, 1 hour after exercise blood pressure was lower than resting levels (106±22 vs. 117±25 mm Hg). No differences in h-FABP, cTnI, myoglobin or CKMB were observed between trial arms. Exercise did not alter circulating concentrations of IL-6, TNF-α or IL-1ra nor clearly suppress neutrophil function. CONCLUSIONS: This study demonstrates fluctuations in blood pressure during haemodialysis in response to exercise. However, since the fall in blood pressure occurred without evidence of cardiac injury, we regard it as a normal response to exercise superimposed onto the haemodynamic response to haemodialysis. Importantly, exercise did not exacerbate systemic inflammation or immune dysfunction; intradialytic exercise was well tolerated.

Comparison of equine articular cartilage thickness in various joints.

PURPOSE: Thicknesses of fresh equine articular cartilage surfaces from the fetlock, carpal and stifle joints were measured employing a needle probe test. MATERIALS AND METHODS: Eighty-seven samples used in measurement were cultivated from fetlock, carpal and stifle joints of 12 deceased within 4 h of death. After approximately three minutes of exposure to air during dissection, all cartilage samples were preserved in a saline solution to keep the articular cartilage hydrated for testing. The thickness was measured on five different spots on the same sample. The thicknesses of the fetlock, carpus and stifle were compared. RESULTS: The articular cartilage of the stifle was thicker than the fetlock and carpus, while the fetlock and the carpus had similar thickness values. The average thickness of the fetlock, carpal and stifle joint are 0.86, 0.87 and 2.1 mm, respectively. They were statistically compared using the Student t-test. The differences on the articular cartilage thicknesses between the fetlock and stifle, and carpus and stifle were "very highly significant" (p < 0.001). This indicates that the articular cartilage thickness of the stifle is significantly different from that of the fetlock and carpus. Four different surfaces in the fetlock and four in the carpal joint were also compared. Significant differences between each set of the four surfaces were not observed. In the carpus, the difference in thickness between the distal radius and proximal third carpal bone articular cartilage surfaces as well as the proximal radial carpal bone and distal radial carpal bone articular cartilage surfaces were statistically significant.