A Systematic Review of the Acute Effects of Hemodialysis on Skeletal Muscle Perfusion, Metabolism, and Function.

INTRODUCTION: The underlying mechanisms of skeletal muscle wasting in hemodialysis patients are complex. We performed a systematic review to summarize evidence on whether hemodialysis has acute effects on skeletal muscle perfusion, metabolism, and function. METHODS: The protocol was registered on PROSPERO (Registration number CRD42018103682). A systematic search was performed in MEDLINE, PubMed, Cochrane, Embase, Scopus, and Web of Science. Citation, reference list, and gray literature searches were also performed. Studies were selected in 2 stages: title and abstract review, then full-text review. RESULTS: A total of 65 full-text articles were reviewed, and 14 studies were eligible for inclusion. No studies were identified that assessed muscle perfusion during dialysis. Two studies used near-infrared spectroscopy to indirectly measure skeletal muscle oxygen consumption, which increased during dialysis in 1 study but only in patients with diabetes in the second. Metabolism was examined in 9 studies. A number of acute metabolic changes were reported (e.g., caspase-3 activity, polyubiquitin, and interleukin-6 protein increased in response to hemodialysis) as was a net negative protein balance over the dialysis session. Three studies examining muscle function did not produce consistent findings. CONCLUSION: Gaps remain in understanding the acute effects of hemodialysis on skeletal muscle, particularly for changes in perfusion and function, although there does appear to be an acute effect on muscle metabolism.

Do clinical trials reflect reality? A systematic review of inclusion/exclusion criteria in trials of renal transplant immunosuppression.

Renal transplant recipients and donors are becoming increasingly more marginal, with more expanded criteria (ECD) and donation after circulatory death (DCD) donors and older recipients. Despite this, high-risk donors and recipients are often excluded from clinical trials, leading to uncertainty about the generalizability of findings. We extracted data regarding inclusion/exclusion criteria from 174 trials of immunosuppression in renal transplant recipients published over a 5-year period and compared criteria with those specified in published trial registries. Frequently reported donor exclusion criteria were age (16.1%), donor type and cold ischaemic time (22.4%). Common recipient exclusion criteria included upper age limit (38.5%), high panel reactive antibody (PRA) (42.5%) and previous transplantation (39.7%). Inclusion/exclusion criteria recorded in trial registries matched those reported in the manuscript in only 6 (7.8%) trials. Of registered trials, 51 (66.2%) trials included additional criteria in the manuscript, 51 (66.2%) were missing criteria in the manuscript specified in the protocol, and in 19 (24.7%) key criteria changed from the protocol to the manuscript. Our findings suggest many recent immunosuppression trials have restrictive inclusion criteria which may not be reflective of current renal transplant populations. Discrepancies between trial protocols and published reports raise the possibility of selection bias.

Variability in the reporting of renal function endpoints in immunosuppression trials in renal transplantation: time for consensus?

Early measures of graft function are increasingly used to assess efficacy in clinical trials of kidney transplant immunosuppression. This study aimed to assess the variability and quality of reporting of these endpoints in contemporary trials. Data regarding renal function endpoints were extracted from 213 reports from randomized controlled trials comparing immunosuppressive interventions in renal transplant recipients published between 2010 and 2014. A total of 174 (81.7%) reports included a measure of renal function; in 44 (20.7%), this was the primary endpoint. A total of 103 manuscripts (48.4%) reported serum creatinine, 142 (66.6%) reported estimated glomerular filtration rate (eGFR), and 26 (12.2%) reported measured GFR. Formulas used for GFR estimation were modification of diet in renal disease (42.3%), Cockroft-Gault (23.5%), Nankivell (15.0%), and CKD-EPI (0.9%). Six studies (2.8%) did not report the formula used to estimate GFR. A total of 13.9% of endpoints had missing data. In 10 studies, disagreement was found in the significance of findings using different measures of renal function. There is a great deal of variability in the reporting of renal function endpoints, with a significant proportion of studies using underperforming or inappropriate estimates. There is a need for consensus as to the best tool for monitoring and reporting renal function post-transplant, and in particular for use in clinical trials and registries.

Quality and consistency of outcome reporting in clinical trials of immunosuppression in renal transplantation.

Interpretation, comparison, and combination of results of clinical trials are reliant on accurate and complete reporting of outcomes. This study aimed to assess the quality and variability in outcome reporting in immunosuppression trials following renal transplantation. All randomized controlled trials comparing immunosuppressive interventions in renal transplant recipients published over a 5-year period were included. Outcomes reported in these studies were extracted, along with data regarding completeness of reporting and whether a clear definition of the method used to measure the outcome was provided. A total of 4760 outcomes were identified from 182 studies. Overall, 90.3% outcomes were completely reported; the remainder had missing data that would preclude use in meta-analysis; 31.5% manuscripts did not define a primary endpoint. Efficacy outcomes were more likely to be clearly defined than safety outcomes (OR: 0.022, P<.001) or patient-reported outcome measures (PROMs) (OR: 0.014, P<.001). PROMs were reported in less than half of manuscripts, and only five reported quality-of-life data using a validated tool. There was significant variability in the way that common efficacy and safety outcomes were defined. Variability in the way that endpoints are selected and reported in trials in renal transplantation makes interpretation and comparison between studies difficult.

Role of the Timed Up and Go Test in Patients With Chronic Obstructive Pulmonary Disease.

PURPOSE: The Timed Up and Go (TUG) test is a measure of functional mobility. It is a short test and requires minimal space. We determined the potential role of TUG test as a measure of function in patients with chronic obstructive pulmonary disease (COPD) and compared with controls. Furthermore, we wanted to determine the association and reliability of TUG test time to fall history. METHODS: Patients with COPD (n = 119) and controls with a smoking history (n = 58) were recruited. The TUG test, 6-minute walk distance and subsequent BODE score, spirometry, and history of falls were assessed. The TUG test was measured across observers and on separate days within the same individual. RESULTS: The TUG test time was greater in patients, 11.9 ± 3.7 seconds, than controls, 9.5 ± 1.8 seconds (P < .001). The TUG test was inversely related to 6-minute walk distance in patients (r =-0.74) and controls (r =-0.71); P < .001. In patients, TUG test was related to BODE score (r = 0.53; P < .001) but not spirometry measurements. A receiver operator curve analysis of 0.77 in patients indicated reasonable ability for TUG test to indicate those who had fallen in the past year. A TUG of ≥12 seconds had 74% sensitivity and specificity for a history of a fall in the past year. Inter- and intraobserver values indicated minimal differences between measurements. CONCLUSION: These results support a potential role for the TUG test to be incorporated into community COPD assessment to stratify patients functionally, particularly where time and space are limited. Future studies are required to assess impact of interventions on TUG test and determine the predictive ability to identify future falls.

Weight patterns and perceptions among female university students of Karachi: a cross sectional study.

BACKGROUND: Body weight and its perception play an important role in the physical and mental well-being of a person. Weight perception is found to be a better predictor of weight management behaviour as compared to actual weight. In Pakistan, studies have been done on the prevalence of weight status but weight perception is still unexplored. The study was done to examine relationships between body weight perception, actual weight status, and weight control behaviour among the female university students of Karachi. METHODS: A cross sectional study was carried out during Sep-Nov 2009 on female students in four universities of Karachi, Pakistan. Our final sample size included 338 female university students. Height and weight were measured on calibrated scales. A modified BMI criterion for Asian populations was used. RESULTS: Based on measured BMI; the prevalence of underweight, normal weight and overweight females was 27.2%, 51.5% and 21.3% respectively. As a whole, just over one third (33.73%) of the sample misclassified their weight status. Among underweight (n=92), 45.70% thought they were of normal weight. No one who was truly underweight perceived them self as overweight. Among the normal weight (n= 174), 9.8% thought they were underweight and 23.6% considered themselves overweight. Among the overweight (n=72); 18.3% considered themselves normal. Only one female student thought she was underweight despite being truly overweight. CONCLUSIONS: Our study shows that among female university students in Karachi, the prevalence of being underweight is comparatively high. There is a significant misperception of weight, with one third of students misclassifying themselves. Underweight females are likely to perceive themselves as normal and be most satisfied with their weight. Health policy makers should implement these findings in future development of health interventions and prevention of depression, social anxiety and eating disorders associated with incorrect weight perception among young females. Studies that employ a longitudinal approach are needed to validate our findings.

Target renal damage: the microvascular associations of increased aortic stiffness in patients with COPD.

BACKGROUND: Although renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness. METHODS: Patients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured. RESULTS: The UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log10 UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls. CONCLUSIONS: There is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered.

Persistence of pneumolysin in the cerebrospinal fluid of patients with pneumococcal meningitis is associated with mortality.

Poor prognosis in Pneumococcal meningitis may be associated with high pneumolysin levels in cerebrospinal fluid (CSF). In patient samples we showed that pneumolysin levels in CSF remained high after 48 hours in nonsurvivors of meningitis compared with survivors. Selective antipneumolysin treatment may present a novel therapeutic option.