Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation.

BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes

Parameters for accurate genome alignment

<p>Abstract</p> <p>Background</p> <p>Genome sequence alignments form the basis of much research. Genome alignment depends on various mundane but critical choices, such as how to mask repeats and which score parameters to use. Surprisingly, there has been no large-scale assessment of these choices using real genomic data. Moreover, rigorous procedures to control the rate of spurious alignment have not been employed.</p> <p>Results</p> <p>We have assessed 495 combinations of score parameters for alignment of animal, plant, and fungal genomes. As our gold-standard of accuracy, we used genome alignments implied by multiple alignments of proteins and of structural RNAs. We found the HOXD scoring schemes underlying alignments in the UCSC genome database to be far from optimal, and suggest better parameters. Higher values of the X-drop parameter are not always better. E-values accurately indicate the rate of spurious alignment, but only if tandem repeats are masked in a non-standard way. Finally, we show that γ-centroid (probabilistic) alignment can find highly reliable subsets of aligned bases.</p> <p>Conclusions</p> <p>These results enable more accurate genome alignment, with reliability measures for local alignments and for individual aligned bases. This study was made possible by our new software, LAST, which can align vertebrate genomes in a few hours <url>http://last.cbrc.jp/</url>.</p

The oral health assessment tool - Validity and reliability

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: The Oral Health Assessment Tool (OHAT) was a component of the Best Practice Oral Health Model for Australian Residential Care study. The OHAT provided institutional carers with a simple, eight category screening tool to assess residents’ oral health, including those with dementia. This analysis presents OHAT reliability and validity results. Methods: A convenience sample of 21 residential care facilities (RCFs) in urban and rural Victoria, NSW and South Australia used the OHAT at baseline, three-months and six-months to assess intra- and inter-carer reliability and concurrent validity. Results: Four hundred and fifty five residents completed all study phases. Intra-carer reliability for OHAT categories: percent agreement ranged from 74.4 per cent for oral cleanliness, to 93.9 per cent for dental pain; Kappa statistics were in moderate range (0.51-0.60) for lips, saliva, oral cleanliness, and for all other categories in range of 0.61-0.80 (substantial agreement) (p<0.05). Inter-carer reliability for OHAT categories: percent agreement ranged from 72.6 per cent for oral cleanliness to 92.6 per cent for dental pain; Kappa statistics were in moderate range (0.48-0.60) for lips, tongue, gums, saliva, oral cleanliness, and for all other categories in range of 0.61-0.80 (substantial agreement) (p<0.05). Intraclass correlation coefficients for OHAT total scores were 0.78 for intra-carer and 0.74 for inter-carer reliability. Validity analyses of the OHAT categories and examination findings showed complete agreement for the lips category, with the natural teeth, dentures, and tongue categories having high significant correlations and percent agreements. The gums category had significant moderate correlation and percent agreement. Non-significant and low correlations and percent agreements were evident for the saliva, oral cleanliness and dental pain categories. Conclusion: The Oral Health Assessment Tool was evaluated as being a reliable and valid screening assessment tool for use in residential care facilities, including those with cognitively impaired residents.JM Chalmers, PL King, AJ Spencer, FAC Wright and KD Carte

Transient integral boundary layer method to calculate the translesional pressure drop and the fractional flow reserve in myocardial bridges

BACKGROUND: The pressure drop – flow relations in myocardial bridges and the assessment of vascular heart disease via fractional flow reserve (FFR) have motivated many researchers the last decades. The aim of this study is to simulate several clinical conditions present in myocardial bridges to determine the flow reserve and consequently the clinical relevance of the disease. From a fluid mechanical point of view the pathophysiological situation in myocardial bridges involves fluid flow in a time dependent flow geometry, caused by contracting cardiac muscles overlying an intramural segment of the coronary artery. These flows mostly involve flow separation and secondary motions, which are difficult to calculate and analyse. METHODS: Because a three dimensional simulation of the haemodynamic conditions in myocardial bridges in a network of coronary arteries is time-consuming, we present a boundary layer model for the calculation of the pressure drop and flow separation. The approach is based on the assumption that the flow can be sufficiently well described by the interaction of an inviscid core and a viscous boundary layer. Under the assumption that the idealised flow through a constriction is given by near-equilibrium velocity profiles of the Falkner-Skan-Cooke (FSC) family, the evolution of the boundary layer is obtained by the simultaneous solution of the Falkner-Skan equation and the transient von-Kármán integral momentum equation. RESULTS: The model was used to investigate the relative importance of several physical parameters present in myocardial bridges. Results have been obtained for steady and unsteady flow through vessels with 0 – 85% diameter stenosis. We compare two clinical relevant cases of a myocardial bridge in the middle segment of the left anterior descending coronary artery (LAD). The pressure derived FFR of fixed and dynamic lesions has shown that the flow is less affected in the dynamic case, because the distal pressure partially recovers during re-opening of the vessel in diastole. We have further calculated the wall shear stress (WSS) distributions in addition to the location and length of the flow reversal zones in dependence on the severity of the disease. CONCLUSION: The described boundary layer method can be used to simulate frictional forces and wall shear stresses in the entrance region of vessels. Earlier models are supplemented by the viscous effects in a quasi three-dimensional vessel geometry with a prescribed wall motion. The results indicate that the translesional pressure drop and the mean FFR compares favourably to clinical findings in the literature. We have further shown that the mean FFR under the assumption of Hagen-Poiseuille flow is overestimated in developing flow conditions

Surfactants: their role in preventing the precipitation of proteins by tannins in insect guts

Much more tannic acid or pin oak tannin is required to precipitate the abundant leaf protein, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPC), from Manduca sexta gut fluid adjusted to pH 6.5 than is required to precipitate this protein from an aqueous buffer at the same pH. This finding demonstrates that some characteristic of M. sexta gut fluid, in addition to its basicity, counteracts the potential of tannins to precipitate ingested proteins. Gut fluid of M. sexta has a surface tension of 36–39 dynes/cm, indicating the presence of surfactants. Lysolecithin and linoleoylglycine, surfactants known to be present in insect gut fluids, also interfere with the precipitation of RuBPC by tannins at pH 6.5. It is concluded that detergency is a widespread property of insect gut fluids that counteracts the potential of tannins to precipitate die ary proteins, and it is argued that there is no longer any justification for continuing to refer to tannins as digestibility-reducing-substances. Finding that there has been no formidable barrier to the evolution of mechanisms that counter a generalized antidigestive action by tannins is difficult to reconcile with the idea that reduced digestibility is an evolved anti-herbivore adaptation of apparent plants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47751/1/442_2004_Article_BF00379632.pd

Association of Frailty based on self-reported physical function with directly measured kidney function and mortality

BACKGROUND: Use of serum creatinine to estimate GFR may lead to underestimation of the association between self-reported frailty and kidney function. Our objectives were to evaluate the association of measured GFR (mGFR) with self-reported frailty among patients with CKD and to determine whether self-reported frailty was associated with death after adjusting for mGFR. METHODS: Participants in the Modification of Diet in Renal Disease study (1989–1993) had GFR measured using iothalamate clearance (mGFR), and GFR was estimated based on the CKD-EPI creatinine (eGFRcr) and cystatin C (eGFRcys) equations. We defined self-reported frailty as three or more of: exhaustion, poor physical function, low physical activity, and low body weight. Death was ascertained through 2007 using the National Death Index and the United States Renal Data System. RESULTS: Eight hundred twelve MDRD participants (97 %) had complete data on self-reported frailty (16 % prevalence, N = 130) and mGFR (mean (SD) 33.1 ± 11.7 ml/min/1.73 m(2)). Higher GFR was associated with lower odds of self-reported frailty based on mGFR, (OR 0.71, 95 % CI 0.60–0.86 per 10 ml/min/1.73 m(2)), eGFRcr (OR 0.80, 95 % CI 0.67–0.94 per 10 ml/min/1.73 m(2)), and eGFRcys (OR 0.75, 95 % CI 0.62–0.90 per 10 ml/min/1.73 m(2)). Median follow-up was 17 (IQR 11–18) years, with 371 deaths. Self-reported frailty was associated with a higher risk of death (HR 1.71, 95 % CI 1.26–2.30), which was attenuated to a similar degree when mGFR (HR 1.48, 95 % CI 1.08–2.00), eGFRcr (HR 1.57, 95 % CI 1.15–2.10), or eGFRcys (HR 1.51, 95 % CI 1.10–2.10) was included as an indicator of kidney function. CONCLUSIONS: We found an inverse association between kidney function and self-reported frailty that was similar for mGFR, eGFR and eGFRcys. In this relatively healthy cohort of clinical trial participants with CKD, using serum creatinine to estimate GFR did not substantially alter the association of GFR with self-reported frailty or of self-reported frailty with death