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

A systematic review of changes in women’s physical activity before and during pregnancy and the postnatal period

Objectives: To determine the magnitude and type of naturally occuring physical activity changes in women around the time of pregnancy. Background: This systematic review synthesises the results of studies examining naturally occurring physical activity in women before they become pregnant and the magnitude and type of changes during pregnancy and the postnatal period. Methods: Electronic databases were searched for relevant articles and PRISMA guidelines for selection of articles were used. Only studies examining naturally occurring, non-intervention changes in regular activity levels were included. The quality assessment was based on protocols of the Cochrane Database of Systematic Reviews. Of the initial 720 titles, 24 studies met the inclusion criteria and were included in the final review. Results: Compared to pre-pregnancy, the magnitude of physical activity decreased over the course of pregnancy and postnatally and the types of activities tended to be of lesser intensity than pre-pregnancy. The quality of the research was varied; methodological limitations included using subjective methods of assessment of physical activity (9/24), failing to report reliabilities or validity of measures used (8/24), no information on parity (13/24) or level of fitness prior to pregnancy (11/24). Conclusion: The evidence suggests a marked decrease in the amount and type of moderate to strenuous physical activity during the transition to motherhood, which does not always increase again postpartum. Patient education targeting specific physical activities at regular intervals during and after pregnancy to improve long-term maternal health is necessary

Commentaries on Viewpoint: The ongoing need for good physiological investigation: Obstructive sleep apnea in HIV patients as a paradigm

The final publication is available via http://dx.doi.org/10.1152/japplphysiol.00989.2014[Abstract] The intriguing paradigm put forth by Darquenne et al. (3) highlighted that improved therapy against human immunodeficiency virus (HIV) has come at the cost of elevated rates of chronic diseases, such as obstructive sleep apnea (OSA) and obesity, during the highly active antiretroviral therapy (HAART) era.Ministerio de Economía y Competitividad; TIN2013-40686-P

Risk Factors for Prognosis in Patients With Severely Decreased GFR

Introduction: Patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) < 30 ml/min per 1.73 m 2 (corresponding to CKD stage G4+) comprise a minority of the overall CKD population but have the highest risk for adverse outcomes. Many CKD G4+ patients are older with multiple comorbidities, which may distort associations between risk factors and clinical outcomes. Methods: We undertook a meta-analysis of risk factors for kidney failure treated with kidney replacement therapy (KRT), cardiovascular disease (CVD) events, and death in participants with CKD G4+ from 28 cohorts (n = 185,024) across the world who were part of the CKD Prognosis Consortium. Results: In the fully adjusted meta-analysis, risk factors associated with KRT were time-varying CVD, male sex, black race, diabetes, lower eGFR, and higher albuminuria and systolic blood pressure. Age was associated with a lower risk of KRT (adjusted hazard ratio: 0.74; 95% confidence interval: 0.69–0.80) overall, and also in the subgroup of individuals younger than 65 years. The risk factors for CVD events included male sex, history of CVD, diabetes, lower eGFR, higher albuminuria, and the onset of KRT. Systolic blood pressure showed a U-shaped association with CVD events. Risk factors for mortality were similar to those for CVD events but also included smoking. Most risk factors had qualitatively consistent associations across cohorts. Conclusion: Traditional CVD risk factors are of prognostic value in individuals with an eGFR < 30 ml/min per 1.73 m 2, although the risk estimates vary for kidney and CVD outcomes. These results should encourage interventional studies on correcting risk factors in this high-risk population

Minimally important difference estimates and methods: A protocol

Introduction: Patient-reported outcomes (PROs) are often the outcomes of greatest importance to patients. The minimally important difference (MID) provides a measure of the smallest change in the PRO that patients perceive as important. An anchor-based approach is the most appropriate method for MID determination. No study or database currently exists that provides all anchor-based MIDs associated with PRO instruments; nor are there any accepted standards for appraising the credibility of MID estimates. Our objectives are to complete a systematic survey of the literature to collect and characterise published anchor-based MIDs associated with PRO instruments used in evaluating the effects of interventions on chronic medical and psychiatric conditions and to assess their credibility. Methods and analysis: We will search MEDLINE, EMBASE and PsycINFO (1989 to present) to identify studies addressing methods to estimate anchor-based MIDs of target PRO instruments or reporting empirical ascertainment of anchor-based MIDs. Teams of two reviewers will screen titles and abstracts, review full texts of citations, and extract relevant data. On the basis of findings from studies addressing methods to estimate anchor-based MIDs, we will summarise the available methods and develop an instrument addressing the credibility of empirically ascertained MIDs. We will evaluate the credibility of all studies reporting on the empirical ascertainment of anchorbased MIDs using the credibility instrument, and assess the instrument's inter-rater reliability. We will separately present reports for adult and paediatric populations. Ethics and dissemination: No research ethics approval was required as we will be using aggregate data from published studies. Our work will summarise anchor-based methods available to establish MIDs, provide an instrument to assess the credibility of available MIDs, determine the reliability of that instrument, and provide a comprehensive compendium of published anchor-based MIDs associated with PRO instruments which will help improve the interpretability of outcome effects in systematic reviews and practice guidelines

Design and implementation of the canadian kidney disease cohort study (CKDCS): A prospective observational study of incident hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD).</p> <p>Methods/Design</p> <p>The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions.</p> <p>Preliminary Results</p> <p>Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice.</p> <p>Discussion</p> <p>The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.</p

Prescription Medicines and the Risk of Road Traffic Crashes: A French Registry-Based Study

Using three nationwide databases in France, Ludivine Orriols, Emmanuel Lagarde, and colleagues provide evidence that prescribed medicines contribute to the risk of experiencing a road traffic crash

Considerations on equity in management of end-stage kidney disease in low- and middle-income countries

Achievement of equity in health requires development of a health system in which everyone has a fair opportunity to attain their full health potential. The current, large country-level variation in the reported incidence and prevalence of treated end-stage kidney disease indicates the existence of system-level inequities. Equitable implementation of kidney replacement therapy (KRT) programs must address issues of availability, affordability, and acceptability. The major structural factors that impact equity in KRT in different countries are the organization of health systems, overall health care spending, funding and delivery models, and nature of KRT prioritization (transplantation, hemodialysis or peritoneal dialysis, and conservative care). Implementation of KRT programs has the potential to exacerbate inequity unless equity is deliberately addressed. In this review, we summarize discussions on equitable provision of KRT in low- and middle-income countries and suggest areas for future research

Mixed-effects models for health care longitudinal data with an informative visiting process: A Monte Carlo simulation study.

Electronic health records are being increasingly used in medical research to answer more relevant and detailed clinical questions; however, they pose new and significant methodological challenges. For instance, observation times are likely correlated with the underlying disease severity: Patients with worse conditions utilise health care more and may have worse biomarker values recorded. Traditional methods for analysing longitudinal data assume independence between observation times and disease severity; yet, with health care data, such assumptions unlikely hold. Through Monte Carlo simulation, we compare different analytical approaches proposed to account for an informative visiting process to assess whether they lead to unbiased results. Furthermore, we formalise a joint model for the observation process and the longitudinal outcome within an extended joint modelling framework. We illustrate our results using data from a pragmatic trial on enhanced care for individuals with chronic kidney disease, and we introduce user-friendly software that can be used to fit the joint model for the observation process and a longitudinal outcome