70 research outputs found
Cohort profile: Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT)
Background: The Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT)
is a large, prospective, pan-Canadian, cohort study designed to improve our understanding of determinants of renal and cardiovascular (CV) disease progression in patients with chronic kidney disease (CKD). The primary objective is to clarify the associations between traditional and newer biomarkers in the prediction of specific renal and CV events, and of death in patients with CKD managed by nephrologists. This information could then be used to better understand biological variation in outcomes, to develop clinical prediction models and to inform enrolment into interventional studies which may lead to novel treatments.
Methods/Designs: Commenced in 2008, 2546 patients have been enrolled with eGFR between 15 and 45 ml/min 1.73m2 from a representative sample in 25 rural, urban, academic and non academic centres across Canada. Patients are to be followed for an initial 3 years at 6 monthly intervals, and subsequently annually. Traditional biomarkers include eGFR, urine albumin creatinine ratio (uACR), hemoglobin (Hgb), phosphate and albumin. Newer biomarkers of interest were selected on the basis of biological relevance to important processes, commercial availability and assay reproducibility. They include asymmetric dimethylarginine (ADMA), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), troponin I, cystatin C, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and transforming growth factor beta 1 (TGFβ1). Blood and urine samples are collected at baseline, and every 6 monthly, and stored at −80°C. Outcomes of interest include renal replacement therapy, CV events and death, the latter two of which are adjudicated by an independent panel.
Discussion: The baseline distribution of newer biomarkers does not appear to track to markers of kidney function
and therefore may offer some discriminatory value in predicting future outcomes. The granularity of the data
presented at baseline may foster additional questions.
The value of the cohort as a unique resource to understand outcomes of patients under the care of nephrologists
in a single payer healthcare system cannot be overstated. Systematic collection of demographic, laboratory and
event data should lead to new insights.
The mean age of the cohort was 68 years, 90% were Caucasian, 62% were male, and 48% had diabetes. Forty
percent of the cohort had eGFR between 30–45 mL/min/1.73m2, 22% had eGFR values below 20 mL/min/1.73m2; 61% had uACR < 30. Serum albumin, hemoglobin, calcium and 25-hydroxyvitamin D (25(OH)D) levels were progressively lower in the lower eGFR strata, while parathyroid hormone (PTH) levels increased. Cystatin C, ADMA, NT-proBNP, hsCRP, troponin I and IL-6 were significantly higher in the lower GFR strata, whereas 25(OH)D and TGFβ1 values were lower at lower GFR. These distributions of each of the newer biomarkers by eGFR and uACR categories were variable
Kommerell’s diverticulum and aneurysmal right-sided aortic arch: A case report and review of the literature
AbstractRight-sided aortic arch is a rare variant of the thoracic vascular anatomy that may be accompanied by an aberrant origin of the left subclavian artery. We report a true aneurysm of the distal arch and descending thoracic aorta in a patient with right-sided arch and review previous descriptions of aneurysms of anomalous right-sided aortas. In our patient, the left subclavian artery originated at the junction between the distal arch and the descending thoracic aorta located in the right chest and was aneurysmal (Kommerell’s diverticulum); the thoracic aorta was also aneurysmal. Extra-anatomic left subclavian-to-carotid transposition was performed before the intrathoracic procedure. Subsequently, a right thoracotomy provided adequate exposure for repairing the aortic aneurysm and oversewing the aneurysmal origin of the subclavian artery. Because the distal aortic arch was involved, deep hypothermia and circulatory arrest were used. Only five previous instances of true aneurysms of a right-sided aortic arch have been reported; four of these patients underwent operative repair (via bilateral thoracotomy, median sternotomy, or right thoracotomy). We believe that a right thoracotomy provides good exposure and avoids the morbidity associated with bilateral thoracotomy. The reconstruction of the subclavian artery has not previously been reported in this setting. Performing subclavian reconstruction as an extrathoracic procedure before the intrathoracic repair would be expected to reduce the subsequent risk of distal ischemia or subclavian steal without increasing the overall morbidity associated with the procedure. (J Vasc Surg 2000;32:1208-14.
Endovascular repair of ruptured abdominal aortic aneurysms: A systematic review and meta-analysis
ObjectivesThe perioperative mortality for people with ruptured abdominal aortic aneurysms (RAAA) has not changed for two decades. Of patients who survive long enough to undergo open repair for ruptured aneurysms, half die (48%; 95% confidence interval [CI] 46 to 50). Randomized trials have shown that endovascular aneurysm repair (EVAR) for nonruptured abdominal aortic aneurysms decreases perioperative mortality compared with open repair. EVAR may similarly benefit patients with RAAA. We aimed to summarize studies of patients undergoing EVAR for ruptured aneurysms.MethodsTwo reviewers searched Medline and EMBASE databases from 1994 to July 2006, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effectiveness, the Cochrane Central Register of Controlled Trials, Best Evidence 1994 to 2006, reference lists, clinical trial registries, and conference proceedings; we also contacted authors. All published and unpublished studies in which a group of people with ruptured aneurysms, assessed objectively by imaging, was treated with EVAR (REVAR) were eligible. We used the generic inverse variance function of the REVMAN software to pool results for death in hospital. Sensitivity analyses, using prespecified subgroups, explored heterogeneity between studies.ResultsPooled mortality in 18 observational studies describing 436 people who underwent REVAR was 21% (95% CI 13 to 29); however, 90% of the heterogeneity between studies was not explained by chance alone. Surgical volume explained substantial heterogeneity. According to study-specific criteria, 47% (95% CI 39 to 55) of people with ruptured aneurysms were potentially eligible for REVAR.ConclusionsMortality in people who underwent REVAR is lower than that in historical reports of unselected people undergoing open repair. Further investigation is needed to determine whether the difference in mortality is attributable to patient selection alone or to this new approach to treatment
Waist-to-Hip Ratio, Cardiovascular Outcomes, and Death in Peritoneal Dialysis Patients
Objectives. The primary objective of this study was to determine the relationship between waist-to-hip ratio (WHR), cardiovascular (CV) events, and mortality in peritoneal dialysis (PD) patients. A secondary objective was to investigate the association between abdominal obesity and systemic inflammatory markers. Methods. This is a prospective study of 22 prevalent PD patients. WHR was measured at baseline. C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Main outcomes were first CV event and death from all causes. Survival analysis was used to examine the relationship between anthropomorphic measures and clinical outcomes. Results. Mean follow-up period was 3.1 years. In Kaplan-Meier analysis, survival was lower in those with higher WHR (P = .002). In Cox regression, WHR independently predicted mortality and first CV event after adjustment for known ischemic heart disease (hazard ratio [HR] 1.17, confidence interval [CI] 1.05–1.30 for death; HR 1.13, CI 1.01–1.26 for CV event). WHR correlated with serum TNF-α (r = 0.45; P = .05). Conclusion. The results of this study suggest WHR may be a risk factor for increased CV events and mortality in PD patients. Abdominal obesity is also associated with inflammatory markers. Larger studies are warranted to confirm these findings
Population-Attributable Fractions of Modifiable Lifestyle Factors for CKD and Mortality in Individuals With Type 2 Diabetes: A Cohort Study
BackgroundWe quantified the impact of lifestyle and dietary modifications on chronic kidney disease (CKD) by estimating population-attributable fractions (PAFs).Study DesignObservational cohort study.Setting & ParticipantsMiddle-aged adults with type 2 diabetes but without severe albuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET; n=6,916).FactorsModifiable lifestyle/dietary risk factors, such as physical activity, size of social network, alcohol intake, tobacco use, diet, and intake of various food items.OutcomesThe primary outcome was CKD, ascertained as moderate to severe albuminuria or ≥5% annual decline in estimated glomerular filtration rate (eGFR) after 5.5 years. The competing risk for death was considered. PAF was defined as the proportional reduction in CKD or mortality (within 5.5 years) that would occur if exposure to a risk factor was changed to an optimal level.ResultsAt baseline, median urinary albumin-creatinine ratio and eGFR were 6.6 (IQR, 2.9-25.0) mg/mmol and 71.5 (IQR, 58.1-85.9) mL/min/1.73m2, respectively. After 5.5 years, 704 (32.5%) participants developed albuminuria, 1,194 (55.2%) had a ≥5% annual eGFR decline, 267 (12.3%) had both, and 1,022 (14.8%) had died. Being physically active every day has PAFs of 5.1% (95% CI, 0.5%-9.6%) for CKD and 12.3% (95% CI, 4.9%-19.1%) for death. Among food items, increasing vegetable intake would have the largest impact on population health. Considering diet, weight, physical activity, tobacco use, and size of social network, exposure to less than optimum levels gives PAFs of 13.3% (95% CI, 5.5%-20.9%) for CKD and 37.5% (95% CI, 27.8%-46.7%) for death. For the 17.8 million middle-aged Americans with diabetes, improving 1 of these lifestyle behaviors to the optimal range could reduce the incidence or progression of CKD after 5.5 years by 274,000 and the number of deaths within 5.5 years by 405,000.LimitationsAscertainment of changes in kidney measures does not precisely match the definitions for incidence or progression of CKD.ConclusionsHealthy lifestyle and diet are associated with less CKD and mortality and may have a substantial impact on population kidney health
Modifiable lifestyle factors for primary prevention of chronic kidney disease: a systematic review and meta-analysis
BACKGROUND: Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. METHODS: To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m(2)). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria). RESULTS: We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding. CONCLUSIONS: These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice
Effects of ACE inhibitors and angiotensin receptor blockers: protocol for a UK cohort study using routinely collected electronic health records with validation against the ONTARGET trial.
INTRODUCTION: Cardiovascular disease is a leading cause of death globally, responsible for nearly 18 million deaths worldwide in 2017. Medications to reduce the risk of cardiovascular events are prescribed based on evidence from clinical trials which explore treatment effects in an indicated sample of the general population. However, these results may not be fully generalisable because of trial eligibility criteria that generally restrict to younger patients with fewer comorbidities. Therefore, evidence of effectiveness of medications for groups underrepresented in clinical trials such as those aged ≥75 years, from ethnic minority backgrounds or with low kidney function may be limited.Using individual anonymised data from the Ongoing Telmisartan Alone and the Ramipril Global Endpoint Trial (ONTARGET) trial, in collaboration with the original trial investigators, we aim to investigate clinical trial replicability within a real-world setting in the area of cardiovascular disease. If the original trial results are replicable, we will estimate treatment effects and risk in groups underrepresented and excluded from the original clinical trial. METHODS AND ANALYSIS: We will develop a cohort analogous to the ONTARGET trial within the Clinical Practice Research Datalink between 1 January 2001 and 31 July 2019 using the trial eligibility criteria and propensity score matching. The primary outcome is a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for congestive heart failure. If results from the cohort study fall within pre-specified limits, we will expand the cohort to include under represented and excluded groups. ETHICS AND DISSEMINATION: Ethical approval has been granted by the London School of Hygiene & Tropical Medicine Ethics Committee (Ref: 22658). The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency (protocol no. 20_012). Access to the individual patient data from the ONTARGET trial was obtained by the trial investigators. Findings will be submitted to peer-reviewed journals and presented at conferences
Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Instructional Models for Course-Based Research Experience (CRE) Teaching
The course-based research experience (CRE) with its documented educational benefits is increasingly being implemented in science, technology, engineering, and mathematics education. This article reports on a study that was done over a period of 3 years to explicate the instructional processes involved in teaching an undergraduate CRE. One hundred and two instructors from the established and large multi-institutional SEA-PHAGES program were surveyed for their understanding of the aims and practices of CRE teaching. This was followed by large-scale feedback sessions with the cohort of instructors at the annual SEA Faculty Meeting and subsequently with a small focus group of expert CRE instructors. Using a qualitative content analysis approach, the survey data were analyzed for the aims of inquiry instruction and pedagogical practices used to achieve these goals. The results characterize CRE inquiry teaching as involving three instructional models: 1) being a scientist and generating data; 2) teaching procedural knowledge; and 3) fostering project ownership. Each of these models is explicated and visualized in terms of the specific pedagogical practices and their relationships. The models present a complex picture of the ways in which CRE instruction is conducted on a daily basis and can inform instructors and institutions new to CRE teaching
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