Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated with higher end-of-dialysis blood pressure, suggesting that intradialytic hypertension may play a role in generation of interdialytic hypertension

Association of Glomerular Filtration Rate with High-Sensitivity Cardiac Troponin T in a Community-Based Population Study in Beijing

BACKGROUND: Reduced renal function is an independent risk factor for cardiovascular disease mortality, and persistently elevated cardiac troponin T (cTnT) is frequently observed in patients with end-stage renal disease. In the general population the relationship between renal function and cTnT levels may not be clear because of the low sensitivity of the assay. In this study, we investigated the level of cTnT using a highly sensitive assay (hs-cTnT) and evaluated the association of estimated glomerular filtration rate (eGFR) with detectable hs-cTnT levels in a community-based population. METHODS: The serum hs-cTnT levels were measured in 1365 community dwelling population aged ≥45 years in Beijing, China. eGFR was determined by the Chinese modifying modification of diet in renal disease (C-MDRD) equation. RESULTS: With the highly sensitive assay, cTnT levels were detectable (≥3pg/mL) in 744 subjects (54.5%). The result showed that eGFR was associated with Log hs-cTnT (r = -0.14, P<0.001). After adjustment for the high predicted Framingham Coronary Heart Disease (CHD) risk (10-year risk >20%) and other prognostic indicators, moderate to severe reduced eGFR was independently associated with detectable hs-cTnT, whereas normal to mildly reduced eGFR was not independently associated with detectable hs-cTnT. In addition, after adjustment for other risk factors, the high predicted Framingham CHD risk was associated with detectable hs-cTnT in the subjects with different quartile levels of eGFR. CONCLUSION: The levels of hs-cTnT are detectable in a community-based Chinese population and low eGFR is associated with detectable hs-cTnT. Moreover, eGFR and high predicted Framingham CHD risk are associated with detectable hs-cTnT in subjects with moderate-to-severe reduced renal function

Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors

<p>Abstract</p> <p>Background</p> <p>High-dose erythropoiesis-stimulating agents (ESA) for anemia of chronic kidney disease (CKD) have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR).</p> <p>Methods</p> <p>A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α (< 1 μg/kg/week) and high-dose (≥1 μg/kg/week)).</p> <p>Results</p> <p>Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 μg/kg/week) vs usual-dose (0.5 μg/kg/week) ESA.</p> <p>In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p < 0.05 for both). There was no correlation between high-dose ESA and adipokines. Higher ESA dose correlated with higher levels of sEpoR (r_s= 0.39, p = 0.03). In adjusted analyses, higher ESA dose (per μcg/kg/week) was associated with a 53% greater odds of sEpoR being above the median (p < 0.05).</p> <p>Conclusion</p> <p>High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted.</p> <p>Trial registration</p> <p>Clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00526747">NCT00526747</a></p

(Clinical) trial and error in diabetic nephropathy

Patients with diabetes and nephropathy face a high risk of end-stage renal disease (ESRD) and cardiovascular disease. Trials in the past decades of nephrology research have shown the importance of lowering glucose, blood pressure, and albuminuria as a mean to lower renal and cardiovascular risk in these patients. However, despite the promising and successful results from RAAS inhibition with angiotensin receptor blockers in combination with tight glycemic and blood pressure control, many patients with diabetes and nephropathy are left with a high residual risk and still progress to ESRD. The high residual risk highlights the urgent need for additional therapies. This chapter reviews the clinical trial landscape in diabetic nephropathy and draws lessons for future clinical trials in this area.In order to improve outcome of patients with diabetic nephropathy, novel drugs have been tested in the last decades. After numerous large and expensive trials, unfortunately only a few interventions have been shown to reduce the risk of ESRD. One of the potential explanations why many of the conducted trials failed to prove ultimate efficacy is that all interventions focused on the effect of the drug in the overall population without taking into account how the individual patient responded to the drug. In the past trials, individual patients showed a large variation in drug response: some patients benefitted, and others did not or even experienced an increased risk. Because of this variation, no benefit could be detected in the overall population. The drug response variation may thus play a much bigger and more important role than originally anticipated in clinical trial design.The important lesson learned from a decade of clinical trial failures in nephrology is that more emphasis should be placed on the individual and how the individual responses to the drug rather than evaluating drug effects on a population level. This personalized medicine concept should be integrated in the design of future clinical trials as there are still promising therapies at the horizon for diabetic nephropathy and their potential efficacy should be tested in an appropriate fashion

Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis

BACKGROUND: Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. METHODS: In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. RESULTS: The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P = 0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. CONCLUSIONS: In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis

An advanced clinician practitioner in arthritis care can improve access to rheumatology care in community-based practice

Vandana Ahluwalia,1 Tiffany L H Larsen,2 Carol A Kennedy,3 Taucha Inrig,3 Katie Lundon4 1Division of Rheumatology, Department of Internal Medicine, William Osler Health System, Brampton, ON, Canada; 2Department of Physiotherapy, Headwaters Health Care Center, Orangeville, ON, Canada; 3Musculoskeletal Health and Outcomes Research, St. Michael&rsquo;s Hospital, Toronto, ON, Canada; 4Office of Continuing Professional Development and the Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada Objective: To facilitate access and improve wait times to a rheumatologist&rsquo;s consultation, this study aimed to 1) determine the ability of an advanced clinician practitioner in arthritis care (ACPAC)-trained extended role practitioner (ERP) to triage patients with suspected inflammatory arthritis (IA) for priority assessment by a rheumatologist and 2) determine the impact of an ERP on access-to-care as measured by time-to-rheumatologist-assessment and time-to-treatment-decision.Materials and methods: A community-based ACPAC-trained ERP triaged new referrals for suspected IA. Patients with suspected IA were booked to see the rheumatologist on a priority basis. Diagnostic accuracy of the ERP to correctly identify priority patients; the level of agreement between ERP and rheumatologist (Kappa coefficient and percent agreement); and the time-to-treatment-decision for confirmed cases of IA were investigated. Retrospective chart review then compared time-to-rheumatologist-assessment and time-to-treatment-decision in the solo-rheumatologist versus the ERP-triage model.Results: One hundred twenty-one patients were triaged. The ERP designated 54 patients for priority assessment. The rheumatologist confirmed IA in 49/54 (90.7% positive predictive value [PPV]). Of the 121 patients, 67 patients were designated as nonpriority by the ERP, and none were determined to have IA by the rheumatologist (100% negative predictive value [NPV]). Excellent agreement was found between the ERP and the rheumatologist (Kappa coefficient 0.92, 95% CI: 0.84&ndash;0.99). In the ERP-triage model, time-from-referral-to-treatment-decision for patients with IA was 73.7 days (SD 40.4, range 12&ndash;183) compared with 124.6 days (SD 61.7, range 26&ndash;359) in the solo-rheumatologist model (40% reduction in time-to-treatment-decision).Conclusion: A well-trained and experienced ERP can shorten the time-to-Rheumatologist-assessment and time-to-treatment-decision for patients with suspected IA. Keywords: rheumatology, health services accessibility, interprofessional relations, community health services, integrated delivery system

The effectiveness and cost evaluation of pain exposure physical therapy and conventional therapy in patients with complex regional pain syndrome type 1. Rationale and design of a randomized controlled trial

Contains fulltext : 109801.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Pain Exposure Physical Therapy is a new treatment option for patients with Complex Regional Pain Syndrome type 1. It has been evaluated in retrospective as well as in prospective studies and proven to be safe and possibly effective. This indicates that Pain Exposure Physical Therapy is now ready for clinical evaluation. The results of an earlier performed pilot study with an n = 1 design, in which 20 patients with Complex Regional Pain Syndrome type 1 were treated with Pain Exposure Physical Therapy, were used for the design and power calculation of the present study. After completion and evaluation of this phase III study, a multi-centre implementation study will be conducted. The aim of this study is to determine whether Pain Exposure Physical Therapy can improve functional outcomes in patients with Complex Regional Pain Syndrome type 1. Methods/design This study is designed as a single-blinded, randomized clinical trial. 62 patients will be randomized with a follow-up of 9 months to demonstrate the expected treatment effect. Complex Regional Pain Syndrome type 1 is diagnosed in accordance with the Bruehl/International Association for the Study of Pain criteria. Conventional therapy in accordance with the Dutch guideline will be compared with Pain Exposure Physical Therapy. Primary outcome measure is the Impairment level SumScore, restricted version. DISCUSSION: This is the first randomized controlled study with single blinding that has ever been planned in patients with Complex Regional Pain Syndrome type 1 and does not focus on a single aspect of the pain syndrome but compares treatment strategies based on completely different pathophysiological and cognitive theories. Trial registration Clinical trials NCT00817128; National Trial Register NTR2090

Assessing local capacity to expand rural breast cancer screening and patient navigation: An iterative mixed-method tool

BACKGROUND: Despite federal funding for breast cancer screening, fragmented infrastructure and limited organizational capacity hinder access to the full continuum of breast cancer screening and clinical follow-up procedures among rural-residing women. We proposed a regional hub-and-spoke model, partnering with local providers to expand access across North Texas. We describe development and application of an iterative, mixed-method tool to assess county capacity to conduct community outreach and/or patient navigation in a partnership model. METHODS: Our tool combined publicly-available quantitative data with qualitative assessments during site visits and semi-structured interviews. RESULTS: Application of our tool resulted in shifts in capacity designation in 10 of 17 county partners: 8 implemented local outreach with hub navigation; 9 relied on the hub for both outreach and navigation. Key factors influencing capacity: (1) formal linkages between partner organizations; (2) inter-organizational relationships; (3) existing clinical service protocols; (4) underserved populations. Qualitative data elucidate how our tool captured these capacity changes. CONCLUSIONS: Our capacity assessment tool enabled the hub to establish partnerships with county organizations by tailoring support to local capacity and needs. Absent a vertically integrated provider network for preventive services in these rural counties, our tool facilitated a virtually integrated regional network to extend access to breast cancer screening to underserved women