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1.
Ansgar Reising Saskia Sambale Frank Donnerstag Julius J. Schmidt Carsten Hafer Bernhard M.W. Schmidt Jan T. Kielstein 《PloS one》2013,8(2)
Background
Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness.Methods
Chronic hemodialysis patients (7 male/3 female, mean age 58 years) were recruited. Cerebral blood flow and arterial pulse wave velocity were measured before and immediately after a hemodialysis session. To exclude effects of volume changes we kept ultrafiltration to a minimum, allowing no change in body weight. Isothermic conditions were maintained by using the GENIUS single-pass batch-dialysis system with a high-flux polysulfone dialyser. Cerebral blood flow was measured by contrast-enhanced computed tomography. Pulse wave velocity was measured using the SphygmoCor (AtCor Medical, USA) device by a single operator.Results
This study shows for the first time that isovolemic, isothermic hemodialysis neither affected blood pressure or heart rate, nor total or regional cerebral perfusion. There was also no change in pulse wave velocity.Conclusions
Mechanisms other than the dialysis procedure itself might be causative for the high incidence of ischemic strokes in this patient population. Moreover, the sole removal of uremic toxins does not lead to short-term effects on vascular stiffness, underlying the importance of volume control in this patient population. 相似文献2.
Bruno Guéry Corinne Alberti Aude Servais Elarbi Harrami Lynda Bererhi Brigitte Zins Malik Touam Dominique Joly 《PloS one》2014,9(5)
Objective
In this clinical trial, we aimed to compare three means of performing chronic hemodialysis in patients with contra-indication to systemic heparinization.Methods
This open-label monocentric randomized « n-of-one » trial, conducted in a single tertiary care center, recruited chronic hemodialysis patients with a contra-indication to systemic heparinization for at least 3 consecutive sessions. All patients underwent hemodialysis with an AN69ST dialyzer, and were administered three alternative dialysis procedures in a random sequence: intermittent saline flushes, constant saline infusion, or pre-dialysis heparin coating of the membrane. The primary outcome was the need to interrupt the dialysis session because of clotting events due to either (i) a complete coagulation of the circuit; (ii) a partial coagulation of the circuit; (iii) a>50% rise over baseline in the venous pressure.Results
At the end of the inclusion period (May, 2007 to December, 2008), the number of patients to include (n = 75) was not reached: only 46 patients were included and underwent randomization. The study was terminated, and statistical analysis took into account 224 hemodialysis sessions performed in 44 patients with analyzable data. Heparin adsorption was associated with a significant reduction of the need to interrupt the dialysis session because of clotting events: odds ratio 0.3 (CI 95% 0.2 to 0.6; p<0.001, versus intermittent saline flushes). Heparin adsorption was also associated with higher odds for performing >3 h dialysis sessions and for having complete blood restitution. There were no significant effects of the dialysis procedure on weight loss, online ionic dialysance, and adverse events.Conclusion
Heparin-coated AN69ST dialysis membrane is a safe and effective method to avoid or delay per-dialytic clotting events in patients with contra-indication to systemic anticoagulation. However, results are not generalizable safely to patients with active bleeding, since weak heparinemia, not assessed in this study, may occur.Trial Registration
ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT00473109. NCT00473109相似文献3.
Claire H. den Hoedt Michiel L. Bots Muriel P. C. Grooteman Albert H. A. Mazairac E. Lars Penne Neelke C. van der Weerd Piet M. ter Wee Menso J. Nubé Renée Levesque Peter J. Blankestijn Marinus A. van den Dorpel for the CONTRAST investigators 《PloS one》2013,8(4)
Background
We studied the distribution of causes of death in the CONTRAST cohort and compared the proportion of cardiovascular deaths with other populations to answer the question whether cardiovascular mortality is still the principal cause of death in end stage renal disease. In addition, we compared patients who died from the three most common death causes. Finally, we aimed to study factors related to dialysis withdrawal.Methods
We used data from CONTRAST, a randomized controlled trial in 714 chronic hemodialysis patients comparing the effects of online hemodiafiltration versus low-flux hemodialysis. Causes of death were adjudicated. The distribution of causes of death was compared to that of the Dutch dialysis registry and of the Dutch general population.Results
In CONTRAST, 231 patients died on treatment. 32% died from cardiovascular disease, 22% due to infection and 23% because of dialysis withdrawal. These proportions were similar to those in the Dutch dialysis registry and the proportional cardiovascular mortality was similar to that of the Dutch general population. cardiovascular death was more common in patients <60 years. Patients who withdrew were older, had more co-morbidity and a lower mental quality of life at baseline. Patients who withdrew had much co-morbidity. 46% died within 5 days after the last dialysis session.Conclusions
Although the absolute risk of death is much higher, the proportion of cardiovascular deaths in a prevalent end stage renal disease population is similar to that of the general population. In older hemodialysis patients cardiovascular and non-cardiovascular death risk are equally important. Particularly the registration of dialysis withdrawal deserves attention. These findings may be partly limited to the Dutch population. 相似文献4.
Increased Risk of Acute Pancreatitis in Patients with Chronic Hemodialysis: A 4-Year Follow-Up Study
Background
The risk of acute pancreatitis in patients on long-term peritoneal dialysis is higher as compared to the general population. However, the relationship between long-term hemodialysis and acute pancreatitis has never been established.Objectives
We investigated the incidence of acute pancreatitis among patients on long-term hemodialysis in Taiwan to evaluate if there is a higher risk of acute pancreatitis in comparison to the general population.Methods
We utilized a National Health Insurance (NHI) claims data sample containing one million beneficiaries. We followed all adult beneficiaries from January 1, 2007 until December 31, 2010 to see if they had been hospitalized for acute pancreatitis during this period. We further identified patients on chronic hemodialysis and compared their risk of acute pancreatitis with the general population.Results
This study included 2603 patients with long-term hemodialysis and 773,140 patients without hemodialysis. After controlling for age, gender, Charlson Comorbidity Index Score, geographic region, socioeconomic status and urbanization level, the adjusted hazard ratio was 3.44 (95% Confidence interval, 2.5–4.7).Conclusions
The risk of acute pancreatitis in patients on long-term hemodialysis is significantly higher in comparison to the general population. 相似文献5.
Background
Patients with end stage renal disease often fail to follow prescribed dietary and fluid regimen, leading to undesirable outcomes. This study aimed to examine and identify factors influencing dietary, fluid, medication and dialysis compliance behaviours in patients undergoing hemodialysis.Methods
This was a cross-sectional study which employed purposive sampling design. A total of 188 respondents were recruited from 14 dialysis centres in Malaysia between 2008–2011. Self-reported compliance behaviours and biochemical measurements were used as evaluation tools.Results
Compliance rates of dietary, fluid, medication and dialysis were 27.7%, 24.5%, 66.5% and 91.0%, respectively. Younger, male, working patients and those with longer duration on hemodialysis were found more likely to be non-compliant. Lacks of adequate knowledge, inadequate self-efficacy skills, forgetfulness and financial constraints were the major perceived barriers towards better compliance to fluid, dietary, medication and dialysis, respectively.Conclusions
Healthcare professionals should recognise the factors hindering compliance from the patients'' perspective while assisting them with appropriate skills in making necessary changes possible. 相似文献6.
Heng-Jung Hsu Chiung-Hui Yen I-Wen Wu Kuang-Hung Hsu Chih-Ken Chen Chiao-Yin Sun Chia-Chi Chou Chun-Yu Chen Chi-Jen Tsai Mai-Szu Wu Chin-Chan Lee 《PloS one》2014,9(7)
Background
Cardiovascular disease is the leading cause of mortality in hemodialysis patients and is associated with chronic inflammation. Elevation of uremic toxins, particular protein-bound uremic toxins, is a possible cause of hyper-inflammation in hemodialysis patients. But the association between uremic toxins and inflammatory markers in hemodialysis is still unclear.Methods
We conducted a cross-sectional study to evaluate the association of the serum uremic toxins and inflammatory markers in hemodialysis patients.Results
The uremic toxins were not associated with inflammatory markers- including high sensitivity C-reactive protein, IL(Interleukin) -1β, IL-6, tumor necrosis factor-α. In multiple linear regression, serum levels of total p-cresol sulfate (PCS) were independently significantly associated with serum total indoxyl sulfate (IS) (standardized coefficient: 0.274, p<0.001), and co-morbidity of diabetes mellitus (DM) (standardized coefficient: 0.342, p<0.001) and coronary artery disease (CAD) (standardized coefficient: 0.128, p = 0.043). The serum total PCS levels in hemodialysis with co-morbidity of DM and CAD were significantly higher than those without co-morbidity of DM and CAD (34.10±23.44 vs. 16.36±13.06 mg/L, p<0.001). Serum levels of total IS was independently significantly associated with serum creatinine (standardized coefficient: 0.285, p<0.001), total PCS (standardized coefficient: 0.239, p = 0.001), and synthetic membrane dialysis (standardized coefficient: 0.139, p = 0.046).Conclusion
The study showed that serum levels of total PCS and IS were not associated with pro-inflammatory markers in hemodialysis patients. Besides, serum levels of total PCS were independently positively significantly associated with co-morbidity of CAD and DM. 相似文献7.
Ladan Mansouri Josefin M. Paulsson Ali Moshfegh Stefan H. Jacobson Joachim Lundahl 《PloS one》2013,8(8)
Introduction
In Chronic Kidney Disease (CKD), immune cells are affected by uremic retention toxins. Given this effect, we analyzed lymphocyte proliferative response and immune modulators production following in vitro stimulation.Methods
Whole blood was drawn from healthy controls, patients with eGFR <20 ml/min/1.73 m2 (Pre-dialysis, CKD stages 4 and 5) and hemodialysis patients (stage 5D). Peripheral cells were incubated for six days with pokeweed mitogen, concanavalin A, Staphylococcus enterotoxin A or influenza A vaccine. Peripheral lymphocyte proliferation was then analyzed by the “Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood” (FASCIA) method, and cytokine profile in the cell supernatants was analyzed by the Milliplex multi-array method.Results
The absolute number of lymphoblasts in response to mitogenic stimulation and the number of cells in each CD4+ and CD8+ subpopulation were similar comparing the three groups, except for a single decline in number of lymphoblasts after stimulation with Staphylococcus enterotoxin A, comparing dialysis patients with healthy controls. Levels of interleukin (IL)-2 (p=0.026), -10 (p=0.019) and -15 (p=0.027) in the Staphylococcus enterotoxin A-stimulated supernatant were lower in hemodialysis patients compared to healthy controls. Levels of IL-15 (p=0.017) from pre-dialysis patients and levels of IL-5 (p=0.019) from hemodialysis patients in influenza A vaccine-stimulated supernatants were also lower compared to controls. In pokeweed mitogen–stimulated supernatant, IL-2 levels (p=0.013) were lower in hemodialysis patients compared to pre-dialysis patients. TNF-α, IL-10, IL-12, IL-15, IL-8, MCP-1, IP-10, IFN-α2, IL-1α and eotaxin levels were all significantly higher in plasma obtained from CKD patients.Conclusion
Our results suggest that T-cells from CKD patients have similar proliferative response to stimulation compared with healthy individuals. Moreover, however the immune cells show inability to produce selected cytokines, most likely due to the uremic milieu or dialysis procedure. 相似文献8.
Nikolaos Pagonas Wolfgang Vautz Luzia Seifert Rafael Slodzinski Joachim Jankowski Walter Zidek Timm H. Westhoff 《PloS one》2012,7(9)
Background
Although “uremic fetor” has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia.Methods
Breath analysis was performed in 28 adults with an eGFR ≥60 ml/min per 1.73 m2, 26 adults with chronic renal failure corresponding to an eGFR of 10–59 ml/min per 1.73 m2, and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry.Results
Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10–59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis.Conclusion
Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules. 相似文献9.
Tariq Shafi Timothy W. Meyer Thomas H. Hostetter Michal L. Melamed Rulan S. Parekh Seungyoung Hwang Tanushree Banerjee Josef Coresh Neil R. Powe 《PloS one》2015,10(5)
Background and Objectives
Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney — p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine — with outcomes in hemodialysis patients.Design, Setting, Participants and Measurements
We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/VUREA.Results
Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17–2.25; p=0.004) and first cardiovascular event (1.60; 1.23–2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18–1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05–3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12–2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses.Conclusions
Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients. 相似文献10.
Intermittent hemodialysis (IHD) and continuous renal replacement therapies (CRRT) are used as Acute Kidney Injury (AKI) therapy and have certain advantages and disadvantages. Extended daily dialysis (EDD) has emerged as an alternative to CRRT in the management of hemodynamically unstable AKI patients, mainly in developed countries.
Objectives
We hypothesized that EDD is a safe option for AKI treatment and aimed to describe metabolic and fluid control of AKI patients undergoing EDD and identify complications and risk factors associated with death.Study Selection
This is an observational and retrospective study describing introduction of EDD at our institution. A total of 231 hemodynamically unstable AKI patients (noradrenalin dose between 0.3 and 1.0 ucg/kg/min) were assigned to 1367 EDD session. EDD consisted of 6–8 h of HD 6 days a week, with blood flow of 200 ml/min, dialysate flows of 300 ml/min.Data Synthesis
Mean age was 60.6±15.8 years, 97.4% of patients were in the intensive care unit, and sepsis was the main etiology of AKI (76.2). BUN and creatinine levels stabilized after four sessions at around 38 and 2.4 mg/dl, respectively. Fluid balance decreased progressively and stabilized around zero after five sessions. Weekly delivered Kt/V was 5.94±0.7. Hypotension and filter clotting occurred in 47.5 and 12.4% of treatment session, respectively. Regarding AKI outcome, 22.5% of patients presented renal function recovery, 5.6% of patients remained on dialysis after 30 days, and 71.9% of patients died. Age and focus abdominal sepsis were identified as risk factors for death. Urine output and negative fluid balance were identified as protective factors.Conclusions
EDD is effective for AKI patients, allowing adequate metabolic and fluid control. Age, focus abdominal sepsis, and lower urine output as well as positive fluid balance after two EDD sessions were associated significantly with death. 相似文献11.
Yih-Giun Cherng Chien-Chang Liao Tso-Hsiao Chen Duan Xiao Chih-Hsiung Wu Ta-Liang Chen 《PloS one》2013,8(3)
Background
End-stage renal disease represents a risk complex that complicates surgical results. The surgical outcomes of dialysis patients have been studied in specific fields, but the global features of postoperative adverse outcomes in dialysis patients receiving non-cardiac surgeries have not been examined.Methods
Taiwan’s National Health Insurance Research Database was used to study 8,937 patients under regular dialysis with 8,937 propensity-score matched-pair controls receiving non-cardiac surgery between 2004 and 2007. We investigated the influence of hemodialysis and peritoneal dialysis, effects of hypertension and diabetes, and impact of additional comorbidities on postoperative adverse outcomes.Results
Postoperative mortality in dialysis patients was higher than in controls (odds ratio [OR] 3.33, 95% confidence interval [CI] 2.56 to 4.33) when receiving non-cardiac surgeries. Complications such as acute myocardial infarction, pneumonia, bleeding, and septicemia were significantly increased. Postoperative mortality was significantly increased among peritoneal dialysis patients (OR 2.71, 95% CI 1.70 to 4.31) and hemodialysis patients (OR 3.42, 95% CI 2.62 to 4.47) than in controls. Dialysis patients with both hypertension and diabetes had the highest risk of postoperative complications; these risks increased with number of preoperative medical conditions. Patients under dialysis also showed significantly increased length of hospitalization, more ICU stays and higher medical expenditures.Conclusion
Surgical patients under dialysis encountered significantly higher postoperative complications and mortality than controls when receiving non-cardiac surgeries. Different dialysis techniques, pre-existing hypertension/diabetes, and various comorbidities had complication-specific impacts on surgical adverse outcomes. These findings can help surgical teams provide better risk assessment and postoperative care for dialysis patients. 相似文献12.
Sunny Eloot Daniel Schneditz Tom Cornelis Wim Van Biesen Griet Glorieux Annemie Dhondt Jeroen Kooman Raymond Vanholder 《PloS one》2016,11(1)
Aim
We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage.Methods
This study included 10 patients on standard (3x4h/week) high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V1), total distribution volume (Vtot) and intercompartment clearance (K21). This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies.Results
Dialyzer clearance K, V1 and Vtot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K21was 2.7–5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3x4h dialysis at 300mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated.Conclusion
When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal. 相似文献13.
A Low Serum Bicarbonate Concentration as a Risk Factor for Mortality in Peritoneal Dialysis Patients
Tae Ik Chang Hyung Jung Oh Ea Wha Kang Tae-Hyun Yoo Sug Kyun Shin Shin-Wook Kang Kyu Hun Choi Dae Suk Han Seung Hyeok Han 《PloS one》2013,8(12)
Background and Aim
Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD) patients.Methods
This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic) levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients.Results
Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR), while it was negatively associated with albumin, C-reactive protein (CRP) levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001). In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively.Conclusions
This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings. 相似文献14.
Gürbey Ocak Christiane Drechsler Carla Y. Vossen Hans L. Vos Frits R. Rosendaal Pieter H. Reitsma Michael M. Hoffmann Winfried M?rz Willem H. Ouwehand Raymond T. Krediet Elisabeth W. Boeschoten Friedo W. Dekker Christoph Wanner Marion Verduijn 《PloS one》2014,9(5)
Background
The protein C pathway plays an important role in the maintenance of endothelial barrier function and in the inflammatory and coagulant processes that are characteristic of patients on dialysis. We investigated whether common single nucleotide variants (SNV) in genes encoding protein C pathway components were associated with all-cause 5 years mortality risk in dialysis patients.Methods
Single nucleotides variants in the factor V gene (F5 rs6025; factor V Leiden), the thrombomodulin gene (THBD rs1042580), the protein C gene (PROC rs1799808 and 1799809) and the endothelial protein C receptor gene (PROCR rs867186, rs2069951, and rs2069952) were genotyped in 1070 dialysis patients from the NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort) and in 1243 dialysis patients from the German 4D cohort.Results
Factor V Leiden was associated with a 1.5-fold (95% CI 1.1–1.9) increased 5-year all-cause mortality risk and carriers of the AG/GG genotypes of the PROC rs1799809 had a 1.2-fold (95% CI 1.0–1.4) increased 5-year all-cause mortality risk. The other SNVs in THBD, PROC, and PROCR were not associated with 5-years mortality.Conclusion
Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients. 相似文献15.
Rachel A. Gibson Jon Robertson Harshna Mistry Stewart McCallum Disala Fernando Melody Wyres Gil Yosipovitch 《PloS one》2014,9(7)
Background
Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel widely expressed in skin tissues, and peripheral sensory nerve fibres. Activation of TRPV1 releases neuropeptides; the resulting neurogenic inflammation is believed to contribute to the development of pruritus. A TRPV1 antagonist has the potential to perform as an anti-pruritic agent. SB705498 is a TRPV1 antagonist that has demonstrated in vitro activity against cloned TRPV1 human receptors and when orally administered has demonstrated pharmacodynamic activity in animal models and clinical studies.Objectives
To select a topical dose of SB705498 using the TRPV1 agonist capsaicin; to confirm engagement of the TRPV1 antagonistic action of SB705498 and assess whether the dose selected has an effect on itch induced by two challenge agents.Methods
A clinical study was conducted in 16 healthy volunteers to assess the effects of 3 doses of SB705498 on skin flare induced by capsaicin. Subjects with a robust capsaicin response were chosen to determine if the selected topical formulation of SB705498 had an effect on challenge agent induced itch.Results
Following capsaicin challenge the greatest average reduction in area of flare was seen for the 3% formulation. This dose was selected for further investigation. Itch intensity induced by two challenge agents (cowhage and histamine) was assessed on the Computerised Visual Analogue Scale. The difference in average itch intensity (Weighted Mean Over 15 Mins) between the 3% dose of SB705498 and placebo for the cowhage challenge was −0.64, whilst the histamine challenge showed on average a −4.65 point change.Conclusions
The 3% topical formulation of SB705498 cream was clinically well tolerated and had target specific pharmacodynamic activity. However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo. SB705498 is unlikely to be of symptomatic benefit for histaminergic or non-histaminergic induced itch.Trial Registration
ClinicalTrials.gov NCT01673529相似文献16.
Guy Rostoker Mireille Griuncelli Christelle Loridon Théophile Magna Philippe Janklewicz Gilles Drahi Hervé Dahan Yves Cohen 《PloS one》2014,9(12)
Background and Objectives
Iron overload used to be considered rare among hemodialysis patients after the advent of erythropoesis-stimulating agents, but recent MRI studies have challenged this view. The aim of this study, based on decision-tree learning and on MRI determination of hepatic iron content, was to identify a noxious pattern of parenteral iron administration in hemodialysis patients.Design, Setting, Participants and Measurements
We performed a prospective cross-sectional study from 31 January 2005 to 31 August 2013 in the dialysis centre of a French community-based private hospital. A cohort of 199 fit hemodialysis patients free of overt inflammation and malnutrition were treated for anemia with parenteral iron-sucrose and an erythropoesis-stimulating agent (darbepoetin), in keeping with current clinical guidelines. Patients had blinded measurements of hepatic iron stores by means of T1 and T2* contrast MRI, without gadolinium, together with CHi-squared Automatic Interaction Detection (CHAID) analysis.Results
The CHAID algorithm first split the patients according to their monthly infused iron dose, with a single cutoff of 250 mg/month. In the node comprising the 88 hemodialysis patients who received more than 250 mg/month of IV iron, 78 patients had iron overload on MRI (88.6%, 95% CI: 80% to 93%). The odds ratio for hepatic iron overload on MRI was 3.9 (95% CI: 1.81 to 8.4) with >250 mg/month of IV iron as compared to <250 mg/month. Age, gender (female sex) and the hepcidin level also influenced liver iron content on MRI.Conclusions
The standard maximal amount of iron infused per month should be lowered to 250 mg in order to lessen the risk of dialysis iron overload and to allow safer use of parenteral iron products. 相似文献17.
Yu-Jen Yu I-Wen Wu Chun-Yu Huang Kuang-Hung Hsu Chin-Chan Lee Chio-Yin Sun Heng-Jung Hsu Mai-Szu Wu 《PloS one》2014,9(11)
Background
The multidisciplinary pre-dialysis education (MPE) retards renal progression, reduce incidence of dialysis and mortality of CKD patients. However, the financial benefit of this intervention on patients starting hemodialysis has not yet been evaluated in prospective and randomized trial.Methods
We studied the medical expenditure and utilization incurred in the first 6 months of dialysis initiation in 425 incident hemodialysis patients who were randomized into MPE and non-MPE groups before reaching end-stage renal disease. The content of the MPE was standardized in accordance with the National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines.Results
The mean age of study patients was 63.8±13.2 years, and 221 (49.7%) of them were men. The mean serum creatinine level and estimated glomerular filtration rate was 6.1±4.0 mg/dL and 7.6±2.9 mL⋅min−1⋅1.73 m−2, respectively, at dialysis initiation. MPE patients tended to have lower total medical cost in the first 6 months after hemodialysis initiation (9147.6±0.1 USD/patient vs. 11190.6±0.1 USD/patient, p = 0.003), fewer in numbers [0 (1) vs. 1 (2), p<0.001] and length of hospitalization [0 (15) vs. 8 (27) days, p<0.001], and also lower inpatient cost [0 (2617.4) vs. 1559,4 (5019.6) USD/patient, p<0.001] than non-MPE patients, principally owing to reduced cardiovascular hospitalization and vascular access–related surgeries. The decreased inpatient and total medical cost associated with MPE were independent of patients'' demographic characteristics, concomitant disease, baseline biochemistry and use of double-lumen catheter at initiation of hemodialysis.Conclusions
Participation of multidisciplinary education in pre-dialysis period was independently associated with reduction in the inpatient and total medical expenditures of the first 6 months post-dialysis owing to decreased inpatient service utilization secondary to cardiovascular causes and vascular access–related surgeries.Trial Registration
ClinicalTrials.gov NCT00644046相似文献18.
Background
Many patients with chronic kidney disease (CKD) suffer from fatigue caused by anemia, but that anemia can be reversed. Successful treatment can be measured as a decrease in fatigue and an increase in energy or vitality, particularly on the vitality (VT) subscale of the SF-36. Changes in VT scores are most commonly interpreted in terms of minimally important differences or standardized effect sizes, but neither a minimally important difference nor a standardized effect size provides information about how patients’ activities are affected. Therefore, we analyzed the association between differences in VT scores and a variable that is meaningful to patients and to society the frequency of going out.Study Design
Questionnaire survey. Analyses of differences among participants at bseline, and analyses of differences within participants over time.Setting and Participants
CKD patients who were not on dialysis and were involved in a study of anti-anemia therapy.Predictor
VT scores.Outcome
Frequency of going out.Measurements
VT scores and the frequency of going out.Results
At baseline, higher VT scores and younger age were associated with going out more often, while sex and the presence of diabetic nephropathy were not associated with the frequency of going out. Greater changes in VT scores over time were associated with greater changes in the frequency of going out, in univariate and multivariate analyses.Conclusions
At baseline, VT was associated with the frequency of going out. Increases in VT were also associated with increases in the frequency of going out. These results show how VT scores can be linked to daily activities that are important to individual patients and to society. 相似文献19.
Ferruh Artunc Christian Mueller Tobias Breidthardt Raphael Twerenbold Andreas Peter Claus Thamer Peter Weyrich Hans-Ulrich Haering Bjoern Friedrich 《PloS one》2012,7(10)
Background
In hemodialysis patients, elevated plasma troponin concentrations are a common finding that has even increased with the advent of newly developed sensitive assays. However, the interpretation and relevance of this is still under debate.Methods
In this cross-sectional study, we analyzed plasma concentrations of sensitive troponin I (TnI) and troponin T (TnT) in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors and mortality.Results
In all of the enrolled patients, plasma TnI or TnT was detectable at a median concentration of 14 pg/ml (interquartile range: 7–29) using the Siemens TnI ultra assay and 49 pg/ml (31–74) using the Roche Elecsys high sensitive TnT assay. Markedly more patients exceeded the 99th percentile for TnT than for TnI (95% vs. 14%, p<0.0001). In a multivariate linear regression model, TnT was independently associated with age, gender, systolic dysfunction, time on dialysis, residual diuresis and systolic blood pressure, whereas TnI was independently associated with age, systolic dysfunction, pulse pressure, time on dialysis and duration of a HD session. During a follow-up period of nearly two years, TnT concentration above 38 pg/mL was associated with a 5-fold risk of death, whereas elevation of TnI had a gradual association to mortality.Conclusion
In hemodialysis patients, elevations of plasma troponin concentrations are explained by cardiac function and dialysis-related parameters, which contribute to cardiac strain. Both are highly predictive of increased risk of death. 相似文献20.
Wu VC Lai CF Shiao CC Lin YF Wu PC Chao CT Hu FC Huang TM Yeh YC Tsai IJ Kao TW Han YY Wu WC Hou CC Young GH Ko WJ Tsai TJ Wu KD 《PloS one》2012,7(3):e30836