Post‐Dilution Hemodiafiltration With a Heparin‐Grafted Polyacrylonitrile Membrane

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post‐dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty‐four patients from eight centers were included in the study and treated by means of post‐dilution on‐line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000‐unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low‐molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post‐dilution hemodiafiltration with reduced doses of LMWH.     

Soluble Vascular Endothelial‐Cadherin Levels in Patients With Sepsis Treated With Direct Hemoperfusion With a Polymyxin B‐immobilized Fiber Column

Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. Several molecules are investigated as associated factors with capillary permeability and vascular endothelial (VE)‐cadherin internalization by vascular endothelial growth factor (VEGF)‐induced signaling through VEGF receptors leads to increased vascular endothelial cell detachment and trans‐endothelial permeability. We investigated serum soluble VE‐cadherin levels in septic patients. An enzyme‐linked immunoassay was used to measure serum soluble VE‐cadherin levels in 47 septic patients treated by direct hemoperfusion with a polymyxin B‐immobilized fiber column (DHP‐PMX). The serum soluble VE‐cadherin level of septic patients before PMX‐DHP was 3424.1 ± 2033.0 ng/mL, which was significantly lower than that of the controls (5862.0 ± 1521.2 ng/mL; P < 0.0001). The time course of serum soluble VE‐cadherin levels remained unchanged during PMX‐DHP therapy. There was no significant difference in serum soluble VE‐cadherin levels before PMX‐DHP therapy between survivors and non‐survivors, and there was no significant difference in those levels between the groups at any time after the initiation of PMX‐DHP therapy. There was no correlation between soluble VE‐cadherin levels and clinical data, except white blood cell count (r = ?0.277, P = 0.0009). There was no correlation between soluble VE‐cadherin levels and the levels of angiopoietin 1 and 2. In summary, the relationship between VE‐cadherin and capillary permeability in sepsis could not be demonstrated. Soluble VE‐cadherins are not reflected in the balance between intercellular junction plasticity and integrity, but VE‐cadherin stabilization by its phosphorylation or internalization may be associated with capillary permeability.     

Cost‐Effectiveness of LDL‐C Lowering With Evolocumab in Patients With High Cardiovascular Risk in the United States

Randomized trials have shown marked reductions in low‐density lipoprotein cholesterol (LDL‐C), a risk factor for cardiovascular disease (CVD), when evolocumab is administered. We hypothesized that evolocumab added to standard of care (SOC) vs SOC alone is cost‐effective in the treatment of patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic CVD (ASCVD) with or without statin intolerance and LDL‐C >100 mg/dL. Using a Markov cohort state transition model, primary and recurrent CVD event rates were predicted considering population‐specific trial‐based mean risk factors and calibrated against observed rates in the real world. The LDL‐C–lowering effect from population‐specific phase 3 randomized studies for evolocumab was used together with estimated LDL‐C–lowering effect on CVD event rates per 38.67‐mg/dL LDL‐C lowering from a statin‐trial meta‐analysis. Costs and utilities were included from published sources. Evolocumab treatment was associated with both increased cost and improved quality‐adjusted life‐years (QALY): HeFH (incremental cost: US$153 289, incremental QALY: 2.02, incremental cost‐effectiveness ratio: US$75 863/QALY); ASCVD (US$158 307, 1.12, US$141 699/QALY); and ASCVD with statin intolerance (US$136 903, 1.36, US$100 309/QALY). Evolocumab met both the American College of Cardiology/American Heart Association (ACC/AHA) and World Health Organization (WHO) thresholds in each population evaluated. Sensitivity and scenario analyses confirmed that model results were robust to changes in model parameters. Among patients with HeFH and ASCVD with or without statin intolerance, evolocumab added to SOC may provide a cost‐effective treatment option for lowering LDL‐C using ACC/AHA intermediate/high value and WHO cost‐effectiveness thresholds. More definitive information on the clinical and economic value of evolocumab will be available from the forthcoming CVD outcomes study.     

Extended Swan‐Neck Catheter With Upper Abdominal Exit‐Site Reduces Peritoneal Dialysis‐Related Infections

Extended catheters with an upper abdominal exit‐site (UAE) are reportedly associated with a lower incidence of peritoneal dialysis (PD)‐related infections. However, little information about the optimal peritoneal catheter configuration for UAE is available. In this nonrandomized multicenter trial, 147 consecutive cases of a UAE involving either a conventional straight (CS; 80 cases) or extended swan‐neck catheter (SN; 67 cases) were analyzed to compare exit‐site and tunnel infections (ESTI), peritonitis, and catheter survival. The ESTI‐free and catheter survival rates were significantly lower in the SN than in the CS group (P <0.01). However, the peritonitis‐free survival rate was not different (P = 0.26). In terms of analyses for infection rates, fewer episodes of ESTI (1.284 vs 0.608 episodes/patient‐year; P <0.01) and peritonitis (0.345 vs 0.152 episodes/patient‐year; P = 0.06) were observed in the SN than CS group. Recurrence analyses showed that the mean number of cumulative episodes of ESTI and peritonitis between two groups were significantly different.     

Heparin‐Induced Thrombocytopenia Associated With Pulmonary Embolism

Type II heparin‐induced thrombocytopenia (HIT) is a potentially severe adverse effect of heparin treatment triggered by an immune response. Although most cases occur in patients receiving unfractioned heparin, HIT can also arise after low‐molecular‐weight heparin (LMWH). We report a case of HIT in a postoperative orthopedic 75‐year‐old woman in treatment with LMWH (nadroparin) complicated by pulmonary embolism and treated successfully with recombinant hirudin. Early recognition and proper treatment are fundamental for the management of this life‐threatening disorder. Copyright © 2010 Wiley Periodicals, Inc.     

Improvement in All‐Cause Mortality With Blood Pressure Control in a Group of US Veterans With Drug‐Resistant Hypertension

The current definition of drug‐resistant hypertension includes patients with uncontrolled (URH) (taking ≥3 antihypertensive medications) and controlled hypertension (CRH; blood pressure [BP] ≤140/90 mm Hg) (taking ≥4 medications). The authors hypothesized that all‐cause mortality is reduced when URH is controlled. Qualified patients followed at the Washington DC VA Medical Center were included. BPs were averaged for each year of follow‐up. In 2006, among 2906 patients who met the criteria for drug‐resistant hypertension, 628 had URH. During follow‐up, 234 patients were controlled (group 1) and 394 patients remained uncontrolled (group 2). The mortality rate among patients with URH was 28% (110 of 394) and among patients with CRH was 13% (30 of 234), a 54% reduction (P<.01). Multivariate analysis identified independent predictors of mortality as uncontrolled HTN (hazard ratio, 2.5; 95% confidence interval, 1.67–3.75; P<.01), age (hazard ratio, 1.03; 95% confidence interval, 1.01–1.04; P<.01), and diabetes (hazard ratio, 1.46; 95% confidence interval, 1.04–2.05; P<.027). The authors conclude that controlling drug‐resistant hypertension markedly reduces all‐cause mortality.     

A Double‐Blind,Placebo‐Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol Dependence

Background: This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Methods: Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12‐week, placebo‐controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions‐Severity of Illness score. Results: Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was ?0.36 with quetiapine and ?0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. Conclusions: The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence.