Prevention of catheter-related bloodstream infection in critically ill patients using a disinfectable, needle-free connector: a randomized controlled trial

OBJECTIVE: The aim of this study was to assess the efficacy of a disinfectable, needle-free connector in the prophylaxis of catheter-related bloodstream infection. METHODS: A randomized controlled trial was performed in a polyvalent intensive care unit. Patients who needed multilumen central venous catheters were randomly assigned to a study or a control group. All catheters were inserted and manipulated according to the Centers for Disease Control and Prevention (CDC) recommendations. Study group patients were equipped with catheters with disinfectable, needle-free connectors whereas control group patients were equipped with catheters with 3-way stopcocks. Two peripheral blood cultures and a semiquantitative culture of the catheter tip were performed on removal of the catheter. RESULTS: The study included 243 patients, with a total of 278 central venous catheters. The catheters' mean insertion duration was 9.9 days. Both groups were comparable regarding patient and catheter characteristics. Incidence rate of catheter-related bloodstream infection was 0.7 per 1000 days of catheter use in the study group, compared with 5.0 per 1000 days of catheter use in the control group (P=.03). CONCLUSIONS: To add a disinfectable, needle-free connector to the CDC recommendations reduces the incidence of catheter-related bloodstream infection in critically ill patients with central venous catheters.     

Dexamethasone decreases contraction to electrical field stimulation in mesenteric arteries from spontaneously hypertensive rats through decreases in thromboxane A2 release

Glucocorticoids play a role in the control of vascular smooth muscle tone through the alteration of vasoconstrictor and vasodilator factor production. We studied the effect of dexamethasone on vasoconstriction induced by electrical field stimulation (EFS) in rat mesenteric arteries (MAs) and the role of hypertension in this effect. Endothelium-denuded MAs were obtained from Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs). EFS response was analyzed by isometric tension recordings and cyclooxygenase (COX-1 and COX-2) expression by Western blot. Noradrenaline (NA) release was evaluated in segments incubated with [(3)H]NA. Dexamethasone (0.1 and 1 microM; 2-8 h) reduced vasoconstriction to EFS (200 mA, 0.3 ms, 1-16 Hz), in a dose- and time-dependent manner only in SHRs. However, the EFS-induced release of [(3)H]NA was increased in SHR arteries preincubated with dexamethasone (1 microM; 6 h). The thromboxane A(2) (TxA(2)) synthase inhibitor furegrelate (10 microM), the selective COX-2 inhibitor NS-398 (N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide; 10 microM), or the TxA(2) receptor antagonist SQ 29548 (1 microM), reduced EFS and NA induced vasoconstrictor responses. However, the effect of these drugs was abolished in arteries preincubated with dexamethasone. Both dexamethasone and phentolamine (1 microM) inhibited the increased thromboxane B(2) levels observed after EFS. COX-2 protein expression was reduced by dexamethasone in SHR arteries. Results suggest that dexamethasone reduces vasoconstriction to EFS in MAs from SHRs by decreasing COX-2 expression, thereby decreasing the smooth muscle TXA(2) release induced by alpha-adrenoceptor activation. The undetectable COX-2 expression in MAs from normotensive animals explains the noneffect of dexamethasone in their arteries.     

Intracellular trafficking during liver regeneration. Alterations in late endocytic and transcytotic pathways

BACKGROUND/AIMS: Liver growth, induced by partial hepatectomy of the organ is a precisely regulated process during which a radical reorganisation of metabolism occurs as the hepatocytes become committed to enter the cell cycle. Recent studies have shown the importance of the endocytic compartment in the control of lipid and protein intracellular trafficking but also in the control of the signal transduction events, which eventually will trigger the initiation of DNA synthesis and the subsequent cell division. METHODS: We isolated endosomes at different times after partial hepatectomy in male rats and compared with endosomes isolated from sham-operated animals. Also, bile was collected and analysed by 2D-gel electrophoresis. RESULTS: The amount of late endosomes isolated from regenerating livers decreased, concomitant with decreased cathepsin D specific enzyme activity. Furthermore, secretion of horseradish peroxidase, pIgA and transferrin increased in the pre-replicative phase of liver regeneration. CONCLUSIONS: At the early stages of liver regeneration, the hepatocellular transport pathway towards degradation (late endosomes and lysosomal pathway) decreases, but the transcytosis and the bile secretion of several major proteins increases.     

Systems Medicine: from molecular features and models to the clinic in COPD

Background and hypothesis

Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice.

Objective and method

Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework.

Results

In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice.

Conclusions

The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models. Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them.

     

Impact of pulmonary rehabilitation on psychosocial morbidity in patients with severe COPD

STUDY OBJECTIVE: To assess the effect of pulmonary rehabilitation (PR) on psychosocial morbidity, functional exercise capacity, and health-related quality of life (HRQL) in patients with severe COPD. DESIGN: A prospective, randomized, controlled trial with blinding of outcome assessment and data analysis. SETTING: A tertiary-care respiratory service. PATIENTS: Forty patients (mean age, 65 +/- 8 years [+/- SD]) with severe chronic flow limitation (FEV(1), 35 +/- 13%) without respiratory failure (Pao(2), 72 +/- 9 mm Hg; Paco(2), 42 +/- 5 mm Hg) were randomized either to a control group or to a PR group (PRG). INTERVENTIONS: Sixteen weeks of PR that included breathing retraining and exercise. MEASUREMENTS: At baseline and 16 weeks, we evaluated psychosocial morbidity using two questionnaires (the Millon Behavior Health Inventory [MBHI] and the Revised Symptom Checklist [SCL-90-R]) and measured 6-min walk distance (6WMD) and HRQL using the Chronic Respiratory Questionnaire (CRQ). RESULTS: We found differences in favor of the PRG in the following MBHI domains: introversive, forceful, and sensitive personality styles (all p 相似文献   

Heme oxygenase attenuates oxidative stress and inflammation, and increases VEGF expression in portal hypertensive rats

BACKGROUND/AIMS: The pathophysiological significance of heme oxygenase-1 up-regulation in portal hypertension is not completely understood. In this study, we determined the role of heme oxygenase-1 on oxidative stress, inflammation, angiogenesis, and splanchnic hemodynamics in rats with portal hypertension induced by partial portal vein ligation. METHODS: Rats were treated with the heme oxygenase inhibitor SnMP or vehicle for 7 days. Then, oxidative stress was quantified by superoxide anion production, and inflammatory response was assessed by immunofluorescence. Expression of angiogenesis mediators was determined by western blotting, and the extent of portosystemic collaterals by radioactive microspheres. Hemodynamic studies were performed by flowmetry. RESULTS: Oxidative stress was significantly increased in the mesentery of portal hypertensive rats, as compared with sham-operated controls. In portal hypertensive rats, chronic heme oxygenase inhibition (1) potentiated oxidative stress and inflammation, (2) significantly decreased VEGF expression, without modifying the extent of collaterals or the splanchnic neovascularization, and (3) significantly decreased superior mesenteric artery blood flow and portal pressure. CONCLUSIONS: This study demonstrates that heme oxygenase plays an important (beneficial) role attenuating oxidative stress and inflammation, but it also plays a detrimental role in stimulating VEGF production, and contributing to the development of hyperdynamic splanchnic circulation in rats with portal hypertension.     

Dialectical Behavior Therapy in the Treatment of Borderline Personality Disorder and Eating Disorders Comorbidity: A Pilot Study in a Naturalistic Setting

Dialectical behavior therapy (DBT) has been shown to be successful in the treatment of borderline personality disorder and eating disorders separately. The present study compares Standard Dialectical Behavior Therapy with a Treatment as Usual Cognitive Behavior Therapy (TAU CBT) for the treatment of borderline personality disorder and eating disorders comorbid features. A total of 118 women diagnosed with borderline personality disorders and eating disorders were assigned to one of two treatment groups in a naturalistic setting (DBT?=?71; TAU CBT?=?47). DBT showed a greater decrease in dysfunctional behaviors used to regulate emotions and related to borderline personality disorder (i.e. substance abuse, impulsive money spending, unprotected sex, etc.), non-suicidal self-injuries, and depressive symptoms, as well as an increase in cognitive reappraisal and global functioning. DBT and TAU CBT showed similar improvements in suicide attempts, dysfunctional eating behaviors (i.e. binge eating, purgative behaviors, and restriction), hospitalizations, negative and positive affect, and expressive suppression. Results of this study support the utility and effectiveness of standard DBT for comorbid borderline personality disorder and eating disorders in naturalistic settings. Replications of this study and randomized controlled trials are needed.     

Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections

Purpose

To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators.

Methods

Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance.

Results

Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions.

Conclusions

This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.