Pharmacokinetics of zanamivir in critically ill patients undergoing continuous venovenous hemofiltration.

Background: Limited data exist for dosing of zanamivir in the setting of CVVH in the intensive care unit (ICU). Our objective is to report the pharmacokinetics and sieving coefficient (S) of zanamivir in patients receiving continuous venovenous hemofiltration (CVVH).

Methods: In this prospective observational study, patients of ≥18 years admitted to the ICU with a life-threatening Influenza A or B infection, treated with zanamivir i.

Target attainment and pharmacokinetics of cefotaxime in critically ill patients undergoing continuous kidney replacement therapy.

Objectives: Limited data exist about the antimicrobial target attainment and pharmacokinetics of cefotaxime in critically ill patients in the ICU undergoing continuous kidney replacement therapy (CKRT). We conducted a prospective observational study in two large teaching hospitals [Isala Hospital (IH) and Zwolle and Maasstad Hospital (MH)] to investigate target attainment and pharmacokinetics of cefotaxime in patients undergoing CKRT.

Patients And Methods: Patients aged ≥18 years admitted to the ICU treated with IV cefotaxime 1000 mg three times daily (IH) or 4 times daily (MH) were included.

The impact of COVID-19 on nursing workload and planning of nursing staff on the Intensive Care: A prospective descriptive multicenter study.

Introduction: The impact of the care for COVID-19 patients on nursing workload and planning nursing staff on the Intensive Care Unit has been huge. Nurses were confronted with a high workload and an increase in the number of patients per nurse they had to take care of.

Objective: The primary aim of this study is to describe differences in the planning of nursing staff on the Intensive Care in the COVID period versus a recent non-COVID period.

The objective nursing workload and perceived nursing workload in Intensive Care Units: Analysis of association.

Background: A range of classification systems are in use for the measurement of nursing workload in Intensive Care Units. However, it is unknown to what extent the measured (objective) nursing workload, usually in terms of the amount of nursing activities, is related to the workload actually experienced (perceived) by nurses.

Objectives: The aim of this study was to assess the association between the objective nursing workload and the perceived nursing workload and to identify other factors associated with the perceived nursing workload.

Workload scoring systems in the Intensive Care and their ability to quantify the need for nursing time: A systematic literature review.

Introduction: The Intensive Care Unit is a resource intense service with a high nursing workload per patient resulting in a low ratio of patients per nurse. This review aims to identify existing scoring systems for measuring nursing workload on the Intensive Care and assess their validity and reliability to quantify the needed nursing time.

Methods: We conducted a systematic review of the literature indexed before 01/Mar/2018 in the bibliographic databases MEDLINE, Embase, and Cinahl.

RELAx - REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: protocol for a randomized controlled trial.

Background: Evidence for benefit of high positive end-expiratory pressure (PEEP) is largely lacking for invasively ventilated, critically ill patients with uninjured lungs. We hypothesize that ventilation with low PEEP is noninferior to ventilation with high PEEP with regard to the number of ventilator-free days and being alive at day 28 in this population.  METHODS/DESIGN: The "REstricted versus Liberal positive end-expiratory pressure in patients without ARDS" trial (RELAx) is a national, multicenter, randomized controlled, noninferiority trial in adult intensive care unit (ICU) patients with uninjured lungs who are expected not to be extubated within 24 h.

Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial.

Importance: It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation.

Objective: To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization.

Design, Setting, And Participants: Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands.

[Resuscitation for myocardial infarction and head injury: first the heart or first the head?].

Loss of circulation in a patient results in collapse and therefore possible head injury. After percutaneous coronary intervention (PCI) including anticoagulation, comatose patients are sedated for mild therapeutic hypothermia. Recognised or unrecognised head trauma may have dramatic clinical consequences.

Endoscopic clip-assisted feeding tube placement reduces repeat endoscopy rate: results from a randomized controlled trial.

Objectives: To determine whether endoscopic clip-assisted nasoenteral feeding tube placement is more effective than standard feeding tube placement with transnasal endoscopy.

Methods: Between August 2009 and February 2011, 143 patients referred for endoscopic nasoenteral feeding tube placement were randomized between clip-assisted and standard nasoenteral tube placement. Endoscopies were performed in the endoscopy unit and intensive care unit in a tertiary referral center in the Netherlands.

A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis.

Objective: Chemokines such as CCL2/monocyte chemotactic protein 1 (MCP-1) play a key role in leukocyte migration and are potential targets in the treatment of chronic inflammatory disorders. The objective of this study was to evaluate the effects of human anti-CCL2/MCP-1 monoclonal antibody (ABN912) treatment in patients with rheumatoid arthritis (RA).

Methods: Patients with active RA were enrolled in a randomized, placebo-controlled, dose-escalation study of ABN912.

Synovial tissue analysis in clinical trials.

Synovial tissue analysis has considerable potential for future randomized controlled trials (RCT). The synovial membrane is the target tissue in treatment strategies of rheumatoid arthritis and other arthropathies. Effective modulation of synovitis is critical when attempting to control symptoms and signs, to prevent joint damage, and to maintain function.

Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis.

Background: Chemokine receptors and chemokines have a crucial role in leucocyte recruitment into inflamed tissue.

Objective: To examine the expression of an extensive number of chemokines and receptors in a unique bank of paired samples of synovial tissue (ST) and peripheral blood (PB) from patients with different forms of arthritis to assist in identifying suitable targets for therapeutic intervention.

Methods: Synovial biopsy specimens were obtained from 23 patients with rheumatoid arthritis (RA), 16 with osteoarthritis, and 8 with reactive arthritis.

Reliability of computerized image analysis for the evaluation of serial synovial biopsies in randomized controlled trials in rheumatoid arthritis.

Analysis of biomarkers in synovial tissue is increasingly used in the evaluation of new targeted therapies for patients with rheumatoid arthritis (RA). This study determined the intrarater and inter-rater reliability of digital image analysis (DIA) of synovial biopsies from RA patients participating in clinical trials. Arthroscopic synovial biopsies were obtained before and after treatment from 19 RA patients participating in a randomized controlled trial with prednisolone.

Targeting cellular adhesion molecules, chemokines and chemokine receptors in rheumatoid arthritis.

The development of specific targeted therapies, such as anti-TNF-alpha treatment, for chronic inflammatory disorders such as rheumatoid arthritis, has significantly improved treatment, although not all patients respond. Targeting cellular adhesion molecules and chemokines/chemokine receptors as regulators of the extravasation and migration of leukocytes may provide a novel approach for the treatment of these diseases. Moreover, the possibility of developing small-molecule antagonists offers an excellent method for the oral delivery of compounds with a short half-life.

Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis.

Objective: To create greater understanding of the changes in synovial tissue parameters that occur in conjunction with clinical response by using an effective therapy, in order to facilitate the planning of future studies with therapeutic agents for rheumatoid arthritis (RA).

Methods: Twenty-one patients with active RA were randomized to receive either oral prednisolone (n = 10) or placebo (n = 11) for 2 weeks. In all patients, synovial tissue biopsy specimens were obtained by arthroscopy directly before treatment and after 14 days of treatment.

Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis.

Background: Previous work identified synovial sublining macrophage numbers as a potential biomarker for clinical efficacy in rheumatoid arthritis.

Objective: To investigate the association between changes in infiltration of synovial macrophages and clinical improvement after antirheumatic treatment.

Methods: 88 patients who participated in various clinical trials were studied.

[Blockade of chemokines in chronic inflammatory diseases].

Chemokines form a relatively new family of chemotactic cytokines that seem to play a central role in the migration and activation of leukocytes in a wide variety of immune-mediated disorders. Specific therapy targeted against these proteins may well become an effective treatment in many of these disorders. The efficacy and safety of chemokine blockade is currently being investigated in clinical trials on patients with HIV infection, multiple sclerosis, rheumatoid arthritis and other chronic inflammatory disorders.

Chemokine blockade: a new era in the treatment of rheumatoid arthritis?

Blockade of chemokines or chemokine receptors is emerging as a new potential treatment for various immune-mediated conditions. This review focuses on the therapeutic potential in rheumatoid arthritis, based on studies in animal models and patients. Several knockout models as well as in vivo use of chemokine antagonists are discussed.

T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells are associated with joint damage in patients with recent onset rheumatoid arthritis.

Objective: To determine immunohistological markers in synovial tissue of patients with early rheumatoid arthritis (RA) which are associated with unfavourable disease outcome.

Methods: Synovial tissue was obtained from 36 patients with RA within 1 year after the initial symptoms and before starting disease modifying antirheumatic drug treatment. Clinical, laboratory, and radiological assessments (Larsen score) were performed at the time of the biopsy and at the end of follow up (mean 58 months, range 38-72).

Chemokines in joint disease: the key to inflammation?

Targeting chemokines and/or chemokine receptors appears to be an intriguing new approach to treating chronic inflammatory disorders like rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and transplant rejections. The involvement of chemokines and chemokine receptors in inflammatory joint diseases, the in vitro and in vivo characteristics of the chemokine family in inflammatory joint disease, and initial clinical data on chemokine blockade in patients with rheumatoid arthritis suggest that targeting the chemokine and chemokine receptor family might provide a new, promising antirheumatic strategy.

Chemokine blockade and chronic inflammatory disease: proof of concept in patients with rheumatoid arthritis.

Background: Chemokines and their receptors are considered important contributors in cell migration and inflammation in chronic inflammatory disorders. Chemokines affecting monocytes/macrophages are considered potential therapeutic targets, but no studies of the effects of blocking the chemokine repertoire in humans with a chronic inflammatory disease have been reported.

Objective: To carry out a double blind, placebo controlled, phase Ib clinical trial with a specific, oral CCR1 antagonist.