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PubMed | University Hospital of Tuebingen, Ghent University, University Hospital St Luc, Free University of Colombia and 5 more.
Type: | Journal: Clinical immunology (Orlando, Fla.) | Year: 2016

Immunogenicity and safety of different adjuvants combined with a model antigen (HBsAg) were compared. Healthy HBV-nave adults were randomized to receive HBs adjuvanted with alum or Adjuvant Systems AS01B, AS01E, AS03A or AS04 at Days 0 and 30. Different frequencies of HBs-specific CD4+ T cells 14days post dose 2 but similar polyfunctionality profiles were induced by the different adjuvants with frequencies significantly higher in the AS01B and AS01E groups than in the other groups. Antibody concentrations 30days post-dose 2 were significantly higher in AS01B, AS01E and AS03A than in other groups. Limited correlations were observed between HBs-specific CD4+ T cell and antibody responses. Injection site pain was the most common solicited local symptom and was more frequent in AS groups than in alum group. Different adjuvants formulated with the same antigen induced different adaptive immune responses and reactogenicity patterns in healthy nave adults. The results summary for this study (GSK study number 112115 - NCT# NCT00805389) is available on the GSK Clinical Study Register and can be accessed at www.gsk-clinicalstudyregister.com.


Nagakane Y.,University of Melbourne | Christensen S.,Royal Melbourne Hospital | Brekenfeld C.,University of Melbourne | Brekenfeld C.,University of Bern | And 18 more authors.
Stroke | Year: 2011

Background and Purpose-The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated. Methods-Patients were classified as having mismatch if perfusion-weighted imaging divided by coregistered diffusionweighted imaging volume ratio was >1.2 and total coregistered mismatch volume was >10 mL. The primary outcome was a comparison of infarct growth in alteplase vs placebo patients with coregistered mismatch. Results-Of 99 patients with baseline diffusion-weighted imaging and perfusion-weighted imaging, coregistration of both images was possible in 95 patients. Coregistered mismatch was present in 93% (88/95) compared to 85% (81/95) with standard volumetric mismatch. In the coregistered mismatch patients, of whom 45 received alteplase and 43 received placebo, the primary outcome measure of geometric mean infarct growth was significantly attenuated by a ratio of 0.58 with alteplase compared to placebo (1.02 vs 1.77; 95% CI, 0.33- 0.99; P=0.0459). Conclusions-When using coregistration techniques to determine the presence of mismatch at study entry, alteplase significantly attenuated infarct growth. This highlights the necessity for a randomized, placebo-controlled, phase III clinical trial of alteplase using penumbral selection beyond 3 hours. © 2010 American Heart Association, Inc.


Leroux-Roels I.,Ghent University | Devaster J.-M.,Glaxosmithkline | Leroux-Roels G.,Ghent University | Verlant V.,Glaxosmithkline | And 9 more authors.
Vaccine | Year: 2015

Background: The protection elicited by polysaccharide pneumococcal vaccines against community-acquired pneumonia in older adults remains debatable. Alternative vaccine targets include well-conserved pneumococcal protein antigens, such as pneumococcal histidine triad protein D (PhtD). Objective: To evaluate humoral and cellular immune responses and safety/reactogenicity following immunisation with PhtD vaccine with or without adjuvant (alum or AS02V) in older (≥65 years) and young (18-45 years) healthy adults. Methods: Two phase I/II, single-blind, parallel-group studies were conducted in 150 older and 147 young adults. Participants were randomised to receive 2 doses (months 0 and 2) of PhtD 30μg, PhtD 10μg plus alum, PhtD 30μg plus alum, PhtD 10μg plus AS02V or PhtD 30μg plus AS02V, or the 23-valent polysaccharide pneumococcal vaccine (23PPV) at month 0 with placebo (saline solution) at month 2. Safety/reactogenicity was assessed. PhtD-specific antibody, T cell and memory B cell responses were evaluated. Results: Solicited adverse events were more common in young participants and with adjuvanted vaccines. No vaccine-related serious adverse events were reported. Although anti-PhtD geometric mean antibody concentrations (GMCs) were consistently lower in the older adult cohort than in young adults, GMCs in the older cohort following PhtD 30μg plus AS02V were comparable to those induced by plain PhtD or PhtD 30μg plus alum in the young cohort. Compared with alum adjuvant, AS02V adjuvant system was associated with an increased frequency of PhtD-specific CD4 cells in both cohorts and a significantly higher specific memory B cell response in the older cohort, similar to responses obtained in the young cohort. Conclusion: The improved immune response to PhtD vaccine containing the AS02V adjuvant system in comparison to alum suggests that the reduced immune response to vaccines in older adults can be partially restored to the response level observed in young adults. ClinicalTrials.gov identifiers: NCT00307528/NCT01767402. © 2014 The Authors.


Leroux-Roels G.,Ghent University | Van Belle P.,Glaxosmithkline | Vandepapeliere P.,Glaxosmithkline | Vandepapeliere P.,University of Paris Descartes | And 6 more authors.
Vaccine | Year: 2015

Background: Recombinant hepatitis B surface antigen (HBsAg) was used as a model antigen to evaluate persistence of cellular and humoral immune responses when formulated with three different Adjuvant Systems containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS-21, in an oil-in-water emulsion (AS02B and AS02V), or with liposomes (AS01B). Methods: This is an open, 4-year follow-up of a previous randomised, double-blind study. Healthy subjects aged 18-40 years received three vaccine doses on a month 0, 1, 10 schedule and were initially followed for 18 months. A total of 93 subjects (AS02B: n=30; AS02V: n=28; AS01B: n=35) were enrolled in this follow-up and had an additional blood sample taken at Year 4 (NCT02153320). The primary endpoint was the frequency of HBsAg-specific CD4+ and CD8+ T-cells expressing cytokines upon short-term in vitro stimulation of peripheral blood mononuclear cells with HBsAg-derived peptides. Secondary endpoints were anti-HBs antibody titres and frequency of HBsAg-specific memory B-cells. Results: A strong and persistent specific CD4+ T-cell response was observed at Year 4 in all groups. HBsAg-specific CD4+ T-cells expressed mainly CD40L and IL-2, and to a lesser extent TNF-α and IFN-γ. HBsAg-specific CD8+ T-cells were not detected in any group. A high, persistent HBsAg-specific humoral immune response was observed in all groups, with all subjects seroprotected (antibody titre ≥10mIU/mL) at Year 4. The geometric mean antibody titre at Year 4 was above 100,000mIU/mL in all groups. A strong memory B-cell response was observed post-dose 2, which tended to increase post-dose 3 and persisted at Year 4 in all groups. Conclusion: The MPL/QS-21/HBsAg vaccine formulations induced persistent immune responses up to 4 years after first vaccination. These Adjuvant Systems offer potential for combination with recombinant, synthetic or highly purified subunit vaccines, particularly for vaccination against challenging diseases, or in specific populations, although additional studies are needed. © 2014 The Authors.


Piquilloud L.,University of Lausanne | Tassaux D.,University of Geneva | Bialais E.,University Hospital St Luc | Lambermont B.,Medical Intensive Care Unit | And 5 more authors.
Intensive Care Medicine | Year: 2012

Purpose: To determine if, compared to pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces patient-ventilator asynchrony in intensive care patients undergoing noninvasive ventilation with an oronasal face mask. Methods: In this prospective interventional study we compared patient-ventilator synchrony between PS (with ventilator settings determined by the clinician) and NAVA (with the level set so as to obtain the same maximal airway pressure as in PS). Two 20-min recordings of airway pressure, flow and electrical activity of the diaphragm during PS and NAVA were acquired in a randomized order. Trigger delay (Td), the patient's neural inspiratory time (Tin), ventilator pressurization duration (T iv), inspiratory time in excess (Tiex), number of asynchrony events per minute and asynchrony index (AI) were determined. Results: The study included 13 patients, six with COPD, and two with mixed pulmonary disease. Td was reduced with NAVA: median 35 ms (IQR 31-53 ms) versus 181 ms (122-208 ms); p = 0.0002. NAVA reduced both premature and delayed cyclings in the majority of patients, but not the median Tiex value. The total number of asynchrony events tended to be reduced with NAVA: 1.0 events/min (0.5-3.1 events/min) versus 4.4 events/min (0.9-12.1 events/min); p = 0.08. AI was lower with NAVA: 4.9 % (2.5-10.5 %) versus 15.8 % (5.5-49.6 %); p = 0.03. During NAVA, there were no ineffective efforts, or late or premature cyclings. PaO2 and PaCO2 were not different between ventilatory modes. Conclusion: Compared to PS, NAVA improved patient ventilator synchrony during noninvasive ventilation by reducing Td and AI. Moreover, with NAVA, ineffective efforts, and late and premature cyclings were absent. © Copyright jointly held by Springer and ESICM 2012.


Piquilloud L.,University of Geneva | Vignaux L.,University of Geneva | Bialais E.,University Hospital St Luc | Roeseler J.,University Hospital St Luc | And 4 more authors.
Intensive Care Medicine | Year: 2011

Purpose: To determine if, compared with pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces trigger delay, inspiratory time in excess, and the number of patient-ventilator asynchronies in intubated patients. Methods: Prospective interventional study in spontaneously breathing patients intubated for acute respiratory failure. Three consecutive periods of ventilation were applied: (1) PS1, (2) NAVA, (3) PS2. Airway pressure, flow, and transesophageal diaphragmatic electromyography were continuously recorded. Results: All results are reported as median (interquartile range, IQR). Twenty-two patients were included, 36.4% (8/22) having obstructive pulmonary disease. NAVA reduced trigger delay (ms): NAVA, 69 (57-85); PS1, 178 (139-245); PS2, 199 (135-256). NAVA improved expiratory synchrony: inspiratory time in excess (ms): NAVA, 126 (111-136); PS1, 204 (117-345); PS2, 220 (127-366). Total asynchrony events were reduced with NAVA (events/min): NAVA, 1.21 (0.54-3.36); PS1, 3.15 (1.18-6.40); PS2, 3.04 (1.22-5.31). The number of patients with asynchrony index (AI) >10% was reduced by 50% with NAVA. In contrast to PS, no ineffective effort or late cycling was observed with NAVA. There was less premature cycling with NAVA (events/min): NAVA, 0.00 (0.00-0.00); PS1, 0.14 (0.00-0.41); PS2, 0.00 (0.00-0.48). More double triggering was seen with NAVA, 0.78 (0.46-2.42); PS1, 0.00 (0.00-0.04); PS2, 0.00 (0.00-0.00). Conclusions: Compared with standard PS, NAVA can improve patient-ventilator synchrony in intubated spontaneously breathing intensive care patients. Further studies should aim to determine the clinical impact of this improved synchrony. © Copyright jointly held by Springer and ESICM 2010.


PubMed | Glaxosmithkline, Ghent University and University Hospital St Luc
Type: Clinical Trial, Phase I | Journal: Vaccine | Year: 2014

The protection elicited by polysaccharide pneumococcal vaccines against community-acquired pneumonia in older adults remains debatable. Alternative vaccine targets include well-conserved pneumococcal protein antigens, such as pneumococcal histidine triad protein D (PhtD).To evaluate humoral and cellular immune responses and safety/reactogenicity following immunisation with PhtD vaccine with or without adjuvant (alum or AS02V) in older (65 years) and young (18-45 years) healthy adults.Two phase I/II, single-blind, parallel-group studies were conducted in 150 older and 147 young adults. Participants were randomised to receive 2 doses (months 0 and 2) of PhtD 30 g, PhtD 10 g plus alum, PhtD 30 g plus alum, PhtD 10 g plus AS02V or PhtD 30 g plus AS02V, or the 23-valent polysaccharide pneumococcal vaccine (23PPV) at month 0 with placebo (saline solution) at month 2. Safety/reactogenicity was assessed. PhtD-specific antibody, T cell and memory B cell responses were evaluated.Solicited adverse events were more common in young participants and with adjuvanted vaccines. No vaccine-related serious adverse events were reported. Although anti-PhtD geometric mean antibody concentrations (GMCs) were consistently lower in the older adult cohort than in young adults, GMCs in the older cohort following PhtD 30 g plus AS02V were comparable to those induced by plain PhtD or PhtD 30 g plus alum in the young cohort. Compared with alum adjuvant, AS02V adjuvant system was associated with an increased frequency of PhtD-specific CD4 cells in both cohorts and a significantly higher specific memory B cell response in the older cohort, similar to responses obtained in the young cohort.The improved immune response to PhtD vaccine containing the AS02V adjuvant system in comparison to alum suggests that the reduced immune response to vaccines in older adults can be partially restored to the response level observed in young adults. ClinicalTrials.gov identifiers: NCT00307528/NCT01767402.


PubMed | Laboratory of Toxicology and Therapeutic Drug Monitoring, Scientific Institute of Public Health, Ghent University and University Hospital St Luc
Type: Evaluation Studies | Journal: Clinical biochemistry | Year: 2015

Lithium remains a mainstay in the management of mood disorders. As with many psychotropic drugs, lithium treatment requires continuous observation for adverse effects and strict monitoring of serum concentrations. The present study aimed to assess the appropriateness of lithium assays used by Belgian laboratories, and to evaluate acceptability of their clinical interpretations.Nine in-house serum samples spiked with predetermined concentrations of lithium were distributed to 114 participants in the Belgian external quality assessment scheme. Laboratories were requested to report the assay technique, lithium measurements and interpretations with regard to measured concentrations. Inter/intramethod imprecision and bias were reported and acceptability of clinical interpretations was assessed. The intramethod variability was evaluated by selecting methods used by 6 laboratories or more. Flame photometry (IL 943) was considered as the reference method.Laboratories returned assay results using colorimetry (69.3%), ion selective electrode (15.8%), flame photometry (8.8%), atomic absorption spectroscopy (5.2%) or mass spectrometry (0.9%). Lithium concentrations were systematically higher when measured with the Vitros assay (median bias: 4.0%), and were associated with consecutive biased interpretations. In contrast, the Thermo Scientific Infinity assay showed a significant negative bias (median bias: 9.4%). 36.0% of laboratories reported numerical values below their manufacturer cut-off for the blank sample; 16.6% of these laboratories detected residual lithium concentrations.The present study revealed assay-related differences in lithium measurements and their interpretations. Overall, there appeared to be a need to continue EQA of therapeutic drug monitoring for lithium in Belgium.


Mitra S.,University of Manchester | Cress C.,Washington University in St. Louis | Goovaerts T.,University Hospital St Luc
Hemodialysis International | Year: 2015

Creating and maintaining a successful home hemodialysis (HD) program is highly dependent on the workforce model and quality of staff. We describe the minimum staff required to start a home HD program (e.g., a clinical champion and lead nurse) and detail what additional workforce (e.g., renal technician, dietitian, psychologist, and others) may be necessary as the program evolves and expands. The goal of the program and allied staff should be to provide a seamless patient journey, a process that requires consideration of a patient recruitment strategy, a patient training pathway, thoughtful initiation of home HD, and development of support systems for routine care and emergencies at home. This module describes how care models are implemented at centers of excellence in various locations around the world, highlights the importance of an integrated care pathway, and describes workforce challenges that programs may encounter. © 2015 International Society for Hemodialysis.


Finet P.,University Hospital St Luc | Delavallee M.,University Hospital St Luc | Raftopoulos C.,University Hospital St Luc
Acta Neurochirurgica | Year: 2015

Idiopathic intracranial hypertension (IIH) is a syndrome characterized by an increased intracranial pressure of unknown origin arising mainly in overweight females. The typical symptoms of IIH are headaches and papilledema associated with visual disorders, which can often evolve to blindness. We describe the first patient who developed a clinical syndrome related to an IIH following a bilateral subthalamic deep brain stimulation (DBS) procedure for Parkinson’s disease with the particularity that the clinical expression of the IIH syndrome was atypical because of the presence of intracerebral electrodes. © 2015, Springer-Verlag Wien.

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