Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.

BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.

Recursos governatius. Doctrina de la Direcció General de Dret i Entitats Jurídiques (maig-setembre 2008)

Comentaris a les Resolucions de la Direcció General de Dret i Entitats Jurídiques de 5 de maig 2008, 16 de juliol 2008 i 29 de setembre 2008.

Recursos governatius. Doctrina de la Direcció General de Dret i Entitats Jurídiques IV

Comentaris a les Resolucions de la Direcció General de Dret i Entitats Jurídiques 22 de gener 2007, de 24 de gener 2007, de 15 de febrer 2007, de 16 de febrer 200 i de 19 de febrer 2007.

Recursos governatius. Doctrina de la Direcció General de Dret i Entitats Jurídiques (maig 2007-febrer 2008)

Comentaris a les Resolucions de la Direcció General de Dret i Entitats Jurídiques de 2 de maig 2007, de 10 de juliol 2007, d'11 de juliol 2007, de 16 de juliol 2007, de 17 de juliol 2007, de 22 d'octubre 2007, de 21 de desembre 2007 i 4 de febrer 2008.

Recursos governatius. Doctrina de la Direcció General de Dret i Entitats Jurídiques (febrer-abril 2008).

Comentaris a les Resolucions de la Direcció General de Dret i Entitats Jurídiques de 6 de febrer 2008, 8 de febrer 2008, 20 de febrer 2008, 2 d'abril 2008 i 18 d¿abril 2008.

Recursos governatius. Doctrina de la Direcció General de Dret i Entitats Jurídiques V

Comentaris a les Resolucions de la Direcció General de Dret i Entitats Jurídiques de 20 de març 2007, de 26 d'abril 2007, de 27 d'abril 2007 i de 30 d'abril 2007

Comparison of two oral probiotic preparations in a randomized crossover trial highlights a potentially beneficial effect of Lactobacillus paracasei NCC2461 in patients with allergic rhinitis.

BACKGROUND: There is promising but conflicting evidence to recommend the addition of probiotics to foods for prevention and treatment of allergy. Based on previous studies with fermented milk containing Lactobacillus paracasei NCC2461, we aimed to compare the effect of a powder form of the latter probiotic with the effect of a blend of Lactobacillus acidophilus ATCC SD5221 and Bifidobacterium lactis ATCC SD5219 in patients with allergic rhinitis. METHODS: A double-blind, randomized, cross-over study, involving 31 adults with allergic rhinitis to grass pollen, was performed outside the grass pollen season (registration number: NCT01233154). Subjects received each product for 4-weeks in two phases separated by a wash-out period of 6 to 8 weeks. A nasal provocation test was performed before and after each 4-week product intake period, and outcome parameters (objective and subjective clinical symptoms; immune parameters) were measured during and/or 24 hours after the test. RESULTS: Out of the 31 subject enrolled, 28 completed the study. While no effect was observed on nasal congestion (primary outcome), treatment with NCC2461 significantly decreased nasal pruritus (determined by VAS), and leukocytes in nasal fluid samples, enhanced IL-5, IL-13 and IL-10 production by peripheral blood mononuclear cells in an allergen specific manner and tended to decrease IL-5 secretion in nasal fluid, in contrast to treatment with the blend of L. acidophilus and B. lactis. CONCLUSIONS: Despite short-term consumption, NCC2461 was able to reduce subjective nasal pruritus while not affecting nasal congestion in adults suffering from grass pollen allergic rhinitis. The associated decrease in nasal fluid leukocytes and IL-5 secretion, and the enhanced IL-10 secretion in an allergen specific manner may partly explain the decrease in nasal pruritus. However, somewhat unexpected systemic immune changes were also noted. These data support the study of NCC2461 consumption in a seasonal clinical trial to further demonstrate its potentially beneficial effect.

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients.

INTRODUCTION: Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 microg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo. RESULTS: Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 +/- 3.2 versus -4.2 +/- 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045). CONCLUSION: The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation. TRIALS REGISTRATION: Clinical Trials.gov RCT Register: NCT00515736.

Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies.

BACKGROUND: Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring. METHODS AND RESULTS: We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7±1.6% versus 8.6±1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally. CONCLUSIONS: Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.

Case management for frequent users of the emergency department: study protocol of a randomised controlled trial.

BACKGROUND: We devised a randomised controlled trial to evaluate the effectiveness and efficiency of an intervention based on case management care for frequent emergency department users. The aim of the intervention is to reduce such patients' emergency department use, to improve their quality of life, and to reduce costs consequent on frequent use. The intervention consists of a combination of comprehensive case management care and standard emergency care. It uses a clinical case management model that is patient-identified, patient-directed, and developed to provide high intensity services. It provides a continuum of hospital- and community-based patient services, which include clinical assessment, outreach referral, and coordination and communication with other service providers. METHODS/DESIGN: We aim to recruit, during the first year of the study, 250 patients who visit the emergency department of the University Hospital of Lausanne, Switzerland. Eligible patients will have visited the emergency department 5 or more times during the previous 12 months. Randomisation of the participants to the intervention or control groups will be computer generated and concealed. The statistician and each patient will be blinded to the patient's allocation. Participants in the intervention group (N = 125), additionally to standard emergency care, will receive case management from a team, 1 (ambulatory care) to 3 (hospitalization) times during their stay and after 1, 3, and 5 months, at their residence, in the hospital or in the ambulatory care setting. In between the consultations provided, the patients will have the opportunity to contact, at any moment, the case management team. Participants in the control group (N = 125) will receive standard emergency care only. Data will be collected at baseline and 2, 5.5, 9, and 12 months later, including: number of emergency department visits, quality of life (EuroQOL and WHOQOL), health services use, and relevant costs. Data on feelings of discrimination and patient's satisfaction will also be collected at the baseline and 12 months later. DISCUSSION: Our study will help to clarify knowledge gaps regarding the positive outcomes (emergency department visits, quality of life, efficiency, and cost-utility) of an intervention based on case management care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01934322.

Validation of rotational thromboelastometry during cardiopulmonary bypass: A prospective, observational in-vivo study.

BACKGROUND: Rotational thromboelastometry (ROTEM) is a whole blood point-of-test used to assess the patient's coagulation status. Three of the available ROTEM tests are EXTEM, INTEM and HEPTEM. In the latter, heparinase added to the INTEM reagent inactivates heparin to reveal residual heparin effect. Performing ROTEM analysis during cardiopulmonary bypass (CPB) might allow the anaesthesiologist to anticipate the need for blood products. OBJECTIVE: The goal of this study was to validate ROTEM analysis in the presence of very high heparin concentrations during CPB. DESIGN: Prospective, observational trial. SETTING: Single University Hospital. PARTICIPANTS: Twenty patients undergoing coronary artery bypass grafting. MAIN OUTCOME MEASURE: ROTEM analysis was performed before heparin administration (T0), 10 min after heparin (T1), at the end of CPB (T2) and 10 min after protamine (T3). The following tests were performed: EXTEM, INTEM, and HEPTEM. Heparin concentrations were measured at T1 and at the end of bypass (T2). RESULTS: At T1, EXTEM differed from baseline for coagulation time: +26.7 s (18.4 to 34.9, P < 0.0001), α: -3° (1.0 to 5.4, P = 0.006) and A10: -4.4 mm (2.3 to 6.5, P = 0.0004). INTEM at T0 was different from HEPTEM at T1 for coagulation time: + 47 s (34.3 to 59.6, P >0.0001), A10: -2.3 mm (0.5 to 4.0, P = 0.01) and α -2° (1.0 to 3.0; P = 0.0007). At T2, all parameters in EXTEM and HEPTEM related to fibrin-platelet interaction deteriorated significantly compared to T1. At T3, EXTEM and INTEM were comparable to EXTEM and HEPTEM at T2. CONCLUSION: HEPTEM and EXTEM measurements are valid in the presence of very high heparin concentrations and can be performed before protamine administration in patients undergoing cardiac surgery with CPB. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01455454.

Can PR voting serve as a shelter against declining turnout ? : Evidence from Swiss municipal elections

To assess the impact of electoral systems on voting turnout, cross-national studies can be usefully complemented by studies of turnout in local elections in countries using more than one electoral system at that level. In this article, we look at data from a 1998 survey of Swiss municipalities to revisit the findings of our earlier study. This previous study, based on a 1988 survey, concluded, in particular, that there exists a positive relationship between proportional representation elections, party politicization, and voter turnout. The moment is opportune since, in the interval, turnout has markedly declined in Swiss municipalities, as elsewhere. By testing whether municipalities with proportional representation voting were more or less successful in stemming the decline, we learn more about the relationship among these three phenomena. We use the results for those Swiss municipalities which participated in both surveys as our primary source.