Evidence of impaired microvascular dilatation in preterms with acute respiratory distress syndrome.

BACKGROUND: Evaluating microcirculatory function in severely ill neonates is a relevant, unmet clinical need. Inappropriate peripheral microvascular vasodilatation is thought to contribute to cardiovascular alterations in preterm infants with acute respiratory distress syndrome (ARDS). We directly evaluated microcirculatory function in preterms with ARDS. METHODS: Peripheral microvascular function was assessed in 50 newborns, divided in three groups: preterms with ARDS; at-term newborns with mild-moderate congenital cardiac disease (Cardio group); healthy controls. Skin microvascular perfusion was assessed using an operator-independent, laser-Doppler camera, under basal conditions and during post-ischemic hyperemia, allowing objective quantification of microcirculatory flow reserve (MFR). RESULTS: At baseline, perfusion was similar among the three groups. During post-ischemic phase, microcirculatory perfusion significantly increased in controls compared to baseline (baseline perfusion units [PU] 3.65±1.8 to 4.59±2.1 during hyperemia; p for trend=0.041), whereas in ARDS group perfusion tended to decrease. Comparing results across groups, ARDS showed lower values compared to either controls or Cardio groups (p<0.05). Controls, and to a lesser extent Cardio group, showed recruitable MFR (1.78±1.13 and 1.19±0.30 in controls and Cardio group, respectively). MFR was absent in ARDS (0.88±0.48; p<0.05), documenting impaired microcirculatory response. CONCLUSION: We demonstrate that it is possible to assess, non-invasively and quantitatively, vasodilator response of skin microcirculation to physiological stimuli in neonates. We also documented that microvascular vasodilation is impaired in preterms with ARDS.

A prospective, randomised, placebo-controlled, double-masked, three-armed, multicentre phase II/III trial for the Study of a Topical Treatment of Ischaemic Central Retinal Vein Occlusion to Prevent Neovascular Glaucoma - the STRONG study: study protocol for a randomised controlled trial.

BACKGROUND: Neovascular glaucoma (NVG) is rare, comprising only 3.9% of all glaucoma cases. The most common cause of NVG is ischaemic central retinal vein occlusion (iCRVO). NVG frequently results in blindness and painful end-stage glaucomatous damage leading to the need for enucleation. Currently, there is no preventive therapy for NVG following iCRVO. Rescue treatments have severe drawbacks. Accordingly, there is a great need for preventing the often visually devastating outcomes of NVG. The STRONG study is designed to test whether the topically active anti-angiogenic agent aganirsen is able to inhibit the formation of neovascularisation leading to the development of secondary NVG in eyes with iCRVO. At the same time, STRONG will provide important information on the natural course of iCRVO and NVG in a large and well-characterised cohort of such patients. METHODS/DESIGN: This protocol describes a phase II/III, prospective, randomised, placebo-controlled, double-masked, three-armed multicentre study for the investigation of aganirsen, a new topical treatment for iCRVO in order to prevent NVG. The study will evaluate the efficacy of two different doses of this newly developed antisense oligonucleotide formulated in an eye emulsion to avoid new vessel formation by blocking insulin receptor substrate-1 (IRS)-1. This leads to subsequent down-regulation of both angiogenic as well as proinflammatory growth factors such as vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF). Eligible patients (n = 333) will be treated with topical aganirsen or placebo for a period of 24 weeks. They will also be invited to participate in substudies involving analysis of gonioscopic images, detection of biomarkers for NVG and risk factors for iCRVO. DISCUSSION: The STRONG study has the potential to offer a new treatment modality for patients suffering from iCRVO with a high risk of developing NVG. The topical administration can reduce patients' burden and risk related to rescue treatment, such as destructive laser treatment or enucleation, but requires a high level of patient compliance. TRIAL REGISTRATION: EudraCT: 2014-000239-18; ClinicalTrials.gov, ID: NCT02947867 . (Registered on 15 October 2016); see also http://strong-nvg.com .

Factors influencing clinical trial site selection in Europe: the Survey of Attitudes towards Trial sites in Europe (the SAT-EU Study).

OBJECTIVES: Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. DESIGN: The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. SETTING AND PARTICIPANTS: Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. PRIMARY OUTCOME: weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. RESULTS: Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). CONCLUSIONS: Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe.

High-temperature natural antioxidant improves soy oil for frying.

The objectives of this study were to determine the frying stability of soybean oil (SBO) treated with a natural citric acid-based antioxidant, EPT-OILShield able to withstand high temperatures and to establish the oxidative stability of food fried in the treated oil. Soybean oil with 0.05% and 0.5% EPT-OILShield and an untreated control SBO were used for intermittent batch frying of tortilla chips at 180 degrees C for up to 65 h. Oil frying stability was measured by free fatty acids (FFA) and total polar compounds (TPC). Chips were aged for up to 4 mo at 25 degrees C and evaluated for rancid flavor by a 15-member, trained, experienced analytical sensory panel and for hexanal content as an indicator of oxidation. Oil with 0.05% EPT-OILShield had significantly less FFA and TPC than the control. The effect of EPT-OILShield was apparently retained in aged chips because hexanal levels were significantly lower in chips fried in oil with 0.05% EPT-OILShield than in chips fried in the control. Tortilla chips fried in the control were rancid after 2 mo at 25 degrees C at sampling times evaluated from 25 to 65 h; however, chips fried in oil with 0.05% EPT-OILShield and used for 65 h were described as only slightly rancid after 4 mo. Gamma tocopherol levels were significantly higher in the chips fried in the oil with 0.05% EPT-OILShield than in the control, helping to inhibit oxidation in the tortilla chips during storage.

Spinal Cord Stimulation vs. Conventional Medical Management: A Prospective, Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery Syndrome (PROCESS Study).

Introduction. Since its first application in 1967, numerous case series indicate that spinal cord stimulation (SCS) is an effective treatment for the management of failed back surgery syndrome (FBSS). However, only one randomized controlled trial has demonstrated that SCS provides more effective pain relief than re-operation and conventional medical management. The PROCESS randomized, controlled, multicenter trial aims to assess the clinical effectiveness and cost-effectiveness of SCS when added to conventional medical management compared to conventional medical management alone in patients with FBSS. Methods/Design. A total of 100 FBSS patients with predominantly neuropathic leg pain will be recruited from 12 centers and randomized to receive either conventional medical management alone or in combination with SCS for a period of 24 months. Patients will be evaluated at 1, 3, 6, 9, 12, 18, and 24 months. At the 6-month visit, patients will be classified as successful (≥  50% pain relief in the legs) or unsuccessful (< 50% pain relief in the legs). If the results of the randomized treatment are unsuccessful, patients can cross over to the alternative treatment arm. Discussion. This paper highlights the rationale, design, methods, and challenges of an ongoing prospective, randomized, controlled, multicenter clinical trial that has been undertaken to obtain conclusive evidence of the clinical efficacy and cost-effectiveness of an SCS system in patients with FBSS.