Elizabeth Irene Reiser, By And Through Her Guardian, Richard E. Reiser And Eleanor Reiser v. Richard Lohner And Howard Francis, Medical Doctors, And Provo Obstetrical And Gynecology Clinic, Inc., A Professional Corporation : Brief of Defendants-Respondents

Appeal from a Verdict of the Fourth Judicial District Court of Utah County, State of Utah Honorable James S. Sawaya, Presidin

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Development of an ex vivo aneurysm model for vascular device testing

An ex vivo aneurysm model that closely resembles the in vivo situation can provide an important tool for testing therapies. The model should mimic a variety of conditions, such as in vivo hemodynamics and native arterial structure and characteristics, avoiding animal experimentation.  Therefore, the aim of this study is to develop an ex vivo aneurysm model by vessel wall stiffening to be used to assess treatment strategies. Porcine carotid arteries from slaughterhouse animals were used to evaluate the acute effect of different concentrations of Rose Bengal on distensibility. This sono-sensitive compound was activated by several ultrasound frequencies, resulting in stiffening of the treated arteries of which the most effective combination was selected. In a pulsatile ex vivo vascular bioreactor treated and control porcine carotid arteries were subjected to physiological conditions for 10 days. During culture, hemodynamics showed increased mean pressure and decreased pulsatility in treated arteries compared to controls. Change in vessel morphology and significant increase of distal diameter was observed in the treated arteries but not in the controls. Histology of treated arteries revealed dissection-like lesions distally and aneurysm-like structure proximally. Finally, a stent graft was deployed in one treated artery and cultured demonstrating the feasibility of testing endovascular devices in the model. In conclusion, we developed an ex vivo model reproducing the onset of aneurysm formation. This could represent a promising tool for early stage device testing thereby reducing the need for animal studies

Continuous Postoperative Pericardial Flushing: A Pilot Study on Safety, Feasibility, and Effect on Blood Loss

Background: Prolonged or excessive blood loss is a common complication after cardiac surgery. Blood remnants and clots, remaining in the pericardial space in spite of chest tube drainage, induce high fibrinolytic activity that may contribute to bleeding complications. Continuous postoperative pericardial flushing (CPPF) with an irrigation solution may reduce blood loss by preventing the accumulation of clots. In this pilot study, the safety and feasibility of CPPF were evaluated and the effect on blood loss and other related complications was investigated. Methods: Between November 2011 and April 2012 twenty-one adult patients undergoing surgery for congenital heart disease (CHD) received CPPF from sternal closure up to 12 h postoperative. With an inflow Redivac drain that was inserted through one of the chest tube incision holes, an irrigation solution (NaCl 0.9% at 38 °C) was delivered to the pericardial cavity using a volume controlled flushing system. Safety aspects, feasibility issues and complications were registered. The mean actual blood loss in the CPPF group was compared to the mean of a retrospective group (n = 126). Results: CPPF was successfully completed in 20 (95.2%) patients, and no method related complications were observed. Feasibility was good in this experimental setting. Patients receiving CPPF showed a 30% (P = 0.038) decrease in mean actual blood loss 12 h postoperatively. Conclusions: CPPF after cardiac surgery was found to be safe and feasible in this experimental setting. The clinically relevant effect on blood loss needs to be confirmed in a randomized clinical trial

Attenuated cardiac function degradation in ex vivo pig hearts

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, −14.9 ± 6.3%/h vs −9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, −11.8 ± 3.4%/h vs −5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform