Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

Experience with FiberWire for pectus bar attachment.

BACKGROUND: Minimally invasive repair of pectus excavatum has become an established method for repair of pectus excavatum. Bar displacement or rotation remains the most common complication of this repair requiring return to the operating room. METHODS: Retrospective review of all patients at a single institution who underwent repair of pectus excavatum using FiberWire for bar stabilization between December 2009 and March 2013 was undertaken. RESULTS: 93 patients underwent minimally invasive pectus repair using FiberWire during the study period. The patients included 73 males and 20 females, with an average age of 14.6years (range 7-21years). Mean operative time was 102minutes (range 56-198minutes). No patients developed wound complications, two patients developed pain because of bar migration and required return to the OR, and no patients had recurrence of their pectus defect because of bar migration during the study period. Median length of follow-up was 17months (range 3-36months). CONCLUSION: Stabilization of pectus bars using circumferential rib fixation with FiberWire at multiple points on both sides of the bar appears to be effective in preventing bar rotation and displacement, and requires minimal change to the operation as it has been previously described. Early experience shows a low rate of complications.

Compressive orthotics in the treatment of asymmetric pectus carinatum: a preliminary report with an objective radiographic marker.

BACKGROUND/PURPOSE: Pectus carinatum (PC) traditionally has been managed with surgical reconstruction. Compressive orthosis also has resulted in subjective improvement in this defect. The goal of the authors was to develop an alternative brace and an objective radiographic marker to monitor the effects of chest wall compression on sternal protrusion. METHODS: Baseline chest computed tomography (CT) scans were obtained for 5 teenage boys with chondrogladiolar type of PC. The angle at the point of greatest sternal rotation was measured as the baseline deformity. Compressive orthosis was initiated using a custom-fitted brace. Follow-up chest CT scans were obtained to document change in sternal rotation. RESULTS: One patient was lost to follow-up after 6 months with subjective improvement. Another opted for surgical correction after 3 months, having shown a 16% decrease in sternal rotation preoperatively. Two patients showed subjective improvement corroborated by 33% and 44% decreases in sternal rotation. The fifth patient, who discontinued bracing after 1 month, showed a 25% increase 6 months later. CONCLUSIONS: Preliminary results indicate a potential role for compressive orthosis in the management of pectus carinatum. The objective radiographic marker described may be used to monitor the effects of growth or treatment with compressive orthosis.

Carotid endarterectomy: a comparison of regional versus general anesthesia in 500 operations.

The outcomes of 489 patients undergoing 500 carotid endarterectomies were reviewed to compare results from using general anesthesia with those from using regional (cervical block) anesthesia. From September 1982 to May 1998, 228 procedures (221 patients) were performed under general anesthesia and 272 procedures (268 patients) were performed under local anesthesia. A detailed comparison of the two groups revealed close similarity in age, sex, presenting symptoms, and associated risk factors. Overall, perioperative mortality was 0.8%. In comparison to regional anesthesia, the general anesthesia group had greater overall morbidity (23.3 vs. 13. 6%, p < 0.008) and more frequent use of postoperative vasoactive drugs to control blood pressure (40.4 vs. 26.1%, p < 0.001). Furthermore, anesthesia time, operative time, and frequency of shunt use were significantly greater in the general anesthesia group (p < 0.03).

Attenuation of renal ischemia-reperfusion injury with selectin inhibition in a rabbit model.

BACKGROUND: The selectin glycoproteins are involved in the pathogenesis of renal ischemia-reperfusion injury. We investigated the ability of glycyrrhizin, a known selectin inhibitor, to attenuate renal ischemia-reperfusion injury. METHODS: Eighteen New Zealand white rabbits underwent midline laparotomy with renal artery cross-clamping. After 30 minutes of reperfusion, group 1 (control, n = 10) animals received a saline infusion, while group 2 (GLY, n = 8) animals received a glycyrrhizin infusion. Renal function was compared between the two groups after 72 hours of reperfusion. A t test was utilized, with alpha set at P<0.05. RESULTS: Group 1 and group 2 animals had similar baseline renal function. However, after 72 hours of reperfusion, group 1 animals had a significantly higher mean blood urea nitrogen creatinine ratio than group 2 animals (P<0.01), indicating preserved renal function in rabbits treated with glycyrrhizin. CONCLUSIONS: Selectin blockade using glycyrrhizin attenuates renal ischemia-reperfusion injury when given 30 minutes after the onset of reperfusion in a rabbit model.

The effects of pneumoperitoneum on gastric blood flow and traditional hemodynamic measurements.

BACKGROUND: The purpose of this study was to investigate the effects of increasing intraabdominal pressure (IP) on gastric blood flow, as measured by gastric tonometry and traditional hemodynamic measurements. METHODS: Nine swine were anesthetized, intubated, and ventilated. Arterial and pulmonary artery catheters were placed by cutdown, a trocar was placed in the abdomen, and a gastric tonometer was placed in the stomach. Serial measurements of arterial and mixed venous blood gases, cardiac output, wedge pressure, lactic acid, and gastric intramucosal pH (pHi) were collected at intraperitoneal pressures of 0, 8, 10, 12, 14, 16, and 18 mm Hg after 30 min equilibration. Statistical analysis included Pearson correlation and Student's t test. RESULTS: Increasing levels of IP were correlated with decreased arterial pH (p < 0.00003), increased mixed venous CO2 (p < 0.003), decreased intramucosal pH (p < 0.014), and increased arterial CO2 (p < 0.015). Gastric pHi differed significantly from baseline at IP levels of 16 mm Hg (p < 0.004) and 18 mm Hg (p < 0.01). No significant effects were observed on cardiac output or arterial lactate. No significant effects were observed in a control group that had been insufflated to 8 mm Hg and held constant over 3 h. CONCLUSIONS: In this model, gastric blood flow is adversely affected by increasing i.p. with pronounced effects in excess of 15 mm Hg. These results suggest that gastric tonometry may be used to monitor the adverse effects of pneumoperitoneum. Gastric pHi may be an earlier indicator of altered hemodynamic function during laparoscopy than traditional measures.

Transinguinal laparoscopic examination of the contralateral groin in pediatric herniorrhaphy.

The authors laparoscopically assessed the contralateral groin (CG) via the symptomatic inguinal hernia in 91 patients to avoid unnecessary CG exploration and to allow for identification of asymptomatic CG hernias. Once the symptomatic hernia sac was opened, a 4.5-mm trocar was placed intraperitoneally and the CG internal ring was inspected with a 4-mm laparoscope. When compared with the authors' previous surgical policy for routine CG exploration in children younger than 2 years of age, laparoscopic findings altered the procedure performed in 42 of 91 patients (46.2%). In patients younger than 2 years of age, the CG did not require repair of an unsuspected hernia in 55.9% of patients based on laparoscopic findings. Conversely, in children 2 years of age or older, 40.4% required CG repairs of unsuspected hernias or patent processus vaginalis (PPV). Transinguinal laparoscopic examination in pediatric herniorrhaphy provides important information about the CG without the need for additional trocar sites.