SPIRIT Women, evaluation of the safety and efficacy of the XIENCE V everolimus-eluting stent system in female patients: referral time for coronary intervention and 2-year clinical outcomes

SPIRIT Women is the first interventional trial dedicated exclusively to women, focusing on symptoms at presentation, referral time to coronary intervention and the safety and performance of the XIENCE V stent.

Safety of non-therapeutic atomoxetine exposures - a national poison data system study

AIMS This study's objective is to assess the safety of non-therapeutic atomoxetine exposures reported to the US National Poison Database System (NPDS). METHODS This is a retrospective database study of non-therapeutic single agent ingestions of atomoxetine in children and adults reported to the NPDS between 2002 and 2010. RESULTS A total of 20 032 atomoxetine exposures were reported during the study period, and 12 370 of these were single agent exposures. The median age was 9 years (interquartile range 3, 14), and 7380 were male (59.7%). Of the single agent exposures, 8813 (71.2%) were acute exposures, 3315 (26.8%) were acute-on-chronic, and 166 (1.3%) were chronic. In 10 608 (85.8%) cases, exposure was unintentional, in 1079 (8.7%) suicide attempts, and in 629 (5.1%) cases abuse. Of these cases, 3633 (29.4 %) were managed at health-care facilities. Acute-on-chronic exposure was associated with an increased risk of a suicidal reason for exposure compared with acute ingestions (odds ratio 1.44, 95% confidence interval 1.26-1.65). Most common clinical effects were drowsiness or lethargy (709 cases; 5.7%), tachycardia (555; 4.5%), and nausea (388; 3.1%). Major toxicity was observed in 21 cases (seizures in nine (42.9%), tachycardia in eight (38.1%), coma in six (28.6%), and ventricular dysrhythmia in one case (4.8%)). CONCLUSIONS Non-therapeutic atomoxetine exposures were largely safe, but seizures were rarely observed.

Automated low flow pump system for the treatment of refractory ascites: A multi-center safety and efficacy study

BACKGROUND & AIMS: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA. METHODS: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance. RESULTS: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p <0.01]. Cirrhosis-related adverse events decreased along follow-up. CONCLUSIONS: The automated pump seems an efficacious tool to move out ascites from the peritoneal cavity to the bladder. Its safety is still moderate, but a broad use in different countries will improve the surgical technique as well as the medical surveillance. A prospective randomized clinical trial vs. large volume paracentesis is underway to confirm these preliminary results.

Real-Time Multimodal Retinal Image Registration for a Computer Assisted Laser Photocoagulation System

An algorithm for the real-time registration of a retinal video sequence captured with a scanning digital ophthalmoscope (SDO) to a retinal composite image is presented. This method is designed for a computer-assisted retinal laser photocoagulation system to compensate for retinal motion and hence enhance the accuracy, speed, and patient safety of retinal laser treatments. The procedure combines intensity and feature-based registration techniques. For the registration of an individual frame, the translational frame-to-frame motion between preceding and current frame is detected by normalized cross correlation. Next, vessel points on the current video frame are identified and an initial transformation estimate is constructed from the calculated translation vector and the quadratic registration matrix of the previous frame. The vessel points are then iteratively matched to the segmented vessel centerline of the composite image to refine the initial transformation and register the video frame to the composite image. Criteria for image quality and algorithm convergence are introduced, which assess the exclusion of single frames from the registration process and enable a loss of tracking signal if necessary. The algorithm was successfully applied to ten different video sequences recorded from patients. It revealed an average accuracy of 2.47 ± 2.0 pixels (∼23.2 ± 18.8 μm) for 2764 evaluated video frames and demonstrated that it meets the clinical requirements.

Systematic review of medication safety assessment methods

Purpose The accuracy, efficiency, and efficacy of four commonly recommended medication safety assessment methodologies were systematically reviewed. Methods Medical literature databases were systematically searched for any comparative study conducted between January 2000 and October 2009 in which at least two of the four methodologies—incident report review, direct observation, chart review, and trigger tool—were compared with one another. Any study that compared two or more methodologies for quantitative accuracy (adequacy of the assessment of medication errors and adverse drug events) efficiency (effort and cost), and efficacy and that provided numerical data was included in the analysis. Results Twenty-eight studies were included in this review. Of these, 22 compared two of the methodologies, and 6 compared three methods. Direct observation identified the greatest number of reports of drug-related problems (DRPs), while incident report review identified the fewest. However, incident report review generally showed a higher specificity compared to the other methods and most effectively captured severe DRPs. In contrast, the sensitivity of incident report review was lower when compared with trigger tool. While trigger tool was the least labor-intensive of the four methodologies, incident report review appeared to be the least expensive, but only when linked with concomitant automated reporting systems and targeted follow-up. Conclusion All four medication safety assessment techniques—incident report review, chart review, direct observation, and trigger tool—have different strengths and weaknesses. Overlap between different methods in identifying DRPs is minimal. While trigger tool appeared to be the most effective and labor-efficient method, incident report review best identified high-severity DRPs.

Patient safety--who cares?

Medical errors and adverse events are a serious threat to patients worldwide. In recent years methodologically sound studies have demonstrated that interventions exist, can be implemented and can have sustainable, measurable positive effects on patient safety. Nonetheless, system-wide progress and adoption of safety practices is slow and evidence of improvements on the organisational and systems level is scarce and ambiguous. This paper reports on the Swiss Patient Safety Conference in 2011 and addresses emerging issues for patient safety and future challenges.

Review of the fibrinolytic system: comparison of different antifibrinolytics used during cardiopulmonary bypass

Antifibrinolytic agents are often used in different clinical situations, especially in cardiac surgery. During several years, aprotinin was the drug of choice because more than antifibrinolytic properties, aprotinin offers a direct effect on kallikrein and inflammatory pathways. In 2008, The Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) initiated a discussion about real risks associated with aprotinin administration. Tranexamic acid and epsilon-aminocaproic acid appear to be interesting alternatives in our daily practice. The exact mechanism of action, the pharmacokinetic parameters, the efficacy, and the safety profile need to be clarified for lysine analogs. In this review, the different antifibrinolytics will be described with a special interest into the route of work, and recent patents. Current studies about the pharmacokinetic and the pharmacodynamic profile will be described, and finally the benefit-to-risk balance in patients undergoing cardiac surgery with cardiopulmonary bypass will be discussed.

An early warning system for hypoglycemic/hyperglycemic events based on fusion of adaptive prediction models

Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia/hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy.

An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension

OBJECTIVES: To assess perioperative outcomes and blood pressure (BP) responses to an implantable carotid sinus baroreflex activating system being investigated for the treatment of resistant hypertension. METHODS: We report on the first seventeen patients enrolled in a multicenter study. Bilateral perivascular carotid sinus electrodes (CSL) and a pulse generator (IPG) are permanently implanted. Optimal placement of the CSL is determined by intraoperative BP responses to test activations. Acute BP responses were tested postoperatively and during the first four months of follow-up. RESULTS: Prior to implant, BP was 189.6+/-27.5/110.7+/-15.3 mmHg despite stable therapy (5.2+/-1.8 antihypertensive drugs). The mean procedure time was 202+/-43 minutes. No perioperative strokes or deaths occurred. System tests performed 1 or up to 3 days postoperatively resulted in significant (all p < or = 0.0001) mean maximum reduction, with standard deviations and 95% confidence limits for systolic BP, diastolic BP and heart rate of 28+/-22 (17, 39) mmHg, 16+/-11 (10, 22) mmHg and 8+/-4 (6, 11) BPM, respectively. Repeated testing during 3 months of therapeutic electrical activation demonstrated a durable response. CONCLUSIONS: These preliminary data suggest an acceptable safety of the procedure with a low rate of adverse events and support further clinical development of baroreflex activation as a new concept to treat resistant hypertension.

The Cardica C-Port System: clinical and angiographic evaluation of a new device for automated, compliant distal anastomoses in coronary artery bypass grafting surgery--a multicenter prospective clinical trial

OBJECTIVES: The C-Port System (Cardica, Inc, Redwood City, Calif) integrates in one tool all functions necessary to enable rapid automated distal coronary anastomoses. The goal of this prospective, nonrandomized, and multicenter study is to determine the safety and efficacy of this novel anastomotic system. METHODS: Five centers enrolled 133 patients awaiting elective coronary artery bypass grafting surgery. Outcome variables were intraoperative device performance, incidence of device-related adverse events, predischarge and 6-month angiographic graft patency, and 12-month clinical outcome. Independent core laboratories performed qualitative and quantitative angiographic and computed tomographic assessments. RESULTS: The C-Port was used to perform a vein-to-coronary anastomosis in 130 patients. Intraoperative conversion to a hand-sewn anastomosis was necessary in 11 patients because of inadequate target site preparation, inappropriate target vessel selection, or both. Inadequate blood flow related to poor runoff required conversion in 3 additional patients. Three patients died before discharge of causes unrelated to the device. At discharge, 113 patients had a C-Port implant in place, and 104 C-Port anastomoses were studied by means of angiography, resulting in 100 FitzGibbon A, 3 FitzGibbon B, and 1 FitzGibbon 0 classifications. At 6 months, one additional patient died of a device-unrelated cause, and 98 patients were evaluated by means of angiography (n = 89). Overall patency (FitzGibbon A) was 92.1%. Three C-Port anastomoses were rated FitzGibbon B, and 4 were rated FitzGibbon 0. At 12 months, 107 (98.2%) of 109 alive patients were followed up, without any reports of device-related major adverse cardiac events. CONCLUSIONS: The C-Port System allows for a rapid, reliable, and compliant distal anastomosis and yields favorable 6-month angiographic and 12-month clinical results when compared with published studies.

Genetic engineering and the world trade system

While the WTO agreements do not regulate the use of biotechnology per se, their rules can have a profound impact on the use of the technology for both commercial and non-commercial purposes. This book seeks to identify the challenges to international trade regulation that arise from biotechnology. The contributions examine whether existing international obligations of WTO Members are appropriate to deal with the issues arising for the use of biotechnology and whether there is a need for new international legal instruments, including a potential WTO Agreement on Biotechnology. They combine various perspectives on and topics relating to genetic engineering and trade, including human rights and gender; intellectual property rights; traditional knowledge and access and benefit sharing; food security, trade and agricultural production and food safety; and medical research, cloning and international trade.

Transferability of geoscientific information from various sources (study sites, underground rock laboratories, natural analogues) to support safety cases for radioactive waste repositories in argillaceous formations

In studies related to deep geological disposal of radioactive waste, it is current practice to transfer external information (e.g. from other sites, from underground rock laboratories or from natural analogues) to safety cases for specific projects. Transferable information most commonly includes parameters, investigation techniques, process understanding, conceptual models and high-level conclusions on system behaviour. Prior to transfer, the basis of transferability needs to be established. In argillaceous rocks, the most relevant common feature is the microstructure of the rocks, essentially determined by the properties of clay–minerals. Examples are shown from the Swiss and French programmes how transfer of information was handled and justified. These examples illustrate how transferability depends on the stage of development of a repository safety case and highlight the need for adequate system understanding at all sites involved to support the transfer.

Radiographic and safety details of vertebral body stenting: results from a multicenter chart review

BACKGROUND Up to one third of BKP treated cases shows no appreciable height restoration due to loss of both restored height and kyphotic realignment after balloon deflation. This shortcoming has called for an improved method that maintains the height and realignment reached by the fully inflated balloon until stabilization of the vertebral body by PMMA-based cementation. Restoration of the physiological vertebral body height for pain relief and for preventing further fractures of adjacent and distant vertebral bodies must be the main aim for such a method. A new vertebral body stenting system (VBS) stabilizes the vertebral body after balloon deflation until cementation. The radiographic and safety results of the first 100 cases where VBS was applied are presented. METHODS During the planning phase of an ongoing international multicenter RCT, radiographic, procedural and followup details were retrospectively transcribed from charts and xrays for developing and testing the case report forms. Radiographs were centrally assessed at the institution of the first/senior author. RESULTS 100 patients (62 with osteoporosis) with a total of 103 fractured vertebral bodies were treated with the VBS system. 49 were females with a mean age of 73.2 years; males were 66.7 years old. The mean preoperative anterior-middle-posterior heights were 20.3-17.6-28.0 mm, respectively. The mean local kyphotic angle was 13.1[degree sign]. The mean preoperative Beck Index (anterior edge height/posterior edge height) was 0.73, the mean alternative Beck Index (middle height/posterior edge height) was 0.63. The mean postoperative heights were restored to 24.5-24.6-30.4 mm, respectively. The mean local kyphotic angle was reduced to 8.9[degree sign]. The mean postoperative Beck Index was 0.81, the mean alternative one was 0.82. The overall extrusion rate was 29.1%, the symptomatic one was 1%. In the osteoporosis subgroup there were 23.8% extrusions. Within the three months followup interval there were 9% of adjacent and 4% of remote new fractures, all in the osteoporotic group. CONCLUSIONS VBS showed its strengths especially in realignment of crush and biconcave fractures. Given that fracture mobility is present, the realignment potential is sound and increases with the severity of preoperative vertebral body deformation.

Food-safety hazards in the pork chain in Nagaland, North East India: implications for human health.

Pork occupies an important place in the diet of the population of Nagaland, one of the North East Indian states. We carried out a pilot study along the pork meat production chain, from live animal to end consumer. The goal was to obtain information about the presence of selected food borne hazards in pork in order to assess the risk deriving from these hazards to the health of the local consumers and make recommendations for improving food safety. A secondary objective was to evaluate the utility of risk-based approaches to food safety in an informal food system. We investigated samples from pigs and pork sourced at slaughter in urban and rural environments, and at retail, to assess a selection of food-borne hazards. In addition, consumer exposure was characterized using information about hygiene and practices related to handling and preparing pork. A qualitative hazard characterization, exposure assessment and hazard characterization for three representative hazards or hazard proxies, namely Enterobacteriaceae, T. solium cysticercosis and antibiotic residues, is presented. Several important potential food-borne pathogens are reported for the first time including Listeria spp. and Brucella suis. This descriptive pilot study is the first risk-based assessment of food safety in Nagaland. We also characterise possible interventions to be addressed by policy makers, and supply data to inform future risk assessments.

Initial clinical experience with the Coherex FlatStent™ and FlatStent™ EF PFO closure system for in-tunnel PFO closure: Results of the Coherex-EU study

OBJECTIVE The Coherex-EU Study evaluated the safety and efficacy of PFO closure utilizing novel in-tunnel PFO closure devices. BACKGROUND Transcatheter closure of patent foramen ovale (PFO) followed the development of transcatheter closure devices designed to patch atrial septal defects (ASDs). The Coherex FlatStent™ and FlatStent™ EF devices were designed specifically to treat PFO anatomy. METHODS A total of 95 patients with a clinical indication for PFO closure were enrolled in a prospective, multicenter first in man study at six clinical sites. Thirty-six patients received the first-generation FlatStent study device, and 57 patients received the second-generation FlatStent EF study device, which was modified based on clinical experience during the first 38 cases. Two patients enrolled to receive the first generation did not receive a device. RESULTS At 6 months post-procedure, 45% (17/38) of the intention-to-treat (ITT) cohort receiving the first-generation FlatStent device had complete closure, 26% (10/38) had a trivial residual shunt, and 29% (11/38) had a moderate to large residual shunt. In the ITT cohort receiving the second-generation FlatStent EF device, 76% (43/57) had complete closure, 12% (7/57) had a trivial shunt, and 12% had a moderate to large shunt. Five major adverse events occurred, all without sequelae. CONCLUSION This initial study of the Coherex FlatStent/FlatStent EF PFO Closure System demonstrated the potential for in-tunnel PFO closure. The in-tunnel Coherex FlatStent EF may offer an alternative to septal repair devices for PFO closure in appropriately selected patients; however, further investigation will be necessary to establish the best use of this device.