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Competing Interests: Conflict-of-Interest Disclosures: Dr. Lewis-Hall discloses that she is a member of the board of directors for SpringWorks Therapeutics, Exact Sciences, and 1Life Healthcare; she is a consultant for PhRMA; and she is an advisor to SAAMA Technologies, Topography Health, and Catalio. Dr. Mammen discloses that his employer received funding from the US government to develop a COVID-19 vaccine; that his employer collaborated with BCG; that his employer’s COVID-19 vaccine has received emergency use authorization in the US, European Union, and other countries; and that Johnson & Johnson is a multi-faceted company that has pharmaceutical, consumer, and medical devices businesses. Dr. Narasimhan discloses that his employer is currently undertaking an internal drug discovery program toward a pan-Coronavirus Mpro inhibitor; that his employer has an option and license agreement to develop, manufacture and commercialize two Molecular Partners’ anti-COVID-19 DARPin® candidates; and that his employer has initial agreements with Pfizer-BioNTech and CureVac to manufacture their COVID-19 vaccines, and with Roche for the production of the API for Actemra/RoActemra®. Mr. Schechter discloses that his employer has performed COVID-19 diagnostic and antibody testing, supported COVID-19 clinical trials and study opportunities of potential treatments and vaccines with external sponsors, and worked with the U.S. Centers for Disease Control and Prevention to provide sequencing of samples of SARS-CoV-2 and that for these laboratory testing and drug development services, his employer has received reimbursement from various sources, including governmental agencies; and that in preparing the submitted work, Labcorp consulted with the American Clinical Laboratory Association, the national trade association representing leading clinical laboratories.

Background More than 600 000 coronary stents are implanted during percutaneous coronary interventions (PCIs) annually in the United States. Because no real-world surveillance system exists to monitor their long-term safety, claims data are often used for this purpose. The extent to which adverse events identified with claims data can be reasonably attributed to a specific medical device is uncertain. Methods and Results We used deterministic matching to link the NCDR (National Cardiovascular Data Registry) CathPCI Registry to Medicare fee-for-service claims for patients aged ≥65 years who underwent PCI with drug-eluting stents (DESs) between July 1, 2009 and December 31, 2013. We identified subsequent PCIs within 1 year of the index procedure in Medicare claims as potential safety events. We linked these subsequent PCIs back to the NCDR CathPCI Registry to ascertain how often the revascularization could be reasonably attributed to the same coronary artery as the index PCI (ie, target vessel revascularization). Of 415 306 DES placements in 368 194 patients, 33 174 repeat PCIs were identified in Medicare claims within 1 year. Of these, 28 632 (86.3%) could be linked back to the NCDR CathPCI Registry; 16 942 (51.1% of repeat PCIs) were target vessel revascularizations. Of these, 8544 (50.4%) were within a previously placed DES: 7652 for in-stent restenosis and 1341 for stent thrombosis. Of 16 176 patients with a claim for acute myocardial infarction in the follow-up period, 4446 (27.5%) were attributed to the same coronary artery in which the DES was implanted during the index PCI (ie, target vessel myocardial infarction). Of 24 288 patients whose death was identified in claims data, 278 (1.1%) were attributed to the same coronary artery in which the DES was implanted during the index PCI. Conclusions Most repeat PCIs following DES stent implantation identified in longitudinal claims data could be linked to real-world registry data, but only half could be reasonably attributed to the same coronary artery as the index procedure. Attribution among those with acute myocardial infarction or who died was even less frequent. Safety signals identified using claims data alone will require more in-depth examination to accurately assess stent safety.

There is a growing gap between available science and evidence and the ability of service providers to deliver high-quality care in a cost-effective way to the entire population. We believe that the chasm between knowledge and action is due to a lack of concerted effort among all organizations that deliver health care services across the life span of patients. Broad participation is needed and necessitates a far more explicit and concerted public-private partnership focused on large-scale transformation. In this context, the National Heart, Lung, and Blood Institute convened a panel made up of leaders of corporate health care entities, including academic health centers, and government agency representatives to inform contemporary strategic partnerships with health care companies. This article provides insights from the meeting on how to execute a transformative innovation research agenda that will foster improvements in health care service delivery by leveraging the translation of biomedical research evidence in real-world settings., (Copyright © 2018 World Heart Federation (Geneva). All rights reserved.)

The Yale University Open Data Access (YODA) Project has facilitated access to clinical trial data since 2013. The purpose of this article is to provide an overview of the Project, describe key decisions that were made when establishing data sharing policies, and suggest how our experience and the experiences of our first two data generator partners, Medtronic, Inc. and Johnson & Johnson, can be used to enhance other ongoing or future initiatives.

Purpose: To estimate medical device utilization needed to detect safety differences among implantable cardioverter defibrillators (ICDs) generator models and compare these estimates to utilization in practice., Methods: We conducted repeated sample size estimates to calculate the medical device utilization needed, systematically varying device-specific safety event rate ratios and significance levels while maintaining 80% power, testing 3 average adverse event rates (3.9, 6.1, and 12.6 events per 100 person-years) estimated from the American College of Cardiology's 2006 to 2010 National Cardiovascular Data Registry of ICDs. We then compared with actual medical device utilization., Results: At significance level 0.05 and 80% power, 34% or fewer ICD models accrued sufficient utilization in practice to detect safety differences for rate ratios <1.15 and an average event rate of 12.6 events per 100 person-years. For average event rates of 3.9 and 12.6 events per 100 person-years, 30% and 50% of ICD models, respectively, accrued sufficient utilization for a rate ratio of 1.25, whereas 52% and 67% for a rate ratio of 1.50. Because actual ICD utilization was not uniformly distributed across ICD models, the proportion of individuals receiving any ICD that accrued sufficient utilization in practice was 0% to 21%, 32% to 70%, and 67% to 84% for rate ratios of 1.05, 1.15, and 1.25, respectively, for the range of 3 average adverse event rates., Conclusions: Small safety differences among ICD generator models are unlikely to be detected through routine surveillance given current ICD utilization in practice, but large safety differences can be detected for most patients at anticipated average adverse event rates., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Machine learning methods may complement traditional analytic methods for medical device surveillance., Methods and Results: Using data from the National Cardiovascular Data Registry for implantable cardioverter-defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%-20.9%; nonfatal ICD-related adverse events, 19.3%-26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%-37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, k =0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, k =-0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, k =-0.042)., Conclusion: Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance., Competing Interests: Disclosure JSR receives support from the US FDA as part of the Centers for Excellence in Regulatory Science and Innovation program and from the Laura and John Arnold Foundation to support the Collaboration on Research Integrity and Transparency at Yale. JSR, NRD, HMK, and GMG receive research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing. JSR and GMG receive research support from the Blue Cross Blue Shield Association to better understand medical technology evidence generation. JSR, JPC, NRD, SXL, SLTM, IR, HMK, and CSP work under contract to the Centers for Medicare and Medicaid Services to develop and maintain performance measures that are used for public reporting. JVF receives salary support from the American College of Cardiology NCDR, and modest consulting fees from Janssen Pharmaceuticals. RK is an employee of Medtronic Inc. DMD is an employee of the FDA. HMK chairs a cardiac scientific advisory board for United Health, is a participant/participant representative of the IBM Watson Health Life Sciences Board, is a member of the Advisory Board for Element Science and the Physician Advisory Board for Aetna, and is the founder of Hugo, a personal health-information platform. The authors report no other conflicts of interest in this work.

Current research in prosthetic device design aims to mimic natural movements using a feedback system that connects to the patient's own nerves to control the device. The first step in using neurons to control motion is to make and maintain contact between neurons and the feedback sensors. Therefore, the goal of this project was to determine if changes in electrode resistance could be detected when a neuron extended a neurite to contact a sensor. Dorsal root ganglia (DRG) were harvested from chick embryos and cultured on a collagen-coated carbon nanotube microelectrode array for two days. The DRG were seeded along one side of the array so the processes extended across the array, contacting about half of the electrodes. Electrode resistance was measured both prior to culture and after the two day culture period. Phase contrast images of the microelectrode array were taken after two days to visually determine which electrodes were in contact with one or more DRG neurite or tissue. Electrodes in contact with DRG neurites had an average change in resistance of 0.15 MΩ compared with the electrodes without DRG neurites. Using this method, we determined that resistance values can be used as a criterion for identifying electrodes in contact with a DRG neurite. These data are the foundation for future development of an autonomous feedback resistance measurement system to continuously monitor DRG neurite outgrowth at specific spatial locations.

Modular, bioactive, macroporous scaffolds were formed by crosslinking poly(ethylene glycol) (PEG) microspheres around living cells. Hydrogel microspheres were produced from reactive PEG derivatives in aqueous sodium sulfate solutions without the use of surfactants or copolymers. Microspheres were formed following thermally induced phase separation if the gel point was reached prior to extensive coarsening of the PEG-rich domains. Three types of PEG microspheres with different functionalities were used to form scaffolds: one type provided mechanical support, the second type provided controlled delivery of the angiogenesis-promoting molecule, sphingosine 1-phosphate (S1P) and the third type served as a slowly dissolving non-cytotoxic porogen. Scaffolds were formed by centrifuging microspheres in the presence of HepG2 hepatoma cells, resulting in a homogenous distribution of cells. During overnight incubation at 37 degrees C, the microspheres reacted with serum proteins in cell culture medium to stabilize the scaffolds. Within 2 days in culture, macropores formed due to the dissolution of the porogenic PEG microspheres, without affecting cell viability. Gradients in porosity were produced by varying the buoyancy of the porogenic microspheres. Conjugated RGD cell adhesion peptides and the delivery of S1P promoted endothelial cell infiltration through macropores in the scaffolds. The scaffolds presented here differ from previous hydrogel scaffolds in that: (i) cells are not encapsulated in hydrogel; (ii) macropores form in the presence of cells; and (iii) scaffold properties are controlled by the modular assembly of different microspheres that perform distinct functions.

Context: Holmium laser enucleation of the prostate (HoLEP) and 532-nm laser vaporisation of the prostate (with potassium titanyl phosphate [KTP] or lithium borate [LBO]) are promising alternatives to transurethral resection of the prostate (TURP) and open prostatectomy (OP)., Objective: To assess safety, efficacy, and durability by analysing the most recent evidence of both techniques, aiming to identify advantages, pitfalls, and unresolved issues., Evidence Acquisition: A Medline search of recently published data (2006-2008) regarding both techniques over the last 2 yr (January 2006 to September 2008) was performed using evidence obtained from randomised trials (level of evidence: 1b), well-designed controlled studies without randomisation (level of evidence: 2a), individual cohort studies (level of evidence: 2b), individual case control studies (level of evidence: 3), and case series (level of evidence: 4)., Evidence Synthesis: In the last 2 yr, several case-control and cohort studies have demonstrated reproducibility, safety, and efficacy of HoLEP and 80-W KTP laser vaporisation. Four randomised controlled trials (RCTs) were available for HoLEP, two compared with TURP and two compared with OP, with follow-up >24 mo. Results confirmed general efficacy and durability of HoLEP, as compared with both standard techniques. Only two RCTs were available comparing KTP laser vaporisation with TURP with short-term follow-up, and only one RCT was available comparing KTP laser vaporisation with OP. The results confirmed the overall low perioperative morbidity of KTP laser vaporisation, although efficacy was comparable to TURP in the short term, despite a higher reoperation rate., Conclusions: Although they are at different points of maturation, KTP or LBO laser vaporisation and HoLEP are promising alternatives to both TURP and OP. Sufficient data proves HoLEP's durability for most prostate sizes at long-term follow-up; KTP laser vaporisation needs further evaluation to define the reoperation rate. Increasing the number of quality prospective RCTs with adequate follow-up is mandatory to tailor each technique to the right patient.

Poly(ethylene glycol) (PEG) hydrogels have become a popular material for biomedical applications because of their versatility in use and design. As these gels are readily crosslinked under UV, microfabrication techniques have been investigated to manufacture complex three dimensional structures to better mimic the in vivo environment. This work investigated whether a layering technique to fabricate gels offered sufficient strength between the layers to perform similarly in mechanical testing to unlayered gels. Two mechanical tests were performed: tensile tests and peel tests. The tensile tests, which examined sample gels whose test sections were crosslinked for different durations, demonstrated no statistical differences in elastic modulus between sample and control gels. As expected, a statistical increase in the elastic modulus was found with increased PEG concentration. Comparison of the yield stress between samples and controls illustrated differences with total crosslinking duration, which may be due to the decreased molecular weight of the chains with decreased crosslinking time. In peel tests, no statistical differences of maximum peel force were found between samples and controls. However, an increase in the maximum peel force was found with increasing concentration of PEG. Overall, this study demonstrates that the layering process described for the PEG gels has minimal impact on the tested mechanical properties of the system. As mechanical properties are critical to the design of tissue engineered devices, these results demonstrate that this fabrication method may be appropriate for further study as a scaffold for complex cellular systems.

Large ruminants respond to changing plant phenology during winter by decreasing voluntary food intake, increasing gut passage time and utilizing body fat reserves. It is uncertain, however, how other large mammals with a non-ruminant digestive physiology cope with winter forage conditions. Therefore, we investigated seasonality of energy intake in a large herbivorous wild mammal, the Przewalski horse (Equus ferus przewalskii). Throughout all seasons we used the n-alkane method to measure daily dry matter intake (DMI), diet composition and digestion, and determined an index of gut passage time in horses living under close to natural conditions. DMI correlated positively with its content of crude protein and nitrogen-free extract. Independent of these effects, DMI further varied seasonally with a peak in autumn and a nadir in late winter. Fluctuations of DMI corresponded to the annual change in body condition, which decreased during winter while energy reserves were depleted, and increased during the fattening period. Gut passage time varied in the course of the year and was longer during winter when the diet was high in crude fibre. Nevertheless, changes in gut passage time occurred rather independently of changes in forage composition and DMI, suggesting endogenous control for timely adaption of the digestive strategy to meet predictable changes in forage quality.

Many large mammals show pronounced seasonal fluctuations of metabolic rate (MR). It has been argued, based on studies in ruminants, that this variation merely results from different levels of locomotor activity (LA), and heat increment of feeding (HI). However, a recent study in red deer (Cervus elaphus) identified a previously unknown mechanism in ungulates--nocturnal hypometabolism--that contributed significantly to reduced energy expenditure, mainly during late winter. The relative contribution of these different mechanisms to seasonal adjustments of MR is still unknown, however. Therefore, in the study presented here we quantified for the first time the independent contribution of thermoregulation, LA and HI to heart rate (f(H)) as a measure of MR in a free-roaming large ungulate, the Przewalski horse or Takhi (Equus ferus przewalskii Poljakow). f(H) varied periodically throughout the year with a twofold increase from a mean of 44 beats min(-1) during December and January to a spring peak of 89 beats min(-1) at the beginning of May. LA increased from 23% per day during December and January to a mean level of 53% per day during May, and declined again thereafter. Daily mean subcutaneous body temperature (T(s)) declined continuously during winter and reached a nadir at the beginning of April (annual range was 5.8 degrees C), well after the annual low of air temperature and LA. Lower T(s) during winter contributed considerably to the reduction in f(H). In addition to thermoregulation, f(H) was affected by reproduction, LA, HI and unexplained seasonal variation, presumably reflecting to some degree changes in organ mass. The observed phase relations of seasonal changes indicate that energy expenditure was not a consequence of energy uptake but is under endogenous control, preparing the organism well in advance of seasonal energetic demands.

Objectives: To update the complications of transurethral resection of the prostate (TURP), including management and prevention based on technological evolution., Methods: Based on a MEDLINE search from 1989 to 2005, the 2003 results of quality management of Baden-Württemberg, and long-term personal experience at three German centers, the incidence of complications after TURP was analyzed for three subsequent periods: early (1979-1994); intermediate (1994-1999); and recent (2000-2005) with recommendations for management and prevention., Results: Technological improvements such as microprocessor-controlled units, better armamentarium such as video TUR, and training helped to reduce perioperative complications (recent vs. early) such as transfusion rate (0.4% vs. 7.1%), TUR syndrome (0.0% vs. 1.1%), clot retention (2% vs. 5%), and urinary tract infection (1.7% vs. 8.2%). Urinary retention (3% vs. 9%) is generally attributed to primary detrusor failure rather than to incomplete resection. Early urge incontinence occurs in up to 30-40% of patients; however, late iatrogenic stress incontinence is rare (<0.5%). Despite an increasing age (55% of patients are older than 70), the associated morbidity of TURP maintained at a low level (<1%) with a mortality rate of 0-0.25%. The major late complications are urethral strictures (2.2-9.8%) and bladder neck contractures (0.3-9.2%). The retreatment rate range is 3-14.5% after five years., Conclusions: TURP still represents the gold standard for managing benign prostatic hyperplasia with decreasing complication rates. Technological alternatives such as bipolar and laser treatments may further minimize the risks of this technically difficult procedure.

Compounding pharmacists often find themselves on the cutting edge of medical treatment. Prescribers and patients look to compounders for ideas on novel treatments or for more information on standard treatments. Even with the vast supply of information available on the Internet, finding reliable data from trustworhty websites has become increasingly difficult. All too often, an Internet search on a specific medical topic may turn up no dependable material. For complete, science based information about medical topics, the National Library of Medicine's database of medical literature, MEDLINE, is an essential tool for the compounding pharmacist.

Background: Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown., Methods: CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of > or = 60% with a 20 mm Hg systolic pressure gradient or > or = 80% with no gradient necessary and (2) systolic hypertension of > or = 155 mm Hg on > or = 2 antihypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate., Conclusions: CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis.

Background: A preliminary report has been interpreted to suggest that gum chewing reduces duration of postcolectomy ileus., Study Design: We rigorously tested this hypothesis in a prospective, randomized, placebo-controlled study. Patients undergoing open colectomy (n = 66) were randomized to receive 1 of 3 postoperative regimens beginning on postoperative day 1: sips (control, n = 21); sips and accupressure wrist bracelet (placebo, n = 23); and sips and gum chewing (treatment, n = 22). Patients were unaware of which regimen constituted placebo or treatment; end points were assessed by blinded investigators. Power was set a priori at 85% to detect a 0.75-day difference in time to first postoperative passage of flatus between placebo and treatment groups. Groups were compared using the log-rank test., Results: Groups were equivalent with respect to demographic and surgical characteristics. Median times to first postoperative passage of flatus were as follows: sips, 67 hours; bracelet and sips, 72 hours; gum and sips, 60 hours (p = 0.384). There were no significant differences in time to passage of first bowel movement, time until patients were ready for discharge, or time until actual discharge among the three groups. Inpatient and 30-day followup demonstrated no difference in frequency or distribution of postoperative complications., Conclusions: In contrast to findings of a preliminary study, our clinical trial suggests that gum chewing, although safe, does not reduce duration of postcolectomy ileus.

Purpose: The management of diabetic patients with restenosis after percutaneous coronary intervention remains a significant challenge. Diabetic patients remain at significant risk of restenosis despite stent implantation. This retrospective analysis was performed to determine the extent to which vascular brachytherapy improves late clinical and angiographic outcomes in diabetic patients compared to conventional therapy and compared to patients' nondiabetic counterparts., Methods: Pooled data from two studies (START [Stents and Radiation Trial] and START-40 trials) of patients (204 diabetic, 477 nondiabetic) receiving vascular brachytherapy (VBT) with a (90)Sr/(90)Y source after conventional percutaneous coronary intervention for in-stent restenosis comprise the study population. The radiation delivery system used in both studies was the Beta-Cath system. The prescribed dose at 2 mm from the centerline of the source axis was 18.4 Gy or 23 Gy, depending on vessel diameter. The reference vessel diameter, minimal lumen diameter, and percent diameter stenosis were measured before the intervention, at the conclusion of the procedure, and at the 8-month follow-up examination. The Breslow-Day test was used to formally assess the similarity of treatment effect between diabetic and nondiabetic patients., Results: Target lesion and target vessel revascularization rates and angiographic restenosis rates in diabetic and nondiabetic patients treated with beta radiation or placebo were analyzed. Diabetic patients were more likely to have longer and more complex coronary lesions. In-hospital outcomes in diabetic and nondiabetic patients were similar, irrespective of treatment status. At 8 months, patients treated with beta radiation exhibited less target lesion revascularization (diabetic: 10.9% vs. 22.7%, p = 0.02; nondiabetic: 12.8% vs. 22.3%, p = 0.007) and less target vessel revascularization (diabetic: 14.7% vs. 25.3%, p = 0.06; nondiabetic: 16.6% vs. 23.6%, p = 0.06) compared to placebo. In-stent binary angiographic restenosis was lower in irradiated patients (diabetic: 19.4% vs. 37.3% for placebo, p = 0.01; nondiabetic: 12.9% vs. 43% for placebo, p < 0.001). However, restenosis beyond the stent site reduced the impact of VBT, regardless of diabetic status. The magnitude of the treatment effect for target lesion and target vessel revascularization rates was similar between diabetic and nondiabetic patients., Conclusions: Previously published institutional experiences have suggested that diabetic patients benefit from the use of VBT in the management of in-stent restenosis. This analysis now provides direct evidence to support the role of beta radiation VBT in this patient population. Diabetic patients undergoing this therapy are just as likely to benefit from it as their nondiabetic counterparts.

Background: Percutaneous coronary interventions (PCIs) in saphenous vein grafts (SVGs) with thrombus have a high frequency of distal embolization. Acolysis (therapeutic ultrasound) can break up thrombus in vitro in animal models and humans. Whether this is beneficial during percutaneous SVG interventions is unknown., Methods and Results: We performed a trial of coronary ultrasound thrombolysis in which patients with an acute coronary syndrome undergoing PCI in SVGs were randomly assigned to receive acolysis or abciximab. The primary end point was a successful procedure, defined as final luminal diameter stenosis 30% or less with Thrombolysis In Myocardial Infarction grade 3 flow and freedom from major adverse cardiac events (composite of death, Q-wave, and non-Q-wave myocardial infarction [MI], emergency bypass procedure, disabling stroke, and target lesion revascularization). Of 181 enrolled, 92 received acolysis and 89 abciximab. Angiographic procedural success was achieved in 63% of acolysis patients and 82% of abciximab patients (P=0.008). Incidence of major adverse cardiac events at 30 days was 25% with acolysis and 12% with abciximab (P=0.036), attributable mainly to a greater frequency of non-Q-wave MI with acolysis (19.6% versus 7.9%, P=0.03). The incidence of Q-wave MI was also higher with acolysis (5.4% versus 2.2%, P=nonsignificant). The primary end point was achieved in 53.8% of acolysis patients and 73.1% of abciximab patients (P=0.014)., Conclusions: Use of therapeutic ultrasound in vein graft lesions in patients with acute coronary syndrome had poor angiographic outcome and increased the incidence of acute ischemic complications.

We present the development of a flight simulator that allows the user to interact in a created environment by means of virtual reality devices. This environment simulates the sight of a pilot in an airplane cockpit. The environment is projected in a helmet visor and allows the pilot to see inside as well as outside the cockpit. The movement of the airplane is independent of the movement of the pilot's head, which means that the airplane might travel in one direction while the pilot is looking at a 30 degrees angle with respect to the traveled direction. In this environment, the pilot will be able to take off, fly, and land the airplane. So far, the objects in the environment are geometrical figures. This is an ongoing project, and only partial results are available now.

Indinavir sulfate is a protease inhibitor used of the treatment of primary HIV infection either as monotherapy or as part of antiretroviral treatment schemes. Approximately 10% of all patients develop urolithiasis with radiolucent stones consisting of indinavir. We present our results of the treatment in 11 HIV positive patients (9 men, 2 women), who developed Indinavir lithiasis after 5-8 months of antiretroviral therapy. Following the initial procedures (spasmoanalgetic drugs, ureteroscopy, double J-stent or nephrostomy), the patients were further treated by increasing diuresis and urinary acidification. All the patients responded well to the treatment, the obstruction was releieved and their renal function was restored to normal.

Current stent delivery systems make primary stenting (stent placement without predilatation) possible, but few controlled trials have been performed to evaluate the success, safety, cost saving, and potential benefit of this approach in reducing late restenosis. The Comparison of PRE-Dilatation Versus Direct Stenting In Coronary Treatment using the Medtronic AVE S670 Coronary Stent System trial was a 399-patient study comparing results with the Medtronic-AVE S670 stent to objective performance criteria based on prior approved stents, with subrandomization to direct stenting versus stenting after balloon predilatation. Overall, results with the S670 stent showed excellent success and safety, with delivery success of 99%, a 14-day adverse event rate of 6.8% (including 6.5% non-Q-wave myocardial infarction), and favorable angiographic (20%) and clinical (12%) restenosis rates. Direct stenting was successful in 92% of cases, with a 99.5% secondary success rate including additional pretreatment of initially unsuccessful direct-stenting attempts, and no increase in complications. There were modest ( approximately 10%) savings in fluoroscopy time, contrast use, and a decrease in angioplasty balloon use (0.6 vs 1.3 balloons/case), but no reduction in clinical or angiographic restenosis. Patients treated later in the study, with a device that had less balloon extension beyond the edges of the stent, had slightly lower angiographic restenosis rates (19% vs 23%). In conclusion, the S670 stent showed excellent overall performance. Although direct stenting was safe and highly successful, it offered only modest cost savings, and no reduction in late restenosis compared with stenting after predilatation.

In this randomized, prospective, multicenter trial (n = 661) of patients with de novo or restenotic coronary lesions, 330 patients received the MicroStent(R) II (MSII), and 331 received the Palmaz-Schatz (PS) stent. The short-term procedural success rates were 94.4% and 95.7%, respectively (P = 0.47). The 30-day cumulative incidence of major adverse events [death, myocardial infarction, CVA, target lesion revascularization (TLR)] was 6.4% for the MSII and 4.5% for the PS stent (P = 0.31). The in-stent binary restenosis rate at 6 months was 25.2% for the MSII and 22.1% for the PS stent (P = 0.636). Using Kaplan-Meier estimates, the incidence of clinically driven TLR was 8.9% for the MSII and 9.2% for the PS stent at 180 days; at 270 days, it was 12.8% and 12.1%, respectively (P = 0.83). MSII and the PS stents were comparable with respect to short-term procedural success, complications, and late clinical and angiographic restenosis.

A new martensitic nitinol stent with improved flexibility and radiopacity was tested to evaluate whether these differences improve initial or long-term outcome. Patients who underwent percutaneous revascularization of a discrete native coronary lesion were randomly assigned to the new stent (PARAGON, n = 349) or to the first-generation Palmaz-Schatz (PS) stent (n = 339). The primary end point was target vessel failure at 6 months (a composite of cardiac or noncardiac death, any infarction in the distribution of the treated vessel, or clinically indicated target vessel revascularization). Secondary end points were, among others, device and procedural success and angiographic restenosis. Mean age was 62 years; diabetes was present in 21% of patients, prior bypass surgery in 6%, and recent infarction in 22% (p = NS for comparison between the 2 randomized arms). The PARAGON stent group had smaller reference vessels (2.97 vs 3.05 mm, p = 0.05), more prior restenosis (8.0% vs 4.5%, p = 0.07), and a longer average stent length (21.3 vs 19.4 mm, p < 0.05). Device success was significantly higher in the PARAGON arm (99.1% vs 94.3%, p < 0.05). Death and infarction at 6-month follow-up were infrequent in both groups. There was no significant difference in death (2.0% vs 1.2%, p = 0.546), but a higher rate of infarction for the PARAGON cohort (9.2% vs 4.7%, p = 0.025). Although target vessel failure (20.3% vs 12.4%, p = 0.005) and target lesion revascularization (12.0% vs 5.9%, p = 0.005) were higher in the PARAGON group, there was no significant difference in 6-month follow-up in in-stent minimal lumen diameter or in the rate of binary angiographic restenosis. Both PARAGON and PS stents are safe and associated with infrequent adverse events. The PARAGON stent can be delivered more frequently than the first-generation PS stent. Although there was no significant difference in in-stent minimal lumen diameter or the frequency of angiographic restenosis, clinical restenosis was more frequent in the PARAGON group.