High Crossover Rate Research Articles

Prevalence and Impact of Treatment Crossover in Cardiac Surgery Randomized Trials: A Meta-Epidemiologic Study.

BackgroundCrossover dilutes treatment effect and reduces statistical power of intention‐to‐treat analysis. We examined incidence and impact on cardiac surgery randomized controlled trial (RCT) outcomes of crossover from experimental to control interventions, or vice versa.Methods and Results MEDLINE, EMBASE, and Cochrane Library were searched, and RCTs (≥100 patients) comparing ≥2 adult cardiac surgical interventions were included. Crossover from the initial treatment assignment and relative risks (RRs) for each trial's primary end point and mortality at longest available follow‐up were extracted. All RRs were calculated as >1 favored control group and <1 favored experimental arm. Primary outcome was the effect estimate for primary end point of each RCT, and secondary outcome was all‐cause mortality; both were appraised as RR at the longest follow‐up available. Sixty articles reporting on 47 RCTs (25 440 patients) were identified. Median crossover rate from experimental to control group was 7.0% (first quartile, 2.0%; third quartile, 9.7%), whereas from control to experimental group, the rate was 1.3% (first quartile, 0%; third quartile, 3.6%). RRs for primary end point and mortality were higher in RCTs with higher crossover rate from experimental to control group (RR, 1.01 [95% CI, 0.94–1.07] versus RR, 0.80 [95% CI, 0.66–0.97] and RR, 1.02 [95% CI, 0.95–1.11] versus RR, 0.94 [95% CI, 0.82–1.07], respectively). Crossover from control to experimental group did not alter effect estimates for primary end point or mortality (RR, 0.82 [95% CI, 0.63–1.05] versus RR, 0.95 [95% CI, 0.86–1.04] and RR, 0.88 [95% CI, 0.73–1.07] versus RR, 1.02 [95% CI, 0.95–1.09], respectively).ConclusionsCrossover from experimental to control group is associated with outcomes of cardiac surgery RCTs. Crossover should be minimized at designing stage and carefully appraised after study completion.

Dexamethasone Therapy in Symptomatic Chronic Subdural Hematoma (DECSA-R): A Retrospective Evaluation of Initial Corticosteroid Therapy versus Primary Surgery.

Worldwide, different strategies are being applied for symptomatic chronic subdural hematoma (CSDH). The aim of this study was to evaluate the efficacy of two treatment strategies for symptomatic CSDH: initial dexamethasone (DXM) therapy versus primary surgery by burr hole craniostomy (BHC). We retrospectively collected data for 120 symptomatic CSDH patients in two neurotrauma centers between 2014 and 2016, each with their own treatment protocol. Sixty patients received primary BHC (center A), and another 60 initial DXM therapy (center B). Primary outcome was evaluated by dichotomized modified Rankin Scale (mRS) score (0-3 and 4-6) and Markwalder Grading Scale (MGS) score at 3 months. Secondary outcomes were additional interventions, CSDH recurrence, mortality, complications, and duration of hospital stay. Baseline characteristics were similar in both groups. At 3 months, a favorable mRS score (0-3) was observed in 70% and 76% of patients in cohort A and B, respectively (odds ratio [OR] 0.77, 95% CI 0.30-1.98; p = 0.59). A favorable MGS score (0-1) was observed in 96% of patients in both groups (OR 0.98, 95% CI 0.45-2.15; p = 0.95). CSDH recurrence was 12% in cohort A and 22% in cohort B (p = 0.15). Mortality was 10% in both cohorts. In cohort B, additional surgery was performed in 83% at a median of 6 days, and significantly more patients had complications (55% vs. 35%, p = 0.02), a prolonged hospitalization (10 vs. 5 days; p = 0.02), and one or more follow-up cranial CT's (85% vs. 48%; p < 0.001). To achieve a favorable clinical outcome, initial DXM therapy was associated with a high rate of crossover to surgery, significantly longer overall hospital stay, and more complications compared with primary surgery.

High frequency of double crossover recombination facilitates genome engineering in Pseudomonas aeruginosa PA14 and clone C strains

Pseudomonas aeruginosa is a key opportunistic human pathogen. An established procedure to replace a target gene is two-step allelic exchange, i.e. selection of single crossover at homologous sequences and subsequent counter selection to induce double crossover for excision of the suicide vector. In this study, we found that certain strains of P. aeruginosa display a high rate of instant double crossover upon introduction of a suicide vector containing an antibiotic resistance cassette flanked by adjacent sequences for gene replacement, making the counter selection step to achieve the second crossover superfluous. Assessment of a limited panel of target genes commonly showed negligible double crossover with a frequency <20 % in the genetic reference strain PAO1, whereas a high double crossover frequency of >70 % was observed for PA14 and clone C strains. Consequently, for certain P. aeruginosa strains replacement of an ORF by a antibiotic resistance cassette can be shortened by directly selecting for double crossover recombination.

On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial

The His-SYNC pilot trial was the first randomized comparison between His bundle pacing in lieu of a left ventricular lead for cardiac resynchronization therapy (His-CRT) and biventricular pacing (BiV-CRT), but was limited by high rates of crossover. To evaluate the results of the His-SYNC pilot trial utilizing treatment-received (TR) and per-protocol (PP) analyses. The His-SYNC pilot was a multicenter, prospective, single-blinded, randomized, controlled trial comparing His-CRT vs BiV-CRT in patients meeting standard indications for CRT (eg, NYHA II-IV patients with QRS >120 ms). Crossovers were required based on prespecified criteria. The primary endpoints analyzed included improvement in QRS duration, left ventricular ejection fraction (LVEF), and freedom from cardiovascular (CV) hospitalization and mortality. Among 41 patients enrolled (aged 64 ± 13 years, 38% female, LVEF 28%, QRS 168 ± 18 ms), 21 were randomized to His-CRT and 20 to BiV-CRT. Crossover occurred in 48% of His-CRT and 26% of BiV-CRT. The most common reason for crossover from His-CRT was inability to correct QRS owing to nonspecific intraventricular conduction delay (n = 5). Patients treated with His-CRT demonstrated greater QRS narrowing compared to BiV (125 ± 22 ms vs 164 ± 25 ms [TR], P < .001;124 ± 19 ms vs 162 ± 24 ms [PP], P < .001). A trend toward higher echocardiographic response wasalso observed (80 vs 57% [TR], P = .14; 91% vs 54% [PP], P= .078). No significant differences in CV hospitalization or mortality were observed. Patients receiving His-CRT on-treatment demonstrated superior electrical resynchronization and a trend toward higher echocardiographic response than BiV-CRT. Larger prospective studies may be justifiable with refinements in patient selection and implantation techniques to minimize crossovers.

(Invited) Fuel Cells Fueled By Sustainable Liquid Fuels

The Advanced Research Projects Agency (ARPA-E) funds high risk, high reward transformational research to reduce energy related emissions, reduce imports of energy from foreign sources, improve energy efficiency across all economic sectors, and ensure US technological lead in advanced energy technologies, including electrochemical technologies for energy transformation and storage for distributed, grid scale and automotive applications. Recently hydrogen PEM fuel cells (FC) made great progress in performance, durability and cost that reflected in the emerging of multiple commercial vehicles powered by FCs. However their market penetration is hampered mostly by the absence of hydrogen infrastructure including transportation and storage, and high cost of its implementation. On the other side, carbon-neutral liquid fuels (CNLFs) have energy density higher than of liquid hydrogen, better safety, low footprint and cost of transportation and storage. Easily liquefied ammonia and dimethyl ether as well as more traditional lower alcohols are the most promising CNLFs. They can be used with or without internal reforming in direct liquid fuel cells (DLFCs) or as a hydrogen carrier for PEM fuel cells thus allowing the use of existing liquid fuels infrastructure. History of DLFCs started in 1960s from first GE attempts to use diesel fuel in a FC and continued with development of direct methanol fuel cells (DMFCs). In spite intensive research, the latter found very limited application because of low efficiency and power density. As conventional low temperature PEMs and AEMs content a lot of water to support high H+ or OH- conductivity, high crossover rate of most CNLFs is inevitable and leads to low cell voltage and energy efficiency. In addition, traditional platinum group metal catalysts are easily poisoned by CNLFs or by intermediate oxidation products. Therefore, to realize high energy density of CNLFs and provide high FC power density, it is necessary to increase operation temperature of DLFCs, develop more active and less expensive electrocatalysts, develop selective ion conducting membranes and design electrodes and cells for using liquid fuels. Recent advances in the development of novel DLFCs that is being funded by ARPA-E via REFUEL and OPEN 2018 programs will be presented. Possible future ARPA-E program targeting the use of such fuel cells for transportation (in hybrids, range extenders, APUs for aviation and ground transportation) will be also discussed.

A 105\xa0kb interstitial insertion in the Xq27.1 palindrome from pseudoautosomal region PAR1 causes a novel X-linked recessive compound phenotype

BackgroundGenomic disorders present a wide spectrum of unrelated clinical entities that result from genomic rearrangements. Interstitial insertions requiring three points of breakage are rare genomic rearrangement events. The pseudoautosomal region PAR1, homologous between the Xp22 and Yp11 loci, has a high crossover and recombination rate. A 180 bp human-specific palindrome at Xq27.1 appears to be a hotspot for genomic rearrangement, and several genetic diseases/phenotypes associated with Xq27.1 palindrome-driven genomic rearrangement have been reported. Here we investigate a Chinese family with an extremely rare X-linked compound phenotype that remains undiagnosed. We attempt to identify underlying genetic causes by an integrated genome analysis.MethodsA five-generation Chinese family with a distinct X-linked compound phenotype was recruited. Peripheral blood samples were collected and genomic DNA was extracted. Systemic physical and lab examinations were performed to evaluate the phenotype. An integrated genomic analysis was performed. Genotyping and linkage analysis were conducted to map the disease locus. Whole exome sequencing was performed to detect mutations in coding region. Whole genome sequencing was used to detect single nucleotide variations, small insertions, small deletions, or large structural variations. Copy number variation scanning was also performed on the genome scale. Interstitial insertion was confirmed by gap-PCR and quantitative-PCR, and breakpoint junctions were identified by genome walking and direct sequencing. Expression of products of genes nearby to the Xq27.1 palindrome was measured in peripheral blood from patients and unrelated controls via quantitative-PCR.ResultsThe identified compound phenotype of genu varum, cubitus valgus, and everted lipsdoes not match any reported clinical entities. Fine mapping and linkage analysis identified a candidate interval of 4 Mb on the X chromosome. No potential coding region mutations were detected. A 105 kb genomic fragment of PAR1 containing no coding genes was duplicated and inserted into the center of a human-specific palindrome at Xq27.1. The interstitial insertion fully cosegregated with the family phenotype. No expression of FGF13 or SOX3 was detected in peripheral blood from the proband or unrelated controls.ConclusionWe report an extremely rare phenotype associated with an infrequently-seen genomic rearrangement. The novel compound phenotype is X-linked and characterized by genu varum, cubitus valgus, and everted lips. A 105 kb interstitial insertion of a PAR1 fragment into the Xq27.1 palindrome is associated with the phenotype in the family. The present study identified the underlying genetic cause of the phenotype, expanding the spectrum of known human-specific Xq27.1 palindrome insertion events and associated phenotypes.

Maturing institutional experience with the transradial approach for diagnostic cerebral arteriography: overcoming the learning curve

BackgroundDespite growing interest in the transradial approach for neurovascular procedures, prospective data about the learning curve for neurointerventionalists adopting this approach are limited.MethodsA subsequent prospective series of 50 consecutive right...

Intraosseous Basivertebral Nerve Ablation for the Treatment of Chronic Low Back Pain: 2-Year Results From a Prospective Randomized Double-Blind Sham-Controlled Multicenter Study

The purpose of the present study is to report the 2-year clinical outcomes for chronic low back pain (CLBP) patients treated with radiofrequency (RF) ablation of the basivertebral nerve (BVN) in a randomized controlled trial that previously reported 1-year follow up. A total of 147 patients were treated with RF ablation of the BVN in a randomized controlled trial designed to demonstrate safety and efficacy as part of a Food and Drug Administration-Investigational Device Exemption trial. Evaluations, including patient self-assessments, physical and neurological examinations, and safety assessments, were performed at 2 and 6 weeks, and 3, 6, 12, 18, and 24 months postoperatively. Participants randomized to the sham control arm were allowed to cross to RF ablation at 12 months. Due to a high rate of crossover, RF ablation treated participants acted as their own control in a comparison to baseline for the 24-month outcomes. Clinical improvements in the Oswestry Disability Index (ODI), Visual Analog Scale (VAS), and the Medical Outcomes Trust Short-Form Health Survey Physical Component Summary were statistically significant compared to baseline at all follow-up time points through 2 years. The mean percent improvements in ODI and VAS compared to baseline at 2 years were 53.7 and 52.9%, respectively. Responder rates for ODI and VAS were also maintained through 2 years with patients showing clinically meaningful improvements in both: ODI ≥ 10-point improvement in 76.4% of patients and ODI ≥ 20-point improvement in 57.5%; VAS ≥ 1.5 cm improvement in 70.2% of patients. Patients treated with RF ablation of the BVN for CLBP exhibited sustained clinical benefits in ODI and VAS and maintained high responder rates at 2 years following treatment. Basivertebral nerve ablation appears to be a durable, minimally invasive treatment for the relief of CLBP.

SUcceSS, SUrgery for Spinal Stenosis: protocol of a randomised, placebo-controlled trial

IntroductionCentral lumbar spinal stenosis (LSS) is a common cause of pain, reduced function and quality of life in older adults. Current management of LSS includes surgery to decompress the spinal...

Galleria mellonella as a Model to Study the Effect of Antimicrobial Surfaces on Contamination by Staphylococcus aureus

Objective: The role of the inanimate environment in the transmission of healthcare-associated infections (HCAIs) is increasingly recognized. Hence, several self-disinfecting surfaces have gained attention as new infection control strategies. The objective of this study was to assess the antimicrobial efficacy of membrane-active polycation (maPK) surfaces against Staphylococcus aureus (S. aureus) applying the in vivo Galleria mellonella (G. mellonella) contamination model. Methods: In the first set-up maPK surfaces were contaminated with S. aureus and G. mellonella larvae were placed on the surface for 45 min. In the second set-up larvae were contaminated with S. aureus and transferred to maPK surfaces. Finally, the cross-over rates to larvae and maPK-surface were determined. Additionally, log reduction values (LRVs) of S. aureus on contaminated maPK and larvae were calculated. Results: The first experimental set-up revealed a significantly higher cross-over rate of S. aureus to the larvae from contaminated control surface (~2 x 103 colony forming untis (cfu)/mL) when compared to maPK surface (~5.1 x 101 cfu/mL). In the second set-up the cross-over rate of S. aureus from larvae to the control surface was significantly higher (~5.1 x 103 cfu/plate) than to the maPK surface (~2.1 x 101 cfu/plate). In both experiments LRVs were superior on maPK with 98.1% (p=0.0117) and 99.5% (p=0.0001) reduction, respectively. Conclusions: This in vivo study reveals the ability of maPK surfaces to reduce bacterial contamination and highlights the potential power to avoid cross-contamination from environmental surface.

The anatomical relationship between the axillary artery and vein investigated by radial coronary angiography.

To reduce the risk of inadvertent arterial puncture and bleeding, we aimed to define a safe puncture site by demonstrating the relation of the axillary artery and vein. The anatomical course and relation as well as crossover sites of the axillary artery and vein, the presence of small arterial bridges over the axillary vein, and validation of commonly preferred axillary venous puncture sites were determined by simultaneous ipsilateral venography in patients (n=111; 80 men, age 60 ± 10 years) who underwent coronary angiography by radial artery access. The axillary vein was detected at the first costa-clavicular intersection in 62% and at the second anterior and third posterior costal intersection in 60% of the patients. Small arterial bridges over the axillary vein were observed in 77% of the patients and more frequently in females and body mass index ≥25kg/m2 (P=0.034 and P=0.03, respectively). The axillary artery crossed the vein in 24% of the patients and almost always within the region close to the first costa-clavicular intersection site. Our study demonstrated a high crossover rate (24%) of axillary artery and vein and a high degree of variation in the course of axillary vein. Small arterial bridges over the axillary vein were observed in 77% of the patients.

A RANDOMIZED CONTROLLED TRIAL: SUPRAPUBIC ASPIRATION VERSUS URINARY CATHETERIZATION IN THE NEONATAL INTENSIVE CARE UNIT

Abstract BACKGROUND Urinary tract infection (UTI) is common in infants (10%). Urinary catheterization (UC) and supra-pubic aspiration (SPA) allow for sterile collection of urine. Some studies suggest SPA has a lower contamination rate than UC, however the optimal method of urine collection for culture remains unclear. OBJECTIVES To determine if there is: 1) a lower contamination rate in urine obtained by SPA assisted by bladder ultrasound versus UC in infants admitted to a neonatal intensive care unit (NICU); 2) a difference between procedures in: success rates for obtaining urine, short-term complication rates, and number of attempts required. DESIGN/METHODS A multicentre, unblinded, randomized controlled trial from 04/2013 to 05/2016. All gestational age (GA) infants greater than 72 hours of age investigated for UTI were eligible for randomization. Crossover to the other procedure could occur after 2 hours or 2 failed attempts. Target sample size was 165. Contamination was defined as growth of ≥2 microorganisms (SPA, UC) or growth &lt;104 CFU/ml (UC). Primary analysis was by intention-to-treat. RESULTS Enrolment was stopped for futility. 906 families were approached with 151 providing consent. 50 infants were eligible for randomization with 47 randomized (SPA n=23, UC n=24). Table 1 shows participant demographics. UTI incidence was 13% for SPA, 8% for UC (p=0.67). Crossover rates were high: 56% for SPA; 21% for UC. No urine sample was obtained in 2 participants per group despite attempts. There was no statistically significant difference between the 2 groups in contamination rates (14% SPA, 18% UC, p=1.00). No short-term complications were reported in either group. Prior to crossover, there was no difference in the number of attempts (i.e. up to 2 attempts pre-crossover or to successfully obtain urine) per procedure (p=0.08); however, there was a difference in the success rates per procedure (44% SPA, 75% UC, p=0.04). CONCLUSION This trial found no difference in contamination rates between SPA and UC, while noting the low enrolment and high crossover rate. More procedural training (particularly for SPA) may ensure greater procedural confidence and success. Post-procedural consent could improve enrolment given that equipoise on the optimal urine collection method still exists.

Arthroscopic Surgery or Physical Therapy for Patients With Femoroacetabular Impingement Syndrome: A Randomized Controlled Trial With 2-Year Follow-up

Background: Arthroscopic hip surgery has risen 18-fold in the past decade; however, there is a dearth of clinical trials comparing surgery with nonoperative management. Purpose: To determine the comparative effectiveness of surgery and physical therapy for femoroacetabular impingement syndrome. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients were recruited from a large military hospital after referral to the orthopaedic surgery clinic and were eligible for surgery. Of 104 eligible patients, 80 elected to participate, and the majority were active-duty service members (91.3%). No patients withdrew because of adverse events. The authors randomly selected patients to undergo either arthroscopic hip surgery (surgery group) or physical therapy (rehabilitation group). Patients in the rehabilitation group began a 12-session supervised clinic program within 3 weeks, and patients in the surgery group were scheduled for the next available surgery at a mean of 4 months after enrollment. Patient-reported outcomes of pain, disability, and perception of improvement over a 2-year period were collected. The primary outcome was the Hip Outcome Score (HOS; range, 0-100 [lower scores indicating greater disability]; 2 subscales: activities of daily living and sport). Secondary measures included the International Hip Outcome Tool (iHOT-33), Global Rating of Change (GRC), and return to work at 2 years. The primary analysis was on patients within their original randomization group. Results: Statistically significant improvements were seen in both groups on the HOS and iHOT-33, but the mean difference was not significant between the groups at 2 years (HOS activities of daily living, 3.8 [95% CI, –6.0 to 13.6]; HOS sport, 1.8 [95% CI, –11.2 to 14.7]; iHOT-33, 6.3 [95% CI, –6.1 to 18.7]). The median GRC across all patients was that they “felt about the same” (GRC = 0). Two patients assigned to the surgery group did not undergo surgery, and 28 patients in the rehabilitation group ended up undergoing surgery. A sensitivity analysis of “actual surgery” to “no surgery” did not change the outcome. Twenty (33.3%) patients who underwent surgery and 4 (33.3%) who did not undergo surgery were medically separated from military service at 2 years. Conclusion: There was no significant difference between the groups at 2 years. Most patients perceived little to no change in status at 2 years, and one-third of military patients were not medically fit for duty at 2 years. Limitations include a single hospital, a single surgeon, and a high rate of crossover. Registration: NCT01993615 (ClinicalTrials.gov identifier)

Definite stent thrombosis after drug-eluting stent implantation in coronary bifurcation lesions: A meta-analysis of 3,107 patients from 14 randomized trials.

Bifurcation percutaneous coronary intervention (PCI) is a challenging procedure, but there are currently inadequate data about definite stent thrombosis (ST) rates of single-stent versus double-stent strategies (SS and DS, respectively). Randomized clinical trials (RCTs) comparing SS and DS strategies were searched through PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Fourteen RCTs involving 3,107 patients were analyzed. Owing to the high crossover rate (16.49%), both intention-to-treat (ITT) and as-treated (AT) analyses were performed. In the ITT population, there was a significantly lower rate of early definite ST in the SS group (0.26%; DS group 1.14%; P = 0.021). Similarly, in the AT population, there was a significantly lower rate of early definite ST in the SS group (0.23%, DS group 1.07%; P = 0.042). True bifurcation subgroup analysis also showed a significantly lower early definite ST in the SS group (OR = 0.36, 95% CI = 0.15-0.86, P = 0.042) in the ITT population. There was no significant difference of overall, acute, subacute, and late definite ST between the 2 groups. Early definite ST is reduced when a SS strategy is used in bifurcation lesions.

Invited Commentary

Invited Commentary

SYNCOPE: PACING VERSUS RECORDING IN THE LATER YEARS. A RANDOMIZED PRAGMATIC CLINICAL TRIAL OF STRATEGIES OF PERMANENT PACEMAKER VERSUS IMPLANTABLE CARDIAC MONITOR IN OLDER PATIENTS WITH SYNCOPE

Syncope with bifascicular block may be caused by intermittent complete heart block, but competing diagnoses may co-exist. We tested the hypothesis that in patients with syncope and bifascicular heart block a strategy of empiric permanent pacing (PM) reduces major adverse events more effectively than acting on the results of an implantable cardiac monitor (ICM). 115 patients >50.0 y old with bifascicular block, preserved left ventricular function, and ≥1 syncope in the preceding year were randomized to receive a PM or ICM in a prospective, open label, pragmatic randomized trial. The primary outcome measure was a composite of Major Adverse Study-Related Events (MASRE) over ≥2 years up to study completion. MASRE included death, syncope, symptomatic bradycardia, asymptomatic actionable bradycardia, and device complications. Enrollment ended May 22, 2015 with follow-up ending May 22, 2017. There were 56 and 59 subjects randomized to receive a PM or implantable cardiac monitor ICM in 23 sites (17 Canadian). The PM and ICM groups were similar in age (74±9 vs 77±9 y), sex (20 vs 14 female), lifetime syncopes (medians 2), syncope in prior year (medians 2), duration of symptoms (medians 1 year), no prodrome (40/56 vs 39/59), and baseline systolic BP (137±20 vs 133±21 mmHg). 40 pts had left bundle branch block and 75 had right bundle branch block and a left hemiblock. Patients were followed for median 30 months and 21 exited the study (death 8, withdrew consent after 2 years 6, cancer 4, dementia 3). PM effectively prevented the primary outcome with end study MASRE-free survivals in PM (63%) and ICM (22%) group (figure, left panel, p < 0.001 Wilcoxon). Proportions of pts with syncope were similar in PM and ICM groups (figure, middle panel, 27 vs 31%, p=0.50, Wilcoxon). Other outcomes were far higher in ICM than PM pts: asymptomatic actionable heart block (40% vs 0%, p < 0.001), and symptomatic bradycardia (40% vs 0%, p < 0.001). Fully 35/59 ICM pts (59%) crossed over to PM. There were 5 pacemaker complications requiring reintervention. In on treatment analysis syncope-free survival was far higher in the PM group (80% vs 50%, figure, right panel, p=0.002, Wilcoxon). Syncope recurs frequently in elderly pts with few but recent syncopal spells and bifascicular block. Permanent pacing compared to ICM is a preferred strategy due to high crossover rates from ICM to PM, and on-treatment efficacy in prevention of syncope by PM.

Antithrombotic strategies in the catheterization laboratory for patients with acute coronary syndromes undergoing percutaneous coronary interventions: insights from the EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units Registry.

In the last decades, several new therapies have emerged for the treatment of acute coronary syndromes (ACS). We sought to describe real-world patterns of use of antithrombotic treatments in the catheterization laboratory for ACS patients undergoing percutaneous coronary interventions (PCI). EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in ACS patients in Italy. Over a 3-week period, a total of 2585 consecutive ACS patients have been enrolled in 203 cardiac care units across Italy. Among these patients, 1755 underwent PCI (923 with ST-elevation myocardial infarction and 832 with non-ST-elevation ACS). In the catheterization laboratory, unfractioned heparin was the most used antithrombotic drug in both ST-elevation myocardial infarction (64.7%) and non-ST-elevation ACS (77.5%) undergoing PCI and, as aspirin, bivalirudin and glycoprotein IIb/IIIa inhibitors (GPIs) more frequently employed before or during PCI compared with the postprocedural period. Any crossover of heparin therapy occurred in 36.0% of cases, whereas switching from one P2Y12 inhibitor to another occurred in 3.7% of patients. Multivariable analysis yielded several independent predictors of GPIs and of bivalirudin use in the catheterization laboratory, mainly related to clinical presentation, PCI complexity and presence of complications during the procedure. In our contemporary, nationwide, all-comers cohort of ACS patients undergoing PCI, antithrombotic therapies were commonly initiated before the catheterization laboratory. In the periprocedural period, the most frequently employed drugs were unfractioned heparin, leading to a high rate of crossover, followed by GPIs and bivalirudin, mainly used during complex PCI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02015624.

Amphoteric Ion-Exchange Membranes with Significantly Improved Vanadium Barrier Properties for All-Vanadium Redox Flow Batteries.

All-vanadium redox flow batteries (VRBs) have attracted considerable interest as promising energy-storage devices that can allow the efficient utilization of renewable energy sources. The membrane, which separates the porous electrodes in a redox flow cell, is one of the key components in VRBs. High rates of crossover of vanadium ions and water through the membrane impair the efficiency and capacity of a VRB. Thus, membranes with low permeation rate of vanadium species and water are required, also characterized by low resistance and stability in the VRB environment. Here, we present a new design concept for amphoteric ion-exchange membranes, based on radiation-induced grafting of vinylpyridine into an ethylene tetrafluoroethylene base film and a two-step functionalization to introduce cationic and anionic exchange sites, respectively. During long-term cycling, redox flow cells containing these membranes showed higher efficiency, less pronounced electrolyte imbalance, and significantly reduced capacity decay compared to the cells with the benchmark material Nafion 117.

Bevacizumab (Bev) to reduce the negative impact of glioblastoma (GBM) tumor size on survival from first recurrence.

2052 Background: Bev was FDA approved for recurrent GBM in 2009. However, the survival benefit from Bev in GBM remains to be demonstrated. Methods: We retrospectively identified 168 primary GBM patients diagnosed between 2001-2015 at UCLA and Kaiser Permanente LA, who received upfront radio-chemotherapy, followed with Bev and/or Lomustine (CCNU) at 1st recurrence. We measured tumor size at 1st recurrent treatment initiation, using bi-dimensional (2D) and volumetric (3D) techniques. We analyzed overall survival (OS) from 1st recurrence by Kaplan-Meier analysis. Results: Three groups of patients diagnosed from 2009-2015 were identified: patients treated with Bev alone (n = 49), CCNU alone (n = 36), and concurrent Bev/CCNU (n = 53). Patients were statistically different in performance status at 1st recurrence and tumor size; the CCNU alone group had smaller tumor sizes at diagnosis compared to the Bev groups. The CCNU group showed substantially greater survival (median OS (mOS) = 14.1 mo) compared to the Bev and Bev/CCNU groups (mOS = 6.9 and 7.1 mo, respectively), which may be explained by the imbalance in tumor sizes among the groups, and high rate of crossover (69%) to Bev in subsequent recurrences. To minimize selection bias, we identified another control group (n = 30) diagnosed from 2001-2004 who received CCNU only (CCNU 01-04). These patients had tumor size and KPS more comparable to both Bev groups, and a low rate of crossover (7%). OS for CCNU 01-04 (mOS = 5.7 mo) was similar to the Bev groups. Across all patients, we observed poor OS associated with larger 2D size vs. those with small tumors (mOS = 6.7 vs. 8.8 mo; p = 0.003). In separate stratification of each treatment group by tumor size, this association was retained in the CCNU 01-04 group (mOS = 4.0 vs. 8.4 mo, p &lt; 0.001), but not in either Bev (mOS = 6.7 vs. 7.3 mo) or BEV/CCNU (mOS = 7.0 vs. 8.8 mo). Analysis of effect of tumor size by 3D measurement yielded similar results. Conclusions: Bev appears to reduce the negative impact of large tumor size on GBM patient survival from 1st recurrence. 2D and 3D measurements were correlated, suggesting the adequacy of use of conventional tumor bi-dimensional measurement to predict benefit of Bev in patients based on tumor size.

Comparative Effectiveness of Routine Invasive Coronary Angiography for Managing Unstable Angina.

Non-ST-segment elevation acute coronary syndromes include unstable angina and non-ST-segment elevation myocardial infarction. Most randomized controlled trials of routine versus selective invasive coronary angiography have high rates of crossover from control to intervention groups and do not include subgroup analysis for unstable angina. Consequently, no clear, specific recommendations exist regarding the use of angiography in unstable angina. To assess the effect of angiography on mortality in unstable angina, incorporating the results of additional cardiac procedures and events. Longitudinal study using hospital discharge data, discrete-time survival analysis with propensity score adjustment, and sensitivity analysis. Victoria, Australia, 2001 to 2011. All residents, all ages. Routine invasive coronary angiography. 12-month all-cause mortality. Emergently admitted patients with unstable angina (n= 33901) who did or did not receive angiography during their first hospitalization were balanced on 44 covariates of propensity score. Routine angiography was associated with a 52% decrease in 12-month mortality (hazard ratio, 0.48 [95% CI, 0.38 to 0.61]); revascularization offered no additional statistical mortality benefit compared with diagnostic angiography alone. The predicted cumulative probability of death at 12 months was 0.024 (CI, 0.021 to 0.027) for patients receiving angiography within 2 months of their index unstable angina versus 0.097 (CI, 0.090 to 0.105) for those not receiving it. Sensitivity analysis demonstrated that to negate the observed effect size, an unmeasured confounder must independently decrease mortality by 90% and have a prevalence gap of 15% or greater between the angiographic groups. Nonrandom allocation of angiography. Patients with unstable angina benefit from an invasive management pathway initiated by invasive coronary angiography during their hospitalization and up to 2 months after discharge. National Health and Medical Research Council, Australia and BUPA Health Foundation.