Initial Assignment Research Articles

Dosing of Rviii-Singlechain Based on Clinical Bleeding Phenotypes Results in Low Bleeding Rates and Low Consumption in Patients Treated with Prophylaxis Two or Three Times Weekly

Introduction: Safety and efficacy of rVIII-SingleChain (AFSTYLA) was investigated in two pivotal and one extension study, comprising the Affinity program. The study design and instructions provided to the investigators allowed the physician to freely choose the dose assignment and regimen, based on the FVIII treatment regimen used prior to enrollment, and the subject's clinical bleeding phenotype. Adjustments of dose and schedule were allowed at any time during the study.Methods: This analysis investigates initial and final dose assignment and the corresponding total and spontaneous bleeding rates in subjects in the adult and adolescent study assigned to prophylaxis two or three times weekly (>80% of the subjects on prophylaxis therapy) in dosing brackets of 20 to <30 IU/kg, 30 to <40 IU/kg and 40 to ≤50 IU/kg.Results: In the final dose assignment, 43 subjects were assigned a dose of 20 to <30 IU/kg, 62 subjects were assigned a dose of 30 to <40 IU/kg, and 38 subjects were assigned a dose of 40 to ≤50 IU/kg. No differences were observed in the analysis by dose brackets in the adult and adolescent (12-65) population (complete or stratified by age); neither in the initial nor the final dose assignment analysis. The median annualized bleeding rate for the dosing brackets of 20 to <30 IU/kg, 30 to <40 IU/kg and 40 to ≤50 IU/kg was 1.93, 1.05 and 2.21, respectively. The median annualized spontaneous bleeding rate was 0, 0 and 0.50, respectively (final dose assignment).Conclusions: This data shows that dosing of rVIII-SingleChain based on clinical bleeding phenotypes results in low bleeding rates and low consumption in patients treated with prophylaxis two or three times weekly, with more than 70% of subjects being maintained at doses of <40 IU/kg. DisclosuresSt Ledger:CSL Behring: Employment. Blackman:CSL Behring: Employment. Veldman:CSL Behring: Employment. Pabinger:CSL Behring: Consultancy.

The quality of metabolic pathway resources depends on initial enzymatic function assignments: a case for maize.

BackgroundAs metabolic pathway resources become more commonly available, researchers have unprecedented access to information about their organism of interest. Despite efforts to ensure consistency between various resources, information content and quality can vary widely. Two maize metabolic pathway resources for the B73 inbred line, CornCyc 4.0 and MaizeCyc 2.2, are based on the same gene model set and were developed using Pathway Tools software. These resources differ in their initial enzymatic function assignments and in the extent of manual curation. We present an in-depth comparison between CornCyc and MaizeCyc to demonstrate the effect of initial computational enzymatic function assignments on the quality and content of metabolic pathway resources.ResultsThese two resources are different in their content. MaizeCyc contains GO annotations for over 21,000 genes that CornCyc is missing. CornCyc contains on average 1.6 transcripts per gene, while MaizeCyc contains almost no alternate splicing. MaizeCyc also does not match CornCyc’s breadth in representing the metabolic domain; MaizeCyc has fewer compounds, reactions, and pathways than CornCyc. CornCyc’s computational predictions are more accurate than those in MaizeCyc when compared to experimentally determined function assignments, demonstrating the relative strength of the enzymatic function assignment pipeline used to generate CornCyc.ConclusionsOur results show that the quality of initial enzymatic function assignments primarily determines the quality of the final metabolic pathway resource. Therefore, biologists should pay close attention to the methods and information sources used to develop a metabolic pathway resource to gauge the utility of using such functional assignments to construct hypotheses for experimental studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0369-x) contains supplementary material, which is available to authorized users.

“And the lonely voice of youth cries ‘What is truth?’”: Western History and the National Narrative

A couple of years ago, I got a call from my oldest grandson, Jeremy. He was beginning middle school and taking his first class devoted to American history. For their initial homework assignment the teacher asked the students to speak with an older relative about their view of the American past and report on what he or she said. When Jeremy mentioned that two of his grandfathers were history professors (a complete coincidence, by the way), the teacher asked him to interview both of us. “Here’s the question, grandpa,” Jeremy said. “What does the United States of America mean to you as a historian?” “Wow,” I stammered, “that’s big. Can you give me a little more direction?” I was stalling. “I can tell you what Grandpa Lou said,” Jeremy offered. “That would help,” I replied, grateful for a few moments to gather my wits. “He thought about it for a while,” Jeremy said, “then told me that while America meant a lot of things to him, most important was the proclamation of human rights in the Declaration of Independence and the personal liberties guaranteed by the Bill of Rights and the other amendments to the Constitution.” Grandpa Lou had taken the high road. “He’s absolutely right about that,” I said. “Those are the guarantees of our enviable rights and freedoms.” Now it was my turn. “Since Lou emphasized the positive,” I offered, somewhat tentatively, “I’m going with the dark side. America is also about taking the land from hundreds of Indian nations and enslaving millions of Africans.” Jeremy responded with enthusiasm. “Thanks, …

Addressing the Externalities from Genetically Modified Pollen Drift on a Heterogeneous Landscape

Genetically modified (GM) crops have single or multiple genes introduced to obtain crop characteristics that cannot be obtained through conventional breeding. Pollen mediated gene flow from GM to non-GM crops causes some crops planted as non-GM to become GM, and this imposes economic losses on farmers who planted a non-GM crop but then have to sell the harvest on a GM market. The economic losses that result when both crops are grown together depend on the institutional arrangements and the type of property rights in place. We analyze how the spatial heterogeneity of a farmer’s fields affects the land allocation between buffers, the GM, and the non-GM crop based on cross-pollination and initial assignment of property rights. Greater spatial heterogeneity reduces the possibility of coexistence of crops on the landscape and increases the economic losses. Buffer zones enforced to reduce cross-pollination result in less coexistence on heterogeneous landscapes.

Limitation of Infarct Size and the Open Artery Hypothesis: A Conversation With Eugene Braunwald, MD.

Eugene Braunwald received an MD from the New York University School of Medicine. He completed an internal medicine residency at Johns Hopkins Hospital and cardiology fellowships at Mount Sinai Hospital, Columbia University, and the National Heart Institute. He served as chief of cardiology and subsequently clinical director of the institute. From 1968 to 1972, he was the founding chair of medicine at the University of California, San Diego. From 1972 to 1996, he served as chair of medicine at the Brigham and Women’s Hospital. In 1975, he was elected to the National Academy of Sciences. He is now the Distinguished Hersey Professor of Medicine at Harvard Medical School and a senior investigator of the TIMI Study Group, which he founded in 1984. Dr Braunwald replies: I became aware of the importance of AMI in 1951 during an elective in cardiology during my senior year at the New York University School of Medicine. At the time, AMI was by far the most common cause of death in adults in the United States. Of the patients who survived to be admitted to hospitals (no one knew how many AMI patients failed to reach hospital emergency departments), about one third died before discharge, either suddenly, presumably from an arrhythmia, or secondary to pump failure. Of the patients who were discharged alive, about one quarter died within a year, most frequently as a consequence of heart failure or recurrent MI. Pathologists had taught that AMI was usually associated with coronary thrombosis. Indeed, during my cardiology elective, Herrick’s classic article describing AMI was required reading. Its title, “Clinical Features of Sudden Obstruction of the Coronary Arteries,” showed how these 2 conditions (coronary occlusion and AMI) were intertwined.1 My direct involvement in the care of several patients who did not survive the acute event left …

Population-based outreach versus care as usual to prevent suicide attempt: study protocol for a randomized controlled trial.

BackgroundSuicide remains the 10th-ranked most frequent cause of death in the United States, accounting for over 40,000 deaths per year. Nonfatal suicide attempts lead to over 200,000 hospitalizations and 600,000 emergency department visits annually. Recent evidence indicates that responses to the commonly used Patient Health Questionnaire (PHQ9) can identify outpatients who are at risk of suicide attempt and suicide death and that specific psychotherapy or Care Management programs can prevent suicide attempts in high-risk patients. Motivated by these developments, the NIMH-funded Mental Health Research Network has undertaken a multisite trial of two outreach programs to prevent suicide attempts among outpatients identified by routinely administered PHQ9 questionnaires.Methods/designOutpatients who are at risk of suicide attempt are automatically identified using data from electronic health records (EHRs). Following a modified Zelen design, all those identified are assigned to continued usual care (i.e., no contact) or to be offered one of two population-based outreach programs. A Care Management intervention includes systematic outreach to assess suicide risk, EHR-based tools to implement risk-based care pathways, and care management to facilitate recommended follow-up. A Skills Training intervention includes interactive online training in Dialectical Behavior Therapy skills, supported by reminder and reinforcement messages from a skills coach. Each intervention supplements, rather than replaces, usual care; participants may receive any other services normally available. Interventions are delivered primarily by secure messaging through EHR patient portals. Suicide attempts and deaths following randomization are identified using state vital statistics data and health system EHR and insurance claim data. Primary evaluation will compare risk of suicide attempt or death over 18 months according to the initial assignment, regardless of intervention participation. Recruitment is underway in three health systems (Group Health Cooperative, HealthPartners, and Kaiser Permanente Colorado). Over 2500 participants have been randomized as of 1 March 2016, with enrollment averaging approximately 100 per week.DiscussionAssessing the effectiveness of population-based suicide prevention requires adherence to the principles of pragmatic trials: population-based enrollment, accepting variable treatment participation, assessing outcomes using health record data, and analyses based on intent-to-treat.Trial registrationClinicalTrials.gov registration #NCT02326883, registered on 23 December 2014.

An Investigation of Patient Preferences for Music Played Before Electroconvulsive Therapy.

Patients often feel anxious before electroconvulsive therapy (ECT), which can lead to avoidance of treatments. Music is a noninvasive safe option to reduce anxiety in the preoperative setting. Therefore, we examined patients' preferences of listening to music while receiving ECT by providing music-by way of headphones or speakers-to participants before treatment. Patients receiving ECT were recruited for this study. Patients served as their own controls in 3 separate music intervention sessions: 1) randomization to music via headphones or speakers, 2) no music, 3) the remaining music intervention. Patients completed a questionnaire related to satisfaction and preferences of music being played before ECT. Patients received a final questionnaire at the end of the study asking which intervention they preferred. Thirty patients completed the study. Ninety percent enjoyed listening to music through speakers. Eighty percent liked listening to music through headphones. Seventeen percent preferred not having any music. The difference in preference between speakers and headphones was not significant (P = 0.563; McNemar-Bowker test). There was no association between preference at the end of the study and the initial assignment of speakers or headphones (P = 0.542 and P = 0.752, respectively; Pearson χ tests). No adverse events were reported. Music is a low-cost intervention with virtually no side effects that could be offered as an adjunctive therapy for patients receiving ECT. A significant proportion of patients liked hearing music before treatment.

Recalled and current gender role behavior, gender identity and sexual orientation in adults with Disorders/Differences of Sex Development

The magnitude of sex differences in human brain and behavior and the respective contributions of biology versus socialization remain a topic of ongoing study in science. The preponderance of evidence attests to the notion that sexual differentiation processes are at least partially hormonally mediated, with high levels of prenatal androgens facilitating male-typed and inhibiting female-typed behaviors. In individuals with Disorders/Differences of Sex Development (DSD), hormonal profiles or sensitivities have been altered due to genetic influences, presumably affecting gender(ed) activity interests as well as gender identity development in a minority of the affected population. While continued postnatal androgen exposure in a number of DSD syndromes has been associated with higher rates of gender dysphoria and gender change, the role of a number of mediating and moderating factors, such as initial gender assignment, syndrome severity and clinical management remains largely unclear. Limited investigations of the associations between these identified influences and gendered development outcomes impede optimization of clinical care. Participants with DSD (n=123), recruited in the context of a Dutch multi-center follow-up audit, were divided in subgroups reflecting prenatal androgen exposure, genital appearance at birth and gender of rearing. Recalled childhood play and playmate preferences, gender identity and sexual orientation were measured with questionnaires and semi-structured interviews. Data were compared to those of control male (n=46) and female participants (n=79). The findings support that (a) prenatal androgen exposure has large effects on (gendered) activity interests, but to a much lesser extent on sexual orientation and that (b) initial gender of rearing remains a better predictor of gender identity contentedness than prenatal androgen exposure, beyond syndrome severity and medical treatment influences. Nonetheless, 3.3% of individuals with DSD in our sample self-reported gender dysphoria from an early age and changed gender, which further underlines the need for thorough long- term follow-up and specific clinical support.

New local search methods for partial MaxSAT

Maximum Satisfiability (MaxSAT) is the optimization version of the Satisfiability (SAT) problem. Partial Maximum Satisfiability (PMS) is a generalization of MaxSAT which involves hard and soft clauses and has important real world applications. Local search is a popular approach to solving SAT and MaxSAT and has witnessed great success in these two problems. However, unfortunately, local search algorithms for PMS do not benefit much from local search techniques for SAT and MaxSAT, mainly due to the fact that it contains both hard and soft clauses. This feature makes it more challenging to design efficient local search algorithms for PMS, which is likely the reason of the stagnation of this direction in more than one decade.In this paper, we propose a number of new ideas for local search for PMS, which mainly rely on the distinction between hard and soft clauses. The first three ideas, including weighting for hard clauses, separating hard and soft score, and a variable selection heuristic based on hard and soft score, are used to develop a local search algorithm for PMS called Dist. The fourth idea, which uses unit propagation with priority on hard unit clauses to generate the initial assignment, is used to improve Dist on industrial instances, leading to the DistUP algorithm.The effectiveness of our solvers and ideas is illustrated through experimental evaluations on all PMS benchmarks from the MaxSAT Evaluation 2014. According to our experimental results, Dist shows a significant improvement over previous local search solvers on all benchmarks. We also compare our solvers with state-of-the-art complete PMS solvers and a state-of-the-art portfolio solver, and the results show that our solvers have better performance in random and crafted instances but worse in industrial instances. The good performance of Dist has also been confirmed by the fact that Dist won all random and crafted categories of PMS and Weighted PMS in the incomplete solvers track of the MaxSAT Evaluation 2014.

Label-free Raman spectroscopic imaging to extract morphological and chemical information from a formalin-fixed, paraffin-embedded rat colon tissue section.

SummaryAnimal models and archived human biobank tissues are useful resources for research in disease development, diagnostics and therapeutics. For the preservation of microscopic anatomical features and to facilitate long‐term storage, a majority of tissue samples are denatured by the chemical treatments required for fixation, paraffin embedding and subsequent deparaffinization. These aggressive chemical processes are thought to modify the biochemical composition of the sample and potentially compromise reliable spectroscopic examination useful for the diagnosis or biomarking. As a result, spectroscopy is often conducted on fresh/frozen samples. In this study, we provide an extensive characterization of the biochemical signals remaining in processed samples (formalin fixation and paraffin embedding, FFPE) and especially those originating from the anatomical layers of a healthy rat colon. The application of chemometric analytical methods (unsupervised and supervised) was shown to eliminate the need for tissue staining and easily revealed microscopic features consistent with goblet cells and the dense populations of cells within the mucosa, principally via strong nucleic acid signals. We were also able to identify the collagenous submucosa‐ and serosa‐ as well as the muscle‐associated signals from the muscular regions and blood vessels. Applying linear regression analysis to the data, we were able to corroborate this initial assignment of cell and tissue types by confirming the biological origin of each layer by reference to a subset of authentic biomolecular standards. Our results demonstrate the potential of using label‐free Raman microspectroscopy to obtain superior imaging contrast in FFPE sections when compared directly to conventional haematoxylin and eosin (H&E) staining.

SweetNET: A Bioinformatics Workflow for Glycopeptide MS/MS Spectral Analysis.

Glycoproteomics has rapidly become an independent analytical platform bridging the fields of glycomics and proteomics to address site-specific protein glycosylation and its impact in biology. Current glycopeptide characterization relies on time-consuming manual interpretations and demands high levels of personal expertise. Efficient data interpretation constitutes one of the major challenges to be overcome before true high-throughput glycopeptide analysis can be achieved. The development of new glyco-related bioinformatics tools is thus of crucial importance to fulfill this goal. Here we present SweetNET: a data-oriented bioinformatics workflow for efficient analysis of hundreds of thousands of glycopeptide MS/MS-spectra. We have analyzed MS data sets from two separate glycopeptide enrichment protocols targeting sialylated glycopeptides and chondroitin sulfate linkage region glycopeptides, respectively. Molecular networking was performed to organize the glycopeptide MS/MS data based on spectral similarities. The combination of spectral clustering, oxonium ion intensity profiles, and precursor ion m/z shift distributions provided typical signatures for the initial assignment of different N-, O- and CS-glycopeptide classes and their respective glycoforms. These signatures were further used to guide database searches leading to the identification and validation of a large number of glycopeptide variants including novel deoxyhexose (fucose) modifications in the linkage region of chondroitin sulfate proteoglycans.

Effect of NO2 substitution and solvent on UV-visible spectra, redox potentials and electron transfer mechanisms of copper β-nitrotriarylcorroles. Proposed electrogeneration of a Cu(I) oxidation state

Three copper triarylcorroles containing a [Formula: see text]-pyrrole nitro substituent were synthesized and characterized as to their spectral and electrochemical properties in nonaqueous media. The examined compounds are represented as [Formula: see text]-NO2(YPh)3CorCu, where Cor is the trianion of a triphenylcorrole and Y is a Cl, H or CH3 substituent at the para-position of the three meso-phenyl rings of the compound. The data from absorption spectra, electrochemistry and thin-layer spectroelectrochemistry are consistent with an initial assignment of Cu[Formula: see text]-Cor[Formula: see text] in CH2Cl2, DMF and pyridine and electrogeneration of a formal Cu(II) corrole with an unreduced macrocycle, represented as Cu[Formula: see text]-Cor[Formula: see text], after the first one-electron reduction in these solvents. The doubly reduced [Formula: see text]-nitrocorrole has a sharp Soret band at 439 nm and a well-defined Q-band at 611 nm in CH2Cl2. Similar absorption spectra are seen for the three examined doubly reduced nitrocorroles in DMF and pyridine, suggesting formation of a Cu(I) species with an unreduced macrocycle which is represented as Cu[Formula: see text]-Cor[Formula: see text]. Changes in redox potentials and absorption spectra of the nitrocorroles are examined as a function of solvent and substituents on the meso-phenyl rings of the compounds and comparisons are made between spectral and electrochemical data of the newly synthesized corroles and that of structurally related tetraarylcorroles lacking a [Formula: see text]-nitro group.

Patterns in the Initial Teaching Assignments of Secondary English Teachers: Implications for Teacher Agency and Retention

ABSTRACTThis study examined the teaching assignments of English teachers in 13 Mid-Atlantic high schools across five states. Data on the experience levels of 175 English teachers teaching 246 classes and surveys from 85 teacher participants were collected. Findings reveal that major agency-thwarting challenges face new English teachers: They typically are assigned to teach the students who need the most assistance, do not have their own classrooms and believe that teacher tracking occurs in their schools. Results suggest that in order to increase teacher agency, retention, and student learning, we must shift the working conditions, rhetoric, and culture around new teachers.

Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions

This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing.

Maximum minimum throughput for MIMO system with optimum successive decoding under multi-user co-channel interference

The maximal-minimal-limiting-throughput based power assignment (MMLTPA) and the joint MMSE equalization and power control with maximal-minimal-limiting-throughput based initial power assignment (JMEPC-MMLTIPA) algorithm are proposed for the MIMO system with optimum successive decoding (MIMO-OSD) under multi-user co-channel interference. MMLTPA is used to compensate for the large-scale path loss and the JMEPC-MMLTIPA algorithm employs MMLTPA in the initial power assignment so that it can compensate for the large-scale path loss at startup. Simulation results show that the JMEPC-MMLTIPA algorithm increases the minimal throughput per user of MIMO-OSD under multi-user co-channel interference.

Simultaneous EUV Flare Variation Minimization and CMP Control by Coupling-Aware Dummification

Extreme ultraviolet (EUV) flare and post-chemical mechanical polishing (CMP) metal thickness are two main manufacturability concerns that introduce critical dimension distortions in nanometer process technology. Dummification, the addition of dummy patterns, is an effective technique to address the two concerns. However, while the two dummification objectives are competing in nature, existing works only tackle them separately, leading to problem-prone solutions because optimizing one would unavoidably deteriorate the other. This paper presents a new and effective method that simultaneously considers both concerns during dummification. Manufacturing sensitivity toward the two concerns are taken into account with a user-specified evaluation model adaptive to the adopted technology. Given the point spread function of a system and the evaluation model, our proposed two-stage method is able to find at the first stage an initial dummy assignment with better EUV flare uniformity than that obtained by a previous quasi-inverse method. With the initial assignment as the starting point, the gradient-guided optimization is then adopted to iteratively refine dummy distribution toward improved CMP quality. Experimental results on industrial test cases show the effectiveness of our method.

Architecture for the Automatic Generation of Plans for Multiple UAS from a Generic Mission Description

A planning approach for a platform composed of multiple unmanned aerial systems is presented in this paper. The research activities are focused on the interoperability, task allocation and task planning problems within the system. In order to tackle with the interoperability problem between the vehicles of the platform and other external systems, C-BML has been chosen as the standard language to formalize the description of the missions. Regarding the planning problems involved, several planners have been applied to solve them: a task allocation planner to create an initial assignment of tasks to vehicles, a symbolic planner for high-level reasoning and tools for geometric reasoning. The main contribution of the paper is the use of consolidated task planning techniques to automatically generate low-level plans from a mission described in C-BML, filling the gap between interoperability and automatic plan generation for missions where multiple heterogeneous aerial platforms are involved. The approach has been tested in missions involving multiple surveillance and 3D map generation tasks and the paper includes experimental results.

An Assignment-Balance-Optimization Algorithm for Minimizing Production Cycle Time of a Printed Circuit Board Assembly Line

This paper deals with the cycle time minimization problem that determines the productivity in printed circuit board (PCB) with n components using the m placement machines. This is known as production cycle time determination problem (PCTDP). The polynomial time algorithm to be obtain the optimal solution has been unknown yet, therefore this hard problem classified by NP-complete. This paper gets the initial assignment result with the machine has minimum unit placement time per each component firstly. Then, the balancing process with reallocation from overhead machine to underhead machine. Finally, we perform the swap optimization and get the optimal solution of cycle time within O(mn) computational complexity. For experimental data, the proposed algorithm can be obtain the same result as integer programming+branch-and-bound (IP+B&B) and B&B.

Load rebalancing games in dynamic systems with migration costs

We consider the following dynamic load balancing game: Given an initial assignment of jobs to identical parallel machines, the system is modified; specifically, some machines are added or removed. Each job's cost is the load on the machine it is assigned to; thus, when machines are added, jobs have an incentive to migrate to the new unloaded machines. When machines are removed, the jobs assigned to them must be reassigned. Consequently, other jobs might also benefit from migrations. In our job-extension penalty model, for a given extension parameterδ≥0, if the machine on which a job is assigned to in the modified schedule is different from its initial machine, then the job's processing time is extended by δ.We provide answers to the basic questions arising in this model. Namely, the existence and calculation of a Nash Equilibrium and a Strong Nash Equilibrium, and their inefficiency compared to an optimal schedule. Our results show that the existence of job-migration penalties might lead to poor stable schedules; however, if the modification is a result of a sequence of improvement steps or, better, if the sequence of improvement steps can be supervised in some way (by forcing the jobs to play in a specific order) then any stable modified schedule approximates well an optimal one.Our work adds two realistic considerations to the study of job scheduling games: the analysis of the common situation in which systems are upgraded or suffer from failures, and the practical fact according to which job migrations are associated with a cost.

Efficacy of Early Invasive Management After Fibrinolysis for ST-Segment Elevation Myocardial Infarction in Relation to Initial Troponin Status

BackgroundWe examined whether the efficacy of an early invasive strategy after fibrinolysis in ST-segment elevation myocardial infarction (STEMI) differs in relation to the initial troponin status. MethodsIn the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), patients with STEMI presenting to a non-percutaneous coronary intervention (PCI)-capable hospital who received fibrinolysis were randomized to either a pharmacoinvasive or standard strategy for subsequent angiography and PCI. In this post hoc subgroup analysis, we compared the efficacy of these strategies in relation to the initial troponin status at hospital presentation for the primary composite end point of mortality, reinfarction, recurrent ischemia, heart failure, and cardiogenic shock at 30 days. We assessed the heterogeneity of treatment effect with initial troponin status using the Breslow-Day test and tested for interaction after adjustment for baseline Global Registry of Acute Coronary Events (GRACE) risk score. ResultsAmong 1059 patients, those with abnormal initial troponin levels (n = 514 [48.5%]) were older with worse Killip class, had a longer time from symptom onset to fibrinolysis, and had higher GRACE and Thrombolysis In Myocardial Infarction risk scores. Patients with abnormal troponin levels had higher rates of the primary end point (17.5% vs 10.8%; P = 0.002) and cumulative mortality or reinfarction at 1 year (14.0% vs 8.1%; P = 0.003). In stratified analyses, pharmacoinvasive management reduced the primary end point only among patients with normal initial troponin status. However, there was no significant treatment heterogeneity (all P ≥ 0.10) and no interaction between initial troponin status and treatment assignment after adjusting for GRACE risk score. ConclusionsPatients with STEMI and abnormal initial troponin levels had worse short-term and long-term outcomes. Accounting for overall baseline risk with the GRACE risk score, troponin status did not modulate the efficacy of pharmacoinvasive management.