Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network

BACKGROUND: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. METHODS AND RESULTS: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy \u3c9 \u3emonths\u27 duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% wereold, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three-year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46-0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups. CONCLUSIONS: In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results from the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators

Background In US clinical practice, many patients who undergo placement of an implantable cardioverter‐defibrillator (ICD) for primary prevention of sudden cardiac death receive dual‐chamber devices. The superiority of dual‐chamber over single‐chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single‐ and dual‐chamber ICDs for primary prevention. Methods and Results We identified patients receiving a single‐ or dual‐chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter‐Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all‐cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital‐level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single‐chamber device and 46.0% (n=479) received a dual‐chamber device. In a propensity‐weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59–1.38 [P=0.65]), all‐cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87–1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72–1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93–1.53 [P=0.17]). Conclusions Among patients who received an ICD for primary prevention without indications for pacing, dual‐chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single‐chamber devices. This study does not justify the use of dual‐chamber devices to minimize inappropriate shocks

Effects of An Acute Increase in Atrial Pressure on Atrial Refractoriness in Humans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73199/1/j.1540-8159.1992.tb02954.x.pd

Manipulating Kondo Temperature via Single Molecule Switching

Two conformations of isolated single TBrPP-Co molecules on a Cu(111) surface are switched by applying +2.2 V voltage pulses from a scanning tunneling microscope tip at 4.6 K. The TBrPP-Co has a spin-active cobalt atom caged at its center and the interaction between the spin of this cobalt atom and free electrons from the Cu(111) substrate can cause a Kondo resonance. Tunneling spectroscopy data reveal that switching from the saddle to a planar molecular conformation enhances spin-electron coupling, which increases the associated Kondo temperature from 130 K to 170 K. This result demonstrates that the Kondo temperature can be manipulated just by changing molecular conformation without altering chemical composition of the molecule.Comment: To appear in Nano Lett (2006

Carbon nanomaterials for targeted cancer therapy drugs: a critical review.

Cancer represents one of the main causes of human death in developed countries. Most current therapies, unfortunately, carry a number of side effects, such as toxicity and damage to healthy cells, as well as the risk of resistance and recurrence. Therefore, cancer research is trying to develop therapeutic procedures with minimal negative consequences. The use of nanomaterial-based systems appears to be one of them. In recent years, great progress has been made in the field of possible use of nanomaterials with high potential in biomedical applications. Carbon nanomaterials, thanks to their unique physicochemical properties, are gaining more and more popularity in cancer therapy. They are valued especially for their ability to deliver drugs or small therapeutic molecules to these cells. Through surface functionalization, they can specifically target tumor tissues, increasing the therapeutic potential and significantly reducing the adverse effects of therapy. Their potential future use could, therefore, as vehicles for drug delivery. This review presents the latest findings of research studies using carbon nanomaterials in the treatment of various types of cancer. To carry out this study, different databases such as Web of Science, PubMed, MEDLINE and Google Scholar were employed. The findings of research studies chosen from more than 2000 viewed scientific publications from the last 15 years were compared

Promotion of oxygen reduction by a bio-inspired tethered iron phthalocyanine carbon nanotube-based catalyst

Electrocatalysts for oxygen reduction are a critical component that may dramatically enhance the performance of fuel cells and metal-air batteries, which may provide the power for future electric vehicles. Here we report a novel bio-inspired composite electrocatalyst, iron phthalocyanine with an axial ligand anchored on single-walled carbon nanotubes, demonstrating higher electrocatalytic activity for oxygen reduction than the state-of-the-art Pt/C catalyst as well as exceptional durability during cycling in alkaline media. Theoretical calculations suggest that the rehybridization of Fe 3d orbitals with the ligand orbitals coordinated from the axial direction results in a significant change in electronic and geometric structure, which greatly increases the rate of oxygen reduction reaction. Our results demonstrate a new strategy to rationally design inexpensive and durable electrochemical oxygen reduction catalysts for metal-air batteries and fuel cells.close34

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks

Place, Space and Memory in the Old Jewish East End of London: an Archaeological Biography of Sandys Row Synagogue, Spitalfields and its Wider Context

Sandys Row (London E1) is the only functioning Ashkenazi (Eastern European Jewish) Synagogue in Spitalfields and the oldest still functioning Ashkenazi synagogue in London. Located in an area, which from the mid­late nineteenth century until WWII was the centre of London’s Jewish population, it is one of the last surviving witnesses to a once vibrant and dynamic heritage that has now virtually disappeared. This area has been the first port of call for refugees for centuries, starting with French Protestant Huguenots in the eighteenth century, then Jews fleeing economic hardship and pogroms in Eastern Europe in the nineteenth century followed by Bangladeshi Muslims in the twentieth century. Using a broadly archaeological analysis based very closely on the sort of practice widely used in church archaeology, the authors argue that much can be inferred about wider social and cultural patterns from a study of architectural space at Sandys Row and its associated material culture. This is the first such archaeological study undertaken of a synagogue in Britain and offers a new perspective on wider issues regarding the archaeological definition of religious practice and religious material culture

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease

Phthalocyanine-nanocarbon ensembles: From discrete molecular and supramolecular systems to hybrid nanomaterials

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Accounts of Chemical Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/ar5004384Conspectus Phthalocyanines (Pcs) are macrocyclic and aromatic compounds that present unique electronic features such as high molar absorption coefficients, rich redox chemistry, and photoinduced energy/electron transfer abilities that can be modulated as a function of the electronic character of their counterparts in donor-acceptor (D-A) ensembles. In this context, carbon nanostructures such as fullerenes, carbon nanotubes (CNTs), and, more recently, graphene are among the most suitable Pc companions. Pc-C60 ensembles have been for a long time the main actors in this field, due to the commercial availability of C60 and the ell-established synthetic methods for its functionalization. As a result, many Pc-C60 architectures have been prepared, featuring different connectivities (covalent or supramolecular), intermolecular interactions (self-organized or molecularly dispersed species), and Pc HOMO/LUMO levels. All these elements provide a versatile toolbox for tuning the photophysical properties in terms of the type of process (photoinduced energy/electron transfer), the nature of the interactions beteen the electroactive units (through bond or space), and the kinetics of the formation/decay of the photogenerated species. Some recent trends in this field include the preparation of stimuli-responsive multicomponent systems ith tunable photophysical properties and highly ordered nanoarchitectures and surface-supported systems shoing high charge mobilities. A breakthrough in the Pc-nanocarbon field as the appearance of CNTs and graphene, hich opened a ne avenue for the preparation of intriguing photoresponsive hybrid ensembles shoing light-stimulated charge separation. The scarce solubility of these 1-D and 2-D nanocarbons, together ith their loer reactivity ith respect to C60 stemming from their less strained sp2 carbon netorks, has not meant an unsurmountable limitation for the preparation of variety of Pc-based hybrids. These systems, hich sho improved solubility and dispersibility features, bring together the unique electronic transport properties of CNTs and graphene ith the excellent light-harvesting and tunable redox properties of Pcs. A singular and distinctive feature of these Pc-CNT/graphene (single- or fe-layers) hybrid materials is the control of the direction of the photoinduced charge transfer as a result of the band-like electronic structure of these carbon nanoforms and the adjustable electronic levels of Pcs. Moreover, these conjugates present intensified light-harvesting capabilities resulting from the grafting of several chromophores on the same nanocarbon platform.In this Account, recent progress in the construction of covalent and supramolecular Pc-nanocarbon ensembles is summarized, ith a particular emphasis on their photoinduced behavior. e believe that the high degree of control achieved in the preparation of Pc-carbon nanostructures, together ith the increasing knoledge of the factors governing their photophysics, ill allo for the design of next-generation light-fueled electroactive systems. Possible implementation of these Pc-nanocarbons in high performance devices is envisioned, finally turning into reality much of the expectations generated by these materialsFinancial support from the Spanish MICINN (CTQ2011-24187/BQU), the Comunidad de Madrid (S2013/MIT-2841 FOTOCARBON) and the EU (“SO2S” FP7-PEOPLE-2012-ITN, no.: 316975) is acknowledge