Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

Asambleas barriales paranaenses.: Una experiencia de participación ciudadana.

A fines del año 2001 nuestro país atravesó una profunda crisis institucional, hecho social y político que generó una ruptura en el sistema de representación y legitimidad social. Este acontecimiento provocó, desde su génesis, la constitución de diversos movimientos sociales, instituyentes e instituidos, entre los que se encuentran las Asambleas Barriales como una forma de organización alternativa a las tradicionales formas democráticas de nuestro país. En el desarrollo de este trabajo de exploración de un acontecimiento local, intento secuenciar los antecedentes de esta crisis a partir de su contexto histórico y abordar lo sucedido en esos trágicos días de diciembre, que gestaron el movimiento de asambleas barriales y, específicamente, en relación a las asambleas analizarlas como una forma de participación democrática. Seguramente en este recorte quedan muchas causas, hechos, sentimientos, efectos, que no serán abordados, pero espero sean parte de estudios posteriores referidos a movimientos sociales paranaenses

Professional-Bureaucratic Conflict in Middle Management : Implications for Nursing

This essay focused on the important role of the nurse middle manager in the hospital organization. There is a concensus among authors that this position is pivotal to the organization. However, by virtue of the position, the manager is caught between the bureaucratic demands of the hospital administration and physicians on one side and the demands of subordinates and patients on the other side. Areas of professional bureaucratic conflict are identified and strategies are suggested which may be useful in reducing this conflict. Implications for nurse administrators and educators are identified. These implications include: input from nurse administrators in educational programs; clear, concise expectations of the nurse manager role; and delegation and decentralization of authority and responsibility which would allow operational decisions to be made at the level of organizational impact

In search of sustainable chemical processes : cloning, recombinant expression, and functional characterization of the 7&#945; - and 7&#946;-hydroxysteroid dehydrogenases from Clostridium absonum

Nicotinamide adenine dinucleotide phosphate-dependent 7\u3b1- hydroxysteroid dehydrogenase (7\u3b1-HSDH) and 7\u3b2-hydroxysteroid dehydrogenases (7\u3b2-HSDH) from Clostridium absonum catalyze the epimerization of primary bile acids through 7-keto bile acid intermediates and may be suitable as biocatalysts for the synthesis of bile acids derivatives of pharmacological interest. C. absonum 7\u3b1-HSDH has been purified to homogeneity and the N-terminal sequence has been determined by Edman sequencing. After PCR amplifications of a gene fragment with degenerate primers, cloning of the complete gene (786 nt) has been achieved by sequencing of C. absonum genomic DNA. The sequence coding for the 7\u3b2-HSDH (783 nt) has been obtained by sequencing of the genomic DNA region flanking the 5\u2032 termini of 7\u3b1-HSDH gene, the two genes being contiguous and presumably part of the same operon. After insertion in suitable expression vectors, both HSDHs have been successfully produced in recombinant form in Escherichia coli, purified by affinity chromatography and submitted to kinetic analysis for determination of Michaelis constants (K m) and specificity constants (k cat/K m) in the presence of various bile acids derivatives. Both enzymes showed a very strong substrate inhibition with all the tested substrates. The lowest K S values were observed with chenodeoxycholic acid and 12-ketochenodeoxycholic acid as substrates in the case of 7\u3b1-HSDH, whereas ursocholic acid was the most effective inhibitor of 7\u3b2-HSDH activity