Developing a placebo-controlled trial in surgery:issues of design, acceptability and feasibility

BACKGROUND: Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. METHODS: Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). RESULTS: There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. CONCLUSIONS: Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. TRIAL REGISTRATION NUMBER: The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007

The Realm of the Pairings

Abstract. Bilinear maps, or pairings, initially proposed in a crypto-logic context for cryptanalytic purposes, proved afterward to be an amazingly flexible and useful tool for the construction of cryptosystems with unique features. Yet, they are notoriously hard to implement efficiently, so that their effective deployment requires a careful choice of parameters and algorithms. In this paper we review the evolution of pairing-based cryptosystems, the development of efficient algorithms and the state of the art in pairing computation, and the challenges yet to be addressed on the subject, while also presenting some new algorith-mic and implementation refinements in affine and projective coordinates

Eletroconvulsoterapia na depressão maior: aspectos atuais Electroconvulsive therapy in major depression: current aspects

OBJETIVO: A eficácia da eletroconvulsoterapia em tratar sintomas depressivos está estabelecida por meio de inúmeros estudos desenvolvidos durante as últimas décadas. A eletroconvulsoterapia é o tratamento biológico mais efetivo para depressão atualmente disponível. O objetivo deste estudo foi demonstrar o papel da eletroconvulsoterapia no tratamento da depressão e destacar aspectos atuais relativos à sua prática. MÉTODO: Foram revisados na literatura estudos de eficácia, remissão de sintomas, fatores preditores de resposta, assim como aspectos atuais acerca da qualidade de vida, percepção dos pacientes, mecanismo de ação, técnica e prejuízo cognitivos. RESULTADOS: Os principais achados desta revisão foram: 1) a eletroconvulsoterapia é mais efetiva do que qualquer medicação antidepressiva; 2) a remissão da depressão com a eletroconvulsoterapia varia, em geral, de 50 a 80%; 3) Ainda é controverso o efeito da eletroconvulsoterapia nos níveis de fator neurotrófico derivado do cérebro (acho que aqui pode colocar entre parenteses o "BNDF"); 4) a eletroconvulsoterapia tem efeito positivo na melhora da qualidade de vida; 5) os pacientes submetidos à eletroconvulsoterapia, em geral, têm uma percepção positiva do tratamento. CONCLUSÃO: A eletroconvulsoterapia permanece sendo um tratamento altamente eficaz em pacientes com depressão resistente. Com o avanço da sua técnica, a eletroconvulsoterapia tornou-se um procedimento ainda mais seguro e útil tanto para a fase aguda, quanto para a prevenção de novos episódios depressivos.<br>OBJECTIVE: The efficacy of electroconvulsive therapy in treating depressive symptoms has been established by means of innumerable studies developed along the last decades. Electroconvulsive therapy is the most effective biological treatment for depression currently available. The objective of this study was to demonstrate the role of electroconvulsive therapy in the treatment of depression and highlight present aspects related to its practice. METHOD: We reviewed in the literature studies on efficacy, symptom remission, predictive response factors as well as current aspects regarding quality of life, the patients' perception, mechanism of action, technique and cognitive impairment. RESULTS: The main results found in the this revision were: 1) electroconvulsive therapy is more effective than any antidepressant medication; 2) the remission of depression with electroconvulsive therapy varies, in general, from 50 to 80%; 3) The effect of electroconvulsive therapy in brain-derived neurotrophic factor levels is still controversial; 4) electroconvulsive therapy has a positive effect in the improvement of quality of life; 5) patients submitted to electroconvulsive therapy have, in general, a positive perception about the treatment. CONCLUSION: Electroconvulsive therapy remains a highly efficacious treatment in treatment-resistant depression. With the improvement of its technique, electroconvulsive therapy has become an even safer and more useful procedure both for the acute phase and for the prevention of new depressive episodes