Introduction: Les dispositifs d'auto-prélèvement sanguin permettent des échantillonnages à distance. L'étude explore (i) l'influence des sites de prélèvement et de l'analgésie topique sur le volume sanguin capillaire et la douleur, et (ii) la faisabilité, la sécurité et l'acceptabilité de l'autoprélèvement capillaire avec le dispositif Tasso-SST chez les adultes et les enfants. Méthodes: L'étude comportait deux phases avec la phase expérimentale comprenant deux études transversales conduit sur place, chez des adultes en santé (> 12 ans) et enfants (< 18 ans) en dyades enfant-parent. Les issues principales étaient: le volume capillaire sanguin et la perception de la douleur. La phase de mise en oeuvre portait sur deux essais multicentriques et ciblait les participants ayant opté pour des visites à distance. L’issu principal était le volume capillaire sanguin. Les issues secondaires des études incluaient l’échec du dispositif, les événements indésirables, la satisfaction et la volonté de réutiliser le dispositif. Résultats: L'étude a recruté 90 adultes et 9 enfants avec 7 parents (dyades) dans la phase expérimentale et 15 adultes et 2 enfants en phase de mise en oeuvre. Durant la phase expérimentale chez l'adulte, le dispositif a collecté une médiane (25%, 75%) de 450 (250, 550) μl de sang, sans différence significative entre les sites de ponction et l'usage ou non d’analgésie topique. L'analgésie topique a réduit la perception de la douleur de 0,61 (IC à 95 %: 0,97, 0,24 ; P <0,01) points sur l'échelle de 11 points, avec une réduction plus importante au bas du dos. Le volume médian collecté chez les enfants était de 450 μl avec un score médian de douleur de 0,5. En combinant toutes les études et phases, le volume médian collecté était de 425 (250, 500) μl, avec un taux d’échec de 4,4 % et des effets indésirables mineurs signalés chez 8,9 % des participants. Tous étaient prêts à réutiliser l'appareil. Conclusion: L'auto-prélèvement capillaire, avec un rendement d’un peu moins de 500 μl, est peu douloureux avec un bon profil d’innocuité, un haut degré de satisfaction et peu d'échec chez les adultes et les enfants. Le site de ponction et l'analgésie topique n'influent pas significativement sur le volume sanguin. L'utilisation d'une analgésie topique au bas du dos réduit légèrement la douleur, mais l’importance clinique de la réduction reste incertaine. / Introduction: Blood self-collection devices offer an opportunity to provide remote sampling. The study aimed to explore (i) the impact of puncture sites and topical analgesia on capillary blood volume and pain perception and (ii) the feasibility (volume, failure rate), safety, and acceptability of capillary self-collection using the Tasso-SST blood collection device among adults and children. Methods: The study consisted of two phases, with the investigational phase involving on-site cross-sectional studies in healthy adults (>12 years) and children (<18 years) as child-parent dyads. The primary outcomes were capillary blood volume and pain perception. The implementation phase involved two multicentre trials in participants opting for remote visits. Where the primary outcome was blood volume. Secondary outcomes of the study included device failure, adverse events, satisfaction, and willingness to re-use the device. Results: The study enrolled: 90 adults and 9 children with 7 parents (dyads) in the investigational phase and 15 adults and 2 children in the implementation phase. During the adult investigational phase, the device collected a median of 450 (interquartile range: 250, 550) μl of blood with no significant difference between puncture sites and topical analgesia. Topical analgesia reduced pain perception by 0.61 (95% CI: 0.97, 0.24; P <0.01) points on the 11-point scale, with a magnitude of reduction varying by puncture site, with the lower back showing the most decrease. The median volume collected among children in the dyads was 450 (400, 475) μl with a median pain score of 0.5. During the implementation phase, both participants and research staff expressed willingness to use the device again. Overall, combining all studies and phases, the median volume collected was 425 (250, 500) μl, and the device failure rate was 4.4%; minor adverse effects were reported in 8.9% of the participants, all were willing to use the device again. Conclusion: Capillary blood self-collection, yielding slightly less than 500 μl, proves to be minimally painful with a good safety profile, high satisfaction, and low failure rates for both adults and children. The puncture site and topical analgesia don't significantly affect blood volume, but using topical analgesia on the lower back slightly reduces pain, with unclear clinical importance.

近年來，病人自主權意識高漲，醫療糾紛頻傳，每個醫師無不戒慎恐懼，而醫療爭議之處理模式與醫師專門職業之道德責任都受到社會高度的檢視及廣泛的討論。事實上，醫學的進步需要依賴不斷地創新與大膽地試驗研究，因此人體試驗相關的問題也受到大眾的關注。 由於人體試驗所面對的是複雜而變化多端的情境，所以參與人體試驗之受試者將會面對甚而遭到危險或傷害。我國人體試驗的相關法規，多散置於醫療法、醫師法、藥事法、藥品優良臨床試驗準則、藥品優良臨床試驗規範等，除了無整體之法規範外，且多為行政法令，在法律位階上均較低，加上衛生署主管機關無法落實對試驗過程中之管理與監控，因此參與人體試驗之受試者往往會受到損害而無法得到應有的保障。因為人體試驗的特殊性與常規醫療是不同的，如果僅由既有的傳統醫療糾紛處理方式，如醫療契約於受試者的關係、侵權行為於違反保護他人法律的標準、醫療倫理不傷害原則於人體試驗規範等，這些恐怕都是必須的，但是仍嫌不足。 本文參考國外人體試驗規範包括紐倫堡法則、赫爾辛基宣言、美國貝爾蒙特報告、美國聯邦法規、CIOMS國際生物醫學研究人體試驗倫理準則、國際醫藥法規協和會之優良人體臨床試驗準則等等，然後針對個別議題如受試者保護之告知後同意，受試者權益之醫療契約關係及侵權行為責任，受試者受傷害之損害賠償責任，作一整理分析與檢討，並進一步配合我國現行法律制度與社會倫理規範做出建議。 本文共分為七章，分別為「序論」、「人體試驗」、「人體試驗告知後同意法則」、「國外人體試驗之民事責任」、「我國人體試驗之民事責任」、「人體試驗之賠償責任及機制」及「結論」。 / In recent years, patients’ consciousness of self-determination has raised and many medical disputes occurred; doctors feel discomfort and developed the high intensity of self-defense. The solution of medical malpractice and professional liability of doctors have became the major public issues and received many discussions. We are quite sure that the medical progress is based on innovative and intensive clinical study on human subjects. Under this background, the topics on human subject research have been attracted more attention than ever. Since the situations in human research are complex and variable. If relative clinical standards and legal protections are not adequately provided, the human subjects involved in clinical researches may face many risks and even injured. In Taiwan, we don’t have a systemic regulations on human subject research, all regulations are distributed in different code, act, proceeding, and agreement. Furthermore, the government does not have enough resource and manpower to monitor or inspect the processes of human research, the issues of protection of human rights and benefits of testee has raised serious concern. The human subject research is not exactly the same as the clinical medical treatment, it’s impossible for legislators or institutions to regulate research through traditional medical regulations such as medical ethics doctor-involved informed consent, medical agreement (contract), tort laws, and compensation for injury. In this thesis, firstly, I reviewed the most important publications related to human subject research include Nuremberg Code, Declaration of Helsinki, USA’s Belmont Report and Code of Federal Regulations, CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects, and ICH-GCP; secondly, focus on each specific topics especially the value of informed consent, the importance of medical agreement, the liabilities of torts and the policy of compensation for injury. Finally, I’ll make my comments and suggestions to the health care authorities to update and implement new regulating policies to protect human rights of subjects involved in clinical researches. My thesis is restricted to discuss the impact of civil liability on human subjects research focus on drug clinical trial and divided into seven chapters as follows: “Introduction”, “Human subject research”, “Principles of informed consent”, “International liability of civil law on human subject research”, “Liability of Taiwan civil law on human subject research”, “Policy of compensation for injured human research subject” and “Conclusion”.

Background Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. Methods/design This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. Discussion The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Trial registration Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.

O presente estudo destinou-se a avaliar se os resultados clínicos iniciais da viscossuplementação poderiam ser melhorados com a adição de corticosteróide. As injeções intra-articulares são usadas há muitos anos no tratamento da osteoartrite dos joelhos, principalmente com suspensões cristalinas de corticosteróides. A viscossuplementação é uma intervenção relativamente nova, atualmente recomendada no tratamento da osteoartrite. Trata-se da injeção de ácido hialurônico exógeno em articulações diartrodiais, visando, além de restaurar as propriedades reológicas do líquido sinovial, efeitos modificadores da doença osteoartrite. Revisões sistemáticas mostram que a melhora clínica ocorre em duas a cinco semanas após a viscossuplementação. Comparando-se a viscossuplementação com a injeção intraarticular com corticosteróides, dados recentes sugerem maior eficiência no alívio da dor nas quatro primeiras semanas após a infiltração com corticosteróides, similaridade dos procedimentos ao redor da quarta semana e melhores resultados com a viscossuplementação após a oitava semana. Este inicio de ação mais tardio, associado a relatos de sinovite reacional após a viscossuplementação podem desencorajar médicos e pacientes ao uso desta modalidade de tratamento. No presente estudo foram avaliados 104 pacientes em tratamento para osteoartrite do joelho no grupo de doenças osteometabólicas do Instituto de Ortopedia do Hospital das Clínicas da FMUSP. Os pacientes foram randomizados em dois grupos. Um dos grupos foi denominado VS e recebeu uma única injeção intra-articular de 6ml de Hylan GF-20 (Synvisc One®-Genzyme) no joelho estudado. O segundo grupo foi denominado VS+T e recebeu uma injeção intra-articular de 6ml de Hylan GF-20 (Synvisc One®-Genzyme) mais 1ml (20mg) de Hexacetonido de Triancinolona (Triancil®-Apsen). Foram aplicados a escala visual analógica de dor (EVA) e os questionários de WOMAC e Lequesne uma semana antes da injeção e após uma, quatro, 12 e 24 semanas. Os dois grupos com 52 pacientes cada eram homogêneos. Na primeira semana, o WOMAC e a EVA apresentaram melhores resultados no Grupo VS+T (p < 0,01) em relação ao Grupo VS. Na quarta semana não houve diferença entre os grupos. Ambos apresentaram resultados similares nas semanas 12 e 24. Concluiu-se que a adição de hexacetonido de triancinolona melhorou os resultados clínicos da viscossuplementação no curto prazo, sem interferir nos resultados a longo prazo ou na incidência de efeitos adversos / The present study aims to assess if the initial results of viscosupplementation can be improved by the addition of corticosteroid. Intraarticular injections have been used for many years to treat arthritis and other painful articular disorders, mainly using long-lasting crystalline corticosteroid suspensions. Viscosupplementation is a relatively new intervention that is now widely used and recommended for the treatment of knee osteoarthritis. It is comprised of the injection of exogenous hyaluronic acid in diarthrodial joints, in order to restore the rheological properties of synovial fluid and also to promote osteoarthritis disease-modifying effects. Several placebo-controlled studies reported that clinical improvement began only within two to five weeks after viscosupplementation. When comparing viscosupplementation versus intraarticular injection of corticosteroid, recent data suggest that from baseline to week four, intraarticular steroid were more effective for pain relief. By the fourth week, however, both provided similar relief, but beyond the eighth week, hyaluronic acid provided greater pain reduction. The mechanism of action of hyaluronic acid, with delayed onset of pain/functional improvement, combined with reports of reactional sinovitis may discourage physicians and patients regarding this treatment modality. The present study evaluated 104 patients receiving usual care for knee osteoarthritis at the University of São Paulo Medical Center. Patients were randomized to receive either a single intra-articular injection of 6ml of Hylan GF-20 (Synvisc One®-Genzyme) (Group VS) or a single intra-articular injection of 6ml of Hylan GF-20 (Synvisc One®-Genzyme) plus 1ml (20mg) of Triamcinolone Hexacetonide (Triancil®-Apsen) (Group VS+T). VAS, WOMAC and Lequesne questionnaires were applied one week prior the injection, and after one, four, 12 and 24 weeks. The two groups with 52 patients each were homogeneous. At week one, WOMAC and VAS showed better results for Group VS+T compared to Group VS (p < 0,05). At week four the scores did not show statistically significant differences. The groups showed similar results at weeks 12 and 24. In conclusion, the addition of triamcinolone improved first-week symptom and functional scores of viscosupplementation, but not beyond. It did not seem to alter the likelihood of adverse effects

A tendência de globalização dos ensaios clínicos, observada nos últimos anos, trouxe à tona questões antes não discutidas como a continuidade do tratamento com os medicamentos em investigação, após a conclusão da pesquisa. A inclusão de países em desenvolvimento nesses estudos traz consigo a preocupação com a vulnerabilidade dos participantes da pesquisa. No Brasil, há cerca de cinco anos, os Comitês de Ética em Pesquisa, CEP, e, particularmente, a Comissão Nacional de Ética em Pesquisa, CONEP, passaram a solicitar a manutenção do fornecimento do(s) medicamento(s) do estudo após sua finalização. Embora baseada nos principais documentos éticos que norteiam a pesquisa clínica, essa solicitação apresenta dificuldades práticas para implantação, principalmente no caso de doenças crônicas. O objetivo deste trabalho foi identificar as questões envolvidas na continuidade do fornecimento de medicamentos após a conclusão de ensaio clínico e analisar a perspectiva de atores que compõem o cenário da pesquisa clínica nacional. Questionários e respectivos Termos de Consentimento Livre e Esclarecidos, TCLE, foram enviados por correioeletrônico, entre outubro de 2009 e janeiro de 2010, a membros de CEPs (todos os CEPs credenciados pela CONEP naquela data), pesquisadores (em duas áreas terapêuticas, HIV/AIDS e Diabetes mellitus) e patrocinadores. Aos pesquisadores foi solicitado que aplicassem o questionário a seus pacientes de pesquisa. A taxa de resposta dos CEPs foi de 20,7% (124 responderam, de 599 questionários enviados), 20% para os pesquisadores (58 de 290) e 45,3% para os patrocinadores (24 de 53). Cinquenta e quatro pacientes convidados por seus médicos responderam. Com relação à informação contida no TCLE, o item menos informado é relativo a como obter o medicamento após o estudo, para todos os grupos pesquisados. Com relação à motivação dos pacientes ao participar de uma pesquisa, 96,2% dos pacientes responderam como \"muito importante\", na decisão, a busca de melhores cuidados médicos e atenção à própria saúde, e 94,2% o fato de colaborar para o desenvolvimento da ciência (altruísmo). Entretanto, os demais grupos entrevistados não pensam da mesma forma: para eles, a maior motivação dos pacientes, ao participar de pesquisas clínicas, é a busca de melhores cuidados médicos e atenção à sua saúde, seguido da busca pelo acesso a alternativas de tratamento para sua doença. Ao serem perguntados sobre quem deveria receber o medicamento em investigação após o estudo, os pacientes responderam que todas as pessoas deveriam receber o medicamento após o estudo (60,4%); entre os pesquisadores, a maior parte (43,1%) respondeu que o medicamento deveria ser fornecido às pessoas participantes do estudo e 39,7% deles responderam que o medicamento deveria ser fornecido às pessoas que se beneficiariam do medicamento em estudo. Já os representantes de CEP concordaram com os pacientes que todas as pessoas deveriam receber o medicamento, mas em proporção bem menor (35,3%). Os patrocinadores opinaram que o medicamento do estudo deveria ser fornecido aos participantes da pesquisa que dele se beneficiariam (50%). Houve consenso entre os grupos em que, havendo a continuidade do tratamento, este deveria ser fornecido pelo patrocinador e de forma gratuita. Ao responder a questão relativa a quanto tempo deveria o medicamento ser fornecido, pesquisadores e patrocinadores consideraram que o medicamento deveria ser fornecido até estar disponível na rede pública, enquanto que os membros de CEP, opinaram que isso deveria acontecer durante o período que o paciente fosse beneficiado. Os pacientes responderam que o benefício deveria ser mantido pela vida toda. Devido às várias limitações deste estudo (representatividade da amostra, população restrita a usuários da Internet), seus resultados podem não ser generalizados, mas podem contribuir para a discussão do tema, ao analisar os pontos de vista de vários atores do cenário da pesquisa clínica nacional. / The recent trend of globalization of clinical trials, observed in the last years, raised some non-previously discussed issues, such as the continuity of treatment after the conclusion of the study. The inclusion of developing countries in these trials brings together the concern with the participants\' vulnerability. In Brazil, about 5 years ago, the Ethics Committees (EC) and the National Commission of Ethics in Research (so called CONEP) started requiring the access to study medication after the trial ends. Even being based on the main documents related to ethics and research, some practical issues make this requirement difficult to implement, mainly in the arena of chronic diseases. The goal of this research was to identify the questions related to continuing the supply of the investigational medicine and analyze the perspective of all stakeholders involved in clinical research. Questionnaires and informed consents were sent through e-mail, between Oct 2009 and Jan 2010, to EC members (all ECs mentioned at CONEP site at that moment), clinical investigators (in two therapeutical areas, HIV/AIDS and Diabetes) and sponsors. We also asked the clinical investigators to submit the questionnaire (in paper) to their patients who already participated in clinical research. The response rate in each group was: 20.7% in EC members\' group (599 questionnaires sent, 124 replied), 20% in clinical investigators\' group (58 of 290) and 45.3% in sponsors\' group (24 of 53). Fifty four patients answered the questionnaire through their doctors. Regarding to the information displaced in the informed consent, the item less informed, according to all groups, was related to how to obtain the study medication after the conclusion of the trial. Concerning the motivation of patients which made them accept to participate in a clinical trial, 96.2% of patients answered as \"very important\" to obtain better health care and attention and 94.2% mentioned also as \"very important\" the possibility to collaborate with the progress of the science (altruism). However, among the other groups, the responses were different: for them, the major motivation for the patients would be to have access to better health care and attention (similar to patients) and search for access to treatment alternatives for their diseases. When asked to whom should be given the study medication after the trial, the patients answered that all patients should receive it (60.4%); for the clinical investigators, 43.1% believe that the medication should be given to the participants of the study and 39.7% to the subjects who participated and benefited from the study treatment. The EC members agreed (but to a lesser degree, 35.3%) with the patients that all individuals with the disease should receive the medication after the trial. For 50% of the sponsors, the study medication should be assured to the participants who had benefit from the treatment. In the case of need of access extension after the trial, a consensus could be observed among all groups, concerning to whom should provide the medication (the sponsor) and how (completely free). One question addressed the issue of how long the treatment should be assured after the trial: clinical investigators and sponsors replied that the medication should be kept until be available in the public health sector; the EC members thought it should be furnished while the patient keeps the benefit. The patients answered that the benefit should be assured for all life. Due to the several limitations of this research (such as the sample representativeness, population restrict to internet users), their results can\'t be generalized; however, the data can contribute to the discussion of this very complex topic through analyzing the views of the several stakeholders of the scenario of clinical research in Brazil.

Vorhofflimmern ist die häufigste behandlungsbedürftige Herzrhythmusstörung. Die Erhöhung des Schlaganfallrisikos, die Einschränkung der Herzleistung und nicht zuletzt ein Verlust an Lebensqualität sind bedeutsame Folgen dieser Erkrankung. Bisherige pharmakologische Therapieansätze sind insbesondere beim paroxysmalem Vorhofflimmern nur von unzureichender Wirkung, so dass in letzter Zeit nicht-pharmakologische Therapieoptionen untersucht werden. Elektrophysiologische und klinische Untersuchungen legen nahe, dass bifokale rechtsatriale Schrittmacherstimulation die Rezidivhäufigkeit von paroxysmalem Vorhofflimmern senken kann. In der DUSTI-Studie (DUal-site STImulation for prevention of paroxysmal atrial fibrillation) wurde untersucht, ob bifokale atriale Überstimulation die Rezidivhäufigkeit gegenüber unifokaler Überstimulation und lediglich antibradykarder Stimulation senken kann. Hierzu wurden 19 Patienten (61 ± 12 Jahre, 13 männlich) mit paroxysmalem Vorhofflimmern und einer Indikation zur Schrittmacherimplantation in eine prospektive, einfach-blinde, randomisierte Cross-over-Studie eingeschlossen. Ein herkömmlicher Zwei-Kammer-Schrittmacher, eine ventrikuläre Sonde und zwei über einen Y-Konnektor verbundene rechtsatriale Sonden, eine septal, die andere lateral wurden implantiert. Alle Patienten wurden zunächst 12 Wochen durch Programmierung einer Interventionsfrequenz von 50/min möglichst wenig atrial stimuliert. Danach wurden alle Patienten möglichst immer atrial stimuliert (Überstimulation mit 10/min über der Eigenfrequenz), in zufälliger Reihenfolge 12 Wochen bifokal (septal und lateral) und 12 Wochen unifokal (septal oder lateral). Unter bifokaler Stimulation war die Vorhofflimmerlast ebenso groß wie unter unifokaler Stimulation (6,20% ± 9,91% vs. 6,15% ± 11,09%, Intention-to-treat-Analyse) In den Überstimulationsphasen zeigte sich ein Trend zur Abnahme der Vorhofflimmerlast gegenüber der Phase mit geringen atrialen Stimulationsraten (6,15% ± 10,32% vs. 8,84% ± 11,34%, p=0,09, Intention-to-treat-Analyse). Hinsichtlich der Anzahl der Vorhofflimmerepisoden, der Zeit bis zum Vorhofflimmerrezidiv und der Symptomatik fanden sich signifikante Unterschiede weder zwischen uni- und bifokaler Stimulation, noch zwischen Überstimulation und geringer atrialer Stimulation. Die verwendeten Methoden waren gut durchführbar und sicher. Die schrittmacherbasierte Vorhofflimmerdiagnostik erwies sich, vor allem durch die zusätzliche atriale Elektrode, als technisch kompliziert und teilweise fehlerbehaftet. In einem nicht selektierten Patientenkollektiv ist die bifokale rechtsatriale Schrittmacherstimulation zur Rezidivprophylaxe des paroxysmalen Vorhofflimmerns nicht besser geeignet als unifokale Stimulation. Der höhere Aufwand der Implantation einer zweiten atrialen Sonde scheint nicht gerechtfertigt. Andere Studien müssen zeigen, ob bestimmte Patienten-Subgruppen von der bifokalen rechtsatrialen Stimulation profitieren / Atrial fibrillation is the most common sustained cardiac arrhythmia. It substantially increases the risk of stroke, impairs cardiac output and may lower the quality of life. Because pharmacotherapeutic approaches often yield unsatisfactory results - especially with paroxysmal atrial fibrillation, various non-pharmacological therapies have been studied. Electrophysiological and clinical research suggests, that dual-site atrial stimulation may suppress paroxysms of atrial fibrillation. The DUSTI trial was designed to test the hypothesis that dual-site stimulation prevents atrial fibrillation better than single-site stimulation or support pacing. Nineteen patients (61 ± 12 years, 13 male) with paroxysmal atrial fibrillation and a standard indication for pacemaker implantation were included in a prospective, single-blinded, randomized cross-over-trial. A conventional dual-chamber pacemaker with one ventricular and two atrial leads was implanted. Atrial leads were placed at the atrial septum and at the right atrial wall, and connected via a Y-connector to the atrial port. For the first twelve weeks patients only received support pacing (at 50 bpm). Afterwards patients received continuous atrial pacing (at 10 bpm above the intrinsic heart rate), 12 weeks dual-site pacing (septal and lateral) and 12 weeks single-site pacing (septal or lateral) in random order. Atrial fibrillation burden was the same between dual-site pacing and single-site pacing (6.20% ± 9.91% vs. 6.15% ± 11.09%, intention-to-treat-analysis). A trend towards less atrial fibrillation with continuous pacing compared to support pacing was observed (6.15% ± 10.32% vs. 8.84% ± 11.34%, p=0.09, intention-to-treat-analysis). There was no significant difference in number of atrial fibrillation episodes, time to recurrence and symptoms, neither between dual- and single-site pacing, nor between continuous and support pacing. Dual-site pacing proved to be feasible and safe. The detection of atrial fibrillation by the pacemaker''s diagnostic algorithms was, however, troubled by the additional atrial lead. Dual-site pacing offers no further advantage to single-site pacing for prevention of atrial fibrillation recurrences in unselected patients. The implantation of an additional atrial lead in patients with paroxysmal atrial fibrillation, requiring a pacemaker, seems to be not justified. Future trials will investigate whether certain subgroups of patients will benefit from dual-site atrial pacing.

Introdução. A intervenção coronária percutânea (ICP) é um dos tratamentos para pacientes com doença arterial coronária (DAC). Essa intervenção deve ser acompanhada de outras medidas terapêuticas com o intuito de reduzir as incapacidades e o risco de novos eventos coronários; de controlar a progressão da doença; e de melhorar a qualidade de vida. Essas medidas compreendem a prevenção secundária da DAC e estão, principalmente, relacionadas às mudanças no estilo de vida para o manejo de fatores de risco para DAC. O contato por telefone tem sido utilizado por profissionais da área da saúde para o seguimento do paciente e da família no cuidado com diversas condições crônicas, incluindo a DAC. Objetivo. Desenvolver, implementar e avaliar um programa educativo com seguimento por telefone, durante o período de quatro meses após a alta hospitalar, para pacientes submetidos à ICP com o objetivo de melhorar o estado de saúde percebido, a autoeficácia, a adesão aos medicamentos e o estado emocional desses pacientes, bem como comparar desfechos do Programa Educativo com os de serviços de rotina hospitalar. Método. Ensaio clínico controlado e aleatorizado, realizado no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. A amostra deste estudo foi constituída pelos pacientes submetidos à primeira ICP, entre agosto de 2011 e junho de 2012. Os participantes foram aleatorizados para o Programa Educativo com Seguimento por Telefone (grupo intervenção [GI]: 30 participantes) ou cuidado conforme a rotina da instituição (grupo controle [GC]: 30 participantes). O referencial teórico que fundamentou o Programa Educativo aplicado neste estudo foi o construto de autoeficácia, presente na Teoria Social Cognitiva de Albert Bandura. O desfecho principal foi o estado de saúde percebido, avaliado pelo Medical Outcomes Survey 36- Item Short Form (SF-36), e os desfechos secundários foram a autoeficácia avaliada pela Escala de Autoeficácia Geral Percebida, a adesão aos medicamentos por meio do instrumento Medida de Adesão aos Tratamentos (MAT) e o estado emocional (ansiedade e depressão) avaliado pela Escala Hospitalar de Ansiedade e Depressão (HADS). Os desfechos foram avaliados antes do procedimento (T0) e seis meses após a ICP (T1). A análise foi por análise descritiva, análise de variância para medidas repetidas, teste de Qui-quadrado e risco relativo com intervalo de confiança de 95%. O nível de significância foi de 0,05. Este ensaio clínico foi registrado sob o número NCT01341093. Resultados. Na avaliação do estado de saúde percebido, com um nível de significância de 0,05, nenhuma interação (tempo e grupo) ou grupo foi estaticamente significante, mas houve interação entre tempo e grupo com valores de nível de significância entre 0,05 e 0,10 no Sumário do Componente Mental (p=0,08) e no domínio Aspectos Emocionais (p=0,07) e melhora no domínio Aspectos Sociais no GI (p=0,10). Na avaliação da autoeficácia, não houve diferenças entre os grupos ou tempos. Houve alta percentagem de participantes que relataram adesão aos medicamentos nos tempos T0 e T1, nos dois grupos (mais de 90% inicial e no seguimento). Na avaliação da ansiedade, seis meses após a ICP, houve aumento de não-caso de ansiedade no GI e diminuição no GC, e a associação entre as variáveis foi estatisticamente significante (p=0,04). Ao final do seguimento, o risco relativo do GI de ser não-caso de ansiedade foi de 1,6 (intervalo de confiança [IC] de 95%=1,0 a 2,4) quando comparado com o GC. Em relação à depressão, não houve evidência de diferenças no percentual de pacientes não- caso de depressão entre os grupos (GI e GC), tanto na internação como no seguimento. Ao final do seguimento, o risco relativo do GI de ser não-caso de depressão foi de 0,8 (intervalo de confiança [IC] de 95%=0,6 a 1,1), quando comparado com o GC. Conclusão. O Programa Educativo com Seguimento por Telefone é uma intervenção promissora para melhorar o estado de saúde percebido e para reduzir a ansiedade de pacientes submetidos à ICP. Pode ser necessário aperfeiçoar a intervenção para que haja efeitos na autoeficácia e na depressão. Os instrumentos para medidas de autoeficácia e de adesão aos medicamentos precisam ser melhorados / Introduction. Percutaneous coronary intervention (PCI) is one of the treatments available for coronary artery disease (CAD) patients. This intervention should be accompanied by other therapeutic interventions with the aim of reducing disabilities and the risk of new coronary events, controlling the progression of the disease, and improving the quality of life. These interventions comprise the secondary prevention of CAD and are mainly related to lifestyle changes, aiming to manage risk factors for CAD. Health professionals have used telephone follow-up to monitor patients and families in the delivery of care to different chronic conditions, including CAD. Objective. To develop, to implement and to assess an educational program with telephone follow-up, during four months after hospital discharge, for patients submitted to PCI, with the aim of improving the perceived health status, self-efficacy, medication adherence and emotional status of these patients, as well as to compare outcomes of the Educational Program with routine hospital services. Method. Randomized controlled clinical trial, developed at the Ribeirão Preto Medical School Hospital das Clínicas, Brazil. The study sample included patients who had been submitted to their first PCI between August 2011 and June 2012. The participants were randomly assigned to the Educational Program with Telephone Follow-up (intervention group [IG]: 30 participants) and routine care (control group [CG]: 30 participants). The theoretical framework that supported the Educational Program applied in this study was the self-efficacy construct in Albert Bandura\'s Social Cognitive Theory. The main outcome was the perceived health status, assessed using the Medical Outcomes Survey 36- Item Short Form (SF-36); and the secondary outcomes were self-efficacy, assessed using the Perceived General Self-Efficacy Scale; medication adherence, assessed using the Medida de Adesão ao Tratamento (MAT); and the emotional status (anxiety and depression), assessed using the Hospital Anxiety and Depression Scale (HADS). The outcomes were evaluated before the procedure (T0) and six months after the PCI (T1). Descriptive analysis was applied, as well as variance analysis for repeated measures, the chi-square test and relative risk, with the confidence interval set at 95%. Significance was set at 0.05. This clinical trial was registered under number NCT01341093. Results. In the assessment of the perceived health status, with significance set at 0.05, no interaction (time and group) or group was statistically significant, but interaction between time and group was verified, with significance levels ranging between 0.05 and 0.10 in the Mental Component Summary (p=0.08) and in the Emotional Aspects domain (p=0.07); as well as improvement in the Social Aspects domain for the IG (p=0.10). In the assessment of self-efficacy, no differences were found between the groups or times. Many participants indicated medication adherence at T0 and T1 in the two groups (more than 90% initially and during the follow-up). In the assessment of anxiety levels six months after the PCI, the number of non-cases of anxiety increased in IG and dropped in CG, with a statistically significant association between the variables (p=0.04). At the end of the monitoring, the relative risk of being a non-case of anxiety in IG corresponded to 1.6 (95% confidence interval [CI]=1.0 - 2.4) when compared to CG. As regards depression, no evidence was found of differences in the percentage of patients non-case of depression between the groups (IG and CG), neither during hospitalization nor during follow-up. At the end of the follow-up, the relative risk of IG being a non-case of depression corresponded to 0.8 (95% confidence interval [CI]= 0.6 - 1.1) when compared to CG. Conclusion. The Educational Program with Telephone Follow-up is a promising intervention to improve the perceived health status and reduce the anxiety of patients submitted to PCI. The intervention may need further development to influence self-efficacy and depression. Self-efficacy and medication adherence instruments need improvements

A fibromialgia é uma patologia crônica, de causa desconhecida. É caracterizada por dor, distúrbios do sono e fadiga. Também se observa a presença de distúrbios psicossomáticos como depressão, fobia, síndrome do pânico e ansiedade, aumentando ainda mais a complexidade dos sintomas da doença, além de conduzir a prejuízos na qualidade de vida e capacidade funcional do indivíduo acometido. O tratamento da patologia é difícil, devido à incompleta compreensão da doença e a presença de sintomas muitas vezes atípicos e amplamente diversificados. Diversas modalidades terapêuticas têm sido utilizadas, com diferentes graus de eficácia, incluindo fisioterapia, massagem, acupuntura, exercícios aquáticos, aeróbicos e de fortalecimento, além de terapias cognitivo-comportamentais. Este estudo objetiva avaliar os efeitos de um programa de exercícios respiratórios aquáticos na qualidade de vida, capacidade funcional, dor, dispnéia, ansiedade e qualidade do sono de mulheres com fibromialgia. Foram selecionadas 40 mulheres com idades entre 20 e 60 anos, randomizadas em dois grupos de 20 pacientes: exercícios respiratórios aquáticos (EX) e controle (CT). O grupo EX realizou exercícios durante uma hora, quatro vezes por semana, durante quatro semanas. O programa foi elaborado para seguir uma seqüência incluindo: I) aquecimento (5 minutos); II) exercícios respiratórios, constituídos de cinco padrões respiratórios diferentes e realizados concomitantemente a movimentos de tronco e membros (45 minutos); III) relaxamento (10 minutos). Ambos os grupos realizaram ainda atividades recreacionais, sedentárias, uma hora por semana, uma vez por semana, durante quatro semanas. Foram aplicados questionários antes e depois das intervenções para avaliar a qualidade de vida e capacidade funcional (\"Medical Outcome Study 36 - Item Short Form\" - SF-36, \"Fibromyalgia Impact Questionnaire\" - FIQ), ansiedade (\"Hamilton Anxiety Scale\" - HAS) e qualidade do sono (\"Pittsburg Sleep Quality Index\" - PSQI). O número de pontos dolorosos e dor (VAS - escala visual analógica) também foram avaliados. Na avaliação inicial não foram encontradas diferenças significativas entre os grupos no número de pontos dolorosos, dor e escores de todos os questionários aplicados. Após as intervenções, o grupo EX, comparado com o grupo CT, apresentou melhora dos escores do questionário SF-36 (aspectos físicos p=0,001, dor p=0,001, vitalidade p=0,009, aspectos sociais p=0,001, aspectos emocionais p=0,001), FIQ (escore total p=0,049, faltas ao trabalho p=0,036, fadiga p=0,013, cansaço matinal p=0,007), dor (VAS p=0,029), dispnéia (VAS p=0,004), ansiedade (HAS p=0,005) e qualidade do sono (PSQI p=0,004). Conclui-se que um programa de exercícios respiratórios aquáticos melhora a qualidade de vida, capacidade funcional, dor, dispnéia, ansiedade e qualidade do sono em pacientes com fibromialgia, podendo se tornar uma medida terapêutica relevante no tratamento destes pacientes. / Fibromyalgia syndrome is a chronic rheumatic condition with unknown etiology and unclear pathogenesis. It is characterized by pain, sleep disturbances and fatigue. Psychological symptoms are also observed, including mood disturbance, anxiety, depression, phobia and panic syndrome, contributing to the complex disease symptomatology, as well as to the reduced quality of life and impaired functional capacity observed in these patients. Due to an incomplete understanding of the disease mechanisms, in addition to multiple, non visible symptoms typical of FMS, a patient\'s treatment is a challenging task. Widely varied therapeutic approaches ranging from physical therapy, massage, acupuncture, aerobic and strengthening exercises to cognitive-behavioral therapies have been applied with variable efficacy. This study assessed the effects of aquatic respiratory exercise-based program in the quality of life, functional capacity, pain, dyspnea, anxiety and quality of sleep in patients with fibromyalgia syndrome. Forty women, aged between 20 and 60, were randomly assigned into 2 groups of 20 patients: aquatic respiratory exercise-based program (EX) and control group (CT). EX group performed the exercise program, for 1-hour, 4 times a week, for 4 weeks, which included: I) warm-up; II) respiratory exercises, consisting of 5 different breathing patterns, along with upper, lowers limbs and trunk movements (45min); III) relaxation exercises. Both groups were included in supervised-recreational activities, for 1-hour, once a week, for 4 weeks. Questionnaires were applied before and after intervention to assess quality of life and functional capacity (Medical Outcome Study 36-Item Short Form - SF-36, Fibromyalgia Impact Questionnaire - FIQ), anxiety (Hamilton Anxiety Scale - HAS) and quality of sleep (Pittsburg Sleep Quality Index - PSQI). Number of tender points and pain (VAS - visual analogue scale) were also evaluated. At baseline there was no difference between groups, including number of tender points, pain and questionnaire responses. After intervention, EX group, compared with CT group, showed improvement in SF-36 scores (physical functioning p=.001, bodily pain p=.001, vitality p=.009, social functioning p=.001, emotional role p=.001), in FIQ (total score p=.049, work missed p=.036, fatigue p=.013, morning tiredness p=.007) plus in VAS-pain (p=.029), VAS-dyspnea (p=.004), anxiety (HAS p=.005), and quality of sleep (PSQI p=.004). Short-term aquatic respiratory exercisebased program improved quality of life, functional capacity, pain, dyspnea, anxiety and quality of sleep in patients with fibromyalgia and may be a relevant addition to the treatment of these patients.

INTRODUÇÃO: A Moléstia de Dupuytren (MD) é uma doença crônica progressiva fibroproliferativa caracterizada por contraturas em flexão dos dedos. A origem deste processo está na proliferação de miofibroblastos e na síntese de matriz extracelular. Diversas técnicas já foram descritas no tratamento da MD. A falta de uma técnica capaz de associar altas taxas de sucesso com baixos índices de complicações e recidivas estimulou a procura por novas técnicas. Acredita-se que a propriedade totipotente das células-tronco presentes no tecido adiposo seria capaz de atuar na proliferação e na diferenciação dos fibroblastos em miofibroblastos, interrompendo a formação da fibrose e consequentemente a progressão da deformidade dos dedos. OBJETIVO: O objetivo primário deste estudo foi avaliar o efeito do enxerto de gordura, rico em células-tronco, nos pacientes com MD, submetidos a fasciectomia parcial aberta, por meio de avaliação funcional e goniométrica, e comparar com a técnica convencional (sem adição de enxerto de gordura). MÉTODO: Dois grupos totalizando 45 pacientes (24 pacientes no Grupo Controle e 21 no Grupo com gordura) foram operados pela técnica da fasciectomia parcial aberta. No Grupo controle era realizada apenas a fasciectomia parcial aberta. No Grupo com gordura, era realizada a fasciectomia parcial aberta e injetado, no local da corda ressecada, o enxerto de gordura, após o processamento do lipoaspirado de adipócitos proposto por Coleman (2006). O estudo foi prospectivo, randomizado e terapêutico. Os desfechos foram avaliados pela medida goniométrica do Déficit de Extensão Passiva Total (DEPT) e pelo escore funcional Brief Michigan Hand Questionnaire (BMHQ). As avaliações eram feitas no pré-operatório, com 6 semanas, 6 meses, 1 ano e 2 anos de seguimento. RESULTADOS: Na comparação com 6 semanas de pós-operatório, houve um aumento significativo da dor no Grupo com Gordura [mediana 2 ± 2,82 versus 0 ± 1,86 no grupo Controle (p=0,045)]. Os resultados do DEPT, não mostraram diferença significativa entre os grupos. Observamos piores resultados do escore funcional BMHQ com 6 meses e 1 ano de pós-operatório no Grupo com gordura (p=0,040 e p=0,047, respectivamente). Observamos ainda 9 casos (43%) de complicações no Grupo com gordura e 2 (8%) no Grupo Controle (p=0,019). CONCLUSÃO: O uso do enxerto de gordura associado à fasciectomia parcial aberta promoveu piores resultados funcionais comparado com a fasciectomia parcial aberta convencional, no curto prazo (um ano de seguimento pós-operatório). No entanto, resta a dúvida de qual seriam os resultados a longo prazo e, se as células-tronco, presentes no enxerto de gordura, poderiam interferir na recidiva da doença futuramente / BACKGROUND: Dupuytren\'s disease (DD) is a progressive chronic fibroproliferative disease characterized by flexion contractures of the fingers. The origin of this process is the proliferation of myofibroblasts and extra-cellular matrix synthesis. Several techniques have been described to treat the DD. The lack of a technique capable to associate high success rates with low rates of complications and recurrence stimulated the search for new techniques. It is believed that the totipotent property of the adipose-derived stem cells present in the processed lipoaspirate tissue would be able to inhibit the proliferation and differentiation of fibroblasts in myofibroblasts, interrupting the formation of fibrosis and consequently the progression of finger deformity. The primary objective of this study was to evaluate the effect of adipose-derived stem cells in patients with DD who underwent to open limited fasciectomy and compare with the conventional technique of limited fasciectomy. METHODS: A total of 45 patients were assigned in two groups in a single blind, prospective, randomized, controlled trial. All the patients were treated by the limited fasciectomy technique. In the control group (24 patients), only limited fasciectomy was performed. In the study group (21 patients), after the limited fasciectomy procedure, autologous lipoaspirate was injected at the site of the resected cord. Outcomes were assessed by the Total Passive Extension Deficit (TPED) and by the Brief Michigan Hand Questionnaire (BMHQ) functional score. The evaluations were performed by occupational therapists in the preoperative and at 6 weeks, 6 months, 1 year and 2 years. RESULTS: The study group presented higher rates of pain at 6 weeks postoperative (median 2 ± 2,82 versus 0 ± 1,86 on control group, p=0,045). TPED showed no significant differences between groups. BMHQ score, at 6 months and 1 year after surgery, were significantly inferior in the study group (p=0,040 e p=0,047, respectively). Patients in the study group had higher incidence of complications (9 patients, 43% versus 2, 8% in the control group, p=0,019). CONCLUSIONS: The autologous lipoaspirate associated to limited fasciectomy demonstrates inferior results regarding to functional score and pain compared to conventional limited fasciectomy, in short-term. Further long-term analysis is required to observe the effect of adipose-derived stem cells in the recurrences rates

A fibromialgia é uma patologia crônica, de causa desconhecida. É caracterizada por dor, distúrbios do sono e fadiga. Também se observa a presença de distúrbios psicossomáticos como depressão, fobia, síndrome do pânico e ansiedade, aumentando ainda mais a complexidade dos sintomas da doença, além de conduzir a prejuízos na qualidade de vida e capacidade funcional do indivíduo acometido. O tratamento da patologia é difícil, devido à incompleta compreensão da doença e a presença de sintomas muitas vezes atípicos e amplamente diversificados. Diversas modalidades terapêuticas têm sido utilizadas, com diferentes graus de eficácia, incluindo fisioterapia, massagem, acupuntura, exercícios aquáticos, aeróbicos e de fortalecimento, além de terapias cognitivo-comportamentais. Este estudo objetiva avaliar os efeitos de um programa de exercícios respiratórios aquáticos na qualidade de vida, capacidade funcional, dor, dispnéia, ansiedade e qualidade do sono de mulheres com fibromialgia. Foram selecionadas 40 mulheres com idades entre 20 e 60 anos, randomizadas em dois grupos de 20 pacientes: exercícios respiratórios aquáticos (EX) e controle (CT). O grupo EX realizou exercícios durante uma hora, quatro vezes por semana, durante quatro semanas. O programa foi elaborado para seguir uma seqüência incluindo: I) aquecimento (5 minutos); II) exercícios respiratórios, constituídos de cinco padrões respiratórios diferentes e realizados concomitantemente a movimentos de tronco e membros (45 minutos); III) relaxamento (10 minutos). Ambos os grupos realizaram ainda atividades recreacionais, sedentárias, uma hora por semana, uma vez por semana, durante quatro semanas. Foram aplicados questionários antes e depois das intervenções para avaliar a qualidade de vida e capacidade funcional (\"Medical Outcome Study 36 - Item Short Form\" - SF-36, \"Fibromyalgia Impact Questionnaire\" - FIQ), ansiedade (\"Hamilton Anxiety Scale\" - HAS) e qualidade do sono (\"Pittsburg Sleep Quality Index\" - PSQI). O número de pontos dolorosos e dor (VAS - escala visual analógica) também foram avaliados. Na avaliação inicial não foram encontradas diferenças significativas entre os grupos no número de pontos dolorosos, dor e escores de todos os questionários aplicados. Após as intervenções, o grupo EX, comparado com o grupo CT, apresentou melhora dos escores do questionário SF-36 (aspectos físicos p=0,001, dor p=0,001, vitalidade p=0,009, aspectos sociais p=0,001, aspectos emocionais p=0,001), FIQ (escore total p=0,049, faltas ao trabalho p=0,036, fadiga p=0,013, cansaço matinal p=0,007), dor (VAS p=0,029), dispnéia (VAS p=0,004), ansiedade (HAS p=0,005) e qualidade do sono (PSQI p=0,004). Conclui-se que um programa de exercícios respiratórios aquáticos melhora a qualidade de vida, capacidade funcional, dor, dispnéia, ansiedade e qualidade do sono em pacientes com fibromialgia, podendo se tornar uma medida terapêutica relevante no tratamento destes pacientes. / Fibromyalgia syndrome is a chronic rheumatic condition with unknown etiology and unclear pathogenesis. It is characterized by pain, sleep disturbances and fatigue. Psychological symptoms are also observed, including mood disturbance, anxiety, depression, phobia and panic syndrome, contributing to the complex disease symptomatology, as well as to the reduced quality of life and impaired functional capacity observed in these patients. Due to an incomplete understanding of the disease mechanisms, in addition to multiple, non visible symptoms typical of FMS, a patient\'s treatment is a challenging task. Widely varied therapeutic approaches ranging from physical therapy, massage, acupuncture, aerobic and strengthening exercises to cognitive-behavioral therapies have been applied with variable efficacy. This study assessed the effects of aquatic respiratory exercise-based program in the quality of life, functional capacity, pain, dyspnea, anxiety and quality of sleep in patients with fibromyalgia syndrome. Forty women, aged between 20 and 60, were randomly assigned into 2 groups of 20 patients: aquatic respiratory exercise-based program (EX) and control group (CT). EX group performed the exercise program, for 1-hour, 4 times a week, for 4 weeks, which included: I) warm-up; II) respiratory exercises, consisting of 5 different breathing patterns, along with upper, lowers limbs and trunk movements (45min); III) relaxation exercises. Both groups were included in supervised-recreational activities, for 1-hour, once a week, for 4 weeks. Questionnaires were applied before and after intervention to assess quality of life and functional capacity (Medical Outcome Study 36-Item Short Form - SF-36, Fibromyalgia Impact Questionnaire - FIQ), anxiety (Hamilton Anxiety Scale - HAS) and quality of sleep (Pittsburg Sleep Quality Index - PSQI). Number of tender points and pain (VAS - visual analogue scale) were also evaluated. At baseline there was no difference between groups, including number of tender points, pain and questionnaire responses. After intervention, EX group, compared with CT group, showed improvement in SF-36 scores (physical functioning p=.001, bodily pain p=.001, vitality p=.009, social functioning p=.001, emotional role p=.001), in FIQ (total score p=.049, work missed p=.036, fatigue p=.013, morning tiredness p=.007) plus in VAS-pain (p=.029), VAS-dyspnea (p=.004), anxiety (HAS p=.005), and quality of sleep (PSQI p=.004). Short-term aquatic respiratory exercisebased program improved quality of life, functional capacity, pain, dyspnea, anxiety and quality of sleep in patients with fibromyalgia and may be a relevant addition to the treatment of these patients.