Informed consent for clinical trials in acute coronary syndromes and stroke following the European Clinical Trials Directive: investigators' experiences and attitudes

<p>Abstract</p> <p>Background</p> <p>During clinical trials in emergency medicine, providing appropriate oral and written information to a patient is usually a challenge. There is little published information regarding patients' opinions and competence to provide informed consent, nor on physicians' attitudes towards the process. We have investigated the problem of obtaining consent from patients in emergency-setting clinical trials (such as acute coronary syndromes (ACS) and stroke) from a physicians' perspective.</p> <p>Methods</p> <p>A standardised anonymous 14-item questionnaire was distributed to Polish cardiac and stroke centres.</p> <p>Results</p> <p>Two hundred and fourteen informative investigator responses were received. Of these investigators, 73.8% had experience with ACS and 25.2% had experience with acute stroke trials (and 1% with both fields). The complete model of informed consent (embracing all aspects required by Good Clinical Practice (GCP) and law) was used in 53.3% of cases in emergency settings, whereas the legal option of proxy consent was not used at all. While less than 15% of respondents considered written information to have been fully read by patients, 80.4% thought that the amount of information being given to emergency patients is too lengthy. Although there is no legal obligation, more than half of the investigators sought parallel consent (assent) from patients' relatives. Most investigators confirmed that they would adopt the model proposed by the GCP guidelines: abbreviated verbal and written consent in emergency conditions with obligatory "all-embracing" deferred consent to continue the trial once the patient is able to provide it. However, this model would not follow current Polish and European legislation.</p> <p>Conclusion</p> <p>An update of national and European regulations is required to enable implementation of the emergency trial consent model referred to in GCP guidelines.</p

Global stabilization of the oscillating eccentric rotor

The oscillating eccentric rotor has been widely studied to model resonance capture phenomena occurring in dual-spin spacecraft and rotating machinery. This phenomenon arises during spin-up as a resonance condition is encountered. We consider the related problem of rotor despin. Specifically, we determine nonlinear feedback control laws that not only despin the rotor but also bring its translational motion to rest. These globally asymptotically stabilizing control laws are derived using partial feedback linearization and integrator backstepping schemes. For the case in which the oscillating eccentric rotor is excited by a translational sinusoidal forcing function, the control law is shown to attenuate the amplitude of the translational oscillation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43319/1/11071_2004_Article_BF00114798.pd

Wellness through a comprehensive Yogic breathing program – A controlled pilot trial

<p>Abstract</p> <p>Background</p> <p>Increasing rates of psychosocial disturbances give rise to increased risks and vulnerability for a wide variety of stress-related chronic pain and other illnesses. Relaxation exercises aim at reducing stress and thereby help prevent these unwanted outcomes. One of the widely used relaxation practices is yoga and yogic breathing exercises. One specific form of these exercises is Sudarshan Kriya and related practices (SK&P) which are understood to have favourable effects on the mind-body system. The goal of this pilot study was to design a protocol that can investigate whether SK&P can lead to increased feeling of wellness in healthy volunteers.</p> <p>Methods</p> <p>Participants were recruited in a small university city in Sweden and were instructed in a 6-day intensive program of SK&P which they practiced daily for six weeks. The control group was instructed to relax in an armchair each day during the same period. Subjects included a total of 103 adults, 55 in the intervention (SK&P) group and 48 in the control group. Various instruments were administered before and after the intervention. Hospital Anxiety Depression Scale measured the degree of anxiety and depression, Life Orientation Test measured dispositional optimism, Stress and Energy Test measured individual's energy and stress experiences. Experienced Deviation from Normal State measured the experience of altered state of consciousness.</p> <p>Results</p> <p>There were no safety issues. Compliance was high (only 1 dropout in the SK&P group, and 5 in the control group). Outcome measures appeared to be appropriate for assessing the differences between the groups. Subjective reports generally correlated with the findings from the instruments. The data suggest that participants in the SK&P group, but not the control group, lowered their degree of anxiety, depression and stress, and also increased their degree of optimism (ANOVA; p < 0.001). The participants in the yoga group experienced the practices as a positive event that induced beneficial effects.</p> <p>Conclusion</p> <p>These data indicate that the experimental protocol that is developed here is safe, compliance level is good, and a full scale trial is feasible. The data obtained suggest that adult participants may improve their wellness by learning and applying a program based on yoga and yogic breathing exercises; this can be conclusively assessed in a large-scale trial.</p> <p>Trial Registration</p> <p>Australian Clinical Trial Registry ACTRN012607000175471.</p

Assessing land use and flood management impacts on ecosystem services in a river landscape (Upper Danube, Germany)

Rivers and floodplains provide many regulating, provisioning and cultural ecosystem services (ES) such as flood risk regulation, crop production or recreation. Intensive use of resources such as hydropower production, construction of detention basins and intensive agriculture substantially change ecosystems and may affect their capacity to provide ES. Legal frameworks such as the European Water Framework Directive, Bird and Habitats Directive and Floods Directive already address various uses and interests. However, management is still sectoral and often potential synergies or trade‐offs between sectors are not considered. The ES concept could support a joint and holistic evaluation of impacts and proactively suggest advantageous options. The river ecosystem service index (RESI) method evaluates the capacity of floodplains to provide ES by using a standardized five‐point scale for 1 km‐floodplain segments based on available spatial data. This scaling allows consistent scoring of all ES and their integration into a single index. The aim of this article is to assess ES impacts of different flood prevention scenarios on a 75 km section of the Danube river corridor in Germany. The RESI method was applied to evaluate scenario effects on 13 ES with the standardized five‐point scale. Synergies and trade‐offs were identified as well as ES bundles and dependencies on land use and connectivity. The ratio of actual and former floodplain has the strongest influence on the total ES provision: the higher the percentage and area of an active floodplain, the higher the sum of ES. The RESI method proved useful to support decision‐making in regional planning.BMBF, 033W024A, ReWaM - Verbundprojekt RESI: River Ecosystem Service Index, Teilprojekt

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme