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

The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome

<p>Abstract</p> <p>Background</p> <p>Non-thyroidal illness syndrome (NTIS) is a characteristic functional constellation of thyrotropic feedback control that frequently occurs in critically ill patients. Although this condition is associated with significantly increased morbidity and mortality, there is still controversy on whether NTIS is caused by artefacts, is a form of beneficial adaptation, or is a disorder requiring treatment. Trials investigating substitution therapy of NTIS revealed contradictory results. The comparison of heterogeneous patient cohorts may be the cause for those inconsistencies.</p> <p>Objectives</p> <p>Primary objective of this study is the identification and differentiation of different functional states of thyrotropic feedback control in order to define relevant evaluation criteria for the prognosis of affected patients. Furthermore, we intend to assess the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent (so-called "sub-clinical") thyrotoxicosis.</p> <p>Secondary objective is observation of variables that quantify distinct components of NTIS in the context of independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication.</p> <p>Design</p> <p>The <b>a</b>pproach to a <b>qua</b>ntitative <b>f</b>ollow-up <b>o</b>f <b>n</b>on-<b>t</b>hyroidal <b>i</b>llness <b>s</b>yndrome (AQUA FONTIS study) is designed as both a cross-sectional and prospective longitudinal observation trial in critically ill patients. Patients are observed in at least two evaluation points with consecutive assessments of thyroid status, physiological and clinical data in additional weekly observations up to discharge. A second part of the study investigates the neuropsychological impact of NTIS and medium-term outcomes.</p> <p>The study design incorporates a two-module structure that covers a reduced protocol in form of an observation trial before patients give informed consent. Additional investigations are performed if and after patients agree in participation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00591032</p

Promotion of couples' voluntary counselling and testing for HIV through influential networks in two African capital cities

<p>Abstract</p> <p>Background</p> <p>Most new HIV infections in Africa are acquired from cohabiting heterosexual partners. Couples' Voluntary Counselling and Testing (CVCT) is an effective prevention strategy for this group. We present our experience with a community-based program for the promotion of CVCT in Kigali, Rwanda and Lusaka, Zambia.</p> <p>Methods</p> <p>Influence Network Agents (INAs) from the health, religious, non-governmental, and private sectors were trained to invite couples for CVCT. Predictors of successful promotion were identified using a multi-level hierarchical analysis.</p> <p>Results</p> <p>In 4 months, 9,900 invitations were distributed by 61 INAs, with 1,411 (14.3%) couples requesting CVCT. INAs in Rwanda distributed fewer invitations (2,680 vs. 7,220) and had higher response rates (26.9% vs. 9.6%), than INAs in Zambia. Context of the invitation event, including a discreet location such as the INA's home (OR 3.3–3.4), delivery of the invitation to both partners in the couple (OR 1.6–1.7) or to someone known to the INA (OR 1.7–1.8), and use of public endorsement (OR 1.7–1.8) were stronger predictors of success than INA or couple-level characteristics.</p> <p>Conclusion</p> <p>Predictors of successful CVCT promotion included strategies that can be easily implemented in Africa. As new resources become available for Africans with HIV, CVCT should be broadly implemented as a point of entry for prevention, care and support.</p

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

Determination of desorption isotherms on basis of an experimental fluidized bed drying curve

Zaprezentowano metodę wyznaczenia krzywych równowagi desorpcji w oparciu o eksperymentalne krzywe suszenia fluidalnego substancji zaliczanych do grupy B klasyfikacji Geldarta. W pracy wykorzystano autorski model matematyczny kinetyki okresowego suszenia fluidalnego ciał stałych w złożu pęcherzykowym przy zastosowaniu optymalizacyjnego zagadnienia odwrócenia. Otrzymane równania obejmujące zależność wilgotności względnej od temperatury i zawartości wilgoci zweryfikowano doświadczalnie.The method presented in this paper enables the determination of desorption isotherms. The method uses an experimental drying curve and is appropriate for materials which belong to the group B of the Geldart classification. A solution was reached with the application of reverse calculation methodology used in the fluidized bed drying kinetics mathematical model. The results are presented in a form of equations showing relative humidity as a function of temperature and moisture content. The equations were verified experimentally

Otrzymywanie i właściwości pochodnych skrobi hydroksypropylowej

Starch ethers were obtained under various conditions, i.e. hydroxypropylammonium starch as cationic starch and hydroxypropyl starch. The degree of substitution of starch ethers and their properties were examined.W przeprowadzanych doświadczeniach poddawano zawiesinę skrobi ziemniaczanej w wodzie w obecności wodorotlenku wapniowego w temp. 35 °C w czasie 8 godz. działaniu chlorku trójmetylo-chlorohydroksypropylo-amoniowego. Uzyskaną skrobię hydroksypropyloamoniową poddawano działaniu różnych chemikaliów i suszeniu w suszarce walcowej (najlepsze rezultaty) lub suszarce z przepływem powietrza (tab. 1). Oznaczono wpływ czasu reakcji na stopień podstawienia skrobi grupami hydroksypropyloamoniowymi (tab. 3) oraz wpływ obróbki chemikaliami podstawionej skrobi na lepkość jej kleików i kationowość (tab. 3). W dalszych doświadczeniach poddawano skrobię ziemniaczaną z dodatkiem fosforanu dwusodowego jako katalizatora w stanie powietrznie suchym (zaw. ok. 10% wody) pod ciśnieniem działaniu tlenku propylenu w ilości 1-20% licząc na s.s. skrobi w czasie 8 godz. w temp. 82°C. Stopień podstawienia preparatów skrobi hydroksypropyłowej oznaczano zarówno metodą Lortza z kwasem jodowodorowym, jak i za pomocą jądrowego magnetycznego rezonansu (NMR). Uzyskano interesujące wyniki wprost proporcjonalnej zależności stopnia eteryfikacji skrobi oraz zmiennej zależności lepkości kleików preparatów skrobi hydroksypropylowej od ilości użytego tlenku propylenu (tab. 5). W końcowych doświadczeniach na zawiesinę skrobi działano w alkalicznym roztworze wodnym tlenkiem propylenu w temp. 38°C w ciągu 72 godz. oznaczając wpływ czasu reakcji na stopień eteryfikacji skrobi (tab. 4). Badano również wpływ utleniania podchlorynem na lepkość kleików skrobi hydroksypropylowej w zależności od dawki czynnego chloru, stwierdzając wielokrotne zmniejszenie lepkości

Otrzymywanie i właściwości skrobi modyfikowanych z udziałem mocznika

Starch was modified with the use of urea in presences of magnesium sulphate and sulphuric acid or phosphoric acid. The influence of various factors on the physico-chemical properties of modified starch was examined.Skrobię ziemniaczaną mieszano w podwyższonej temperaturze z roztworem wodnym zawierającym kwas siarkowy, siarczan magnezowy i mocznik, po czym mieszaninę reakcyjną suszono i prażono w temp. 125°C (398 K). W poszczególnych doświadczeniach zmieniano kolejno czas prażenia oraz dawki kwasu siarkowego, mocznika i siarczanu magnezowego. W dalszych badaniach zastępowano również siarczan magnezowy innymi solami, a kwas siarkowy wymieniano na kwas fosforowy, Uzyskano interesujące wyniki wpływu rodzaju i ilości wprowadzanych chemikaliów na lepkość kleików i redukcyjność otrzymanych preparatów modyfikowanej skrobi. Rezultaty doświadczeń pośrednio wskazują na sieciowanie skrobi z udziałem doświadczeń pośrednio wskazują na sieciowanie skrobi z udziałem mocznika nie tylko za pomocą wiązań cząsteczek przy węglu C₁, ale również za pomocą poprzecznych wiązań, np. przy węglach C₆. Te ostatnie wiązania poprzeczne powstają również za pośrednictwem reszt fosforanowych

Adsorption of Oxygen on HF-Etched Si(111) Surfaces: XPS Study

X-ray photoelectron spectroscopy studies of the Si(111) surfaces, after dilute HF etching and methanol rinse, are reported. These included a detailed analysis of the main core-levels (Si 2p, O 1s) and the valence band spectra. The observed asymmetry of the O 1s lines was attributed to two contributing subpeaks: the main (1) and the minor one (2), shifted ≈ 1.5 eV to higher binding energies. Their relative intensity was found to depend on the air exposure time and on the take-off angle. The peaks were assigned to two different positions of surface oxygen: (1) O chemisorbed with methoxy group, (2) bridging O atom. The valence band X-ray photoelectron spectroscopy spectra reveal the influence of surface states induced by the "chemisorbed O"-Si bond